Toxicology Recall

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qxd 11/1/08 1:16 AM Page i
TOXICOLOGY RECALL
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RECALL SERIES EDITOR

Lorne H. Blackbourne, MD, FACS
Trauma, Burn, and Critical Care Surgeon
San Antonio, Texas
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TOXICOLOGY RECALL
EDITORS
CHRISTOPHER P. HOLSTEGE, MD
Director
Division of Medical Toxicology
Associate Professor
Departments of Emergency Medicine & Pediatrics
University of Virginia School of Medicine
Charlottesville, Virginia
MATTHEW P. BORLOZ
Medical Student, Class of 2008
JOHN P. BENNER, NREMT-P

Lieutenant
Madison County EMS
Madison, Virginia
ASSOCIATE EDITORS
DAVID T. LAWRENCE, DO
Assistant Professor
Department of Emergency Medicine
NATHAN P. CHARLTON, MD
Medical Toxicology Fellow
Department of Emergency Medicine
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Acquisitions Editor: Charles W. Mitchell

Managing Editor: Kelley A. Squazzo
Marketing Manager: Emilie Moyer
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987654321
Library of Congress Cataloging-in-Publication Data
Toxicology recall / editors, Christopher P. Holstege, Matthew P. Borloz, John P. Benner ; associate
editors, David T. Lawrence, Nathan P. Charlton.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-7817-9089-5
1. Toxicology—Handbooks, manuals, etc. I. Holstege, Christopher P.
[DNLM: 1. Toxicology—Examination Questions. 2. Poisoning—diagnosis—Examination
Questions. 3. Poisoning—therapy—Examination Questions. 4. Poisons—Examination Questions.
QV 18.2 T7545 2009]
RA1215.T697 2009
615.9—dc22
2008029897
DISCLAIMER
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contents of the publication. Application of this information in a particular situation remains the
professional responsibility of the practitioner; the clinical treatments described and recommended
may not be considered absolute and universal recommendations.
The authors, editors, and publisher have exerted every effort to ensure that drug selection and
dosage set forth in this text are in accordance with the current recommendations and practice at the
time of publication. However, in view of ongoing research, changes in government regulations, and
the constant flow of information relating to drug therapy and drug reactions, the reader is urged to
check the package insert for each drug for any change in indications and dosage and for added
warnings and precautions. This is particularly important when the recommended agent is a new or
infrequently employed drug.
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We dedicate this book to all students, residents, and fellows from the
schools of medicine, nursing, and pharmacy who strive to become the
best caretakers of their patients. We hope this book will aid you in
your quest for excellence.
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Acknowledgments
We wish to acknowledge our spectacular Administrative Assistants, Heather

Collier and Janet Mussleman (deceased), for their tireless support of our work.
We also wish to acknowledge our Managing Director, Steve Dobmeier, who
continually provides the tools necessary for all the work we set to accomplish.
vii
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Contributors
Seth Althoff, MD Jeffrey D. Ferguson, MD,

University of Virginia Department of NREMT-P
Emergency Medicine East Carolina University Department
Resident, Class of 2009 of Emergency Medicine
Charlottesville, Virginia Assistant Professor of Emergency
Medicine
D. Steele Beasley, MD Greenville, North Carolina
University of Virginia Department of
Emergency Medicine F. J. Fernandez, MD
Chief Resident, Class of 2008 University of Cincinnati Department
Charlottesville, Virginia of Emergency Medicine
Resident, Class of 2010
Ashley L. Blair, PhD Cincinnati, Ohio
Charlottesville-Albemarle Rescue
Squad Geoffrey Froehlich
Charlottesville, Virginia Charlottesville-Albemarle Rescue
Squad
William J. Brady, MD Charlottesville, Virginia
University of Virginia Department of
Emergency Medicine Rachel Garvin, MD
Professor & Vice-Chair of University of Cincinnati Department
Emergency Medicine of Emergency Medicine
Charlottesville, Virginia Resident, Class of 2010
Cincinnati, Ohio
William E. Brooks
Jefferson Medical College Ashley E. Gunnell, NREMT-I
Class of 2009 Charlottesville-Albemarle Rescue
Philadelphia, Pennsylvania Squad
Christina M. Burger, MD
University of Virginia Department of Todd Hansen, NREMT-I
Emergency Medicine Charlottesville-Albemarle Rescue
Resident, Class of 2009 Squad
Charlottesville, Virginia Charlottesville, Virginia
Brian T. Fengler, MD Nicholas D. Hartman

University of Virginia Department of University of Virginia School of
Emergency Medicine Medicine
Resident, Class of 2008 Class of 2008
ix
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x Contributors
Joshua Hilton, MD Todd Larson

Northwestern University Department University of Virginia School of
of Emergency Medicine Medicine
Resident, Class of 2009 Class of 2008
Chicago, Illinois Charlottesville, Virginia
Brian B. Hughley Richard M. Law

University of Virginia School of The Ohio State University College
Medicine of Medicine
Class of 2009 Class of 2008
Charlottesville, Virginia Columbus, Ohio
Jason A. Inofuentes Benjamin J. Lehman, MD

Charlottesville-Albemarle Rescue University of Virginia Department of
Squad Emergency Medicine
Charlottesville, Virginia Resident, Class of 2008
Anand Jain
Pauline E. Meekins, MD
Drexel University College of
Medical University of South Carolina
Medicine
Division of Emergency Medicine
Class of 2008
Clinical Faculty
Philadelphia, Pennsylvania
Charleston, South Carolina
Anthony E. Judkins, NREMT-I
Christopher A. Mitchell
Madison County EMS
The Ohio State University College
of Medicine
Class of 2008
Erin S. Kalan
Columbus, Ohio
Charlottesville-Albemarle Rescue
Squad Lisa J. Mitchell
Charlottesville, Virginia Charlottesville-Albemarle Rescue
Squad
Brian J. Kipe Charlottesville, Virginia
University of Virginia School of
Medicine J.V. Nable
Class of 2008 University of Virginia School of
Charlottesville, Virginia Medicine
Class of 2009
Michael C. Kurz, MD, MS-HES Charlottesville, Virginia
Virginia Commonwealth University
Department of Emergency Christopher Pitotti
Medicine University of Virginia School of
Assistant Professor of Emergency Medicine
Medicine Class of 2008
Richmond, Virginia Charlottesville, Virginia
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Contributors xi
James Platts-Mills Stephen Stacey

University of Virginia School of Eastern Virginia Medical School
Medicine Class of 2010
Class of 2009 Norfolk, Virginia
Stephen Thornton, MD
Timothy F. Platts-Mills, MD
University of Kansas Hospital
University of North Carolina at
Clinical Associate Professor
Chapel Hill Department of
Leakwood, Kansas
Emergency Medicine
Assistant Professor of Emergency
Medicine Sara Naomi Tsuchitani, MD
Chapel Hill, North Carolina Eastern Virginia Medical School
Department of Emergency
Michelle A. Ramos Medicine
University of Virginia School of Resident, Class of 2010
Medicine Norfolk, Virginia
Class of 2008
Charlottesville, Virginia Amber Turner
Amy Schutt
Medicine
Texas Tech University Health
Class of 2010
Sciences Center School of
Medicine
Class of 2009
Lubbock, Texas Edward Walsh, MD
Mary Washington Hospital
Robert Schutt III Department of Emergency
Texas Tech University Health Medicine
Sciences Center School of Attending Physician
Medicine Fredericksburg, Virginia
Class of 2009
Lubbock, Texas Michael J. Ward, MD, MBA
University of Cincinnati Department
Landon Smith
of Emergency Medicine
Resident, Class of 2010
Medicine
Cincinnati, Ohio
Class of 2008
Elisabeth B. Wright
Jeffrey St. Amant, MD University of Virginia School of
University of Virginia Department Medicine
of Emergency Medicine Medical Simulation Technology
Resident, Class of 2009 Specialist
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Contents
Dedication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xxi
1 Evaluation of the Poisoned Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Clinical Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Testing in Poisoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
2 Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Acetaminophen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Amantadine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Central . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Local . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Angiotensin-Converting Enzyme Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . 25
Angiotensin Receptor Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Antibacterial Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Anticholinergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Anticonvulsants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Antidepressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Cyclic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Monoamine Oxidase Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Selective Serotonin Reuptake Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . 39
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Antidiarrheal Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Antiemetic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Antifungal Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Antihyperlipidemia Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Antimalarial Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Antipsychotic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Antiviral and Antiretroviral Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Barbiturates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Beta 2-Adrenergic Agonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
xiii
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xiv Contents
Botulin (Botulism) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Caffeine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Camphor and Other Essential (Volatile) Oils . . . . . . . . . . . . . . . . . . . . . 62
Carbamazepine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Chemotherapeutic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Chloroquine and Other Aminoquinolines . . . . . . . . . . . . . . . . . . . . . . . . . 67
Clonidine and Related Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Colchicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Dapsone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Decongestants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Digoxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Disulfiram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Ergot Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Heparin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Hypoglycemic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Insulin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Metformin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Sulfonylureas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Immunosuppressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Ipecac Syrup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Isoniazid (INH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Ketamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Lithium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Magnesium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Neuromuscular Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Nitrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
Nitrites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Nitroprusside . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Nitrous Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Nonsteroidal Anti-inflammatory Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Phenytoin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Rauwolfia Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Salicylates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
Sedative-Hypnotic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Skeletal Muscle Relaxants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
Theophylline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Thyroid Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Type I Antidysrhythmic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Type II Antidysrhythmic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Type III Antidysrhythmic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
Type IV Antidysrhythmic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
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Contents xv
Valproic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

Vasodilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
Warfarin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
3 Drugs of Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Amphetamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Cocaine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Designer Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Dextromethorphan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
Ethanol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Gamma-hydroxybutyrate (GHB) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Hallucinogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
Inhalants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Marijuana . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
Mescaline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Nicotine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
Phencyclidine (PCP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
4 Environmental and Industrial Toxins . . . . . . . . . . . . . . . . . . . . . . 154
Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
Ammonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
Antiseptics and Disinfectants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
Asbestos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
Azide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Benzene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Boric Acid, Borates, and Boron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
Bromates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
Bromides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Camphor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Carbon Disulfide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
Carbon Monoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172
Carbon Tetrachloride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
Caustics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
Chlorates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Chlorine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Chloroform . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Cyanide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Detergents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Dimethyl Sulfoxide (DMSO) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
Dioxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
Disk Batteries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
Ethylene Dibromide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Ethylene Glycol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
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Ethylene Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

Fluorides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Fluoroacetate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
Formaldehyde . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
Freons and Halons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
Gases (Irritant) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
Glycol Ethers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
Hydrocarbons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Hydrogen Sulfide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
Iodine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Isocyanates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
Isopropanol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214
Metaldehyde . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Methanol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
Methemoglobinemia Inducers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
Methyl Bromide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
Methylene Chloride . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
Mothballs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Nitrites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
Nitrogen Oxides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
Nontoxic and Minimally Toxic Household Products . . . . . . . . . . 228
Oxalic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
Pentachlorophenol and Dinitrophenol . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Perchloroethylene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
Phenol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
Phosphine & Phosphides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
Phosphorus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Phthalates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
Polychlorinated Biphenyls (PCBs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Radiation (Ionizing) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
Smoke Inhalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
Strychnine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Sulfur Dioxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Toluene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252
Trichloroethane and Trichloroethylene . . . . . . . . . . . . . . . . . . . . . . . . . . 254
5 Heavy Metals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Aluminum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Antimony and Stibine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Arsenic and Arsine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
Barium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
Beryllium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Bismuth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Cadmium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
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Chromium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
Cobalt . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
Copper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
Gallium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
Germanium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Gold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Iron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
Lead . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
Lithium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
Manganese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Mercury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
Molybdenum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
Nickel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296
Platinum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Rare Earths . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
Selenium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300
Silver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
Thallium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 303
Tin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
Vanadium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
Zinc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Metal Fume Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
6 Pesticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Fungicides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Herbicides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Chlorophenoxy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Diquat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
Paraquat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
Insecticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Carbamates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Organochlorines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
Organophosphates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
Pyrethrins & Pyrethroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
Rodenticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Alpha-naphthylthiourea (ANTU) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Anticoagulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Cholecalciferol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
Sodium Monofluoroacetate (1080) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
Strychnine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
Vacor (PNU) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338
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7 Chemical Agents of Terrorism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342

Botulinum Toxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
Incapacitating Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344
Incendiary Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
Irritants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 346
Nerve Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
Phosgene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
3-Quinuclidinyl Benzilate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Ricin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
Trichothecene Mycotoxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Vesicants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
Vomiting Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
8 Natural Toxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Amphibians . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Arthropods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Black Widow Spiders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Brown Recluse Spiders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
Scorpions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
Ticks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
Botulism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Essential Oils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385
Food Poisoning, Bacterial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386
Herbal Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389
Marine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
Ingested . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392
Invertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398
Vertebrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402
Coprine Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402
Cortinarius Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
Cyclopeptide Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
Gastrointestinal Irritant Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 406
Hallucinogen Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 407
Ibotenic/Muscimol Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
Monomethylhydrazines Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
Muscarine Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
Mycotoxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412
Plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
Anticholinergic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
Cardiac Glycosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
Cyanogenic Glycosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 418
Dermatitis-Producing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420
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Contents xix
Gastrointestinal Irritants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422

Nicotinics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
Oxalates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424
Sodium Channel Openers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Solanine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Toxalbumins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 430
Reptiles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
Snakes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
Elapidae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432
Viperidae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437
Tetanus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
9 Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444
Acetylcysteine (N-acetylcysteine, NAC) . . . . . . . . . . . . . . . . . . . . . . . . . . 444
Antivenom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446
Black Widow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446
Scorpion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447
Snake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448
Atropine and Glycopyrrolate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 450
Barbiturates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451
Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453
Benztropine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454
Bicarbonate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454
Botulinum Antitoxin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456
Bromocriptine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457
Calcium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
Calcium Disodium Ethylenediaminetetraacetic
Acid (CaNa2EDTA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460
L-Carnitine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461
Charcoal (Activated) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 462
Cyproheptadine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
Cyanide Antidote Package . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
Dantrolene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467
Deferoxamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467
Dialysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469
Dimercaptopropanesulfonic Acid (DMPS) . . . . . . . . . . . . . . . . . . . . . . . 470
Diethyldithiocarbamate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471
Digoxin Immune Fab . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471
Dimercaprol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473
Dimethyl-P-Aminophenol (DMAP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474
Diphenhydramine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476
Ethanol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
Flumazenil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478
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Folic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479

Fomepizole (4-Methylpyrazole, 4-MP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480
Glucagon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
Glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
Haloperidol and Droperidol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484
Histamine-2 Receptor Antagonists (H2 Blockers) . . . . . . . . . . . . . . 486
Hydroxocobalamin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
Hyperbaric Oxygen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 488
Inamrinone (previously Amrinone) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
Insulin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 492
Iodide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 494
Ipecac Syrup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
Isoproterenol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496
Leucovorin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497
Lidocaine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 498
Magnesium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
Methylene Blue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 500
Naloxone, Naltrexone, and Nalmefene . . . . . . . . . . . . . . . . . . . . . . . . . . . 502
Neuromuscular Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
Octreotide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505
Penicillamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506
Phentolamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507
Phenytoin and Fosphenytoin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 508
Physostigmine and Neostigmine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 509
Pralidoxime (2-PAM) and Other Oximes . . . . . . . . . . . . . . . . . . . . . . . . 510
Propofol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512
Propranolol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
Protamine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515
Prussian Blue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 516
Pyridoxine (Vitamin B6) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517
Silibinin or Milk Thistle (Silybum marianum) . . . . . . . . . . . . . . . . . . . . . . 518
Succimer (DMSA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519
Thiamine (Vitamin B1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519
Vasopressors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521
Vitamin K1 (Phytonadione) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 525
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 527
10 Visual Diagnosis in Medical Toxicology ................... 531
Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 554
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Preface
Throughout the world each year, millions of people are evaluated by health
care professionals following a poisoning. There are innumerable potential
toxins that can inflict harm to humans, including pharmaceuticals, herbals,
household products, environmental agents, occupational chemicals, drugs of
abuse, and chemical terrorism threats. The Centers for Disease Control
reported that poisoning (both intentional and unintentional) was one of the
top ten causes of injury-related death in the United States in all adult age
groups. From the beginnings of written history, poisons and their effects have
been well-described. Paracelsus (1493–1541) correctly noted that “All
substances are poisons; there is none which is not a poison. The right dose
differentiates a poison . . . .” As life in the modern era has become more
complex, so has the study of toxicology.
This book is intended to assist the reader in learning the pertinent toxicities
of various agents seen in clinical practice. It has become increasingly difficult
for healthcare providers to learn these facts with the emergence of numerous
and vastly different pharmaceuticals, abused drugs, chemicals within the work
place, and agents of terrorism. As the editors, we considered numerous topics
for inclusion in this book. It is our hope that this book will provide both a rapid
insight into specific toxins for medical personnel caring for potentially
poisoned patients and a valuable resource for students pursuing their
education.
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Chapter 1 Evaluation of the

Poisoned Patient
INTRODUCTION
Toxicologic emergencies are commonly encountered in the practice of

medicine. Patients can be exposed to potential toxins either by accident (e.g.,
workplace incidents or drug interactions) or intention (e.g., drug abuse or
suicide attempt). The outcome following a poisoning depends on numerous
factors, such as the dose taken, the time before presentation to the healthcare
facility, and the preexisting health status of the patient. If a poisoning is
recognized early and appropriate supportive care is initiated quickly, the
majority of patient outcomes will be good.
CLINICAL EVALUATION
When evaluating a patient who has presented with a potential poisoning, it is

important not to limit the differential diagnosis. A comatose patient who
smells of alcohol may be harboring an intracranial hemorrhage or an agitated
patient who appears anticholinergic may actually be encephalopathic from an
infectious etiology. Patients must be thoroughly assessed and appropriately
stabilized. There is often no specific antidote or treatment for a poisoned
patient and careful supportive care is the most important intervention.
All patients presenting with toxicity or potential toxicity should be
aggressively managed. The patient’s airway should be patent and adequate
ventilation ensured. If necessary, endotracheal intubation should be
performed. Too often, healthcare providers are lulled into a false sense of
security when a patient’s oxygen saturations are adequate on high flow oxygen.
If the patient has either inadequate ventilation or a poor gag reflex, then the
patient may be at risk for subsequent CO2 narcosis with worsening acidosis or
aspiration. The initial treatment of hypotension consists of intravenous fluids.
Close monitoring of the patient’s pulmonary status should be performed to
ensure that pulmonary edema does not develop as fluids are infused. The
healthcare providers should place the patient on continuous cardiac
monitoring with pulse oximetry and make frequent neurological checks. In all
patients with altered mental status, blood glucose should be checked.
Poisoned patients should receive a large-bore peripheral intravenous line, and
all symptomatic patients should have a second line placed in either the
peripheral or central venous system. Placement of a urinary catheter should be
considered early in the care of hemodynamically unstable poisoned patients to
1
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2 Toxicology Recall
monitor urinary output, as this is one of the best indicators of adequate

perfusion.
Many toxins can potentially cause seizures. In general, toxin-induced
seizures are treated in a similar fashion to other seizures. Clinicians should
ensure the patient maintains a patent airway, and the blood glucose should
be measured. Most toxin-induced seizures will be self-limiting. However, for
seizures requiring treatment, the first-line agent should be parenteral
benzodiazepines. If benzodiazepines are not effective at controlling seizures,
a second-line agent such as phenobarbital should be employed. In rare cases,
such as isoniazid poisoning, pyridoxine should be administered. In cases of
toxin-induced seizures, phenytoin is generally not recommended as it is
usually ineffective and may add to the underlying toxicity of some agents. If
a poisoned patient requires intubation, it is important to avoid the use of
long-acting paralytic agents, as these agents may mask seizures if they
develop.
TOXIDROMES
Toxidromes are toxic syndromes or the constellation of signs and symptoms
associated with a class of poisons. Rapid recognition of a toxidrome, if present,
can help determine whether a poison is involved in a patient’s condition and
can help determine the class of toxin involved. Table 1-1 lists selected
Table 1-1. Toxidromes

Toxidrome Signs and Symptoms
Anticholinergic Mydriasis, dry skin, dry mucous membranes, decreased

bowel sounds, sedation, altered mental status,
hallucinations, dysarthria, urinary retention
Cholinergic Miosis, lacrimation, diaphoresis, bronchospasm,

bronchorrhea, vomiting, diarrhea, bradycardia
Opioid Sedation, miosis, decreased bowel sounds, decreased

respirations
Sedative-hypnotic Sedation, decreased respirations, normal pupil size,

normal vital signs
Serotonin syndrome Altered mental status, tachycardia, hypertension,

hyperreflexia, clonus, hyperthermia
Sympathomimetic Agitation, mydriasis, tachycardia, hypertension,

hyperthermia, diaphoresis
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Chapter 1 / Evaluation of the Poisoned Patient 3
toxidromes and their characteristics. It is important to note that patients may

not present with every component of a toxidrome and that toxidromes can be
clouded in mixed ingestions.
Certain aspects of a toxidrome can have great significance. For example,
noting dry axillae may be the only way of differentiating an anticholinergic
patient from a sympathomimetic patient, and miosis may distinguish opioid
toxicity from a benzodiazepine overdose. There are several notable
exceptions to the recognized toxidromes. For example, some opioid agents
do not cause miosis (e.g., meperidine, tramadol). In most cases, a toxidrome
will not indicate a specific poison but rather a class of poisons. Several
poisons have unique toxidromes which make their presence virtually
diagnostic. An example is botulinum toxin. A patient with bulbar palsy, dry
mouth, mydriasis, and diplopia with intact sensation is almost certain to have
botulism.
TESTING IN POISONING
When evaluating the intoxicated patient, there is no substitute for a thorough

history and physical exam. On today’s television programming, numerous
medical shows depict a universal toxicology screen that automatically
determines the agent causing a patient’s symptoms. Unfortunately, samples
cannot be simply “sent to the lab” with the correct diagnosis to a clinical
mystery returning on a computer printout. Clues from a patient’s physical
exam are generally more likely to be helpful than a “shotgun” laboratory
approach that involves indiscriminate testing of blood or urine for multiple
agents.
When used appropriately, diagnostic tests may be of help in the
management of the intoxicated patient. When a specific toxin or even class
of toxins is suspected, requesting qualitative or quantitative levels may be
appropriate. In the suicidal patient whose history is generally unreliable, or
in the unresponsive patient where no history is available, the clinician may
gain further clues as to the etiology of a poisoning by responsible diagnostic
testing.
ANION GAP
Obtaining a basic metabolic panel from all poisoned patients is generally
recommended. When low serum bicarbonate is discovered on a metabolic
panel, the clinician should determine if an elevated anion gap exists. The
formula most commonly used for the anion gap calculation is:
Anion gap [Na] [Cl HCO3]
This equation allows one to determine if serum electroneutrality is being

maintained. The primary cation (sodium) and anions (chloride and
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4 Toxicology Recall
bicarbonate) are represented in the equation. There are other contributors to

this equation that are “unmeasured.” Other serum cations are not commonly
included in this calculation because either their concentrations are relatively
low (e.g., potassium), or assigning a number to represent their respective
contribution is difficult (e.g., magnesium, calcium). Similarly, there is a
multitude of other serum anions (e.g., sulfate, phosphate, organic anions) that
are also difficult to measure in the serum and quantify in an equation. These
“unmeasured” ions represent the anion gap calculated using the equation
above. The normal range for this anion gap is accepted to be 8 to 16 mEq/L.
Practically speaking, an increase in the anion gap beyond an accepted normal
range, accompanied by a metabolic acidosis, represents an increase in
unmeasured endogenous (e.g., lactate) or exogenous (e.g., salicylates) anions.
A list of the more common causes of this phenomenon is organized in the
classic MUDILES mnemonic:
Methanol
Uremia
Diabetic ketoacidosis
Iron, Inhalants (e.g., carbon monoxide, cyanide, toluene), Isoniazid,
Ibuprofen
Lactic acidosis
Ethylene glycol, Ethanol ketoacidosis
Salicylates, Starvation ketoacidosis, Sympathomimetics
It is imperative that clinicians who admit poisoned patients initially

presenting with an increased anion gap metabolic acidosis investigate the
etiology of that acidosis. Many symptomatic poisoned patients may have an
initial mild metabolic acidosis upon presentation due to the processes
resulting in the elevation of serum lactate. However, with adequate supportive
care including hydration and oxygenation, the anion gap acidosis should
improve. If, despite adequate supportive care, an anion gap metabolic acidosis
worsens in a poisoned patient, the clinician should consider either toxins that
form acidic metabolites (e.g., ethylene glycol, methanol, ibuprofen) or toxins
which cause lactic acidosis by interfering with aerobic energy production (e.g.,
cyanide, iron).
OSMOL GAP
The serum osmol gap is a common laboratory test that may be useful when
evaluating poisoned patients. This test is most often discussed in the context
of evaluating the patient suspected of toxic alcohol (i.e., ethylene glycol,
methanol, isopropanol) intoxication. Though this test may have utility in such
situations, it has many pitfalls and limitations.
Osmotic concentrations are themselves expressed both in terms of osmolality
[milliosmoles/kg of solvent (mOsm/kg)] and osmolarity [milliosmoles/liter of
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solution (mOsm/L)]. This concentration can be measured by use of an

osmometer, a tool that most often utilizes the technique of freezing point
depression and yields values expressed as osmolality (Osmm). A calculated
serum osmolarity (Osmc) may be obtained by any of a number of equations
involving the patient’s glucose, sodium, and urea which contribute almost all of
the normally measured osmolality. One of the most commonly used of these
calculations is expressed below:
[BUN] [glucose]
Osmc 2 [Na]
2.8 18
The correction factors in the equation are based on the relative osmotic
activity of the substance in question. Assuming serum neutrality, sodium as the
predominant serum cation is doubled to account for the corresponding anions.
Finding the osmolarity contribution of any other osmotically active substances
reported in mg/dL (like BUN and glucose) is accomplished by dividing by
one-tenth their molecular weight (MW) in daltons. For BUN this conversion
factor is 2.8, and for glucose it is 18. Similar conversion factors may be added
to this equation in an attempt to account for ethanol and the various toxic
alcohols as shown below:
[BUN] [glucose] [ethanol] [methanol]

Osmc 2 [Na]
2.8 18 4.6 3.2
[ethylene glycol] [isopropanol]

6.6 6.0
The difference between the measured (Osmm) and calculated (Osmc) is the
osmol gap (OG) and is depicted by the equation below:
OG Osmm Osmc
If a significant osmol gap is discovered, the difference in the two values

may indicate the presence of foreign substances in the blood. A list of
possible causes of an elevated osmol gap is provided in Table 1-2.
Unfortunately, what constitutes a normal osmol gap is widely debated.
Traditionally, a normal gap has been defined as 10 mOsm/kg. Analytical
variance alone may account for the variation found in patients’ osmol gaps.
This concern that even small errors in the measurement of sodium can result
in large variations in the osmol gap has been voiced by other researchers.
Overall, the clinician should recognize that there is likely significant
variability in a patient’s baseline osmol gap.
The osmol gap should be used with caution as an adjunct to clinical
decision making and not as a primary determinant to rule out toxic alcohol
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6 Toxicology Recall
Table 1-2. Toxins Causing Elevated Osmol Gap

Acetone
Ethanol
Ethyl ether
Ethylene glycol
Glycerol
Isoniazid
Isopropanol
Mannitol
Methanol
Osmotic contrast dyes
Propylene glycol
Trichloroethane
ingestion. If the osmol gap obtained is particularly large, it suggests that an

agent from Table 1-2 may be present. A “normal” osmol gap should be
interpreted with caution; a negative study may, in fact, not rule out the
presence of such an ingestion. As with any test result, this must be interpreted
within the context of the clinical presentation.
URINE DRUG SCREENING

Many clinicians regularly obtain urine drug screening on “altered” patients or
on those suspected of ingestion. Such routine urine drug testing, however, is
of questionable benefit. The effect of such routine screening on management
is low because most of the therapy is supportive and directed at the clinical
scenario (i.e., mental status, cardiovascular function, respiratory condition).
Interpretation of the results can be difficult even when the objective for
ordering a comprehensive urine screen is adequately defined. Most assays rely
on antibody identification of drug metabolites, with some drugs remaining
positive days after use, and thus provide information potentially unrelated to
the patient’s current clinical picture. The positive identification of drug
metabolites is likewise influenced by chronicity of ingestion, fat solubility, and
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co-ingestions. Conversely, many drugs of abuse (e.g., ketamine, fentanyl) are

not detected on most urine drug screens.
The ordering of urine drug screens is fraught with significant testing
limitations, including false-positive and false-negative results. Many authors
have shown that the test results rarely affect management decisions. Routine
drug screening of those with altered mental status, abnormal vital signs, or
suspected ingestion is not warranted and rarely guides patient treatment or
disposition.
ELECTROCARDIOGRAM
The interpretation of the electrocardiogram (ECG) in the poisoned patient
can challenge even the most experienced clinician. Numerous drugs can cause
ECG changes. The incidence of ECG changes in the poisoned patient is
unclear, and the significance of various changes may be difficult to define.
Despite the fact that drugs have widely varying indications for therapeutic use,
many unrelated drugs share common cardiac electrocardiographic effects if
taken in overdose. Potential toxins can be placed into broad classes based on
their cardiac effects. Two such classes, agents that block the cardiac potassium
efflux channels and agents that block cardiac fast sodium channels, can lead to
characteristic changes in cardiac indices, consisting of QT prolongation and
QRS prolongation, respectively. The recognition of specific ECG changes
associated with other clinical data (e.g., toxidromes) can potentially be life-
saving.
Studies suggest that approximately 3% of all noncardiac prescriptions are
associated with the potential for QT prolongation. Myocardial repolarization is
driven predominantly by outward movement of potassium ions. Drug-induced
blockade of these outward potassium currents prolongs the action potential.
This results in QT-interval prolongation and the potential emergence of T or
U wave abnormalities on the ECG. This prolonged repolarization causes the
myocardial cell to have less charge difference across its membrane, which may
result in the activation of the inward depolarization current (early after-
depolarization) and promote triggered activity. These changes may lead to re-
entry and subsequent polymorphic ventricular tachycardia, most often as the
torsade de pointes. The QT interval is simply measured from the beginning of
the QRS complex to the end of the T wave. Within any ECG tracing, there is
lead-to-lead variation of the QT interval. In general, the longest measurable
QT interval on an ECG is regarded as the overall QT interval for a given
tracing. The QT interval is influenced by the patient’s heart rate. Several
formulas have been developed to correct the QT interval for the effect of heart
rate (QTC) using the RR interval (RR), with Bazett’s formula utilized most
commonly:
QT
QTc
冑RR
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8 Toxicology Recall
QT prolongation is considered to occur when the corrected QT interval (QTC)

is greater than 440 msec in men and 460 msec in women. Arrhythmias are
most commonly associated with values greater than 500 msec. The potential
for an arrhythmia at a given QT interval will vary, however, from drug to drug
and patient to patient. Drugs associated with QT prolongation are listed in
Table 1-3. Other etiologies with the potential to cause prolongation of the QT
interval include congenital long QT syndrome, mitral valve prolapse,
hypokalemia, hypocalcemia, hypomagnesemia, hypothermia, myocardial
ischemia, neurological catastrophes, and hypothyroidism.
The ability of drugs to induce cardiac sodium channel blockade and
thereby prolong the QRS complex has been well described in numerous
literature reports. This sodium channel blockade activity has been described
as a membrane stabilizing effect, a local anesthetic effect, or a quinidine-like
effect. Cardiac voltage-gated sodium channels reside in the cell membrane
and open in conjunction with cell depolarization. Sodium channel blockers
bind to the transmembrane sodium channels and thereby decrease the
number available for depolarization. This creates a delay of Na entry into
the cardiac myocyte during phase 0 of depolarization. As a result, the
upslope of depolarization is slowed and the QRS complex widens. In some
cases, the QRS complex may take the pattern of recognized bundle branch
blocks. In the most severe cases, QRS prolongation becomes so profound
that it is difficult to distinguish between ventricular and supraventricular
rhythms. Continued prolongation of the QRS may result in a sine wave
pattern and eventual asystole. It has been theorized that sodium channel
blockers can cause slowed intraventricular conduction, unidirectional block,
development of a re-entrant circuit, and ultimately ventricular tachycardia.
This can then degenerate into ventricular fibrillation. Differentiating toxic
versus nontoxic etiologies for a prolonged QRS can be difficult. Rightward
axis deviation of the terminal 40 msec of the QRS complex has been
associated with tricyclic antidepressant poisoning; however, the occurrence
of this finding with other sodium channel blocking agents is unknown.
Myocardial sodium channel blocking drugs comprise a diverse group of
pharmaceutical agents (Table 1-4). Patients poisoned with these agents will
have a variety of clinical presentations. For example, sodium channel
blocking medications such as diphenhydramine, propoxyphene, and cocaine
may also yield anticholinergic, opioid, and sympathomimetic syndromes,
respectively. In addition, specific drugs may affect not only the myocardial
sodium channels, but also the calcium influx and potassium efflux channels.
This may result in ECG changes and rhythm disturbances not related
entirely to the drug’s sodium channel blocking activity. All of the agents
listed in Table 1-4, however, are similar in that they may induce myocardial
sodium channel blockade and may respond to therapy with hypertonic saline
or sodium bicarbonate. In patients with a prolonged QRS interval,
particularly those with hemodynamic instability, it is therefore reasonable to
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Table 1-3. Potassium Efflux Channel Blocking Drugs

Antihistamines Class III antidysrhythmics
Astemizole Amiodarone
Clarithromycin Dofetilide
Diphenhydramine Ibutilide
Loratadine Sotalol
Terfenadine
Cyclic Antidepressants
Antipsychotics Amitriptyline
Chlorpromazine Amoxapine
Droperidol Desipramine
Haloperidol Doxepin
Mesoridazine Imipramine
Pimozide Maprotiline
Quetiapine Nortriptyline
Risperidone
Thioridazine Erythromycin
Ziprasidone Fluoroquinolones
Arsenic trioxide Ciprofloxacin
Gatifloxacin
Bepridil Levofloxacin
Moxifloxacin
Chloroquine Sparfloxacin
Cisapride Halofantrine
Citalopram Hydroxychloroquine
Clarithromycin Levomethadyl
Class IA antidysrhythmics Methadone
Disopyramide
Procainamide Pentamidine
Quinidine
Quinine
Class IC antidysrhythmics
Encainide Tacrolimus
Flecainide Venlafaxine
Moricizine
Propafenone
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10 Toxicology Recall
Table 1-4. Sodium Channel Blocking Drugs

Amantadine Diltiazem
Carbamazepine Diphenhydramine
Chloroquine Hydroxychloroquine
Citalopram Loxapine
Class IA antidysrhythmics Orphenadrine

Disopyramide
Procainamide Phenothiazines
Quinidine Mesoridazine
Thioridazine
Class IC antidysrhythmics
Encainide Propoxyphene
Flecainide Propranolol
Propafenone
Quinine
Cocaine
Verapamil
Cyclic antidepressants
treat empirically with 1-2 mEq/kg of sodium bicarbonate. A post-treatment

shortening of the QRS duration can confirm the presence of a sodium
channel blocking agent. In addition, sodium bicarbonate can improve
inotropy and help prevent arrhythmias.
There are multiple agents that can result in human cardiotoxicity and
resultant ECG changes, from those noted above to others, such as bradycardia
and tachycardia. Physicians managing patients who have overdosed on
medications should be aware of the various electrocardiographic changes that
may occur in this setting.
MANAGEMENT
After initial evaluation and stabilization of the poisoned patient, it is time to

initiate specific therapies if appropriate. Decontamination should be
considered. Also, several poisons have specific antidotes which, if utilized in a
timely and appropriate manner, can be of great benefit. Lastly, the final
disposition of the patient must be determined. Most patients may be
discharged home or to a psychiatric facility after a short observation period;
however, a number will need admission due to their clinical condition or
potential for deterioration.
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DECONTAMINATING THE POISONED PATIENT

Approximately 80% of all poisonings occur by ingestion, and the most
common type of subsequent decontamination performed is gastrointestinal
decontamination, using a variety of techniques including emesis, gastric
lavage, activated charcoal, cathartics, and whole bowel irrigation. Poisonings
may also occur by dermal and ocular routes, both of which necessitate external
decontamination. Significant controversy exists concerning the need for
routine gastric emptying in the poisoned patient. Current available evidence
dissuades the routine use of gastric decontamination, though it may be
considered in select cases and specific scenarios. Before performing
gastrointestinal decontamination techniques, the clinician responsible for the
care of the poisoned patient must clearly understand that these procedures are
not without hazards and that any decision regarding their use must consider
whether the benefits outweigh any potential harm.
Dermal Decontamination
Patients with dermal contamination who present to healthcare facilities pose a
potential risk to healthcare personnel. As a result, contaminated patients
should not gain entrance into the healthcare facility prior to decontamination.
Personnel involved in the dermal decontamination may need to don personal
protective equipment (PPE). Most chemical exposures do not pose a risk of
secondary exposure. In general, patients exposed to gas or vapor do not
require decontamination; removal from the site should be sufficient.
However, contaminated clothing should be removed and sealed within plastic
bags to avoid potential off gassing.
Patients exposed to toxic liquids, aerosols, or solids will require dermal
decontamination. Moving from head to toe, irrigate the exposed skin and
hair for 10 to 15 minutes and scrub with a soft surgical sponge, being careful
not to abrade the skin. Patient privacy should be respected if possible, and
warm water should be used to avoid hypothermia. Irrigate wounds for an
additional 5 to 10 minutes with water or saline. Clean beneath the nails with
a brush. Stiff brushes and abrasives should be avoided, as they may enhance
dermal absorption of the toxin and can produce skin lesions that may be
mistaken for chemical injuries. Sponges and disposable towels are effective
alternatives.
Ocular Decontamination
Ocular irrigation should be performed immediately by instillation of a gentle
stream of irrigation fluid into the affected eye(s). The contiguous skin should
also be irrigated. In cases of minor ocular toxicity, this procedure can be
conducted in the home. If irritation persists following home irrigation,
referral to an emergency department may be necessary. In the emergency
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department, the patient should undergo ocular irrigation with sterile normal
saline or lactated Ringer’s solution for a period of at least 15 to 30 minutes.
Tap water is acceptable if it is the only available solution; however, due to its
hypotonicity relative to the stroma, tap water may facilitate penetration of
corrosive substances into the cornea and worsen the outcome. Lactated
Ringer’s solution may be a preferable irrigant due its buffering capacity and
neutral pH. Instillation of tetracaine or another ocular anesthetic agent will
reduce pain and facilitate irrigation. Irrigation of the eyes should be directed
away from the medial canthus to avoid forcing contaminants into the
lacrimal duct. Longer irrigation times may be needed with specific
substances, and the endpoint of irrigation should be determined by
normalization of the ocular pH. If the pH does not normalize with copious
irrigation, it may be necessary to invert the lids to search for retained
material.
Gastrointestinal Decontamination
Emesis, gastric lavage, activated charcoal, cathartics, and whole bowel
irrigation are the available means of gastrointestinal decontamination. As a
result of emerging evidence, gastric lavage and syrup of ipecac-induced
emesis are rarely being utilized to decontaminate the poisoned patient. At
the present time, the documented risks associated with these procedures
should be carefully weighed in light of the rare indications. Activated
charcoal as the sole means of gastric decontamination is increasing in
popularity, but its efficacy has specific limitations. The major issue currently
facing the clinician is the choice of gastrointestinal (GI) decontamination in
the significantly poisoned patient. The choice of decontamination method
for these patients must be individualized using both evidence-based
medicine and clinical acumen. No patient should undergo any of the
available procedures unless it is anticipated that decontamination will
provide clinical benefits that outweigh the potential risks. Emesis, either by
mechanical stimulation (i.e., placing a finger down the throat) or by use of
syrup of ipecac, is contraindicated.
Gastric Lavage
The efficiency of gastric lavage to remove a marker significantly decreases
with increasing time following ingestion. This is due to the fact that as time
increases after ingestion, so too does the amount of marker that has been
absorbed or left the stomach. It is rare that gastric lavage can be performed
within the first hour after toxic ingestion. Not only does it take time for these
patients to present to the emergency department, but initial evaluation and
stabilization consume additional time before gastric lavage can take place.
Based on the available literature, gastric lavage should not be routinely
employed in the management of poisoned patients. Oral charcoal alone is
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considered superior to gastric lavage if the drug in question is adsorbed by

charcoal.
The performance of gastric lavage is contraindicated in any person who
demonstrates compromised airway protective reflexes, unless they are
intubated. Gastric lavage is also contraindicated in persons who have
ingested corrosive substances (i.e., acids or alkalis) or hydrocarbons (unless
containing highly toxic substances, such as paraquat, pesticides, heavy
metals, halogenated and aromatic compounds), in those with known
esophageal strictures, and in those with a history of gastric bypass surgery.
Caution should be exercised in performing gastric lavage in combative
patients and in those who possess medical conditions that could be
exacerbated by performing this procedure, such as patients with bleeding
diatheses.
Numerous complications have been reported in association with gastric
lavage. Depending on the route selected for tube insertion, damage to the
nasal mucosa, turbinates, pharynx, esophagus, and stomach have all been
reported. After tube insertion, it is imperative to confirm correct placement.
Radiographic confirmation of tube placement should especially be considered
in young children and intubated patients. Instillation of lavage fluid and
charcoal into the lungs through tubes inadvertently placed endotracheally has
been reported. Perforation of the esophagus is also a potential complication.
The large amount of fluid administered during lavage has been reported to
cause fluid and electrolyte disturbances. In the pediatric population, these
disturbances have been seen with both hypertonic and hypotonic lavage fluids.
Hypothermia is a possible complication if the lavage fluid is not pre-warmed.
Pulmonary aspiration of gastric contents or lavage fluid is the primary risk
during gastric lavage, especially in patients with compromised airway
protective reflexes.
Activated Charcoal
Activated charcoal acts by adsorbing a wide range of toxins present in the
gastrointestinal tract, as well as by enhancing toxin elimination if systemic
absorption has already occurred. It accomplishes the latter by creating a
concentration gradient between the contents of the bowel and the circulation.
In addition, it has the potential to interrupt enterohepatic circulation if the
particular toxin is secreted in the bile and enters the gastrointestinal tract prior
to reabsorption. Oral activated charcoal is given as a single dose or in multiple
doses.
Single-dose activated charcoal is indicated if the healthcare provider
estimates that a clinically significant fraction of the ingested substance
remains in the GI tract, that the toxin is adsorbed by charcoal, and that
further systemic absorption may result in clinical deterioration. Multiple
doses may be considered if the clinician anticipates that the charcoal will
result in increased clearance of an already absorbed drug. Activated charcoal
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should not be routinely administered, but rather should be reserved for

cases in which serious toxicity is anticipated. It is most effective within the
first 60 minutes after oral overdose and decreases in effectiveness over time.
The administration of charcoal is contraindicated in any person who
demonstrates compromised airway protective reflexes, unless they are
intubated. Intubation will reduce the risk of aspiration pneumonia but will not
totally eliminate it. Charcoal administration is contraindicated in persons who
have ingested corrosive substances (i.e., acids or alkalis). Not only does
charcoal provide no benefit in a corrosive ingestion, but its administration
could precipitate vomiting, obscure endoscopic visualization, and lead to com-
plications if a perforation developed and charcoal entered the mediastinum,
peritoneum, or pleural space. Charcoal should also be avoided in cases of pure
aliphatic petroleum distillate ingestion. Caution should be exercised in using
charcoal in patients who possess medical conditions that could be further
compromised by charcoal ingestion, such as those with gastrointestinal per-
foration or bleeding.
Whole Bowel Irrigation

Whole bowel irrigation (WBI) has emerged as the newest technique in
gastrointestinal decontamination. It involves the enteral administration of an
osmotically balanced polyethylene glycol–electrolyte solution (PEG-ES) in a
sufficient amount and rate to physically flush ingested substances through the
gastrointestinal tract, purging the toxin before absorption can occur. PEG-ES
is isosmotic, is not systemically absorbed, and will not cause electrolyte or fluid
shifts. Available data suggest that the large volumes of this solution needed to
mechanically propel pills, drug packets, or other substances through the gas-
trointestinal tract are safe, even in pregnant women and in young children.
WBI may be considered for ingestions of exceedingly large quantities of
potentially toxic substances, ingestions of toxins that are poorly adsorbed
to activated charcoal, ingestions of delayed-release formulations, late presen-
tations after ingestion of toxins, pharmacobezoars, and in body stuffers or
packers. Common indications for WBI in the emergency department include
the treatment of toxic ingestions of sustained-release medications (e.g., calcium
channel blockers, theophylline, lithium) and iron tablets. WBI is contraindi-
cated in patients with gastrointestinal obstruction, perforation, ileus, or signif-
icant gastrointestinal hemorrhage. It should also be avoided in patients with
hemodynamic instability, an unprotected airway, or when there is suspicion for
a corrosive ingestion.
ANTIDOTES
The number of pharmacologic antagonists or antidotes is quite limited.
There are few agents that will rapidly reverse toxic effects and restore a patient
to a previously healthy baseline state. Administering some pharmacologic
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Table 1-5. Antidotes
Agent or Clinical Finding Antidote
Acetaminophen N-acetylcysteine
Benzodiazepines Flumazenil
Beta blockers Glucagon
Cardiac glycosides Digoxin immune Fab
Crotalid envenomation Crotalidae polyvalent immune Fab
Cyanide Hydroxocobalamin
Ethylene glycol Fomepizole
Iron Deferoxamine
Isoniazid Pyridoxine
Methanol Fomepizole
Methemoglobinemia Methylene blue
Opioids Naloxone
Organophosphates Atropine & Pralidoxime
Sulfonylureas Octreotide
antagonists may actually worsen patient outcome compared to optimization of

basic supportive care. As a result, antidotes should be used cautiously and with
clearly understood indications and contraindications. Table 1-5 provides a list
of antidotes. Selected antidotes will be discussed in further detail later in this
book.
CONCLUSION
Healthcare providers will often be required to care for poisoned patients.

Many of these patients will do well with simple observation and never develop
significant toxicity. However, for patients who present with serious toxic
effects or after potentially fatal ingestions, prompt action must be taken. As
many poisons have no true antidote and the poison involved may initially be
unknown, the first step is competent supportive care. Attention to the latter,
13486_CH01.qxd 10/30/08 6:39 AM Page 16
vital signs and the prevention of complications are the most important steps.
Indeed, these considerations alone will often ensure recovery.
Identifying the poison, either through history, recognition of a toxidrome,
or laboratory analysis may help direct patient care or disposition and should
therefore be attempted. There are several antidotes available which can be
life-saving, and prompt identification of patients who may benefit from these
must be sought.
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Chapter 2 Medications
ACETAMINOPHEN
What is acetaminophen? N-acetyl-p-aminophenol (APAP), an anal-

gesic and antipyretic agent
Where is acetaminophen Acetaminophen is found in a large num-

found? ber of products, both OTC and prescrip-
tion. It is combined with opioids to make
analgesics such as Percocet®, Vicodin®,
and Darvocet®, with antihistamines to
make sleep aids such as Tylenol PM®,
and with antihistamines and deconges-
tants to form products such as NyQuil®
and the Tylenol Cold® preparations.
What is the potentially When there are no coexisting health

hepatotoxic single dose? problems, a single acute overdose of over
150 mg/kg in an adult or 200 mg/kg in
children under age 12 is potentially
hepatotoxic.
How is acetaminophen The majority is usually metabolized in

metabolized? the liver through sulfation and glu-
curonidation with 5% to 10% metabo-
lized by the cytochrome P450 system.
What is the elimination 4 hrs

half-life?
How does overdose result in Acetaminophen overdose overwhelms the

toxicity? sulfation and glucuronidation pathways,
shunting metabolism to the cytochrome
P450 system and producing the toxic
metabolite.
What is the hepatotoxic N-acetyl-p-benzoquinoneimine (NAPQI)

metabolite of
acetaminophen?
17
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How is this metabolite In sub-toxic doses, NAPQI is quickly

normally metabolized by the conjugated with glutathione in
liver? hepatocytes, then renally eliminated.
In overdose, the quantity of NAPQI
overwhelms glutathione stores which
results in accumulation of the toxin.
What is the mechanism of NAPQI binds to hepatic proteins →

toxicity of this metabolite? hepatic centrilobular necrosis
What groups are at high risk 1. Chronic alcoholics who overdose

for acetaminophen toxicity? (↑ risk of liver damage)
2. Pregnant patients who overdose
(↑ risk of fetal death)
3. Patients taking inducers of CYP2E1
(e.g., isoniazid)
4. Patients suffering from malnutrition
(lower glutathione stores)
What are the classic clinical Stage 1 (time of ingestion to 24 hrs) –

stages of acetaminophen anorexia, nausea, vomiting
poisoning? Stage 2 (24–72 hrs post-ingestion) –
elevation of transaminases, bilirubin
and PT; nausea and vomiting may
resolve
Stage 3 (72–96 hrs post-ingestion) –
worsening hepatic necrosis with
corresponding elevation in AST and
ALT; may progress to coagulopathy,
jaundice, hepatic and renal failure,
encephalopathy, and death, or may
progress to stage 4
Stage 4 (⬎96 hrs post-ingestion) –
healing of liver damage with eventual
resolution of enzymatic and metabolic
abnormalities
What laboratory tests should Plasma acetaminophen level 4 hrs post-

be performed? ingestion for nonextended release
preparations. BUN, creatinine, AST,
ALT, PT/INR, and glucose are also
warranted.
What is the Rumack- A graph depicting the treatment line for

Matthew nomogram? probable hepatic toxicity
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Chapter 2 / Medications 19
What is the 4-hr treatment 150 mcg/mL

level?
Is this the same level as in No, the original treatment line was
Europe? 200 mcg/mL at 4 hrs. The level was
lowered to 150 mcg/mL in the U.S. to
provide an extra margin of safety.
What is the recommended 1. Activated charcoal – if presenting

treatment for overdose? within 1 hr of ingestion
2. N-acetylcysteine (NAC) – most
efficacious if given within 8 hrs of
ingestion
3. Antiemetics – ondansetron is
preferred; avoid antiemetics with
sedative properties or that are
metabolized by the liver
How does NAC work? Acts primarily by repleting glutathione. It

also may enhance the sulfation pathway,
↑ blood flow to the liver, bind NAPQI,
and help to reduce NAPQI back to
acetaminophen.
How is NAC supplied? Both IV and PO formulations. IV form

appears to be as efficacious as PO form
and can be given over 20 hrs as opposed
to the 72-hr PO dose.
What is the traditional PO 140 mg/kg ⫻ 1 dose, then 70 mg/kg

dosing schedule as approved q4 hrs for 17 more doses
by the U.S. Food and Drug
Administration (FDA)?
How do you treat a patient In patients with an unknown time of

who is an unreliable ingestion and a detectable acetamino-
historian with a suspected phen level, treat with NAC until aceta-
acetaminophen overdose? minophen level is undetectable and
transaminases are normal or declining.
Does acetaminophen cause While not part of the traditional

an acidosis? MUDILES, acetaminophen in very large
doses appears to act as a metabolic
poison and can cause an anion gap
metabolic acidosis.
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AMANTADINE
What are the indications for It is an antiviral agent that is also used in
amantadine? the treatment of parkinsonian symptoms
and as an arousal agent in patients with
traumatic brain injury.
What is the mechanism of Its antiviral properties are mediated by

action of amantadine? its interference with the M2 protein,
which is necessary for viral “uncoating.”
Amantadine’s anti-parkinsonian proper-
ties are mediated by the release of
dopamine and the blockade of its
reuptake. It also may act as an NMDA
antagonist.
What are some common side Nervousness, anxiety, agitation, insomnia,

effects of amantadine? exacerbations of seizures, and suicidal
ideation in some patients
What are the clinical signs In high doses, amantadine has anti-
of acute toxicity? cholinergic effects including dry mucous
membranes, tachycardia, and delirium.
It also may cause visual hallucinations,
ataxia, tremor, myoclonus, and dysrhyth-
mias. There have been rare reports of
seizures.
What is the treatment for Only supportive care, no antidote

acute toxicity? available
What syndrome can abrupt NMS

withdrawal precipitate?
What is NMS? Neuroleptic malignant syndrome results

from the relative lack of dopaminergic
activity, either from addition of a
dopamine blocker (e.g., antipsychotic
agent) or the withdrawal of a dopamin-
ergic agent (e.g., amantadine, car-
bidopa/levodopa, bromocriptine). This
produces the symptoms of altered men-
tal status, muscle rigidity, hyperthermia,
and autonomic instability.
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What physical exam findings NMS classically lacks hyperreflexia and

help to differentiate NMS clonus.
from serotonin syndrome?
What is the treatment for 1. Aggressive cooling for temperatures

NMS? ⬎39°C (102°F) secondary to NMS
induced by amantadine withdrawal
2. Benzodiazepines for agitation
3. Reinstitution of amantadine or other
dopamine agonists should be
considered.
ANESTHETICS
CENTRAL
What is malignant A rare condition occurring in
hyperthermia? genetically-susceptible individuals. It
is triggered by exposure to halogenated
general anesthetic agents and/or
succinylcholine.
What are the clinical signs Hypercarbia, tachypnea, tachycardia,

of malignant hyperthermia? hyperthermia, muscle rigidity, hyperther-
mia, metabolic acidosis, skin mottling,
and rhabdomyolysis
What is the most valuable A rise in end tidal CO2. Masseter muscle
early sign of malignant spasm may also herald the onset of malig-
hyperthermia? nant hyperthermia.
What are the possible Sustained hypermetabolism can cause

consequences of malignant rhabdomyolysis due to cellular hypoxia.
hyperthermia? This can lead to profound hyperkalemia,
resulting in dysrhythmias or myoglobin-
uric renal failure. Other complications
include compartment syndrome due to
muscle swelling, mesenteric ischemia,
CHF, and disseminated intravascular
coagulation (DIC).
What is the treatment for 1. Discontinue offending drug

malignant hyperthermia? 2. Hyperventilate patient
3. Administer dantrolene
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4. Actively cool patient to a maximum of

38.5°C (101.3°F)
5. Treat hyperkalemia
How does dantrolene work? It inhibits sarcoplasmic calcium release,

thereby relaxing skeletal muscle by
disassociating excitation-contraction
coupling.
What screening tests can be Caffeine-halothane contracture test

used in susceptible patients?
What adverse effects can Megaloblastic anemia and myeloneuropa-

occur with chronic abuse of thy can occur due to a functional vitamin
nitrous oxide? B12 deficiency.
How does the Paresthesias in the feet and hands,

myeloneuropathy present? impaired gait, loss of manual dexterity,
and hypoactive reflexes
By which mechanism can It can displace oxygen and act as a simple

nitrous oxide use or abuse asphyxiant. This can occur if pure nitrous
cause death or brain injury? oxide is delivered during anesthesia.
What are the indications for Induction of anesthesia

etomidate?
What is the mechanism of Depresses the reticular activating system

action of etomidate? and mimics the effects of GABA
What is a common reaction Myoclonus, due to disinhibition of

with etomidate? extrapyramidal activity in some patients
What is a possible Adrenocortical suppression; this is of par-

consequence of long-term ticular concern in critically ill patients.
exposure to etomidate?
Propofol is in what class of Sedative-hypnotic agents

anesthetics?
What is the mechanism of 1. Activation of the GABAA receptor

action of propofol? chloride channel
2. Antagonism of the NMDA receptor
What are the indications for 1. Rapid induction for general anesthesia
propofol? 2. Sedation
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Prior to propofol Lidocaine

administration, what drug
may be given to decrease
pain at the injection site?
What are some common Hypotension, bradycardia, and conduc-

adverse effects of propofol? tion disturbances; the risk of these
adverse effects increases with rapid
boluses in the elderly.
What is propofol infusion A syndrome of bradycardia leading to

syndrome? cardiovascular collapse, accompanied by
at least one of the following: metabolic
acidosis, rhabdomyolysis, hyperlipidemia,
or fatty liver.
What are the risk factors for Prolonged high-dose infusion (⬎48 hrs),
propofol infusion syndrome? concurrent catecholamine administration,
high-dose steroids, and acute neurologi-
cal injury.
How is propofol infusion 1. Stop propofol infusion

syndrome treated? 2. Hemodynamic support
3. Hemodialysis or hemofiltration to
correct acidosis, clear lipemia, and
remove propofol
LOCAL
How are local anesthetics SQ, topical (e.g., skin, mucous mem-
administered? branes), nerve blocks (e.g., epidural,
spinal, regional)
What are the indications for Local anesthetics are sold OTC for such
local anesthesia? afflictions as dental and hemorrhoid pain
and are used in procedures such as lacer-
ation repair and endoscopy.
What is the mechanism of They inhibit sodium influx through the

action of local anesthetics? neuronal sodium channels to prevent an
action potential, thereby inhibiting signal
conduction.
What are the main classes of 1. Ester-linked (aminoesters) –

local anesthetics? Name benzocaine, cocaine, procaine,
some common drugs in each. tetracaine
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2. Amide-linked (aminoamides) –
lidocaine, bupivacaine, mepivacaine,
prilocaine
This class contains two “I’s” in the name
(i.e., bup “I”vaca “I”ne).
What are the clinically 1. Aminoesters are metabolized by

relevant differences plasma cholinesterases
between these classes? 2. Aminoamides are metabolized by
the liver
What are the half-lives of 1. Bupivacaine – 120–300 min

some local anesthetics? 2. Cocaine – 60–150 min
3. Lidocaine – 60–120 min
4. Procaine – 7–8 min
5. Tetracaine – 5–10 min
What are the signs and 1. Local effects – prolonged anesthesia

symptoms of toxicity? 2. Systemic – acute toxicity during
infusion or infiltration results in AMS,
including confusion and disorientation
which may progress to seizures.
3. CV – manifests as hypotension,
dysrhythmias, AV block, and asystole
Which local anesthetics This is most commonly reported with

carry a risk of topical benzocaine; however, there have
methemoglobinemia? also been reports with lidocaine, pro-
caine, and tetracaine.
How common are allergies 1 in 10,000

to local anesthetics?
Can local anesthetics be Yes, with caution. Use the opposite

used if a patient has an class of anesthetic (ester or amide) if
established allergy to a allergy is known. If the class of
specific agent? anesthetic to which the patient is
allergic is unknown, diphenhydramine
can be used as an acceptable alternative
as a local anesthetic.
What drug is often given Epinephrine, to provide local vasocon-

with local anesthetics and striction and slow the systemic absorption
why? of the local anesthetic
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What are the implications of Longer half-life (120 min) and larger
co-administration of this maximum adult SQ dose (7 mg/kg with
drug on the half-life and epinephrine vs. 4 mg/kg without)
maximum adult SQ dose of
lidocaine?
Which local anesthetic can Lidocaine (type Ib antidysrhythmic)

be used as an
antidysrhythmic?
What specific antidote may None. Treatment is primarily supportive

be used in toxicity due to care. Direct-acting vasopressors (e.g.,
local anesthetics? norepinephrine) should be used for re-
fractory hypotension and benzodi-
azepines for seizures. Lipid emulsions
have been studied but cannot be recom-
mended at this time.
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
What commercially available Captopril, enalapril, ramipril, quinapril,

medications are found in perindopril, lisinopril, benazepril,
this class? fosinopril
What is the mechanism of ACE converts inactive angiotensin I to

action of ACE inhibitors? angiotensin II in the pulmonary vascula-
ture. Angiotensin II stimulates both vaso-
constriction and release of aldosterone
and vasopressin, resulting in ↑ BP. ACE
inhibitors ↓ production of angiotensin II
→ ↓ BP.
What clinical uses exist for 1. Treatment of hypertension

ACE inhibitors? 2. Prevention of diabetic renal failure in
patients suffering from diabetic
nephropathy
3. Prevention of CHF and other cardiac
events, even in the absence of
hypertension
What are the adverse effects Dry persistent cough, angioedema,

of this medication? hypotension, hyperkalemia, headache,
dizziness, fatigue, nausea, renal
impairment
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How does ACE inhibitor- Well-demarcated, nonpitting edema,

related angioedema most commonly of the tongue and mu-
present? cous membranes of the upper airway, lips
and eyes; usually painless and nonpruritic
When does ACE inhibitor- At anytime during treatment, with reports

related angioedema occur? of days to many years after initiation
What is the incidence of Commonly reported as 0.1% to 0.2%.

ACE inhibitor-related Some report incidence approaching
angioedema? 0.7%.
What peptide is thought to Bradykinin, normally degraded by ACE

cause both ACE inhibitor-
related angioedema and
cough?
What is the treatment of Airway management should be of pri-

angioedema? mary concern. IV diphenhydramine, cor-
ticosteroids, and SQ epinephrine should
be considered in appropriate cases, but
these agents may not significantly alter
clinical progression.
What are the predominant Acute ACE inhibitor overdose does not
signs and symptoms of ACE often result in significant toxicity.
inhibitor overdose? Hypotension and, occasionally,
bradycardia may occur. Hyperkalemia
may be seen, even in therapeutic doses.
What treatments are 1. Activated charcoal, if given within 1 hr

recommended for overdose of overdose
of ACE inhibitors? 2. Supportive care (e.g., IV fluids for
hypotension)
3. Rarely, vasopressors may be indicated
in refractory hypotension.
4. If hyperkalemia develops, treat with
standard therapies.
ANGIOTENSIN RECEPTOR BLOCKERS
What commercially available Valsartan, telmisartan, losartan, irbesar-

medications are found in tan, olmesartan, candesartan, eprosartan
this class?
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What is the mechanism of Angiotensin receptor blockers prevent

action of angiotensin activation of angiotensin II (AT1)
receptor blockers? receptors, reducing BP. Angiotensin II
normally stimulates vasoconstriction,
aldosterone, and vasopressin release
→ ↑ BP.
What clinical uses exist for 1. Treatment of hypertension in patients

angiotensin receptor intolerant of ACE inhibitors
blockers? 2. Some efficacy in treatment of CHF
and prevention of diabetic renal
failure in patients with diabetic
nephropathy
What are the adverse effects Dizziness, headache, hyperkalemia, first-

of this class of drugs? dose orthostatic hypotension, and rare
cases of angioedema
What are the signs and Acute angiotensin receptor blocker

symptoms of angiotensin overdose data is limited. Hypotension
receptor blocker overdose? and bradycardia may occur in rare cases.
Hyperkalemia may be seen, even in
therapeutic doses.
What treatments are 1. Activated charcoal, if given within 1 hr

recommended for of overdose
angiotensin receptor blocker 2. Supportive care (e.g., IV fluids for
overdose? hypotension)
3. Rarely, vasopressors may be indicated
in refractory hypotension.
4. If hyperkalemia develops, treat with
standard therapies.
ANTIBACTERIAL AGENTS
What mechanism causes Allergic reactions

most serious adverse
reactions to antibacterial
agents?
What symptoms are Primarily GI (i.e., nausea, vomiting,

typically seen with oral diarrhea)
overdose of antibacterial
agents?
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What cardiovascular toxicity QT prolongation with subsequent torsade

is typically associated with de pointes. This is especially relevant
macrolides (e.g., when given with other drugs known
erythromycin) and to prolong the QT interval (i.e.,
quinolones (e.g., antipsychotics, cyclic antidepressants,
ciprofloxacin)? antihistamines).
What neuromuscular Myasthenia gravis. These agents may also

condition may be potentiate pharmacologic neuromuscular
exacerbated by blockade.
administration of
erythromycin or
aminoglycosides?
Which class(es) of Aminoglycosides (e.g., gentamicin,

antibacterial agents are tobramycin), vancomycin, macrolides.
associated with ototoxicity? Macrolide-induced ototoxicity typically
reverses with cessation of drug.
Which class(es) of Aminoglycosides, vancomycin, polymyx-

antibacterial agents are ins, tetracyclines, first-generation
associated with cephalosporins (chronic use)
nephrotoxicity?
Which class(es) of High-dose IV penicillin (⬎50 million

antibacterial agents, in acute units) and imipenem. Both bind to picro-
overdose, may present with toxin site on neuronal chloride channels
seizures and by what and indirectly antagonize nearby GABA
mechanism? binding site.
Which antibacterial agents Metronidazole is the classic example.

are known to cause a However, chloramphenicol, nitrofuran-
disulfiram-like reaction toin, and certain cephalosporins have
when combined with been implicated.
ethanol?
Which antibacterial agent(s) Demeclocycline

may cause nephrogenic
diabetes insipidus?
Which antibacterial agent(s) Nitrofurantoin

is known to cause hemolysis
in patients with G6PD
deficiency?
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Which antituberculosis agent Rifampin

is associated with red
coloration of tears and urine?
What syndromic reactions 1. Hoigne syndrome (minutes post-

can be seen with IM or IV injection) – hallucinations (auditory
administration of large and/or visual), fear of death,
doses of penicillin G? perceptions of changes in body shape,
tachycardia, hypertension
2. Jarisch-Herxheimer reaction (hours
post-injection for syphilis treatment) –
myalgias, fever, chills, diaphoresis, rash,
hypotension, rigors, headache. This
self-limited reaction may also be seen
with treatment of tick-borne diseases.
Overdose with which Ampicillin, amoxicillin, sulfonamides

antibacterial agents may (older, less-soluble forms), norfloxacin,
result in crystalluria? ciprofloxacin
What classic syndrome is Red man syndrome. Anaphylactoid

seen with vancomycin reaction named for the prominent skin
administration? flushing, but also includes hypotension,
dyspnea, pruritis, urticaria. It is related
to the rate of IV administration.
How may this complication Administer slowly and pretreat with

of vancomycin use be diphenhydramine.
avoided?
How does acute and chronic 1. Acute – nausea, vomiting,

chloramphenicol toxicity hypotension, hypothermia, metabolic
present? acidosis, abdominal distention,
cardiovascular collapse
2. Chronic – bone marrow suppression,
“gray baby syndrome”
What is “gray baby Associated with chloramphenicol use in

syndrome”? neonates and toddlers and includes
vomiting, abdominal distention, cyanosis,
irregular respirations, metabolic acidosis,
hypothermia, flaccidity, hypotension,
cardiovascular collapse. Rarely seen prior
to the second day of therapy.
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Why are infants at greater A limited ability to conjugate chloram-

risk for “gray baby phenicol (by glucuronyl transferase)
syndrome”? leaves an abundance of the active form in
the blood.
What specific treatment is Pyridoxine (Vitamin B6)

indicated for isoniazid (INH)
toxicity?
What specific treatment is Leucovorin (folinic acid)

indicated for trimethoprim
toxicity?
What toxic effects can occur Methemoglobinemia, sulfhemoglobine-

with dapsone poisoning? mia, and hemolysis
Which antibiotic is Linezolid

associated with serotonin
syndrome?
ANTICHOLINERGICS
What common drug classes Antihistamines, antiparkinsonian drugs,

may have anticholinergic antispasmodics (GI, urinary), skeletal
effects? muscle relaxants, tricyclic anti-
depressants, belladonna alkaloids,
antipsychotics
What are some natural 1. Jimson weed (Datura stramonium)

sources of anticholinergic 2. Black henbane (Hyocyamus niger)
alkaloids? 3. Deadly nightshade (Atropa
belladonna)
Name the classic drug that Atropine

causes the anticholinergic
toxidrome.
What is the mechanism of Competitive antagonism of ACh at mus-

toxicity of the carinic cholinergic receptors; nicotinic
anticholinergic agents? cholinergic receptors (neuromuscular
junction) remain unaffected.
What part(s) of the body Exocrine glands (e.g., sweat, salivary),

is/are most affected by muscle cells (smooth and cardiac), CNS
anticholinergic drugs?
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What is the typical clinical Warm, dry, and flushed skin; dry mucous
presentation of the membranes; hyperthermia; tachycardia;
anticholinergic toxidrome? mydriasis; cycloplegia; delirium; ileus;
urinary retention
What are the key aspects to Dry skin and mucous membranes,
differentiate this from the hypoactive bowel sound, urinary retention
sympathomimetic
toxidrome?
What is the mnemonic (and “Dry as a bone (dry skin); blind as a bat
the classic findings) of the (mydriasis); red as a beet (flushed skin);
anticholinergic toxidrome? hot as a hare (hyperthermia); mad as a
hatter (delirium); full as a flask (urinary
retention)”
What is the classic Diphenhydramine

antihistamine that causes
anticholinergic toxicity?
What are the other features Seizures and QRS widening, with subse-
of diphenhydramine quent risk of ventricular dysrhythmias
poisoning?
What is the mechanism of Sodium channel blockade

QRS widening?
How is sodium channel IV sodium bicarbonate

blockade treated?
What is the mechanism by Antihistamine effect; pure anticholinergic

which diphenhydramine agents rarely cause seizures
causes seizures?
How does the chemical Tertiary amines (e.g., atropine, scopo-

structure of the lamine) exhibit more central effects
anticholinergic agent govern owing to their penetration of the blood-
its effects? brain barrier, whereas quaternary amines
(e.g., glycopyrrolate) are not well-
absorbed centrally.
How does anticholinergic Decreased GI motility may delay absorp-

overdose affect other tion and cause delayed or prolonged
ingestions? toxicity.
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How is the diagnosis of Principally based upon the history and

anticholinergic toxicity features of the classic toxidrome
made?
Is there an antidote? Physostigmine may provide improvement

or reversal of symptoms if used in the
appropriate context. Physostigmine
inhibits acetylcholinesterase and ↑ ACh
available at the synaptic cleft.
What are the side effects of Salivation, weakness, nausea, vomiting,

physostigmine? diarrhea, and ↑ respiratory secretions.
There have been reports of seizures and
asystole when given to patients intoxi-
cated with tricyclic antidepressants.
ANTICONVULSANTS
PLEASE NOTE THAT THE FOLLOWING COMPOUNDS ARE

ADDRESSED IN THEIR OWN SECTIONS: BARBITURATES,
BENZODIAZEPINES, CARBAMAZEPINE, PHENYTOIN, AND
VALPROIC ACID.
What are the known 1. Affect ion flux (especially sodium ion
mechanisms of currents) across cell membranes
anticonvulsants? Give an (e.g., zonisamide, felbamate)
example for each 2. Enhance postsynaptic action of GABA
mechanism. (e.g., tiagabine, vigabatrin)
3. Inhibit release of excitatory
neurotransmitters (e.g., lamotrigine)
4. Inhibit carbonic anhydrase (possibly
topiramate and zonisamide)
What signs and symptoms 1. AMS (including lethargy, anxiety,

are commonly seen with an confusion, irritability, somnolence)
anticonvulsant overdose? 2. Ataxia
3. Nausea and vomiting
4. Coma, respiratory depression, and
hypotension are typically seen only
with large overdoses.
What are the common Rash, dizziness, hangover, behavioral dis-

chronic adverse reactions to turbances (e.g., emotional lability, de-
anticonvulsants? pression, suicidality, impaired judgment,
inattention to personal hygiene)
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What forms of anticonvulsant Allergic reaction and hemotoxicity

toxicity necessitate immediate
cessation of treatment?
What are the pertinent 1. Pregnancy – almost all anticonvulsants

considerations of are teratogenic
anticonvulsant therapy in 2. Children – anticonvulsants often
special populations? induce hyperactivity
Which anticonvulsant carries Lamotrigine, due to its potential to in-

a “black-box” warning? duce life-threatening rashes (i.e.,
Stevens-Johnson syndrome, toxic
epidermal necrolysis)
Which anticonvulsants have Tiagabine, lamotrigine, topiramate, car-

been associated with bamazepine, and phenytoin in massive
seizures in overdose? overdose
Which anticonvulsant is Topiramate, due to carbonic anhydrase

associated with non-anion inhibition
gap metabolic acidosis and
hyperkalemia?
Which anticonvulsants are Phenytoin, carbamazepine, phenobarbi-

associated with tal, primidone, lamotrigine
anticonvulsant
hypersensitivity syndrome?
ANTIDEPRESSANTS
CYCLIC
What are cyclic Ring-structured antidepressants used
antidepressants (CA)? to treat disorders such as depression,
chronic pain, migraines, and attention
deficit hyperactivity disorder (ADHD)
What are some examples of Amitriptyline, amoxapine, clomipramine,

commonly prescribed CAs? dothiepin, doxepin, imiprimine, maproti-
line, nortriptyline, protriptyline,
trimipramine
What should the clinician Be prepared for rapid deterioration,

anticipate in the CA which includes CNS depression, seizures,
overdose patient? dysrhythmias, and/or cardiovascular
instability. Even an asymptomatic patient
13486_CH02.qxd 10/30/08 7:16 AM Page 34
Figure 2-1. QRS prolongation.
can decompensate in ⬍1 hr following

overdose.
What are the reported ECG 1. Sinus tachycardia

manifestations of CA 2. QRS complex widening ⬎100 msec
toxicity? (Fig. 2-1)
3. QTc prolongation that can result in
torsade de pointes (Fig. 2-2)
4. A rightward axis often is present at
the frontal plane terminal 40 msec
(T 40-msec) of the QRS. This
manifests as a negative S wave in
lead I and a tall, positive R wave
in lead aVR (“terminal R wave”)
(Fig. 2-3).
5. Right bundle branch block; this
decreased conduction to the right
fascicle is the presumed mechanism
by which reentrant ventricular
rhythms develop, causing VT in
severe ingestions (Fig. 2-4).
Figure 2-2. Torsade de pointes.

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Figure 2-3. Right axis deviation and “terminal R wave.”
Which ECG findings predict A QRS interval ⬎100 msec and/or a ter-
serious toxicity? minal R wave in lead aVR measuring
over 3 mm in height. One study showed
that half the patients with a QRS interval
⬎160 msec experienced dysrhythmias.
What are the 7 mechanisms 1. Fast cardiac Na⫹ channel blockade –

of CA toxicity and the slows phase 0 depolarization, widening
subsequent effects of each? the QRS; decreased cardiac
contractility and dromotropy lead to
hypotension
2. Cardiac K⫹ efflux channel blockade –
slows phase 3 repolarization of the
action potential, resulting in
elongation of the QT interval
3. Alpha 1-adrenergic receptor blockade
– peripheral vasodilation leads to
hypotension
Figure 2-4. Right bundle branch block.

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4. Cholinergic (muscarinic) receptor

blockade – anticholinergic toxidrome
5. Histaminergic (H1) receptor
blockade – sedation and seizures
6. GABA receptor blockade – seizures
7. Presynaptic monoamine reuptake
inhibition (serotonin, norepinephrine,
dopamine) – tachycardia and
hypertension seen during initial stages
of toxicity, followed by hypotension
due to depletion of norepinephrine
What are the hallmark signs 1. Cardiotoxicity – dysrhythmias and/or

of CA toxicity? QRS duration ⱖ100 msec
2. CNS toxicity – seizures and/or AMS
Which CAs have been Amoxapine and maprotiline

reported to cause isolated
status epilepticus with no
QRS widening or
anticholinergic signs?
What considerations should 1. Treat seizures with IV

be made regarding the CA- benzodiazepines.
toxic patient experiencing 2. Avoid phenytoin as it may exacerbate
seizures? cardiac Na⫹ channel blockade.
3. Monitor for acidosis and
hyperthermia.
4. Avoid paralytic agents, as they can
mask seizure activity.
How should the CA 1. QRS prolongation – sodium

overdose be treated? bicarbonate
2. Hypotension unresponsive to IV fluids
and sodium bicarbonate – direct
vasopressors (e.g., phenylephrine;
avoid dopamine)
3. Seizures – benzodiazepines
4. QT prolongation – magnesium sulfate
Does sodium bicarbonate No, seizures are caused by other mecha-

treat seizures? nisms. However, sodium bicarbonate can
attenuate the acidosis caused by pro-
longed seizure activity that may predis-
pose the patient to dysrhythmias.
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Are there any other 1. Physostigmine has been reported to

contraindicated treatments? induce seizure activity and asystole.
2. Flumazenil may induce seizure
activity.
3. Type Ia and Ic antidysrhythmics may
↑ QRS interval and the likelihood of
dysrhythmias.
MONOAMINE OXIDASE INHIBITORS

What is monoamine oxidase? An enzyme that degrades biogenic amines.
It, along with catechol-O-methyl trans-
ferase (COMT), prevents the build-up of
biogenic amines in the neuronal synapse.
What are the indications for 1. Severe depression (especially atypical

MAOIs? depression)
2. Phobias and anxiety disorders
3. Parkinson’s disease (selegiline only)
What are the broad classes 1. 1st generation – isocarboxazid,

of MAOIs? phenelzine, tranylcypromine
2. 2nd generation – selegiline,
moclobemide
What are the subtypes of 1. MAO-A – found in neurons, the liver,

MAO, and where are they and intestinal walls
found? 2. MAO-B – found in neurons
Which neurotransmitters are Biogenic amines – serotonin, tyramine,

preferentially degraded by norepinephrine
MAO-A?
Which neurotransmitters are Dopamine

preferentially degraded by
MAO-B?
What are some common Primarily tyramine-containing products,

foods that interact with including beer, fava beans, aged cheese,
MAOIs? aged meats, pickled foods, red wine,
yeast extracts, and pepperoni
What is the mechanism by MAOIs inhibit intestinal MAO-A,

which foods cause MAOI allowing dietary tyramine to be absorbed
toxicity? in the intestine. Tyramine indirectly
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releases norepinephrine, causing a hyper-

adrenergic response.
Which MAOIs are less likely Selegiline is selective for MAO-B,

to cause food interactions? and moclobemide binds reversibly to
MAO. Both are unlikely to cause food
interactions.
Name some common drugs Amphetamines, cocaine, phentermine,

that may precipitate a PCP
hyperadrenergic response in
association with MAOIs.
What is the mechanism? These drugs cause release of norepineph-

rine from the presynaptic terminal, re-
sulting in a sympathomimetic syndrome.
What hyperthermic Serotonin syndrome

syndrome can result from
MAOI use?
Which medications increase Concurrent use of any medication that ↑

this risk? serotonin levels, including SSRIs, LSD,
dextromethorphan, meperidine, and
tramadol
What are the clinical signs AMS, hyperthermia, autonomic instabil-

of serotonin syndrome? ity, hyperreflexia, and clonus
What is the primary Benzodiazepines for sedation, aggressive

treatment for serotonin cooling for hyperthermia, and IV fluids
syndrome?
What 5-HT2A antagonist is Cyproheptadine

considered an “antidote” for
serotonin toxicity?
Are there any drawbacks to It can only be administered PO, and it

using cyproheptadine? has anticholinergic properties.
What are the clinical signs Severe hypertension, hyperthermia, delir-

of an acute MAOI overdose? ium, seizures, cardiovascular collapse,
and multi-system organ failure
What is the treatment of Supportive care. Short-acting IV agents

MAOI toxicity? should be used to control hypertension.
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Beta-blockers are contraindicated

secondary to the risk of worsening
hypertension due to unopposed alpha-
adrenergic activity. As vital signs may be
labile, hypotension should be treated
with a direct-acing agent like norepi-
nephrine. First-line treatment for
seizures is benzodiazepines; however,
pyridoxine should be considered in
refractory seizures, as some of the
MAOIs are derived from hydrazine.
What other common drugs Procarbazine and linezolid

exhibit MAOI-like activity?
SELECTIVE SEROTONIN REUPTAKE INHIBITORS

What is the mechanism of Inhibition of serotonin reuptake into the
action of selective serotonin presynaptic neuron, resulting in ↑ sero-
reuptake inhibitors (SSRIs)? tonin in the synaptic cleft
Why are SSRIs preferred Safety profile; unlike CAs, SSRIs are
over cyclic antidepressants lethal only in very high doses and essen-
(CAs)? tially lack serious cardiovascular effects.
What are some common Nausea, drowsiness, headache, vivid

adverse effects of SSRIs? dreams, weight gain, anorgasmia
What is the clinical CNS effects – sedation, ataxia, tremor,

presentation of an SSRI lethargy, seizures, coma
overdose?
Is there a specific treatment No

for SSRI overdose?
What is serotonin A constellation of varied symptoms that

syndrome? occurs secondary to a large dose of a
serotonergic drug or combination of two
or more serotonergic agents
Name some of the agents 1. Medications that inhibit serotonin

that induce serotonin reuptake (e.g., SSRIs, CAs,
syndrome. venlafaxine, meperidine,
dextromethorphan, tramadol)
2. Medications that inhibit serotonin
breakdown (e.g., MAOIs, linezolid)
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3. Agents that ↑ serotonin release (e.g.,

amphetamines, cocaine, reserpine)
4. Agents that act as serotonin agonists
(e.g., lithium, LSD, sumatriptan)
5. Agents that ↑ serotonin synthesis (e.g.,
L-tryptophan)
How does serotonin It is classically described as a triad of

syndrome present? AMS, autonomic instability, and neuro-
muscular hyperactivity. It presents as a
continuum of symptoms, often starting
with milder nonspecific symptoms, such as
akathisia, agitation, diaphoresis, tachycar-
dia, and hypertension. These progress to
delirium, hyperthermia, clonus, and hy-
perreflexia. If not recognized and treated,
it can lead to coma, rigidity, rhabdomyoly-
sis, multisystem organ failure, and death.
How is serotonin syndrome 1. Discontinue and avoid any

treated? serotonergic medicines.
2. Aggressive supportive care is the
preferred treatment for this condition.
Cyproheptadine is an antihistamine
with 5HT1a and 5HT2a antagonist
properties and has been proposed as
an antidote for serotonin syndrome;
however, it can only be administered
orally, has potential side effects, and
has little solid evidence of efficacy.
3. Benzodiazepines should be given and
titrated to control agitation and
neuromuscular hyperactivity.
4. Monitor temperature and treat
hyperthermia with active cooling.
5. Monitor for rhabdomyolysis and
administer IV fluids.
What is “discontinuation A constellation of withdrawal symptoms

syndrome”? seen within 24 hrs of stopping or rapidly
decreasing the dose of SSRIs
What are the symptoms Xerostomia, headache, insomnia, tremor,

associated with the abrupt akathisia, “brain zap” or electric shock
discontinuation of SSRIs? sensations
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What population is at A black box warning exists for patients

increased risk for suicide ⬍18 years of age
when starting SSRIs?
OTHER
List the 4 categories of 1. Serotonin and norepinephrine
atypical antidepressants. reuptake inhibitors (SNRIs)
2. Norepinephrine and dopamine
reuptake inhibitors (NDRIs)
3. Serotonin antagonist and reuptake
inhibitors (SARIs)
4. Norepinephrine and serotonin
antagonists (NASAs)
List examples of each class. 1. SNRIs – venlafaxine, duloxetine,

atomoxetine
2. NDRIs – bupropion
3. SARIs – nefazodone, trazodone
4. NASAs – mirtazapine
What are the toxic effects of CNS depression, tachycardia, seizures,

SNRIs? QTc prolongation (may be delayed), QRS
prolongation has been reported, sero-
tonin syndrome
What are the toxic effects of CNS depression, seizures (bupropion

NDRIs? lowers seizure threshold), sinus tachycar-
dia, exacerbation of psychosis
What are the toxic effects of Peripheral alpha-adrenergic blockade,

both SARIs and NASAs? CNS depression, serotonin syndrome
How does atypical Acute mental status change, ataxia,

antidepressant toxicity nausea and vomiting, tachycardia with
typically present? hypotension, seizures, and serotonin
syndrome
Which atypical SARIs (e.g., trazodone) and NASAs (e.g.,

antidepressants can cause mirtazapine), due to alpha-adrenergic
hypotension and priapism, blockade
and by what mechanism?
How can bupropion Excessive dopaminergic effects at higher

exacerbate psychosis? doses
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Which atypical Venlafaxine

antidepressant may cause
QT prolongation?
How is atypical Principally clinical. Should be suspected

antidepressant toxicity if there is a history of depression.
diagnosed?
Are drug serum levels Drug levels are not routinely available
helpful?
List the basic principles of 1. Supportive care and monitoring

treatment for atypical 2. Activated charcoal, if available shortly
antidepressant toxicity. following ingestion
3. Benzodiazepines for seizures
4. QTc prolongation may be treated with
IV magnesium sulfate
5. QRS prolongation may be treated with
IV sodium bicarbonate
6. Direct-acting vasopressors are
indicated for hypotension
unresponsive to IV fluids
What syndrome may result Serotonin syndrome

from use of antidepressants?
Define serotonin syndrome. An iatrogenic toxidrome due to excessive

serotonergic activity in the CNS by over-
dose or combination of serotonergic
medications
Name some of the agents 1. Medications that inhibit serotonin

that induce serotonin reuptake (i.e., SSRIs, CAs,
syndrome. venlafaxine, meperidine,
dextromethorphan, and tramadol)
2. Medications that inhibit serotonin
breakdown (i.e., MAOIs and linezolid)
3. Agents that ↑ serotonin release (i.e.,
amphetamines, cocaine, and
reserpine)
4. Agents that act as serotonin
agonists (i.e., lithium, LSD, and
sumatriptan)
5. Agents that ↑ serotonin synthesis
(L-tryptophan)
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What is the triad of effects 1. CNS effects – mental status change,

of serotonin syndrome? hypomania, agitation, coma
2. Autonomic effects – shivering,
fever, flushing, hypertension,
tachycardia, nausea, vomiting,
diarrhea
3. Neuromuscular effects – myoclonus,
tremor, hyperreflexia
How is serotonin syndrome History consistent with exposure and the

diagnosed? above toxidromic features. There is no
specific diagnostic test.
How is serotonin syndrome 1. Stop the offending agents

treated? 2. Supportive care (e.g., IV fluids)
3. Benzodiazepines for sedation
4. Cooling for hyperthermia
What 5-HT2A antagonist is Cyproheptadine

considered an “antidote” for
serotonin toxicity?
Are there any drawbacks to It can only be administered PO and it has

using cyproheptadine? anticholinergic properties.
ANTIDIARRHEAL AGENTS
What are the three primary 1. Antimotility agents (most dangerous)

classes of antidiarrheal 2. Intraluminal agents
drugs, and which is most 3. Antisecretory agents
dangerous in overdose?
The antimotility agent Opioids and anticholinergics (diphenoxy-

Lomotil® contains a late and atropine, respectively)
combination of drugs from
which two classes?
Why should patients who Both components contribute to slowed

overdose on Lomotil® be gut activity and result in delayed
observed? absorption
How long should a child At least 18 hrs

suspected of ingesting any
amount of Lomotil® be
observed?
13486_CH02.qxd 10/30/08 7:16 AM Page 44
In toxicity due to these Unpredictable; can be before, during,

combination agents, when or after
do the anticholinergic
effects typically present
relative to the opioid
effects?
Diphenoxylate is a structural Meperidine

analog of which opioid
analgesic?
What metabolite of Difenoxin

diphenoxylate is 5 times
more potent as an opioid
than its parent compound
and has a longer elimination
half-life?
What is the antidote for Naloxone. Repeat dosing may be

severe diphenoxylate or necessary due to short duration of action
loperamide overdose? relative to these opioids.
ANTIEMETIC AGENTS
What are the two primary 1. Serotonin (5-HT3) receptor

mechanisms for antiemetic antagonism (e.g., ondansetron,
drugs? dolasetron, granisetron, palonosetron)
2. Dopamine antagonism, such as
phenothiazines (e.g.,
prochlorperazine, promethazine),
butyrophenones (e.g., droperidol), and
benzamides (e.g., metoclopramide)
What is the most common Extrapyramidal reactions (i.e.,

adverse reaction with the akathisia and dystonic reactions).
antiemetic dopamine These can be seen with any antiemetic
antagonists? which acts through central dopamine
antagonism.
What drugs can you use to 1. Dystonic reactions should be treated

treat extrapyramidal with either diphenhydramine or
reactions? benztropine (i.e., anticholinergic
agents).
2. Akathisia can be treated with
diphenhydramine; propranolol and
13486_CH02.qxd 10/30/08 7:16 AM Page 45
benzodiazepines have also been

successfully utilized.
Why does droperidol have a Concerns about QT prolongation, torsade

“black box” warning? de pointes, and unexplained deaths
What are the possible 1. CNS depression (common)

clinical effects of an 2. Extrapyramidal reactions due to
overdose of the dopamine blockade
phenothiazine antiemetics? 3. Hypotension and/or reflex tachycardia
due to alpha-adrenergic blockade
4. QT interval prolongation due to
cardiac potassium channel blockade
Which antiemetics can cause The dopamine antagonists

NMS?
Which antiemetic has been Metoclopramide

associated with
methemoglobinemia?
In which type of patient In patients with suspected mechanical

should metoclopramide be bowel obstruction; it causes accelerated
avoided? GI motility via 5-HT4 agonist activity and
theoretically could worsen colic.
ANTIFUNGAL AGENTS
How is amphotericin B IV
administered
therapeutically?
What is the mechanism of Binds to ergosterol on cell membranes of

action of amphotericin B? fungi → ↑ permeability and cell death
How is amphotericin B Renal

eliminated?
What is the elimination half- 15 days

life of amphotericin B?
What are the acute adverse Fever, chills, nausea, vomiting, diarrhea,
effects of therapeutic chest discomfort, tachycardia, dyspnea
amphotericin B
administration?
13486_CH02.qxd 10/30/08 7:16 AM Page 46
How can these effects be 1. Slow infusion rate

minimized? 2. Pre-treat with antihistamines,
acetaminophen, NSAIDs, and steroids
What adverse effect is Renal dysfunction

commonly seen during
treatment with
amphotericin B?
What is the maximum 1.5 mg/kg/day

therapeutic dose of
amphotericin B?
What may be seen with an Fatal cardiac dysrhythmias

acute overdose of
amphotericin B?
How is flucytosine PO
administered?
What is the mechanism of Converted to fluorouracil in fungal cells,

action of flucytosine? which inhibits DNA synthesis by interfer-
ing with thymidylate synthetase
How is flucytosine Renal

eliminated?
What is the elimination half- 2.5 to 6 hrs

life of flucytosine?
What is the principal Bone marrow suppression

mechanism of toxicity of
flucytosine?
Are enhanced elimination Hemodialysis has been shown to enhance

methods effective for elimination of the drug (minimally
flucytosine? protein-bound)
What specific treatments are Generally supportive. Colony stimulating

available for flucytosine factor has been used for neutropenia.
overdoses?
What is the mechanism of Inhibits sterol synthesis in fungi

action of fluconazole?
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How is fluconazole Renal

eliminated?
What is the elimination half- 30 hrs

life of fluconazole?
What are the untoward Elevated liver enzymes, nausea, vomiting,

effects of fluconazole? headache, rash, pruritus
By which mechanism do Inhibition of CYP3A4

some azole antifungals (e.g.,
fluconazole and miconazole)
cause drug interactions?
ANTIHISTAMINES
What are the indications for 1. Allergy-related symptoms

the use of antihistamines? 2. Common cold symptoms, including
cough
3. Motion sickness
4. Mild insomnia
What differentiates first- Second-generation antihistamines are less

and second-generation lipid-soluble and are thus unable to cross
antihistamines? the blood-brain barrier, rendering them
nonsedating. Second-generation agents
are generally less toxic.
What are examples of first- Diphenhydramine, promethazine,

generation antihistamines? meclizine, chlorpheniramine
What are examples of Loratadine, desloratadine, cetirizine,

second-generation fexofenadine
antihistamines?
What is the mechanism of Blockade at H1 receptors and antimus-

toxicity of first-generation carinic (anticholinergic) effects
antihistamines?
What antihistamines were Terfenadine and astemizole

taken off the market for
reports of cardiac toxicity
(QT prolongation and
torsade de pointes)?
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What is the clinical Flushed skin, anhydrosis, tachycardia,

presentation of first- dry mucous membranes, mydriasis,
generation antihistamine ileus, urinary retention, fever, and
overdose? delirium. In severe cases, this can
progress to seizures, coma, and rhab-
domyolysis. QRS and QT prolongation,
as well as wide complex dysrhythmias
have been reported with specific
antihistamines (e.g., diphenhydramine)
in overdose.
What is the toxidrome this Anticholinergic

constellation of symptoms
represents?
What is the mnemonic for “Dry as a bone (dry skin); blind as a bat
the anticholinergic (mydriasis); red as a beet (flushed skin);
toxidrome? hot as a hare (hyperthermia); mad as a
hatter (delirium); full as a flask (urinary
retention)”
How does diphenhydramine Na⫹ channel blockade

produce QRS widening?
What is the treatment for IV sodium bicarbonate

QRS prolongation?
How is the diagnosis of Primarily based on history and

antihistamine overdose anticholinergic toxidrome. In
made? addition, labs including electrolytes,
glucose, CPK, and ECG should be
obtained.
What specific antidotes exist Physostigmine can be used to reverse an-

for treating antihistamine ticholinergic symptoms, but should be
toxicity? used with extreme care.
Which medicines are Class Ia, Ic, and III antidysrhythmics

contraindicated for (may further prolong QRS or QT
antihistamine-induced interval)
dysrhythmias?
How long should patients Signs or symptoms are expected to de-

with antihistamine overdose velop within 4 hrs of overdose.
be monitored?
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What is the recommended 1. Benzodiazepines for agitation,

treatment for antihistamine seizures, hyperthermia (if related to
overdose? ↑ muscle activity)
2. Assess for co-ingestions (e.g.,
acetaminophen-containing products)
3. Aggressive cooling for severe
hyperthermia ⬎40°C (104°F)
4. Sodium bicarbonate (1–2 mEq/kg) for
QRS prolongation
5. Consider physostigmine for delirium
or diagnostic purposes
6. Activated charcoal may be of benefit,
even if the patient’s presentation is
delayed (slowed gut motility due to
anticholinergic effects)
Are H2 antagonists as toxic H2 antagonists have a high toxic-to-

as H1 antagonists? therapeutic index; these agents rarely
cause significant toxicity, and treatment
consists of supportive care.
ANTIHYPERLIPIDEMIA AGENTS
What is another name for “Statins”

HMG-CoA reductase
inhibitors?
What is the mechanism of Competitive inhibition of 3-hydroxy-3-

action of these agents? methylglutaryl-coenzyme A (HMG-CoA)
reductase, blocking the enzymatic con-
version of HMG-CoA to mevalonate, an
early step in hepatic cholesterol synthesis
What adverse effect on Myopathy with subsequent rhabdomyoly-

muscle may occur with the sis and hyperkalemia
therapeutic use of HMG-
CoA reductase inhibitors?
What are the effects of Overall, HMG-CoA reductase inhibitors

acute HMG-CoA reductase have limited toxicity in acute overdose.
inhibitor toxicity?
Is there a specific treatment Supportive care only

for HMG-CoA reductase
inhibitor toxicity?
13486_CH02.qxd 10/30/08 7:16 AM Page 50
What are some common bile Cholestyramine, colesevelam, colestipol

acid sequestrants?
What is the mechanism of Bind bile acids in the GI tract, forming

action of the bile acid an insoluble complex that undergoes
sequestrants? fecal elimination
Are bile acid sequestrants No

absorbed in the GI tract?
What are the potential toxic Bloating, constipation, impaired GI ab-

effects of bile acid sorption of other xenobiotics
sequestrants?
What is the mechanism of Several mechanisms have been proposed.

action of niacin? Among these are that niacin inhibits
release of free fatty acids from adipose
tissue, ↓ hepatic lipoprotein synthesis,
↑ fecal sterol elimination, and ↑ activity
of lipoprotein lipase.
Extended-release niacin Severe hepatotoxicity

has been associated with
what organ system
dysfunction?
What untoward effect of Flushing (“niacin flush”)

therapeutic niacin therapy
on the skin may occur?
What medication can reduce ASA

the side effect of niacin
flush?
What untoward ocular effect Amblyopia

of therapeutic niacin
therapy may occur?
What substance adds to the Ethanol

hepatotoxic effects of
niacin?
What is the only approved Ezetimibe

drug in the cholesterol
absorption inhibitor class?
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What is the mechanism of Inhibits the absorption of cholesterol in

action of ezetimibe? the small intestine
What drugs are included in Gemfibrozil, fenofibrate, clofibrate

the fibrates category?
What is the mechanism of Generally, they decrease hepatic triglyc-

action of fibrates? eride production and inhibit peripheral
lipolysis.
What adverse effect on the Cholelithiasis

gallbladder is associated
with fibrates?
Increased anticoagulant Warfarin

effects are seen when
fibrates are used with which
other drug?
ANTIMALARIAL AGENTS
Which medications are used Doxycycline, chloroquine, quinine,

for malaria prophylaxis and tetracycline, clindamycin, atovaquone-
treatment? proguanil, mefloquine, hydroxychloro-
quine, dapsone
What are the common side Abdominal pain, nausea, vomiting,

effects of all antimalarial diarrhea
medications?
Which medications can Primaquine, dapsone, quinine,

cause methemoglobinemia chloroquine
and hemolysis in patients
with G6PD deficiency?
Which medication causes Doxycycline

photosensitivity?
What complication of Cardiovascular complications; these

quinine, chloroquine, and agents act both as cardiac fast sodium
hydroxychloroquine can lead channel blockers and potassium efflux
to death in overdose? blockers, causing QRS prolongation
and QTc prolongation, respectively.
Poisoning can lead to AV block and
dysrhythmias.
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Which aminoquinones are Chloroquine and hydroxychloroquine

also used for rheumatoid
arthritis?
What is the classic “Cinchonism,” a constellation of nausea,

“syndrome” caused by vomiting, diarrhea, tinnitus, hearing loss,
quinine? vertigo, headache, and syncope, all asso-
ciated with therapeutic dosing.
What medication is a type Ia Quinine

antidysrhythmic, which has
been used for leg cramps
and may cause retinal
ischemia?
Which medication may Mefloquine; it has been associated with

cause prominent sleep disturbance, anxiety, depression,
neuropsychiatric symptoms? and hallucinations.
What specific treatment 1. QRS prolongation – IV sodium

steps are implemented in bicarbonate
cases of acute toxicity of 2. QTc prolongation – IV magnesium
most antimalarial sulfate
medications? 3. Methemoglobinemia – IV methylene
blue
ANTIPSYCHOTIC AGENTS
What are the names of 1. Phenothiazines – chlorpromazine,

commonly used thioridazine
antipsychotics? 2. Butyrophenones – haloperidol,
droperidol
3. Atypical antipsychotics – risperidone,
chlorpromazine, quetiapine,
olanzapine, ziprasidone
What classification system is Typical vs. atypical

typically used to describe
the older versus newer
antipsychotics?
How do they differ? Typical antipsychotics exert most of

their affects on the dopamine receptor,
while atypical antipsychotics also inhibit
serotonin action and treat both the
“positive” and “negative” symptoms of
schizophrenia.
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What are the primary and Dopamine receptor antagonism is the

secondary mechanisms of primary action; however, atypicals also
action of antipsychotics? block serotonin activity, and many
antipsychotics have some degree of
antimuscarinic activity.
What neurotransmitter Dopamine (D2) receptor

receptor is associated with
movement disorders?
What are the clinical Involuntary muscle contractions that

components to an acute typically affect the neck (torticollis), jaw
dystonic reaction? (trismus), trunk (opisthotonus), or eye
(oculogyric crisis)
What other class of Antiemetics (e.g., metoclopramide,

medications can cause an promethazine)
acute dystonic reaction?
What is akathisia? Uncontrollable restlessness, an adverse

effect of antipsychotics
How do you treat Diphenhydramine or benztropine

akathisia or acute dystonic (anticholinergic agents)
reaction?
What is the rare, life- NMS, which is associated with muscular

threatening adverse effect rigidity, hyperthermia, autonomic
of antipsychotics, and how instability, and AMS.
does it present?
What is the mortality rate of ~5% to 10%

NMS?
How do you treat this Supportive care. Benzodiazepines are

disorder? appropriate for sedation. Aggressive
cooling is warranted for hyperthermia.
Dopamine agonists (e.g., bromocriptine,
levodopa, amantadine) may be
beneficial, but their efficacy is
unproven.
What are the typical CNS depression, hypotension, tachycar-

exam findings in an dia, and miotic pupils
atypical antipsychotic
overdose?
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What is the antipsychotic Alpha 1-adrenergic blockade

mechanism of miosis and
hypotension?
What ECG change may QT prolongation due to myocardial

be associated with an potassium efflux channel blockade
antipsychotic overdose?
What ventricular Torsade de pointes. Treat with magne-

dysrhythmia may be sium and/or overdrive pacing
associated with this ECG
change, and how is it
treated?
The atypical antipsychotic Agranulocytosis

clozapine causes what
life-threatening adverse
effect?
ANTIVIRAL AND ANTIRETROVIRAL AGENTS
What are the clinical uses of Treatment of viral infections

antiviral and antiretroviral
agents?
What are typical 1. Antiherpes drugs – renal crystal

mechanisms of toxicity for deposition causing obstructive acute
each category of this class of renal failure
drugs? 2. Nucleoside reverse transcriptase
inhibitors (NRTI) – disturbs neuronal
mitochondrial function leading to
neurotoxicity, lactic acidosis, and
hepatic steatosis thought to be caused
by impairment of ability to replicate
mitochondrial DNA. This may occur
in acute overdose or with therapeutic
use.
3. Nonnucleoside reverse transcriptase
inhibitors (NNRTI) – little
information is known about acute
overdose; however, they generally
appear to be safe.
4. Protease inhibitors – in chronic use,
peripheral lipodystrophy due to
impaired fat storage and some
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hepatotoxicity may occur. In acute

overdose, GI symptoms predominate,
and rash may occur.
5. Fusion inhibitors – unknown
What antiherpes agent has Foscarnet

been associated with
seizures?
What is the common clinical Primarily GI, although lactic acidosis

presentation of antiviral and (usually with NRTIs) can occur
antiretroviral agent
overdose?
What treatments should be Supportive care is the primary treat-

performed in the event of ment. GI symptoms may be treated with
antiviral and antiretroviral antiemetics and IV fluids. When inges-
agent overdose? tion of an NRTI occurs, evaluation for
lactic acidosis is warranted. Benzodi-
azepines should be the first-line therapy
for seizures. Renal failure should
warrant admission with standard
supportive therapy.
BARBITURATES
What are barbiturates? Medications of the sedative-hypnotic

class that have been used for anesthesia
induction, seizure management, and
pain control. Secondary to their sedative
properties, barbiturates also have a high
abuse potential.
Which drugs are in the 1. Ultra short-acting – thiopental,

barbiturate class? methohexital
2. Short-acting – pentobarbital,
secobarbital
3. Intermediate-acting – amobarbital,
aprobarbital, butabarbital, butalbital
4. Long-acting – mephobarbital,
phenobarbital
What are some common Downers, yellow jackets, purple hearts,

street names for double trouble
barbiturates?
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Describe the mechanism of They bind to GABA-mediated chloride

action of barbiturates. channels, increasing the duration of open-
ing, which results in synaptic inhibition.
What are the signs of Signs of CNS depression, including

barbiturate intoxication? slurred speech, somnolence, and ataxia.
If severe, hypotension, coma, and respi-
ratory arrest can occur.
What are physical exam Patients typically have somnolence and

findings characteristic of respiratory depression. They may have
barbiturate intoxication? nystagmus and in severe cases, mid-fixed
pupils. Deep barbiturate comas may re-
sult in loss of primitive reflexes causing
the patient to appear brain-dead.
What are “barbiturate Cutaneous bullae that may appear follow-

burns”? ing overdose, seen not only on regions
where the body has pressure points, but
also on nondependent areas of the body
Can barbiturates be Yes, both. Barbiturates are detected on

detected in either the serum most standard urine drug screens.
or the urine?
What treatments are 1. Supportive care is considered standard

possible for barbiturate therapy.
intoxication? 2. Activated charcoal may be helpful if
given within 1 hr after ingestion.
3. Alkalinization of the urine may help ↑
phenobarbital excretion.
4. Hemodialysis can ↑ elimination of the
longer-acting agents but is rarely
indicated.
5. Because barbiturate-induced coma
can resemble brain death, patients
should not be pulled from life support
without documenting that the levels
are nontoxic.
BENZODIAZEPINES
How are benzodiazepines Benzodiazepines are sedative-hypnotics.

used? They are used primarily for sedation, anx-
iolysis, and seizure management.
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What is the mechanism of Benzodiazepines induce a conformational

action of benzodiazepines? change in the GABA receptor to enhance
binding of endogenous GABA, resulting
in ↑ frequency of chloride channel
opening and subsequent neuronal
hyperpolarization.
What is the result of CNS depression, but typically mild in

overdose? isolated overdose. Coma and respiratory
arrest are more common if used in com-
bination with other CNS/respiratory de-
pressants (e.g., barbiturates, ethanol).
What other signs and Ataxia, slurred speech, lethargy, hypoten-

symptoms may be seen in sion, hypothermia, memory impairment
overdose? (short-term)
What physical exam findings Other than CNS depression, the exam
are characteristic of may be unremarkable. Pupillary exam is
benzodiazepines? variable.
Which benzodiazepines have Chlordiazepoxide, clorazepate, diazepam,

active metabolites that flunitrazepam, flurazepam, midazolam,
prolong their effects during quazepam
overdose?
Which benzodiazepine is Flunitrazepam

known as the date rape drug
“roofies”?
Why is flunitrazepam used It is a potent sedative that induces amne-

for nefarious purposes? sia, has a rapid onset, and is easily dis-
solved in liquids. It is often not detected
on routine urine benzodiazepine drug
screens.
What laboratory methods are Urine screening and serum drug levels
used to evaluate exposure to
benzodiazepines?
What is the specific antidote Flumazenil. Its effect is limited, so rese-

for benzodiazepine toxicity? dation may occur.
Are there any pitfalls in Yes. Flumazenil may precipitate seizures

using flumazenil? in chronic benzodiazepine users and in
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patients with multi-drug ingestions. Use

can be considered in the “benzo-naïve,”
following iatrogenic overdose, or possibly
to avoid painful or difficult procedures
(e.g., an anticipated difficult intubation).
BETA 2-ADRENERGIC AGONISTS
What are some examples of Albuterol, metaproterenol, ritodrine,

beta 2-adrenergic agonists? terbutaline
What is the mechanism of These agents stimulate the beta

beta 2-adrenergic activity? 2-adrenergic receptor → ↑ intracellular
cAMP. This stimulation causes smooth
muscle relaxation (vascular, bronchial,
uterine).
How do beta 2-adrenergic Reflex tachycardia, secondary to vasodila-

agonists cause tachycardia? tion and to nonspecific activation of
beta 1-adrenergic receptors (all adrener-
gic agents tend to lose specificity in high
doses)
What are the signs and Tachycardia, hypotension with widened

symptoms of beta pulse pressure, tremor, agitation,
2-adrenergic agonist toxicity? headache, vomiting, seizures, dysrhyth-
mias. Ischemic events may occur in those
with heart disease.
What laboratory Hypokalemia and hyperglycemia are two

abnormalities may be seen common findings. Elevation of CPK can
in cases of toxicity? occur, as can lactic acidosis.
Describe the mechanism of Beta-adrenergic stimulation causes

hypokalemia. potassium influx.
What are some clues to Tachycardia and hypotension with

diagnosis? hypokalemia and hyperglycemia are
suggestive of toxicity.
What specific treatments are 1. Hypotension is commonly ameliorated

indicated? simply with IV fluids
2. Hypotension refractory to IV fluids
should be treated with peripheral
alpha-adrenergic agonists (e.g.,
phenylephrine)
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3. Nonselective beta-adrenergic blockers

(e.g., propranolol) may, theoretically,
block the hypotension (beta 2-
adrenergic) and tachycardia (beta 1-
adrenergic); however, extreme care
should be taken when administering
them secondary to potential worsening
of hypotension. Avoid beta-adrenergic
blockers in asthma/severe COPD.
4. Hypokalemia rarely warrants
treatment, as total body stores are not
usually depleted.
BOTULIN (BOTULISM)
What is botulism? A syndrome of symmetric, descending,

flaccid paralysis caused by a bacterial
exotoxin
Which bacterium causes Clostridium botulinum, a gram-positive,

botulism? spore-forming obligate anaerobe
How does botulinum toxin Inhibits ACh release at peripheral volun-

cause paralysis? tary motor and autonomic synapses
How many different 7, named A, B, C, D, E, F, G

botulinum exotoxins exist?
Which exotoxins are most A, B, and E

frequently involved in
human toxicity?
What is the major cause of Respiratory failure due to respiratory

death from botulism? muscle weakness
Name the most potent toxin Botulinum toxin (inhalation LD50 is

known. 0.01 ␮g/kg)
Name the major forms of Food-borne, infant, wound, inhalational

botulism.
What are the symptoms of Nausea and vomiting may initially

adult type (food-borne) be present, followed by dysphonia;
botulism? blurred vision; dysphagia; diplopia;
and descending, bilaterally symmetric
motor paralysis.
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Which form of botulinum Botulinum toxin subtype A, administered

toxin is used as a medical as a local injection
treatment?
What are approved FDA uses 1. Strabismus

for botulinum toxin type A? 2. Blepharospasm
3. Cervical dystonias
4. Cosmesis – for glabellar facial lines
5. Axillary hyperhydrosis
What factor primarily Location of injection site, as the toxin

determines side effects to produces local side effects
botulinum toxin type A
treatment?
Is there an antidote for Yes, equine bivalent (A, B) and triva-

botulinum toxin? lent (A, B, and E) are the classic
antitoxins; however, a heptavalent form
has recently been approved for use in
humans.
Does the antidote reverse No, the SNARE (docking) proteins at the
symptoms? nerve terminal are destroyed by the toxin
and must be regenerated for symptoms
to improve.
What are the symptoms of Constipation, feeble cry, diffusely ↓

infant botulism? muscle tone, and difficulty feeding and
sucking
What is the preferred Human IV botulism immune globulin

treatment for infant
botulism?
Can botulism be used as an Yes, the toxin is small, easily aerosolized,

agent of terrorism? and readily absorbed in the lungs. Identi-
fication of types C, D, F, or G in humans
should raise suspicion.
CAFFEINE
Where is caffeine found? It is found naturally in plants such as

Coffea arabica (coffee), Theobroma cacao
(cocoa), and Thea sinesis (tea) and is
ubiquitous in our society, as it is found in
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coffee, tea, energy drinks, energy tabs,

and chocolate.
What is caffeine used for? Caffeine is a stimulant, diuretic, appetite

suppressant, and analgesic agent.
In what structural class is Methylxanthines

caffeine found?
What are two metabolites of Theophylline and theobromine

caffeine?
What is the mechanism of It inhibits the adenosine receptor; it causes

toxicity of caffeine? release of endogenous catecholamines; it
also acts as a phosphodiesterase inhibitor.
What is the significance of Activation of adenosine receptors causes

adenosine blockade? cerebral vasodilatation and helps to atten-
uate seizure activity. Blocking these re-
ceptors can cause prolonged, refractory
seizure activity with a relative lack of
blood flow to the brain.
How is caffeine metabolized? In the liver by the cytochrome P450

enzymes
What is the half-life of Up to 15 hrs

caffeine in overdose?
What drugs can interact Metabolism by CYP1A2 is inhibited by

with caffeine metabolism? oral contraceptives, cimetidine,
norfloxacin, ethanol
What other habits affect Smoking (tobacco or marijuana) increases

caffeine metabolism? the metabolism
What are commonly 1. Brewed coffee – 100–200 mg

reported caffeine contents 2. Espresso – 30–90 mg
in foods and supplements? 3. Energy drinks – 70–140 mg
4. Energy tabs – 100–200 mg
5. Soda – 30–40 mg
6. Tea – 40–120 mg
What is the lethal PO dose 150–200 mg/kg or about 10 g in adults

of caffeine?
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What are the signs and Tremor and restlessness, which may
symptoms of caffeine progress to nausea, vomiting,
toxicity? tachycardia, tachydysrhythmias, and
seizures
What are two commonly 1. Hypokalemia (beta-adrenergic

seen metabolic stimulated influx into the cell)
abnormalities in caffeine 2. Hyperglycemia
toxicity?
By what mechanism does Beta 2-adrenergic stimulation, also

caffeine overdose cause resulting in bronchodilation
hypotension?
What are the effects of Chronic ingestion can lead to insomnia,

chronic caffeine ingestion? tremulousness, irritability, anxiety, and
palpitations.
How is caffeine toxicity Clinically. A history of caffeine

diagnosed? exposure helps, but tremor, tachycardia,
vomiting, and seizures (especially
refractory) with hypokalemia are
strongly suggestive.
Is there a diagnostic test for Yes, but caffeine levels are only available
caffeine? at large institutions. A theophylline
level, since it is a metabolite, may be
more readily available and may clue
the provider in to the presence of
caffeine.
What intervention has been Hemodialysis

utilized in severe caffeine
toxicity?
CAMPHOR AND OTHER ESSENTIAL

(VOLATILE) OILS
What is camphor? A volatile, aromatic compound initially

isolated from the Cinnamomum
camphora tree
What are the major uses of Liniments, plasticizers, preservatives in

camphor? pharmaceuticals and cosmetics, moth
repellants, decongestants
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What are the signs and Nausea, vomiting, tachycardia,

symptoms of camphor confusion, agitation, sedation; seizures
intoxication, and how long is often develop within 30 min of
the onset of action? ingestion. Camphor odor may be
evident on the breath.
What oral doses of camphor Adults – as little as 2 g

may be toxic in adults and Children – as little as 1 g
children?
What is the treatment for a Supportive care is the primary

camphor ingestion? treatment, including benzodiazepines
for seizures. There is no role for
activated charcoal in the management
of camphor oil ingestion due to its rapid
absorption.
What are essential oils? Volatile, polyaromatic hydrocarbons that

are used in liniments, cold preparations,
and herbal remedies. There are more
than 100 of these oils.
What is the general sign of Primarily sedation; pneumonitis may

intoxication with essential develop if aspiration occurs
oils?
What is the active ingredient Methyl salicylate

in oil of wintergreen?
What products contain oil of Topical analgesics

wintergreen?
Why is this oil so dangerous? Each teaspoon of oil of pure oil of

wintergreen is equivalent to 7 g (or
about 21 tablets) of ASA. It is rapidly
absorbed and is a potentially lethal
dose to a child.
Which essential oils have Clove oil and pennyroyal oil

caused fulminant hepatic
failure?
Which essential oil causes Eucalyptus oil

coma following less than a
5 mL ingestion?
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Which essential oil is used as Pennyroyal oil

an=illicit abortifacient?
Which oil has been abused Nutmeg

for its hallucinogenic
properties?
What is the hallucinogenic Myristicin

ingredient in nutmeg?
Which oils may cause Lavender and tea tree oils

gynecomastia and
photosensitivity?
What is the treatment for an Supportive care including benzodiazepines

essential oil ingestion? for seizure activity; N-acetylcysteine may
be effective for hepatonecrosis in penny-
royal and clove oil ingestions.
CARBAMAZEPINE
What is carbamazepine? An anticonvulsant used for the treatment

of epilepsy, trigeminal neuralgia, psychi-
atric illnesses, restless leg syndrome, and
alcohol withdrawal
To which class of drugs is Tricyclic antidepressants; therefore, urine

carbamazepine structurally drugs screens may be positive for cyclic
similar? antidepressants in patients taking
carbamazepine.
What is the mechanism of In therapeutic doses, carbamazepine

action? blocks neuronal sodium channels and is an
adenosine receptor agonist. In overdose, it
becomes an adenosine receptor antagonist.
What is the rate of Absorption is typically slow and erratic.

absorption? Peak levels can be delayed 6–24 hrs
following overdose.
Where is carbamazepine Liver, by P450 oxidation

metabolized?
What is considered a 4–12 mg/L

therapeutic level of
carbamazepine?
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What neurotransmitter Adenosine receptors

receptors are blocked in
toxicity?
What are the clinical effects CNS symptoms predominate with

of carbamazepine toxicity? altered consciousness, dizziness, ataxia,
headache, and nystagmus. GI symptoms
may be present. Severe toxicity can
result in cardiac dysrhythmias and
seizures.
What cardiac effects have QRS and QTc prolongation → ventricu-

been reported with lar dysrhythmias
carbamazepine toxicity?
Name the standard IV sodium bicarbonate and IV magne-

treatments for QRS and QTc sium sulfate, respectively
prolongation.
What endocrine abnormality Syndrome of inappropriate anti-diuretic

can result from toxicity? hormone (SIADH)
Are there any specific No

antidotes for carbamazepine
toxicity?
CHEMOTHERAPEUTIC AGENTS
What are the clinical uses Inhibit tumor growth and progression.
and major classes of Major classes include alkylating agents,
chemotherapeutic agents? antibiotics, antimetabolites, hormones
(prevent synthesis of, or competitively
antagonize hormones), mitotic inhibitors,
monoclonal antibodies, platinum com-
plexes, topoisomerase inhibitors, and
miscellaneous.
What are typical therapeutic 1. Interference with DNA synthesis and

mechanisms of action of this replication
class of drugs? 2. Interference with growth signaling
pathways
3. Generation of free radicals
which damage/destroy rapidly
dividing cells
4. Interference with RNA synthesis
5. Inhibition of cell division
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6. Inhibition of specific enzymes or

receptors over-expressed in cancerous
cells
7. Inhibition of protein synthesis
What are typical Most are cytotoxic by nature, thus toxic

mechanisms of toxicity for effects resemble extremes of pharmaco-
this class of drugs? logic effects. Those that target DNA
replication and cell division exert toxic ef-
fects most readily on the GI and
hematopoietic systems (i.e., those sys-
tems with rapid turnover). Free radical
generation can be a major side effect,
particularly with antibiotics. Local tissue
damage may be caused by extravasation.
What are possible clinical 1. Heme – leukopenia (with subsequent

manifestations of infection), thrombocytopenia (with
chemotherapeutic agent subsequent hemorrhage), anemia
overdose? 2. GI – nausea, vomiting, and diarrhea
(with resultant dehydration),
stomatitis, peptic ulcer formation, GI
bleeding
3. Skin necrosis at injection sites due to
extravasation injury
What is the standard rescue Leucovorin (folinic acid)

therapy for methotrexate
overdose?
Which agents commonly Anthracyclines (dactinomycin,

cause cardiotoxicity? doxorubicin)
Name two agents known to Cyclophosphamide and ifosfamide

cause hemorrhagic cystitis.
Overdose of what agents can Nitrogen mustards

result in seizures?
What treatments may be 1. Actinomycin, daunorubicin,

considered in specific doxorubicin, idarubicin, and
chemotherapeutic agent mitoxantrone – ice to injection site
extravasation? (15 min, QID ⫻ 3d), consider topical
dimethyl sulfoxide (DMSO) to
alleviate symptoms
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2. Mitomycin – moderate heat to

injection site, consider topical DMSO
3. Mechlorethamine, dacarbazine, and
cisplatin – flush injection site with
10 mL sterile 2.5% sodium thiosulfate
solution
4. Etoposide, paclitaxel, vincristine, and
vinblastine – heating pad to injection
site (intermittently ⫻ 24 hrs), elevate
limb, consider local injection of
hyaluronidase
CHLOROQUINE AND OTHER AMINOQUINOLINES
Name the commonly used Chloroquine, hydroxychloroquine,

aminoquinolines. primaquine, mefloquine
What are these drugs used Malaria, systemic lupus erythematosus,

for? rheumatoid arthritis
How does chloroquine work? Inhibits DNA and RNA synthesis
What are some of the GI upset, anxiety, depression, pruritus,

adverse effects of headache, visual disturbance
aminoquinolines?
How do the aminoquinolines Chloroquine and hydroxychloroquine

produce cardiotoxic effects possess quinidine-like cardiotoxicity, re-
in humans? sulting in QRS prolongation. QT prolon-
gation may also occur through potassium
channel blockade.
What are the effects of acute CNS and respiratory depression,

chloroquine/ hydroxy- hypokalemia, hypotension, cardiac
chloroquine overdose? dysrhythmias, possibly seizures
Which aminoquinoline is Mefloquine

highly associated with
neuropsychiatric
disturbance?
What hematological Methemoglobinemia and subsequent

abnormality is associated hemolysis
with primaquine and
quinacrine?
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What electrolyte Hypokalemia, from direct intracellular

abnormality is associated shifts
with chloroquine toxicity?
Describe the management Secondary to severe toxicity, aggressive

of acute overdose. decontamination should be considered in
the airway-protected patient. Early me-
chanical ventilation may be required.
Seizures should be treated with benzodi-
azepines. Vasopressors may be needed
for hypotension.
How should cardiotoxicity For QRS widening, sodium bicarbonate

be treated? boluses are the standard treatment. QTc
prolongation may be treated with IV
magnesium sulfate.
CLONIDINE AND RELATED AGENTS
What are some common Hypertension and attenuation of opioid

uses for clonidine? withdrawal symptoms
What are the pharmacologic 1. Stimulation of presynaptic alpha

mechanisms of action of 2-adrenergic (inhibitory) receptors
clonidine? centrally, thereby reducing
sympathetic outflow
2. Stimulation of alpha 2-adrenergic
receptors peripherally → transient,
paradoxical ↑ HR and ↑ BP
3. Stimulation of imidazoline receptors
What other medicines act as Oxymetazoline (e.g., nasal spray),

centrally-acting adrenergic tetrahydrozoline (e.g., eye drops),
antagonists? tizanidine, guanfacine, methyldopa,
guanabenz
What are the routes of PO, transdermal patches

administration of clonidine?
When is the usual time to 30–60 min

onset of effect of oral
clonidine?
What type of overdose can a Opioid overdose (triad of miosis, CNS,

clonidine overdose mimic? and respiratory depression)
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What are the primary Hypotension and bradycardia

cardiovascular effects of a
clonidine overdose?
Should paradoxical No, it is self-limited.

hypertension from an acute
clonidine overdose be
treated?
What is characteristic about Pinpoint

the pupils of a patient who
has overdosed on clonidine?
Is there an antidote for 1. Naloxone has been reported to reverse

clonidine overdose? CNS depression.
2. Yohimbine and tolazoline have been
reported to reverse hypotension and
bradycardia, but their use is
controversial.
COLCHICINE
For what condition is Gout

colchicine most commonly
prescribed?
What is the mechanism of It primarily acts to disrupt cellular micro-

action of colchicine? tubule formation, which halts chemotaxis,
phagocytosis, and mitosis. Therapeuti-
cally, this results in anti-inflammatory
properties.
What is the maximum 8–10 mg daily

therapeutic dose?
What plants contain 1. Autumn crocus (Colchicum

colchicine? autumnale)
2. Glory lily (Gloriosa superba)
What are the effects of an Symptoms are delayed in onset, usually

acute overdose of from 2–12 hrs depending on the dose.
colchicine? Initial symptoms are GI in nature and
include nausea, vomiting, and bloody
diarrhea. Severe volume loss may result,
followed by multisystem organ failure.
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Are there cardiovascular Colchicine is directly toxic to both

complications of colchicine cardiac and skeletal muscle. This
overdose? may lead to dysrhythmias and
cardiovascular collapse, as well as
rhabdomyolysis.
What are late complications The arrest of cellular division results in

of a colchicine overdose? bone marrow suppression with leukopenia
and thrombocytopenia. Hair loss may
also occur.
What are some side effects Myopathy and polyneuropathy

of chronic colchicine
therapy?
Is there a test for colchicine No blood or urine test exists; however,

intoxication? bone marrow biopsies may reveal
“pseudo-Pelger-Huet” cells, which are
cells in metaphase arrest.
How is a colchicine overdose 1. Aggressive supportive care with fluid

treated? and electrolyte monitoring
2. Orogastric lavage can be considered if
the patient presents within 1 hr of
ingestion, as colchicine possesses
extreme toxicity with little available
treatment.
3. Neutropenia precautions should be
followed for those with bone marrow
suppression.
4. Case reports of granulocyte colony-
stimulating factor (G-CSF) improving
neutropenia have been reported.
Is hemodialysis effective? No, due to extensive volume of

distribution and tissue-binding
What other natural toxin Podophyllin, from the American man-

has colchicine-like drake (Podophyllum peltatum)
properties?
DAPSONE
What is dapsone? Dapsone is an antibiotic agent that can be

administered for leprosy, toxoplasmosis,
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malarial prophylaxis, and Pneumocystis

pneumonia prophylaxis in immunocom-
promised individuals. It is used topically
for acne vulgaris.
What is the approximate 30 hrs for therapeutic dosing, up to

half-life of dapsone? 77 hrs in overdose
What is the mechanism of It prevents the formation of folate by

action of dapsone? inhibiting dihydropteroate synthase.
How is dapsone Acetylation and cytochrome P450

metabolized? oxidation
What is the mechanism of Dapsone is an oxidizing agent. Oxidation

acute toxicity of dapsone? of iron in heme produces methemoglo-
binemia. Oxidative stress on red blood
cells may result in hemolysis. Sulfhemo-
globinemia may result from sulfation of
heme groups.
Are certain patients more Yes, patients with congenital hemoglobin

affected by dapsone abnormalities and G6PD deficiency are
exposure? more likely to experience toxicity.
What are acute effects of Nausea, vomiting, abdominal pain,

dapsone toxicity? hemolytic anemia, methemoglobinemia,
sulfhemoglobinemia, tachycardia,
dyspnea, headache, and CNS stimula-
tion (including hallucinations and
agitation)
What is the clinical Fatigue, cyanosis, and dyspnea may be

presentation of dapsone- present. Cyanosis is refractory to O2 ther-
induced apy, as hemoglobin is unable to become
methemoglobinemia? saturated. If significant methemoglobin is
present (ⱖ15%–20%), blood may appear
brown in color.
What is the diagnostic An arterial blood gas with co-oximetry

test for
methemoglobinemia?
What is the antidote for Methylene blue

methemoglobinemia?
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How does methylene blue It induces the reduction of ferric iron

work? (Fe3⫹ ⫽ methemoglobin) back to ferrous
iron (Fe2⫹ ⫽ hemoglobin).
What clinical and laboratory Primarily indicated by cyanosis that fails

findings indicate to respond to methylene blue in the ap-
sulfhemoglobinemia? propriate clinical setting
What finding is seen on a Heinz bodies (evidence of precipitated

peripheral blood smear in Hgb). Hemolytic anemia may be delayed
patients with dapsone- up to 1 week.
induced hemolytic anemia?
What is the toxic dose of Toxic dose varies by individual, but gen-
dapsone? erally 3–15 g for severe toxicity in adults.
Deaths reported at doses as low as 1.4 g.
DECONGESTANTS
Which general class of Sympathomimetics

medications is primarily
utilized as decongestants?
Which peripheral Alpha-adrenergic receptors

neuroreceptors mediate
vasoconstriction?
Which sympathomimetics Pseudoephedrine and phenylephrine

are used in decongestant
preparations?
What other medications are Imidazoline and propylhexedrine

used as decongestants?
Why was phenyl- Due to ↑ risk of hypertensive crisis and

propanolamine removed hemorrhagic stroke associated with its use
from the market?
What are the most common Antihistamines, acetaminophen, salicy-

classes of medications used lates, dextromethorphan
in combination with
decongestants
| in OTC
“cold” medications?
Name some specific Oxymetazoline, naphazoline, tetrahydro-

imidazoline preparations. zoline, xylometazoline
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How are imidazolines As topical vasoconstrictors—ophthalmic

generally used? or nasal preparations
What is the therapeutic Topical use produces vasoconstriction by

mechanism of action for the activating alpha-adrenergic receptors.
imidazoline class of
medications?
What is the toxic affect of Toxic effects are similar to a clonidine

imidazolines? ingestion and include miosis, lethargy,
hypotension, bradycardia, respiratory
depression, and coma. This is due to a
central alpha 2-adrenergic agonist effect
when absorbed systemically.
Which ophthalmic solution None. This is an urban legend and, in

that is known to “get the red fact, the CNS depression produced
out” produces diarrhea? by imidazolines, combined with their liq-
uid formulation, makes them popular for
drug-facilitated sexual assault or robbery.
What is the mechanism of Alpha-adrenergic agonist, similar to

action of propylhexedrine, amphetamine; toxic effects include
and what are its toxic hypertension, pulmonary edema,
effects? ophthalmoplegia, nystagmus, CNS
stimulation, injection site necrosis.
What are the signs and Tachycardia, mydriasis, hypertension

symptoms of (especially with phenylpropanolamine),
pseudoephedrine, agitation, tremor, visual and auditory
phenylpropanolamine, and hallucinations, seizures
phenylephrine toxicity?
What ephedrine-containing Ma Huang

herbal supplement used to
be used as a decongestant
and is now banned in the
United States?
DIGOXIN
In what class of drugs is Cardiac glycosides

digoxin found?
Where may cardiac glyco- Digitalis purpurea (foxglove), Nerium

sides be found in nature? oleander (oleander), Thevetia peruviana
(yellow oleander), Convallaria majalis
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(lily of the valley), Urginea maritima

(red squill), secretions of Bufo alvarius
(Colorado River toad)
What are the typical Digoxin is used as an inotropic agent in

indications for digoxin? CHF and as an AV nodal blocker in atrial
tachydysrhythmias.
What is the mechanism of Digoxin binds to the extracellular surface

action of digoxin? of the Na-K-ATPase, blocking its activity
and increasing residual sodium inside the
cell. This decreased gradient drives the
sodium-calcium antiporter to extrude
sodium from the cell, driving calcium into
the cell. The increased calcium inside the
cell during systole increases the force of
contraction. Digoxin-induced increase in
vagal tone decreases SA and AV nodal
dromotropy.
What are the adverse effects Increasing calcium inside the cell elevates
of sodium-potassium pump the membrane potential, allowing for eas-
blockade? ier depolarization and predisposition to
dysrhythmias. At the same time, increased
vagal tone leads to AV nodal blockade,
which results in the classic atrial tachycar-
dia with AV block seen in digoxin toxicity.
What ECG abnormalities Scooped ST segments and T wave inver-

are associated with sions in the lateral leads
therapeutic dosing?
Describe the distribution of It follows the two-compartment model.

digoxin.
How is digoxin eliminated? Primarily by the kidneys
What is the therapeutic level 0.5–2.0 ng /mL

of digoxin?
What are the signs and GI distress (e.g., nausea, vomiting, abdom-
symptoms of acute inal pain), lethargy, confusion, atrial and
overdose? ventricular ectopy (including progression
to VT or VF), sinus bradycardia, sinus
arrest, high-degree AV block
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What laboratory Hyperkalemia

abnormality is classically
associated with acute
digoxin toxicity?
What is the most common PVCs

dysrhythmia associated with
digoxin toxicity?
What dysrhythmia is Biventricular tachycardia

pathognomic of digoxin
toxicity?
What are the signs and GI distress (e.g., nausea, vomiting, ab-
symptoms of chronic dominal pain); anorexia with weight loss;
toxicity? delirium; headaches; seizures; visual dis-
turbances; weakness; sinus bradycardia;
ventricular dysrhythmias (more common
than in acute toxicity)
What laboratory testing Digoxin levels, but these may not accu-
should be done? rately indicate severity of ingestion for the
initial 6 hours due to distribution kinetics.
Serum potassium levels reflect the amount
of sodium-potassium pump poisoning in
acute overdose.
What is the role of calcium While normally an integral part of treat-

in digoxin toxicity? ment in hyperkalemia, there have been
case reports of cardiac standstill when
giving calcium for hyperkalemia in
digoxin toxicity.
What is the treatment of 1. In acute overdose, digoxin-specific

digoxin overdose? antibody (Fab) fragments are
indicated for patients with potassium
levels greater than 5.0 mEq/L for high
degree heart blocks, and for
dysrhythmias.
2. Standard therapy is indicated for
hyperkalemia.
3. Use caution in cardioversion of atrial
dysrhythmias (use lowest energy
possible), as the irritable myocardium
is prone to ventricular dysrhythmias.
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4. Atropine can be used for bradycardia.

Use caution with temporary cardiac
pacemakers.
5. Phenytoin may be used for ventricular
irritability if Fab fragments are not
available.
Does hemodialysis have a No, as digoxin has a large volume of

role in cardiac glycoside distribution
poisoning?
For a known steady state [Drug level (ng/mL) ⫻ patient weight in

digoxin blood level, what is kg]/100 ⫽ number of vials (round up)
the dose calculation for Fab
fragments?
DISULFIRAM
What is the chemical name Tetraethylthiuram disulfide—a chemical

of disulfiram, and how is it used in the treatment of alcoholism to
used? produce an unpleasant effect following
ingestion of ethanol
By what route is disulfiram Primarily PO, although SQ implants are

administered? available outside the U.S.
What are the modes of Acute overdose, disulfiram-ethanol inter-

toxicity of disulfiram? action, and chronic toxicity
What are the primary 1. Inhibition of aldehyde dehydrogenase,

mechanisms of toxicity of causing systemic accumulation of
disulfiram? acetaldehyde, an intermediate product
in the metabolism of ethanol
2. Blockade of dopamine beta-
hydroxylase, a crucial enzyme in
norepinephrine synthesis, causing
depletion of presynaptic
norepinephrine, resulting in
vasodilation and orthostatic
hypotension
What industrial solvent and Carbon disulfide

toxin is produced during
the metabolism of
disulfiram?
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When is the peak efficacy of 8–12 hrs

disulfiram reached?
Where is disulfiram Liver

metabolized?
What is the elimination half- 7–8 hrs, with the potential for clinical
life of disulfiram? effects to persist for several days
What is the toxic dose of Patients on maintenance therapy of

ethanol when on disulfiram 200 mg/day have had severe reactions to
therapy? as little as 7 mL of ethanol.
What are the signs and symp- Vomiting, confusion, lethargy, ataxia,
toms of an acute disulfiram coma
overdose (without ethanol)?
What are the signs and Flushing, headache, vomiting, dyspnea,

symptoms of ethanol vertigo, confusion, and orthostatic
ingestion in patients on hypotension with peripheral vasodilation
chronic disulfiram therapy?
What anti-protozoal Metronidazole

medicine commonly causes a
disulfiram-like reaction?
DIURETICS
What is the primary medical As antihypertensives

use of diuretics?
What type of OTC Weight-loss drugs

medications may contain
diuretics?
What groups of people are Athletes, dieters, people with eating

likely to abuse diuretics? disorders
What organ do diuretics Kidney

primarily act upon?
Describe the mechanism of 1. Thiazide and thiazide-like diuretics—

the four major classes of inhibit sodium-chloride transporter in
diuretics. distal convoluted tubule, increasing
Na⫹/Cl⫺excretion
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2. Loop diuretics—inhibit Na⫹/K⫹/2Cl⫺

transporter in thick ascending limb,
blocking reuptake of these electrolytes,
as well as calcium and magnesium
3. Potassium-sparing diuretics—act at a
variety of sites (depending upon the
drug) including distal tubule and
collecting duct to prevent the
reabsorption of sodium while
inhibiting potassium excretion
4. Carbonic anhydrase inhibitors—
inhibit renal carbonic anhydrase,
preventing the reabsorption of
NaHCO3 from the tubular lumen
What is the most common, Hearing loss

reversible side effect of loop
diuretics?
What is the effect of In general, diuretics have low toxicity in

diuretics in acute overdose? acute overdose. Nausea, vomiting, and
diarrhea may occur, as may dehydration.
What is the effect of chronic Electrolyte and acid-base abnormalities

use/abuse?
How do you treat a diuretic Fluid resuscitation and electrolyte

overdose? repletion as needed
ERGOT DERIVATIVES
What are ergot alkaloids? Derivatives of methylergoline that

possess central serotonergic activity and
peripheral vasoconstrictive properties
From which fungus is ergot Claviceps purpurea

derived?
Name the common 1. Amine alkaloids—ergonovine,

medicinal preparations methylergonovine, methysergide,
included in each of the pergolide
three groups of ergot 2. Amino acid alkaloids—ergotamine,
alkaloid derivatives. bromocriptine
3. Dihydrogenated amino acid
alkaloids—dihydroergotamine
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Classically, ergotism is 1. Convulsive—the symptoms include

divided into what two headache, muscle spasms, miosis,
syndromes? paresthesias, mania, psychosis, lethargy,
and seizures. GI effects (i.e., nausea,
vomiting, and diarrhea) precede CNS
effects. Hallucinations may occur,
resembling those produced by LSD.
2. Gangrenous—the dry gangrene is
ultimately a result of profound tissue
hypoxia and subsequent peripheral
ischemic injury. Symptoms include
cool /mottled extremities, loss of
peripheral sensation and/or an
irritating “burning” sensation, edema,
severe distal pain, diminished
peripheral pulses, and possible loss of
affected tissues or digits.
How do people develop 1. Ingesting grain contaminated with

ergotism? ergot fungus
2. Ergotamine treatment for diseases
such as migraines
3. Drug–drug interactions between any
ergot therapy and drugs that inhibit
the cytochrome CYP3A4 enzymes
(e.g., macrolide antibiotics)
Ergot is theorized to have The Salem witch trials

contributed to what 1692
Massachusetts event?
Gangrenous ergotism during St. Anthony’s fire (ignis sacer)

the Middle Ages was also
known by what other name?
In 1951, a case of mass- Mercury

poisoning occurred
following the consumption
of bread in the French
village of Pont-Saint-Esprit.
Although misidentified as
ergotism, what fungicidal
compound has been
implicated as the cause of
the toxic event?
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What is the treatment for 1. Withdraw drug

ergot poisoning? 2. Benzodiazepines for seizures
3. Sodium nitroprusside or phentolamine
for treatment of vasoconstriction
4. Nitroglycerin for myocardial ischemia
5. Vascular surgery consultation for
irreversible ischemia
HEPARIN
What are the different types Unfractionated and low molecular weight
of heparin? (LMWH) forms
What are the different 1. IV (intermittent or continuous)

routes of administration? 2. SQ
What is the mechanism of Heparin acts as a catalyst for antithrom-

action of heparin? bin III, increasing its activity by approxi-
mately a thousand times. Antithrombin
III is a plasma enzyme that inactivates
certain activated serine proteases of the
coagulation cascade, most importantly
activated factors II (thrombin) and X.
The larger heparin species (found in
unfractionated heparin) catalyzes the
inactivation of activated factor II and X.
In contrast, LMWH chiefly inactivates
activated factor X.
What is the half-life of 1–2 hrs in healthy adults, which increases

heparin? with long-term IV administration
What is the half-life of 4–7 hrs

LMWH?
Where is heparin Primarily hepatic, with some metabolism

metabolized? in the reticuloendothelial system
How are LMWHs Renal

eliminated?
What lab test is used to aPTT

monitor patients on
heparin?
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What two forms of Two forms of heparin-induced thrombo-

thrombocytopenia are cytopenia (HIT) have been observed.
induced by heparin? The first (HIT I) is a transient, mild, and
benign thrombocytopenia seen soon after
initiation of heparin therapy (usually
within 2 days) and is thought to be due to
inherent platelet-aggregating properties
of heparin. A second, more severe form
of HIT (HIT II) is typically seen later
and is immune-mediated. The incidence
of HIT II is estimated at 3% to 5%. The
onset is generally 3–14 days after initia-
tion of heparin therapy but may occur
sooner with repeat exposure. HIT II may
occur with any dose and type of heparin,
but the frequency is highest with contin-
uous IV infusions of unfractionated he-
parin. HIT with subsequent thrombosis is
a feared complication. These thrombi can
form in the venous or arterial circulation.
Thrombotic complications include
necrotic skin lesions, myocardial infarc-
tion, stroke, and gangrene.
What type of electrolyte Hyperkalemia may be seen with heparin

disorder may occur with therapy due to inhibition of aldosterone
heparin therapy? synthesis.
Is heparin safe in Pregnancy category C. It does not cross

pregnancy? the placenta and is not expressed in
breast milk.
What is the antidote to Protamine sulfate

heparin?
What is protamine? A protein found in fish sperm that binds

and inactivates heparin
HYPOGLYCEMIC AGENTS
INSULIN
What are the IV insulin has a circulating half-life of
pharmacokinetics of insulin? 5–10 min. SQ insulin has a bioavailability
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of 55% to 77% and a half-life that differs

based on the type of insulin. It is ex-
creted unchanged by the kidneys and
metabolized by the kidneys and liver.
Insulin does not cross the placenta.
What does insulin do? 1. Stimulates cellular uptake and

metabolism of glucose
2. Stimulates entry of proteins into
the cell
3. Shifts potassium and magnesium
intracellularly
4. Promotes formation of glycogen, fatty
acids, and proteins
What is the duration of 1. Regular—5–8 hrs

action of the 7 common 2. Lispro—3–8 hrs
insulins when 3. Aspart—3–5 hrs
administered SQ? 4. NPH—16–24 hrs
5. Lente—16–24 hrs
6. Ultralente—28–36 hrs
7. Glargine—22–24 hrs
What patients are at an Renal failure, hypopituitarism, adrenal

increased risk for failure, autonomic neuropathy, those on
hypoglycemia? beta-blocker therapy
How does hypoglycemia Confusion, tachycardia, diaphoresis,

present? coma, seizures, and stroke-mimicking
symptoms. The sympathetic response
may be blunted in patients taking beta-
blockers.
What are diagnostic clues in 1. History of insulin or sulfonylurea use

the evaluation of 2. Physical exam findings that include
hypoglycemia? injection sites
3. Finger-stick blood sugar should be
used to rapidly assess glucose status.
4. Potassium may be low after insulin
injection.
5. ↑ BUN and creatinine may explain
↓ renal excretion.
6. ↑ LFTs may reveal ↓ liver function.
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How can hyperinsulinemia C-peptide will be present in the blood

from exogenous insulin of patients with endogenous insulin
administration be secretion.
differentiated from that due
to oversecretion of
endogenous insulin (e.g., in
patients with an
insulinoma)?
How can sulfonylurea The two can be differentiated only by

poisoning be differentiated obtaining a sulfonylurea panel. Both an
from an insulinoma? insulinoma and sulfonylurea poisoning
will have elevated insulin and C-peptide
levels.
How should insulin-induced 1. Oral glucose therapy if the patient is

hypoglycemia be treated? awake and alert
2. IV dextrose if the patient is obtunded
3. The patient must be observed past the
peak of the type of insulin used.
4. Check for renal insufficiency that
may have contributed to ↓ insulin
metabolism.
What is the disposition for With short- to medium-acting agents,

patients with accidental patients may be discharged with a
insulin overdose? responsible party if their blood glucose
remains elevated 3–4 hrs following a
standard carbohydrate meal. Admission
is recommended after accidental over-
dose of a long-acting insulin, especially
in those patients who develop
hypoglycemia.
What is the usual bolus Adults—1–2 mL/kg D50W

dose of IV glucose in Children—2–4 mL/kg D25W
hypoglycemic patients Infants—2 mL/kg D10W
with AMS?
Is there a role for activated No. Enteral administration of insulin is

charcoal or gastric lavage in harmless, as no insulin is absorbed from
patients who have ingested the GI tract.
insulin?
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METFORMIN
In what class of antidiabetic Biguanides
agents is metformin found?
What biguanide was taken Phenformin

off the U.S. market in 1976
due to its association with
lactic acidosis?
What is the mechanism of 1. ↓ hepatic glucose production

action of metformin? 2. ↓ intestinal glucose absorption
3. ↓ fatty acid oxidation
4. ↑ insulin sensitivity
What is the mechanism of Almost no hepatic metabolism, 90% to

elimination of metformin? 100% excreted unchanged by the kidneys
Does an acute overdose of No, metformin does not cause insulin re-
metformin induce lease; therefore, hypoglycemia with an iso-
hypoglycemia? lated metformin overdose does not occur.
What is the most serious Lactic acidosis, which can present with
adverse effect of metformin? nonspecific symptoms such as fatigue,
nausea, vomiting, myalgias, and abdomi-
nal pain.
What are risk factors for Renal insufficiency, cardiovascular

lactic acidosis with disease, severe infection, alcoholism,
metformin use? advanced age
What is a potential treatment Hemodialysis or continuous venovenous

option following a metformin hemodiafiltration can speed the elimina-
overdose that induces a tion of metformin and may be used to
marked lactic acidosis? correct life-threatening lactic acidosis.
SULFONYLUREAS
What are sulfonylureas? PO hypoglycemic agents that ↑ insulin
secretion
Name some common Chlorpropamide, glipizide, glyburide,

sulfonylureas. glimepiride, tolbutamide
What is the mechanism of 1. Inhibits an ATP-dependent

action? potassium channel on pancreatic
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beta-islet cells, resulting in cell

membrane depolarization. This
causes calcium influx and subsequent
release of stored insulin from
secretory granules.
2. ↓ hepatic insulin clearance → ↑
serum insulin
3. ↑ peripheral insulin receptor sensitivity
4. ↓ glycogenolysis
What is the average duration 16–24 hrs

of action of the second- and
third-generation agents?
What is the principal effect Hypoglycemia

of toxicity associated with
sulfonylureas?
What factors contribute to Young or advanced age, poor nutrition,

an increased risk of alcohol consumption, renal and hepatic
hypoglycemia? insufficiency, polypharmacy
By what mechanism does Suppresses the secretion of insulin and

octreotide help in glucagon by coupling to G proteins on
sulfonylurea-induced beta-islet cells
hypoglycemia?
What is the mechanism by Although not the preferred method of

which diazoxide treats treatment, diazoxide enhances the release
sulfonylurea-induced of glucose from the liver, inhibits en-
hypoglycemia? dogenous insulin release, and decreases
peripheral glucose utilization. Although
diazoxide may be used for this indication,
octreotide is preferred.
How long should All sulfonylureas show a time-to-peak

asymptomatic patients with effect of less than 8 hrs, except for ex-
sulfonylurea overdose be tended-release glipizide. A patient who is
observed? receiving no supplemental glucose par-
enterally and who has normal blood glu-
cose checks during an 8-hr observation
period can be safely discharged. Any sig-
nificant drop in blood glucose after initial
stabilization warrants admission to the
hospital.
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With what other toxicity/side Hyponatremia, due its induction of inap-

effect is chlorpropamide propriate antidiuretic hormone secretion
associated? (SIADH)
Which sulfonylureas have Chlorpropamide, glyburide, glimepiride

active metabolites eliminated
by the kidney and should not
be used in patients with
renal insufficiency?
OTHER
What are some examples of Rosiglitazone and pioglitazone
thiazolidinediones (TZDs)?
What TZD was taken off the Troglitazone

market in 2000 after cases
of acute liver failure?
What is the mechanism of TZDs bind to peroxisomal proliferator-

action of TZDs? activated receptors and change insulin-
dependent gene expression to enhance
the effect of insulin in skeletal muscle
and in adipose and hepatic tissues.
How are TZDs eliminated? Extensive hepatic metabolism with prod-

ucts excreted in urine and feces
What adverse effects are No hypoglycemia is expected to occur in

seen with TZDs? overdose; only fluid retention, peripheral
edema, and the potential for hepatotoxicity
What TZD has recently been Rosiglitazone

associated with serious
adverse cardiac events?
What are the names of the Nateglinide and repaglinide

meglitinides on the market?
What is the mechanism of Binds to ATP-sensitive potassium chan-

action of meglitinides? nels on pancreatic beta-islet cells to
stimulate insulin secretion
How is this drug eliminated? Predominately metabolized by the liver,

then excreted in the bile, with 6%
excreted by the kidneys
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What are the clinical effects Meglitinides cause the release of insulin
of overdose? from the pancreas and, therefore, have
the potential to cause hypoglycemia.
Overdose data is limited, but hypo-
glycemia seems to be brief and easily
treated with dextrose solutions.
What is the treatment of PO or IV glucose

meglitinide-induced
hypoglycemia?
What are the common Acarbose and miglitol

alpha-glucosidase inhibitors?
What is the mechanism of Inhibit alpha-glucosidase, an intestinal

action of the alpha- brush border enzyme that aids in carbo-
glucosidase inhibitors? hydrate absorption
What are the side effects Primarily GI—bloating, flatulence,

of alpha-glucosidase diarrhea, abdominal pain
inhibitors?
What is the mechanism of 1. Acarbose is poorly absorbed and

elimination of the alpha- eliminated predominantly in the feces.
glucosidase inhibitors? 2. Miglitol is fully absorbed with
unknown implications for its systemic
absorption. It is cleared by the kidney
and may thus exhibit toxicity in the
presence of renal impairment.
What are the Cirrhosis, inflammatory bowel disease,

contraindications for alpha- predisposition for bowel obstruction,
glucosidase inhibitor use? malabsorption syndromes
What is the presentation of Limited data exists, but patients would

an alpha-glucosidase likely present with GI symptoms and
inhibitor overdose? electrolyte abnormalities. No hypo-
glycemia is expected to occur.
What are the dipeptidyl A new class of drugs for glycemic control
peptidase-4 (DPP-4) in type 2 diabetes.
inhibitors?
What are the names of the Vildagliptin, sitagliptin, saxagliptin

DPP-4 inhibitors?
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What is the mechanism of Inhibits the degradation of incretin hor-

action of the DPP-4 mones, causing:
inhibitors? 1. ↑ insulin synthesis and release
2. ↓ glucagon release
3. ↓ hepatic glucose production
4. Delayed gastric emptying
5. ↑ satiety
What are the adverse effects They appear to be relatively benign in

of the DPP-4 inhibitors? overdose. While overdose data is sparse,
hypoglycemia seems to be limited.
IMMUNOSUPPRESSANTS
What are some of the 1. Prevent rejection of transplanted

indications for organs
immunosuppressant drugs? 2. Management of autoimmune diseases
(e.g., Crohn’s disease, systemic lupus
erythematosus, myasthenia gravis)
3. Management of chronic
nonautoimmune disease (e.g., asthma)
What are the types of Monoclonal and polyclonal antibodies,

immunosuppressants? interferons, methotrexate, cyclosporine,
sirolimus, glucocorticoids
What are some of the major 1. Action can be nonselective.

adverse effects of these 2. Can impair ability to fight infection
drugs? 3. Hypertension
4. Specific organ toxicity (especially liver,
lung, and kidney)
5. Dyslipidemia
How do patients with acute Nausea and vomiting may be followed

immunosuppressant by diarrhea, myelosuppression, and
overdose present? signs of immunosuppression (e.g.,
infection).
What about individual drugs 1. Mono/polyclonal antibodies – fever,

and their toxicities? rigors, anaphylaxis, serum sickness
2. Methotrexate – nausea, vomiting,
myelosuppression, anemia, aphthous
ulcers, neutropenia
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3. Cyclosporine – gingivitis, burning

paresthesias, hepatotoxicity,
nephrotoxicity, neurotoxicity
4. Sirolimus – interstitial lung disease
5. Glucocorticoids – adrenal suppression,
hyperglycemia, osteoporosis
Name the rescue therapy for Leucovorin (folinic acid)

methotrexate poisoning.
What herbal product used St. John’s wort – it induces CYP3A4.

for depression may enhance Both are metabolized via CYP3A4.
cyclosporine elimination and
result in transplant
rejection?
Name the number one cause Chronic glucocorticoid use

of secondary adrenal
insufficiency.
How should a patient 1. CBC, electrolytes, and renal function

poisoned with an studies can evaluate for
immunosuppressant agent myelosuppresion and nephrotoxicity.
be managed? 2. Hyponatremia and hyperkalemia may
indicate adrenal insufficiency in
patients that have been on long-term
glucocorticoids.
3. While data is limited, treatment is
primarily supportive. Granulocyte
colony-stimulating factor (G-CSF) has
been used to treat myelosuppression.
IPECAC SYRUP
What is ipecac syrup? An alkaloid oral suspension that induces

vomiting
Where is this found in It is derived from the plant Psychotria

nature? ipecacuanha, which belongs to the family
Rubiaceae.
Name the two key 1. Emetine

components. 2. Cephaeline
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How is ipecac used? Historically, ipecac was used as an emetic

in the case of a potentially poisonous
ingestion or intentional overdose. Ipecac
is no longer recommended for GI
decontamination.
What is the mechanism of Emetine produces irritation of the gastric

action of ipecac? mucosa, while cephaeline causes stimula-
tion of the chemoreceptor trigger zone in
the medulla.
What two groups of patients 1. Bulimics who regularly use ipecac

are reported to have chronic syrup to induce vomiting
ipecac toxicity? 2. Victims of Munchausen’s syndrome by
proxy
How long is the onset of 15–30 min

action of ipecac?
What are the symptoms of Nausea, vomiting, and diarrhea

an acute ingestion?
What are the cellular effects Emetine-mediated inhibition of protein

of chronic use? synthesis in skeletal muscle
How do acutely toxic Nausea, vomiting, lethargy, and elec-

patients present? trolyte abnormalities; gastritis. Gastritis,
gastric rupture, Mallory-Weiss tears, and
pneumomediastinum all have been
reported. Airway compromise may occur
secondary to aspiration.
How do chronic ipecac-toxic Dehydration and electrolyte abnormali-

patients present? ties secondary to vomiting and diarrhea,
muscle weakness and tenderness, and
↓ reflexes. Elevated serum CPK indicates
skeletal muscle myopathy. Cardiomyopa-
thy with resultant dysrhythmias and CHF
have been reported.
How is ipecac toxicity Primarily by patient history. Suspect

diagnosed? chronic exposure in patients with eating
disorders. Urine emetine levels (present
for several weeks following ingestion) can
confirm the diagnosis.
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ISONIAZID (INH)
What is the indication for Tuberculosis

isoniazid (INH) therapy?
What is the mechanism of Isoniazid is a prodrug and must be acti-

action of INH? vated by bacterial catalase; it inhibits the
synthesis of mycolic acid in the mycobac-
terial cell wall.
How is INH metabolized? Hepatic
What is the half-life of INH? 0.5–1.6 hrs in fast acetylators, 2–5 hrs in
slow acetylators
What is the mechanism of INH metabolites inhibit pyridoxine

toxicity of INH? kinase and bind pyridoxal-5-phosphate,
a cofactor for glutamic acid decarboxy-
lase, thereby decreasing levels of the
inhibitory neurotransmitter GABA.
What are the signs of acute Nausea, vomiting, slurred speech, ataxia,
overdose? CNS depression, and seizures
What are the metabolic A marked lactic acidosis may develop in

effects of acute overdose? patients who present with seizures. INH
inhibits lactate dehydrogenase that
converts lactate to pyruvate, thereby
prolonging the metabolic acidosis.
How is the diagnosis made? Generally by history; however, INH toxi-

city should be in the differential diagnosis
for all refractory seizures, especially in
high risk patients (history of HIV, tuber-
culosis, homelessness, or incarceration).
What are the adverse effects Peripheral neuritis, optic neuritis, hepati-
of chronic overdose? tis, pancreatitis, drug-induced systemic
lupus erythematosus, and pyridoxine
deficiency
What drugs are used to treat Pyridoxine (vitamin B6) – 1 g IV for each g
INH overdose? of INH ingested or 5 g IV for an unknown
amount ingested. Standard seizure treat-
ments also apply (i.e., benzodiazepines).
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KETAMINE
What is ketamine? A psychoactive, dissociative agent similar

to phencyclidine (PCP), which is often
used as a sedative agent in medical and
veterinary practice, but has a high abuse
potential secondary to its ability to cause
an “out-of-body” experience.
Which demographic group is Teenagers and young adults who

most likely to abuse frequent “rave” or “techno” parties
ketamine? popular in large urban cities
What are some common Bump, Cat Valium, Green, Honey Oil,
street names for ketamine? Jet, K, Purple, Special K, Special LA
Coke, Super Acid, Super C, Vitamin K
What are street sources of Veterinary offices. Mexico is a major

ketamine? country of origin.
What is the reported street $20–$40 per dosage unit, $65–$100 per
price of ketamine? 10 mL vial containing 1 g of ketamine
What desirable effects of Distorts perceptions of sight and sound,

ketamine support its makes the user feel disconnected and not
illicit use? in control. Sensations ranging from a
pleasant feeling of floating to being
separated from one’s body have been
reported.
What undesirable effects of Terrifying feeling of almost complete

ketamine are reported by sensory detachment, likened to a near-
illicit users? death experience
What are recreational doses 10–250 mg intranasally, 40–450 mg

of ketamine? PO/PR, 10–100 mg IM
How is ketamine prepared Generally evaporated to form a powder.

and administered for illicit It is often adulterated with caffeine,
uses? ephedrine, heroin, cocaine, or other illicit
drugs. The powder is usually snorted,
mixed in drinks, compressed into pills,
or smoked. Liquid ketamine is injected,
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applied on a smokeable material, or con-

sumed in drinks.
What are the clinical effects Short-acting dissociative anesthesia with

of ketamine, and by what little or no depression of airway reflexes
route(s) is it administered? or ventilation. Clinically, it is adminis-
tered IM or IV.
With which CNS receptors Blocks N-methyl-D-aspartate (NMDA)

does ketamine interact, and receptor (dose-dependent), which in-
what is the effect of each? hibits catecholamine and dopamine reup-
take, resulting in elevated BP and heart
rate. In significant overdoses, it stimu-
lates the sigma (␴) opioid receptor,
resulting in coma.
What is the NMDA A voltage-gated ligand-dependent calcium

receptor? channel to which glutamate (the main
excitatory CNS neurotransmitter) naturally
binds. Activation allows for inward calcium
and sodium currents (and some potassium
efflux), resulting in neuronal depolariza-
tion and action potential initiation.
What is the clinical Similar to PCP (lethargy, euphoria, hallu-

presentation of ketamine cinations, occasional bizarre or violent be-
abuse? havior), but much milder and of shorter
duration. Also, hypersalivation and
lacrimation; vertical and horizontal nystag-
mus may be prominent with intoxication.
What other effects are seen 1. Stimulation of salivary and

clinically (and how is each tracheobronchial secretions (treated
managed)? with atropine and glycopyrrolate)
2. Laryngospasm during oral procedures
(treated with positive-pressure
ventilation, rarely endotracheal
intubation)
3. Slight increase in muscle tone and
myoclonic movements
What is the behavioral effect Patients may be oblivious to pain and

of ketamine intoxication? surroundings due to dissociative anes-
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thetic effects; therefore, self-inflicted

injuries and injuries due to resisting
physical restraints are frequent. A low
index of suspicion for rhabdomyolysis
should be maintained.
What is an “emergence Bizarre behavior characterized by a con-

reaction”? fused state, vivid dreaming, and halluci-
nations observed during the recovery
phase of use
How are emergence Sedation with benzodiazepines or

reactions treated? haloperidol
Can anything be done to 1. Avoid rapid IV administration of

decrease the risk of an the drug
emergence reaction? 2. Avoid excessive stimulation during
recovery
What are therapeutic 1–4 mg/kg IV or 2–4 mg/kg IM

anesthetic doses of
ketamine?
What is the duration of Route-dependent – 15 min for IV,

effect of ketamine? 45–90 min after snorting, 30–120 min
for IM, 4–8 hrs after PO/PR
What are illicit uses of Hallucinogen. A “Special K” trip is touted

ketamine, and what as better than that of LSD or PCP
“advantages” does it have because its hallucinatory effects are of rel-
over PCP? atively short duration, lasting ~30–60 min
vs. several hours.
For what other illicit Date-rape drug. It is odorless and taste-

purpose is ketamine used, less, so it can be added to beverages with-
and what properties allow out detection; it also induces amnesia.
this use?
Is there a readily available No. Diagnosis is suggested by rapidly

diagnostic test for detection fluctuating behavior, vertical nystagmus,
of ketamine in hospitals? and sympathomimetic signs. Ketamine
can cross-react with a urine PCP
immunoassay.
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What OTC drug is abused Dextromethorphan, a widely available

for its dissociative effects cough suppressant analog of codeine.
that are similar to ketamine? In high doses, dextromethorphan and
its first-pass metabolite, dextrorphan,
produce PCP/ketamine-like effects due
to interaction with the PCP binding site
of NMDA receptors.
LITHIUM
What are the indications for As a mood stabilizer, most often in

lithium administration? patients with bipolar disorder
How is lithium metabolized? Excreted unchanged by the kidney
What is the etiology of Acute toxicity occurs when a patient

lithium toxicity? takes a single large dose. Chronic toxic-
ity usually occurs in those taking their
regularly prescribed dose. The levels
become toxic through any mechanism
which alters renal function, including
dehydration, diabetes insipidus, and the
use of diuretics, ACE inhibitors, or
NSAIDs.
What renal side effect is Nephrogenic diabetes insipidus

associated with lithium
therapy?
What are the signs and Nausea and vomiting predominate. With
symptoms of acute toxicity? a large enough ingestion, lithium can
cause delayed neurological effects after
redistribution to the tissues.
What signs and symptoms Tremor, confusion, ataxia, slurred

are seen with chronic speech, myoclonus, and hyperreflexia are
toxicity or in patients in common. Severe poisoning can cause agi-
later stages of acute toxicity? tated delirium, coma, hyperthermia, and
convulsions.
What does the ECG show in T-wave flattening or inversions.

lithium toxicity? Prolongation of the QT interval has also
been reported
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What important 1. Peak levels may be delayed, so serial

considerations must be levels should be obtained.
observed when ordering 2. Avoid lithium heparin tubes as they
lithium levels? can cause false positive results.
3. A patient with chronic toxicity can
have significant clinical findings even
with a mildly elevated serum level.
How is lithium toxicity 1. Whole bowel irrigation can be

treated? considered after significant acute
ingestions.
2. Activated charcoal is not effective.
3. Administer IV normal saline (use care
to avoid hypernatremia).
4. Hemodialysis or continuous
venovenous hemodialysis can be
considered in those with severe
intoxication (i.e., seizures, AMS).
What must be considered if Lithium commonly redistributes from the

hemodialysis is employed? tissues into the serum, and serum lithium
levels will rebound.
What drug interaction can Combining lithium with serotonergic

be seen? drugs (e.g., SSRIs) can precipitate sero-
tonin syndrome.
MAGNESIUM
What are the medical 1. Magnesium citrate (i.e., oral cathartic)

preparations of magnesium? 2. Magnesium hydroxide (i.e., milk of
magnesia as an antacid)
3. Magnesium sulfate (i.e., Epsom salt)
4. Magnesium IV preparations
What is the major source of Inhalation of magnesium oxide dust

magnesium in occupational
exposures?
What is the major source of Oral and parenteral administration in

exposure to magnesium in medicinal preparations
healthcare settings?
What percent of an oral 15% to 30% in the small bowel, negligi-

dose of magnesium is ble amount exchanged across the large
absorbed? bowel mucosa
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How is magnesium filtered 1. Filtered at the glomerulus with 95%

and excreted in the body? reabsorbed at the proximal tubule by
active transport
2. Excess magnesium is excreted in the
urine.
Can hypermagnesemia Rarely, as the renal elimination rate

occur in individuals with can exceed the maximum rate of GI
normal renal function? absorption.
Can a person overdose on Most patients with a single acute over-

oral cathartics/antacids? dose will have only mild symptoms
(nausea, vomiting, diarrhea); however,
after a very large ingestion or with multi-
ple repeat overdoses, more severe symp-
toms may occur.
What are the signs and Nausea, vomiting, weakness, flushing,

symptoms of magnesium loss of reflexes, sedation, paralysis,
poisoning? dysrhythmias
What neurological signs are 1. CNS depression progressing to

seen with acute magnesium lethargy and coma
toxicity? 2. Hyporeflexia and muscular paralysis
3. Hypotonicity
What ECG findings are Bradycardia, PR interval prolongation,

indicative of QRS widening
hypermagnesemia?
For what ECG abnormality QTc prolongation

is magnesium considered
the “antidote”?
What can increase the renal Hypercalcemic and hypernatremic states,

excretion of magnesium? loop diuretics
How should I decontaminate Remove the patient from the scene, and
a patient from a magnesium gently brush any magnesium off of the
exposure and/or hazardous patient prior to the use of water for de-
materials scene? contamination, as magnesium will readily
react with water.
What laboratory tests should Electrolytes with serum magnesium,

I get for suspected CBC, BUN, serum creatinine
magnesium
exposure/toxicity?
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Does the serum magnesium Generally yes, but intracellular concen-

level correspond to the tration is more predictive than plasma
severity of symptoms? concentration.
What symptoms correspond 1. 3–9 mEq/L – erythema (cutaneous

with a given serum vasodilation), vomiting, hypotension,
magnesium concentration? hyporeflexia, bradycardia, sedation
2. 10–14 mEq/L – muscle paralysis
(including respiratory),
hypoventilation, cardiac conduction
abnormalities, stupor
3. ⬎14 mEq/L – asystolic cardiac arrest
Can the inhalation of Yes, it may incite local injury leading

magnesium dust cause lung to pulmonary edema. Also, this may lead
injury? to systemic toxicity, as magnesium is
readily absorbed across alveolar-capillary
membranes.
What is the treatment of 1. Gastric emptying with an NG tube

acute magnesium toxicity? may be attempted within 1 hr of
ingestion.
2. Calcium for cardiac conduction
abnormalities or respiratory symptoms
3. IV fluids and dopamine for
hypotension
4. Hemodialysis for severe cases
5. Activated charcoal does not bind
magnesium and is ineffective.
How does calcium work? Direct antagonism of magnesium at neu-

romuscular and cardiovascular sites
What dose of calcium should 1 g of IV calcium gluconate slowly (over

I give? 3–5 min)
Which magnesium-toxic Symptomatic patients with serum magne-

patients should be treated sium ⬎5 mEq/L
with calcium?
NEUROMUSCULAR BLOCKERS
What are the two kinds of 1. Depolarizing neuromuscular blockers

neuromuscular blockers (DNMB)
(NMB)?
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2. Nondepolarizing neuromuscular
blockers (NDNMB)
What is the effect common Paralysis and subsequent respiratory

to both therapeutic and arrest
nontherapeutic uses of all
NMBs?
What is the mechanism of Agonist at the neuromuscular nicotinic

action of a DNMB? ACh post-junctional receptor, causing
prolonged depolarization of the muscle
fiber with subsequent paralysis
What is the only DNMB Succinylcholine

currently in use?
What is the mechanism of Competitive antagonist of ACh at the

action of a NDNMB? neuromuscular nicotinic post-junctional
receptor, causing paralysis by preventing
depolarization of the muscle
Name some side effects of ↑ potassium and ↑ intracranial, intraocu-

succinylcholine lar, and intraabdominal pressures
administration.
The normal initial dose of 0.5 mEq/L

succinylcholine is
~1–1.5 mg/kg. By what
amount does this raise the
serum potassium in most
patients?
What patient conditions can Recent burns, multi-system trauma/crush

be adversely affected by this injuries; recent (days to months) CNS in-
rise in serum potassium? juries (e.g., paraplegia) or denervation
processes; stroke; neuropathy; myopathy;
renal failure; malignant hyperthermia; or
prolonged NDNMB use
What are the signs and Fever, hypercapnia, metabolic acidosis,

symptoms of potentially fatal mottled skin, muscle rigidity,
malignant hyperthermia tachydysrhythmias
(rarely) associated with
succinylcholine?
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What factors prolong the A decrease in pseudocholinesterase levels

effects of succinylcholine? in the plasma, the presence of a geneti-
cally atypical pseudocholinesterase, or
the presence of a competitive pseudo-
cholinesterase substrate (e.g., cocaine)
Laudanosine is a metabolite Laudanosine is nonpolar and readily

of certain NDNMBs that crosses the blood-brain barrier.
causes seizures by inhibiting
GABA. Since all NMBs are
polar, why does this
metabolite affect the CNS?
What class of drugs can Cholinesterase inhibitors

reverse the effects of
NDNMBs?
Can cholinesterase No, they will prolong neuromuscular

inhibitors be used to reverse blockade in this setting.
succinylcholine?
NITRATES
What are the major Angina pectoris, AMI, CHF

therapeutic uses of nitrates?
What are some other uses of 1. Industrial uses – explosives (e.g.,

nitrates? nitroglycerine in dynamite), food
preservation
2. Therapeutic uses – antidiarrheals and
topical cautery devices (e.g., silver
nitrate)
What is the mechanism of Within smooth muscle cells, nitrates re-

action? lease nitric oxide with the downstream
effect of increasing cGMP, resulting in
smooth muscle relaxation.
What are the effects on the Peripheral vasodilation → ↓ preload and

cardiovascular system? ↓ afterload (with higher doses)
What are the most common Related to vasodilation, most notably

toxic effects of nitrate hypotension
ingestion?
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What are the clinical signs Tachycardia, headache due to meningeal

and symptoms of nitrate artery dilatation, orthostatic hypotension
toxicity?
What adverse effect to Methemoglobin

hemoglobin may occur
following exposure to
nitrates?
What drug class should be Phosphodiesterase inhibitors (e.g.,

used with caution with sildenafil)
nitrates?
When nitrates and these Both ↑ cGMP → synergistic vasodilata-

agents are used together, tion and hypotension with potential
what adverse effects occur? hypoperfusion
NITRITES
What are examples of Sodium nitrite, amyl nitrite, butyl nitrite,

nitrites? methyl nitrite
What are the clinical uses of Sodium nitrite (injectable) and amyl
nitrites? nitrite (inhalant) are components of the
cyanide antidote package. They oxidize
hemoglobin to methemoglobin, which
binds cyanide.
How are nitrites abused? Amyl nitrite ampules are called “Amy,”
“poppers,” “rush,” or “snappers” and are
inhaled.
What is the “high” achieved A “rush” characterized by warm sensa-

by abusing “poppers”? tions and feelings of dizziness. May also
delay and prolong orgasm.
What is the mechanism of Oxidizes hemoglobin to methemoglobin

action of nitrites? and also functions as a vasodilator.
What are signs of acute Headache, skin flushing, orthostatic

toxicity? hypotension with reflex tachycardia,
acidosis, cyanosis, seizures, coma, dys-
rhythmias, “chocolate brown blood” if
methemoglobinemia is present
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What labs are helpful in the Direct measurement of methemoglobin

diagnosis of nitrite toxicity? level through co-oximetry
How should nitrite toxicity High-flow oxygen and methylene blue (if
be treated? methemoglobin level ⬎30% or the pa-
tient is symptomatic)
NITROPRUSSIDE
What two active metabolites 1. Nitric oxide (NO) – causes

are released when vasodilation
nitroprusside is hydrolyzed, 2. Cyanide (CN) – cellular toxin
and what are their effects?
What are the indications for Treatment of severe hypertension and for
nitroprusside use? inducing hypotension in certain surgical
procedures
What is the normal fate of Cyanide is rapidly converted to thio-

cyanide in patients treated cyanate by the enzyme rhodanese.
with nitroprusside? Thiocyanate is then cleared by the
kidneys.
What infusion rate of Infusion rates ⬎10 ␮g/kg/min for ⬎1 hr

nitroprusside may cause put patients at risk for cyanide toxicity.
cyanide toxicity?
A patient with renal Thiocyanate, produced from the metabo-

insufficiency becomes lism of cyanide, may accumulate to toxic
nauseated, confused, and levels in patients treated with nitroprus-
progressively hypertensive side. Symptoms include nausea, vomiting,
after being treated with somnolence, delirium, tremors, hyper-
nitroprusside for 3 days. reflexia, hypertension, and seizures.
What toxin is implicated?
What factors can cause Renal insufficiency and prolonged infu-

thiocyanate accumulation? sion. Nitroprusside infusion should not
be run for ⬎72 hrs.
Does hemodialysis help No. Nitroprusside and cyanide are both

eliminate nitroprusside or metabolized rapidly; however, hemodialy-
cyanide? sis may be useful in clearing thiocyanate,
particularly in patients with impaired
renal function.
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NITROUS OXIDE
How is nitrous oxide (N2O) As a weak anesthetic, mostly in outpa-

used clinically? tient dentistry mixed with oxygen at a
concentration of 25% to 50% for analge-
sia and sedation; principal adjunct to
inhalation and IV general anesthetic
What are the street names Laughing gas, hippie crack

for nitrous oxide?
How is it commonly 1. “Crackers” are nitrite-containing metal

obtained by abusers? or plastic canisters. “Poppers” are
nitrite-containing ampules that are
broken or “popped” to release vapors.
2. “Whipits” are small cartridges of N2O
used for dispensing whipped cream.
What is the onset of action 2–5 min by inhalation

and method of delivery?
By what mechanism is It may act by inhibition of NMDA-

anesthesia achieved? activated currents and stabilize axonal
membranes to partially inhibit action
potentials, leading to sedation.
What are signs and Acute inhalation may lead to euphoria;

symptoms of acute toxicity? however, acute toxicity is related to
asphyxia, causing headache, dizziness,
confusion, syncope, seizures, and
cardiac dysrhythmias.
What are the results of Megaloblastic anemia, thrombocytopenia,

chronic abuse? leukopenia, peripheral neuropathy (espe-
cially posterior column findings),
myelopathy, birth defects, and sponta-
neous abortion
Name the vitamin depleted Vitamin B12 (cyanocobalamin)

by chronic inhalation.
What is the effect of nitrous Hypotension has been reported, as has

oxide on the cardiovascular methemoglobinemia, which may result
system? from contaminants (nitrates/nitrites).
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How is it eliminated? Almost completely by the lungs, with

some minimal diffusion through the skin
What lab tests could aid in CBC with differential, vitamin B12, and
diagnosis? folic acid levels
Is there a treatment for Folinic acid may help with bone marrow
chronic toxicity? suppression
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
What are the common 1. Propionic acids – ibuprofen, fenopro-

specific drugs that fall into fen, ketoprofen, naproxen, oxaprozin
the five major categories of 2. Acetic acids – diclofenac, etodolac,
NSAIDs? indomethacin, ketorolac, sulindac
3. Fenamic acids – mefenamic acid,
meclofenamic acid
4. Oxicams – piroxicam
5. Pyrazolones – phenylbutazone
Which NSAID is most Ibuprofen

commonly taken in an
overdose?
What is the general Inhibition of cyclooxygenase enzymes

mechanism of action for (COX) I and II with subsequent blockade
NSAIDs? of prostaglandins
Are there NSAIDs with Yes. Celecoxib, rofecoxib, and meloxicam

selective COX inhibition are more COX II selective.
properties?
How are NSAIDs Absorbed primarily in the small intestine

metabolized and eliminated? and undergo hepatic oxidation and glu-
curonidation. Metabolites are mainly
excreted in the urine, but most have some
enterohepatic excretion and reabsorption.
At what dose may symptoms 100 mg/kg

emerge in children
following ibuprofen
overdose?
Which two NSAID classes Pyrazolones and fenamic acids

require more aggressive
management?
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Which drug has the highest Mefenamic acid, usually 2–7 hrs post-
incidence of seizures? ingestion
What are the most common Mild GI symptoms (e.g., nausea, vomit-
side effects with ibuprofen? ing, abdominal pain), which can be
followed by mild CNS disturbances
(e.g., drowsiness, headaches). Seizures,
hypotension, metabolic acidosis, and
renal and hepatic dysfunction may
develop after massive overdoses.
What is the mechanism of Anion gap metabolic acidosis may be

acidosis? related to acidic metabolites and
hypotension. This tends to occur only
in large overdoses.
Are there toxicities associated Yes. GI bleeding and renal dysfunction

with chronic ingestion?
Are hemodialysis and urine Mild renal dysfunction can be seen with
alkalinization indicated in acute overdoses; however, the renal fail-
NSAID overdoses? ure usually resolves with fluid administra-
tion. NSAIDs are highly protein-bound,
and the metabolites are excreted in the
urine, thus hemodialysis and alkalization
of urine have not been proven to
enhance elimination.
Do serum NSAID levels No

predict toxicity?
OPIOIDS
What are the three opiate Delta, kappa, mu

receptors?
What are some slang terms China white, brown, superbuick, black
for various opiates? tar, hot shot, bird’s eye, homicide
How are opioids abused? Depending on the specific substance,

opioids can be insufflated, injected,
smoked, or taken orally.
What is the opioid CNS and respiratory depression with

toxidrome? miotic pupils
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How do opiates differ from Opiates are specific substances derived

opioids? from the opium poppy. Opioids include
all substances (both natural and syn-
thetic) that are capable of producing
opium-like effects.
With opioid urine drug These screens detect morphine metabo-

screens, what three opioids lites; therefore, only morphine, as well as
are reliably detected? heroin and codeine (both of which are
metabolized to morphine), are detected
by such screens. Other opioids (i.e., fen-
tanyl, oxycodone, hydrocodone, meperi-
dine, propoxyphene, hydromorphone,
tramadol) may not be detected.
Which synthetic opioid Meperidine. MAOIs block the reuptake

should be avoided in of serotonin, and the interaction between
patients taking MAOIs and meperidine and the serotonin receptors
why? could induce serotonin syndrome.
Which by-product of illicit Illicit synthesis of the meperidine ana-

opioid production causes logue MPPP (1-methyl-4-phenyl-4-
parkinsonian symptoms? propionoxypiperidine) has been shown to
accidentally produce MPTP (1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine) as a
by-product. When MPTP is used intra-
venously, it is subsequently metabolized
into MPP⫹ (by MAO-B), which inter-
feres with mitochondrial oxidative phos-
phorylation at complex I and causes free
radical-mediated cell destruction within
the substantia nigra.
How are opioids Hepatic metabolism with renal excretion

metabolized and excreted?
What percentage of the Approximately 7% of the Caucasian pop-

population lacks the ability ulation lacks the appropriate enzyme
to metabolize codeine to (CYP2D6).
morphine?
Is there an antidote for Naloxone. It should be given slowly

opiate overdose? (0.4 mg over a few min) and titrated with
the return of spontaneous respiratory
13486_CH02.qxd 10/30/08 7:17 AM Page 107
effort. As the half-life of naloxone is

shorter than that of most opioids, the pa-
tient should be monitored for re-sedation
or development of opioid-induced non-
cardiogenic pulmonary edema, typically
manifesting within 4 hrs in people with
normal renal function.
What is the general Primarily supportive care. Respiratory

treatment of opioid depression will be the main concern.
poisoning? Naloxone may be used as a diagnostic
tool or to avoid intubation.
Other than respiratory Noncardiogenic pulmonary edema

depression, what acute
pulmonary complication is
associated with opioid use?
What are the signs of CNS excitation (e.g., restlessness,

withdrawal? agitation, anxiety, dysphoria), nausea,
vomiting, abdominal cramps, diarrhea,
piloerection, lacrimation, rhinorrhea,
diaphoresis. AMS and fever are not
associated with opioid withdrawal and
those signs should prompt further diag-
nostic testing.
Which medications have Methadone, clonidine, buspirone

been used to alleviate opioid
withdrawal symptoms?
Name three opioids that do Meperidine, propoxyphene, tramadol

not cause miosis.
PHENYTOIN
What electrolyte channel is Neuronal sodium channels are blocked

primarily affected by
phenytoin?
Why does rapid IV While originally thought to come solely

administration of phenytoin from the propylene glycol diluent, pheny-
cause myocardial depression toin also seems to have a direct cardio-
and cardiac arrest? depressant effect.
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How should IV phenytoin be Slowly (maximum 50 mg/min) and with

administered? ECG monitoring
Is oral phenytoin No
cardiotoxic?
Why is it important that It causes tissue necrosis.

phenytoin not be
administered IM or through
an infiltrated IV?
What is fosphenytoin? A disodium phosphate ester of phenytoin

that does not contain propylene glycol, is
better tolerated IV and can be adminis-
tered IM
What happens to the half- First-order elimination switches to zero-

life of phenytoin as the order elimination, and the half-life
levels rise? increases.
How is phenytoin Cytochrome P450 pathway, resulting in

metabolized? multiple drug interactions
What are the symptoms of Nystagmus, dysarthria, ataxia, nausea,

mild to moderate vomiting, diplopia
intoxication?
What are the symptoms of a Stupor, coma, respiratory arrest

severe intoxication?
What are some potential Fever, rash, blood dyscrasia, hepatitis,

side effects of phenytoin? Stevens-Johnson syndrome, gingival
hyperplasia
Can a serum phenytoin level Yes, the therapeutic range is 10–20 mg/L.
be obtained?
What is the correlation 1. ⬎20 mg/L – nystagmus

between phenytoin levels 2. ⬎30 mg/L – ataxia, slurred speech,
and symptoms? nausea, vomiting
3. ⬎40 mg/L – lethargy, confusion, stupor
4. ⬎50 mg/L – coma, seizures
Is there a specific antidote No, treatment is supportive.

for phenytoin toxicity?
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RAUWOLFIA ALKALOIDS
In what general class of Antihypertensives

medications are rauwolfia
alkaloids found?
From where are rauwolfia The roots of Rauwolfia serpentina,

alkaloids derived? a plant native to India
What was once a commonly Reserpine

used rauwolfia alkaloid?
What is the significance of First drug used in the modern era of

reserpine? hypertension management
Describe the mechanism of It depletes stores of serotonin, dopamine,

action of reserpine. and norepinephrine by initially pre-
venting their reuptake, then binds to
catecholamine storage vesicles in the
presynaptic adrenergic neuron terminals.
This is effectively a pharmacological sym-
pathectomy, which leads to decreased
vascular tone and bradycardia with subse-
quent hypotension.
Why was reserpine used as a Depletion of catecholamines in the brain

treatment for schizophrenia? can produce a sedative effect.
Why is reserpine not used CNS side effects and newer drugs that
commonly in the United are as effective
States?
List some of the common Sedation and inability to concentrate

side effects of reserpine. are most common. Also, psychotic
depression, parkinsonism, headache,
nightmares, dysrhythmias, bradycardia,
hypotension. Concomitant use of MAOIs
can lead to adrenergic storm.
What is the clinical Symptoms are typically seen within

presentation of acute 3–7 hrs post-ingestion and may last
reserpine toxicity? 2–4 days. Signs and symptoms are related
to initial catecholamine excess, then
subsequent depletion with unbalanced
parasympathetic activity.
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1. CNS – ataxia, AMS, stupor, coma

2. CV – tachycardia followed by
bradycardia, hypertension followed by
hypotension
3. Parasympathetic effects – miosis,
facial flushing, excessive salivation,
hypothermia, diarrhea, excessive
gastric acid secretion
What neurologic disorders Parkinson’s disease and depression

may be induced with
chronic reserpine use?
Why is reserpine starting to Reserpine at low doses, used in combina-

be used more in the United tion with diuretics, has proven effective
States? in the treatment of hypertension, specifi-
cally in the elderly.
Why is reserpine use still The cost is cheaper than that of other
prevalent in developing antihypertensives.
nations?
How long does it take to 2–3 wks

synthesize vesicles once
reserpine is stopped?
How long after the first 2–3 wks

dose of reserpine does it
take for hypotensive effects
to be seen?
What is the treatment of Supportive care. Short-acting, titratable

acute reserpine overdose? cardiovascular agents should be used, as
initial hypertension may progress to
hypotension.
SALICYLATES
What are the clinical uses of Analgesia, anti-inflammatory, anti-pyretic

salicylates?
What are common forms of 1. Aspirin (acetylsalicylic acid)

salicylates? 2. Oil of wintergreen (methyl salicylate)
3. Bismuth salicylate
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How many grams of aspirin About 7 g or 21 regular strength aspirin

are equal to 5 mL of oil of tablets
wintergreen?
What factors can 1. Large tablet masses (bezoars) in the

dramatically delay GI tract
absorption in salicylate 2. Enteric-coated products
overdoses? 3. Pylorospasm
4. ↓ gastric motility
What are the metabolic 1. Respiratory alkalosis – stimulation of

effects of a salicylate the central respiratory center causes
overdose? hyperpnea and tachypnea. Also occurs
to compensate for metabolic acidosis
in more severe cases.
2. Metabolic acidosis – uncoupling of
oxidative phosphorylation and
interruption of Krebs cycle
dehydrogenases → ↑ CO2 production
3. Metabolic alkalosis – may occur
secondary to vomiting
How are salicylates Hepatic metabolism predominates at

eliminated? therapeutic doses, but due to saturation
of hepatic metabolism, renal excretion is
also important in overdoses.
What is the toxic dose in 1. ⬍150 mg/kg – no toxicity to mild

acute ingestions? toxicity
2. 150–300 mg/kg – mild to moderate
toxicity
3. 300–500 mg/kg – severe toxicity
What is the clinical Initial symptoms include GI upset, tinni-

presentation of an acute tus, and tachypnea/hyperpnea, followed
overdose of salicylates? in severe cases by coma, seizures, hyper-
thermia, hypotension, pulmonary and
cerebral edema, and death.
What is the clinical Hearing loss/tinnitus, confusion, dehy-

presentation of chronic dration, metabolic acidosis, seizures,
toxicity? lethargy, pulmonary and cerebral
edema, coma
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Which has higher morbidity Chronic

and mortality, acute or
chronic overdose?
What acid-base abnormality Mixed respiratory alkalosis and metabolic

is seen on ABG analysis with acidosis
salicylate overdoses?
What is considered a toxic Above 30 mg/dL (300 mg/L). Note the

salicylate level? units, as some laboratories report in
mg/dL and others in mg/L. Failure to pay
attention to this detail can lead to unnec-
essary transfers and treatment.
How often should salicylate Initially, consider drawing levels every

levels be drawn following 2 hrs until the salicylate level begins
acute overdose? declining, then every 4 hrs until they
return to the therapeutic range.
How should a salicylate GI decontamination with activated char-

overdose be treated? coal. Sodium bicarbonate should be given
to alkalinize the urine and serum in order
to prevent salicylate from crossing the
blood-brain barrier and to promote
excretion. Dialysis should be considered
in severe overdoses.
Why is charcoal important in Due to the possibility of delayed absorp-

treatment? tion, even if administered late, charcoal
has the potential to bind a significant
amount of the drug.
How should sodium Boluses of 1–2 mEq/kg, followed by

bicarbonate be an infusion of 5% dextrose in water with
administered? 150 mEq of sodium bicarbonate to
maintain the urine pH at 7.5 to 8.
After assuring urine output, add
potassium to each liter of fluid to avoid
hypokalemia.
If a salicylate toxic patient is Hyperventilate to compensate for the

intubated, how should they metabolic acidosis. Placing an acute
be ventilated? salicylate overdose on typical ventilator
settings may kill the patient.
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What are the indications for 1. Salicylate level ⬎100 mg/dL after
urgent hemodialysis? acute overdose
2. Salicylate level ⬎60 mg/dL after
chronic overdose with AMS or
acidosis
3. Severe manifestations – coma,
seizures, cerebral edema, acute
respiratory distress syndrome
(ARDS), renal failure, severe /
refractory acidosis or electrolyte
abnormality
4. Inability to tolerate sodium
bicarbonate alkalinization (due to
renal failure, pulmonary edema, etc.)
SEDATIVE-HYPNOTIC AGENTS
What are the common uses Anxiety, insomnia, sedation, alcohol with-
of sedative-hypnotic agents? drawal, seizure management
Name some common Barbiturates, benzodiazepines, buspirone,

sedative-hypnotic agents. zolpidem, chloral hydrate, carisoprodol
What is the sedative- CNS depression with variable respira-

hypnotic toxidrome? tory depression. The remainder of
the physical exam may be otherwise
unremarkable.
What subversive acts are Drug-facilitated sexual assault (“date-

these drugs often used for? rape”) or robbery
What benzodiazepine used Flunitrazepam (Rohypnol), also known as

in drug-facilitated assault is “Roofies”
not detected on many
routine drug assays?
What properties make it It is a potent sedative-hypnotic that is

popular for this use? tasteless, easily dissolved in liquids, and
is not detectable on most routine urine
drug screens. It is still legally manufac-
tured in European countries but is
Schedule I in the U.S. The manufacturer
has recently added a blue dye to the for-
mulation in an attempt to make it more
detectable in beverages.
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Which agent has been Chloral hydrate

associated with ventricular
dysrhythmias in children?
What is the term used for “Mickey Finn”

the combination of chloral
hydrate and ethanol?
What is the treatment of The mainstay of treatment of all

sedative-hypnotic overdose? sedative-hypnotics is supportive care.
Respiratory support should be provided
as needed, and evaluation for co-
ingestions is important.
Is there an antidote for Yes. Flumazenil is a competitive benzodi-

benzodiazepine overdose? azepine antagonist.
Do sedative-hypnotics have Yes. Withdrawal from these agents can

a withdrawal syndrome? have severe and life-threatening compli-
cations. CNS and autonomic excitation
occur, resulting in tremor, tachycardia,
hypertension, hyperthermia, and
seizures.
SKELETAL MUSCLE RELAXANTS
What are some examples of Baclofen, carisoprodol, chlorzoxazone,

common skeletal muscle cyclobenzaprine, metaxolone, methocar-
relaxants? bamol, orphenadrine, tizanidine
Under what class do most of Sedative-hypnotic agents

these medicines fall?
Which three skeletal muscle Cyclobenzaprine, carisoprodol, baclofen

relaxants are the most
abused as recreational
drugs?
Does the clinical No, as this is a broad class of drugs with

presentation of all skeletal varying effects on specific receptors.
muscle relaxants in overdose
look the same?
What skeletal muscle Baclofen. Overdose is consequently asso-

relaxant has GABA-B agonist ciated with coma, respiratory depression,
activity? seizures, and bradycardia.
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What two skeletal muscle Cyclobenzaprine and orphenadrine

relaxants induce an
anticholinergic syndrome in
overdose?
What skeletal muscle Orphenadrine

relaxant has been associated
with SVT and lidocaine-
refractory VT in overdose?
Which skeletal muscle Tizanidine (CNS depression, miosis,

relaxant has alpha 2- bradycardia, and hypotension following
adrenergic effects and acts overdose)
like clonidine following
overdose?
Is there a specific antidote No, management is supportive.

for skeletal muscle relaxant
overdoses?
THEOPHYLLINE
What are the clinical uses COPD and asthma

for oral theophylline?
What is aminophylline, and Theophylline ethylenediamine, a salt of

how does it differ from theophylline. It is less potent and may be
theophylline? given IV.
What are the clinical uses 1. Refractory asthma

for aminophylline? 2. CHF
3. Nonasthmatic bronchospasm
4. Neonatal apnea, as a respiratory
stimulant
By what mechanisms does 1. Stimulation of beta 1- and beta

theophylline exert its 2-adrenergic receptors
therapeutic and toxic 2. Inhibition of phosphodiesterase
effects? 3. Inhibition of adenosine receptors
What is the significance of Adenosine-1 receptors cause feedback

adenosine blockade? inhibition of neuronal firing. Adenosine-2
receptors cause cerebral vasodilation.
Theophylline toxicity may, therefore,
result in refractory seizures with a rela-
tive lack of cerebral blood flow.
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What is the toxic dose for ⬎20 ␮g/kg, although toxicity may be
theophylline? seen with lower doses
What serum level signifies a ⬎80–100 mg/L

severe theophylline acute
overdose?
How does acute theophylline 1. Mild or moderate toxicity – GI upset,

overdose present? tachycardia, anxiety, tremor, mild
metabolic acidosis, and electrolyte
abnormalities
2. Severe toxicity – refractory vomiting,
hypotension, metabolic acidosis,
dysrhythmias, seizures
What electrolyte and Hypokalemia, hypophosphatemia,

glucose abnormalities may hypomagnesemia, hypercalcemia,
be seen with acute hyperglycemia
theophylline overdose?
How does chronic In chronic toxicity, GI upset, hypokalemia,

theophylline toxicity differ and hyperglycemia are less common, but
from acute overdose? severe symptoms (e.g., seizures, dysrhyth-
mias) are more frequently seen than in
acute overdose and may occur at lower
serum concentrations (even at 40 mg/L).
What criteria may be used Serum theophylline levels. The diagnosis

to positively diagnose is suggested by a history of refractory
theophylline overdose? vomiting, tachycardia, hypokalemia,
tremors, hyperreflexia, and hyperglycemia.
What treatments should be 1. Primarily supportive

performed in the event of 2. Nonselective beta blockers have been
theophylline overdose? reported to improve hypotension and
tachycardia in case reports but should
be used cautiously, as no clinical trials
have been conducted to determine
efficacy.
3. Hypokalemia is usually transient and
resolves without intervention.
4. Multiple-dose activated charcoal may
be beneficial, as theophylline
undergoes enteroenteric recirculation.
5. Hemodialysis should be considered
for those with severe toxicity.
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THYROID HORMONES
What forms of thyroid 1. Synthetic triiodothyronine

hormone are available for (T3, or liothyronine)
clinical use? 2. Synthetic thyroxine
(T4, or levothyroxine)
3. Synthetic combination of T3 and T4 in
1:4 ratio (liotrix)
4. Natural desiccated animal thyroid
(both T3 and T4), derived from
porcine thyroid glands
For what medical condition Both T3 and T4 are used for

are thyroid hormones hypothyroidism.
administered?
What form of thyroid T3 has 3⫻ more activity than T4. T4

hormone is considered to be undergoes peripheral conversion to T3 by
most potent? a 5⬘-deiodinase, primarily in the liver and
kidney.
How is thyroid hormone Oral (well-absorbed enterally)

administered?
What is the mechanism of Bind to intracellular receptors that

action of thyroid hormones? regulate transcription and translation of
proteins that ↑ oxygen consumption by
promoting Na-K-ATPase activity
In which compartments are Liver and kidneys

thyroid hormones
metabolized?
What is a toxic dose of A dose ⬎3–5 mg T4 or 750 ␮g T3 acutely.

thyroid hormone? The threshold is lower in those with
baseline cardiac disease or chronic
overexposure.
How is the diagnosis of History consistent with ingestion and clin-

acute thyroid hormone ical presentation consistent with sympa-
overdose made? thetic adrenergic excess. Serum thyroid
hormone levels are of little use clinically.
What is the mechanism of Sympathetic adrenergic overstimulation

toxicity of thyroid hormone (targets CV, GI, neuro)
overdose?
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How soon after acute T3 overdose may be evident as soon as

ingestion of thyroid 6 hrs post-ingestion. T4 toxicity may not
hormones will symptoms of be clinically apparent until as long as
overdose appear? 11 days post-ingestion (while being deio-
dinated to T3).
What are the acute effects Anxiety, agitation, tremor, GI symptoms,

of thyroid hormone tachycardia, and hypertension on presen-
overdose? tation may be followed by SVT, hypoten-
sion, hyperthermia, and seizures in
severe overdose.
What is the treatment of Similar to hyperthyroidism – adrenergic

thyroid hormone overdose? symptoms can be treated with
propranolol or esmolol. In cases of T4
overdose, peripheral conversion to T3
may be inhibited by propylthiouracil.
Benzodiazepines also are appropriate
for agitation.
TYPE I ANTIDYSRHYTHMIC AGENTS
What is the basic mechanism They reduce excitability of cardiac tissue

of action of the type I by preventing fast acting sodium chan-
antidysrhythmics? nels from converting from an inactivated
state to a resting or “ready” state, thereby
decreasing the number of active sodium
channels available to generate an action
potential.
What is the physiology By inhibiting the fast acting sodium

behind this mechanism? channels that are normally active during
the upstroke (phase 0) of the action
potential in cardiac tissue, they slow the
rate of depolarization and propagation of
conduction through the myocardium.
How are type I Based on their effects on the duration of

antidysrhythmics further the action potential (AP)
subdivided?
What are the effects of type Ia – prolong

Ia, Ib, and Ic agents on the Ib – shorten
AP? Ic – no effect on the AP
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Which class binds primarily Ib

to inactivated sodium
channels?
Which class also acts at Ia and Ic

myocardial potassium
channels responsible for
repolarization?
How does this potassium Prolongs the QTc

efflux blockade affect the
ECG?
What rhythm can result Torsade de pointes

from QTc prolongation?
What are some type Ia Procainamide (prototypical type Ia

agents? agent), quinidine, disopyramide
What are the physiologic 1. Prolonged AV conduction

effects of type Ia agents at 2. Depressed ventricular conduction
high concentrations? velocity, resulting in prolonged QRS
duration
3. Delayed repolarization, resulting in
prolonged QT interval and
progression to torsade de pointes
4. ↓ cardiac contractility and excitability
What organ systems are Mostly CNS and cardiovascular effects

affected by type Ia toxicity?
What are the clinical signs 1. CNS – anticholinergic toxidrome

and symptoms of type Ia with AMS (quinidine and
agent toxicity? disopyramide), seizures, respiratory
depression, coma
2. CV – wide QRS-complex tachycardia
(sodium channel blockade),
anticholinergic-induced tachycardia,
depressed contractility, and
subsequent hypotension when
confounded by alpha-adrenergic
blockade or ganglionic
blockade
3. GI – nausea, vomiting, diarrhea,
hypoglycemia
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Which agent is associated Procainamide

with a drug-induced lupus
syndrome when used
chronically?
What is cinchonism? Syndrome of headache, tinnitus,

vertigo, deafness, and visual
disturbances
What agent is associated Quinidine

with cinchonism after
chronic use?
What is the management of Sodium bicarbonate for ventricular tachy-

type Ia cardiac toxicity? dysrhythmias and undifferentiated wide
complex tachycardias. Other agents, such
as lidocaine, phenytoin, or pacing can be
used. Never use type Ia or type Ic agents,
as they may exacerbate toxic effects on
the heart.
What is the prototypical Lidocaine

type Ib agent?
Name some other type Ib Tocainamide, mexiletine, phenytoin

agents.
Do type Ib agents cause No, these agent have binding properties

QRS widening? that are fast-on, fast-off and they prefer-
entially bind to the sodium channel in
the inactive state. In contrast, both
type Ia and Ic agents may cause QRS
widening.
What are the CNS effects CNS stimulation, confusion, seizures, res-
with type Ib overdose? piratory arrest
What the effects of toxic Asystole, sinus arrest, AV block, cardiac

exposure to type Ib agents? arrest
Can type Ib agents be No. They have no effect on potassium

associated with torsade de channels, do not prolong repolarization,
pointes? and do not prolong the QTc.
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Which of these agents is Tocainide

associated with
agranulocytosis?
What are some examples of Flecainide, encainide, propafenone,

type Ic agents? moricizine
What the effects of toxic Ventricular dysrhythmias, bradycardia,

exposure to type Ic agents? SA and AV block, asystole
According to the Cardiac Flecainide, encainide, moricizine

Arrhythmia Suppression
Trial (CAST), which of these
agents have been shown to
increase overall mortality?
What electrolyte disturbance Hyperkalemia

increases the cardiac toxicity
of all type I agents?
Which type I agents (Ia, Ib, Type Ic; thus, these agents are typically
or Ic) are most associated used only for dysrhythmias that are
with proarrhythmic effects? refractory to other drugs
TYPE II ANTIDYSRHYTHMIC AGENTS
What is the mechanism of Beta-adrenergic receptor blockade →

action of type II agents? ↓ cAMP → inhibition of sodium and
calcium currents
What cardiac tissues are AV node

most sensitive to the
antidysrhythmic actions of
type II agents?
What are the effects of Same as those for patients taking beta
excessive beta-adrenergic blockers for other medical problems,
blockade in patients including bronchospasm, bradycardia,
requiring antidysrhythmics? hypotension, and first-degree heart
block, but these patients are more
prone to the depressive effects on
cardiac output
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Which type II agent is Propranolol. Because it is lipophilic, it

associated with coma, has more severe CNS toxicity. It also has
respiratory depression, and myocardial sodium channel blocking
convulsions? activity and can therefore lead to prolon-
gation of the QRS complex.
What metabolic Hyperkalemia and hypoglycemia

disturbances can occur with
type II agent toxicity?
Hypotension induced by npc8a

overdose of beta-blockers
can be reversed with which
drug?
What other therapy has been Hyperinsulinemia/euglycemia therapy

utilized to treat persistent
hypotension and bradycardia
induced by beta-blockers?
TYPE III ANTIDYSRHYTHMIC AGENTS
What is the basic mechanism Delays repolarization, prolonging the

of action of type III action potential and increasing the effec-
antidysrhythmics? tive refractory period by blocking the
potassium current
At therapeutic levels, what PR and QTc prolongation

ECG changes can be seen?
Upon which cardiac tissues Atrial and ventricular

do these agents act?
Name examples of type Amiodarone, sotalol, bretylium,

III agents. dofetilide, ibutilide
What dysrhythmia may be Torsade de pointes

induced by these agents?
Can these agents cause toxic Yes. Because they have a narrow thera-
effects at therapeutic doses? peutic index, these agents can be highly
toxic with even small ingestions.
What other actions does Type II effects (beta-adrenergic block-

sotalol have? ade) at low doses and mixed type II and
type III effects at high doses
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What other cardiovascular Bradydysrhythmias and hypotension

disturbances can this drug
precipitate?
Which agent initially Bretylium

releases and later inhibits
catecholamine release?
What can this cause? Transient hypertension followed by

hypotension that may last for hours after
administration
Although amiodarone Types I, II, and IV (all of them)

primarily acts as a type III
agent, what other properties
does it possess?
Because amiodarone has Slows heart rate → bradycardia

type II (beta-adrenergic
blocking) and type IV
(calcium channel blocking)
effects, what can amiodarone
do to the heart rate?
How does this affect the Reduces the propensity to cause new
arrhythmogenicity of this dysrhythmias
type III agent?
What extracardiac side Pulmonary fibrosis, hypo- and hyperthy-

effects are associated with roidism, corneal deposits → vision loss,
chronic amiodarone use? grayish discoloration of the skin
TYPE IV ANTIDYSRHYTHMIC AGENTS
What is the mechanism of Calcium channel blockade that slows

action of type IV agents? calcium entry into the myocardial cells
→ ↓ cardiac contractility and ↓ AV
nodal conduction
What changes are typically PR interval prolongation

seen on ECG at therapeutic
levels?
Which calcium channel Verapamil and diltiazem

blockers (CCB) are
antidysrhythmic agents?
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What are the toxic effects of AV block, bradycardia, hypotension, CNS

calcium channel blockade? depression
What drug interactions Concomitant use with beta blockers,

might exacerbate these especially when given parenterally
effects?
Verapamil in overdose has Cardiac sodium channel blockade

been associated with what
adverse effect on the heart
(besides calcium channel
blockade)?
CCBs in overdose are 1. Prevention of insulin release from

associated with what adverse pancreatic beta cells
insulin effects? 2. Peripheral insulin blockade
In severe CCB overdose, Hyperglycemia

what is more commonly
seen, hyperglycemia or
hypoglycemia?
What specific drugs can be Calcium chloride or calcium gluconate

used in type IV agent can initially be used to augment calcium
toxicity? flow. Glucagon, adrenergic agents (e.g.,
epinephrine), and amrinone may ↑ intra-
cellular cAMP to overcome calcium
channel blockade. Hyperinsulinemia-
euglycemia therapy has been shown to
improve contractility.
Are CCBs dialyzable? No, CCBs are highly protein bound and,
therefore, not dialyzable.
VALPROIC ACID
For which indications is 1. Seizure disorders (prophylaxis or to

valproic acid prescribed? abort status epilepticus)
2. Affective disorders
3. Chronic pain (not an approved use)
4. Migraine headache prophylaxis
Where is valproic acid Liver

metabolized?
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What is the toxic dose? Although highly variable, 200–400 mg/kg

may cause coma. ⬎400 mg/kg has an in-
creased risk for an adverse outcome.
What organ system is most CNS – causes depression

affected by an acute
overdose?
With chronic therapy, what The liver – hepatic failure can occur.
organ may be adversely
affected?
What metabolic Primary hyperammonemia (without coex-

complications can be seen isting hepatic failure) may be seen with
with valproic acid ingestion? therapeutic use or following overdose.
Anion gap metabolic acidosis may be
seen in acute overdose with very large
ingestions.
What is considered a toxic Levels ⬎150 mg/L are considered toxic.

valproate level?
How should the overdose be Multi-dose activated charcoal has been

treated? used to ↑ elimination. Valproate-induced
hyperammonemic encephalopathy may
be treated with carnitine and lactulose.
Hemodialysis may be used for patients
with marked acidosis or very high serum
concentrations.
What hematologic Bone marrow suppression can occur after

abnormality may be seen in massive overdose. This presents within 3
overdose? to 5 days and resolves spontaneously a
few days later.
VASODILATORS
What medications are This class includes a broad spectrum

vasodilators? of medications that dilate peripheral
arteries and veins, producing ↓ BP.
Many medications fit this description,
but only alpha-adrenergic blockers
and direct-acting agents will be dis-
cussed here.
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What are the names and 1. Hydralazine – acts via cGMP in the
mechanisms of the three smooth muscle
direct-acting arterial 2. Minoxidil sulfate – hyperpolarizes
vasodilators? arteriolar smooth muscle cells by
activating ATPase-sensitive potassium
channels
3. Diazoxide – hyperpolarizes arteriolar
smooth muscle cells by activating
ATPase-sensitive potassium channels
How is the alpha-adrenergic Peripheral alpha-1 receptors cause

receptor involved in vasoconstriction when activated. Block-
vasodilation? ade of these receptors, therefore, causes
vasodilation.
How does the typical Hypotension with reflex tachycardia

vasodilator overdose patient
present?
How do vasodilators cause Likely through a baroreceptor-mediated

tachycardia? reflex causing sympathetic stimulation,
increasing myocardial chronotropy, and
inotropy
What treatment for male- Minoxidil

pattern baldness is also used
as a vasodilator?
What types of immunologic Lupus-like syndrome, serum sickness,

reactions are associated with vasculitis, glomerulonephritis, hemolytic
hydralazine? anemia
What test should every An ECG, as myocardial ischemia, tachy-

patient with suspected cardia, and ECG changes all have been
vasodilator toxicity undergo? reported with vasodilator toxicity, partic-
ularly minoxidil
What is the primary Fluid resuscitation followed by alpha-1

treatment for overdose? agonists (e.g., phenylephrine) as necessary
VITAMINS
Which vitamins are most Fat-soluble vitamins (A, D, E, K)

likely to cause acute or
chronic toxicities?
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Are the toxic levels of No. A wide variance in potential toxicity

vitamins well-defined? exists for both acute and chronic
exposures.
What are the acute and 1. Acute – 12,000 IU/kg

chronic toxic doses of 2. Chronic – 25,000 IU/day for 2–3 wks
vitamin A? or 4,000 IU/day for 6–15 months
Name the food associated Polar bear liver

with vitamin A toxicity in
Eskimos.
What are the clinical Nausea, vomiting, headache, drowsiness,

findings of acute vitamin A desquamation
toxicity?
What are the clinical ↑ ICP (causing headache, papilledema,

findings of chronic seizures, blurred vision); dry skin (may
vitamin A toxicity? also see eczema, erythema, alopecia, or
angular cheilitis); bone pain; hepatitis
The measurement of specific Vitamins A and D

levels of which vitamins may
assist in diagnosing an
overdose?
How are vitamin E and PT, aPTT, and bleeding times

vitamin K toxicities
monitored if not measuring
their specific levels?
What are the clinical Hypercalcemia (may see metastatic calci-

findings of chronic vitamin fications and renal calculi); weakness;
D toxicity? AMS; constipation; polyuria; polydipsia;
backache; cardiac dysrhythmias (late sign
associated with hypertension)
What is the mechanism by It antagonizes the effects of vitamin K

which vitamin E exerts its and may act synergistically with warfarin,
anticoagulant effects? affecting factors II, VII, IX, and X.
Acute vitamin E toxicity may Nausea, vomiting, and weakness are most
present with which signs and likely to be reported; however, in a mal-
symptoms? nourished patient or in those on warfarin,
coagulopathy may be reported.
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If a mother receives excess Hemolytic anemia, jaundice, and hyper-

vitamin K during pregnancy, bilirubinemia (particularly if comorbid
what symptoms may result G6PD deficiency)
in the newborn?
Which vitamin is highly Isotretinoin, a form of vitamin A used in

teratogenic in pregnancy? the treatment of acne. Embryonic sensi-
tivity is greatest during the first eight
weeks of pregnancy.
How can chronic beta- In beta-carotene ingestion no scleral

carotene ingestion be icterus is present, while in true jaundice
differentiated from true scleral icterus may be one of the
jaundice? first signs.
Toxic amounts of vitamin K Oral anticoagulants

result in the inactivation of
what drug class?
Which vitamin is also known Vitamin B3

as niacin?
Toxic levels of niacin Prostaglandin D2

increase the release of
which prostaglandin?
What signs and symptoms Cutaneous flushing, pruritus, headache,

does prostaglandin D2 bronchoconstriction, vasodilation
produce?
What medication can be Aspirin, 81 mg ingested 30 min before

used to prevent this side niacin
effect of niacin?
What is the acute toxic dose Ingestion of ⬎1000 mg/day

of niacin?
Name the organ most likely The liver. Elevated transaminases can
affected in chronic niacin occur with both acute and chronic over-
toxicity. dose. Abnormalities usually improve after
discontinuation of niacin.
Which vitamin is also known Vitamin B6

as pyridoxine?
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What are the symptoms of Ataxia, hyporeflexia, and sensory neu-

chronic pyridoxine ropathies, primarily affecting propriocep-
overdose? tion and vibratory sense
What is the chronic toxic 2–5 g/day for several months has resulted
dose of pyridoxine? in peripheral neuropathy
Large doses of B vitamins Intensification of the yellow color of

may result in which benign urine. Riboflavin may cause yellow
clinical sign? perspiration.
WARFARIN
How was warfarin Researchers at the Wisconsin Alumni

discovered? Research Foundation found that cattle
eating spoiled clover were developing co-
agulopathies. This also gave the name
WARFarin.
How is warfarin used? 1. Therapeutic anticoagulant

2. Rodenticide, although longer-acting
“superwarfarins” are now used
What is the mechanism of Blocks hepatic synthesis of vitamin K-

warfarin? dependent coagulation factors by inhibit-
ing the enzyme vitamin K(1) 2, 3-epoxide
reductase
Which coagulation factors II, VII, IX, X

are dependent on vitamin K
for synthesis?
What is a “superwarfarin”? A fat-soluble warfarin derivative that is

used as a rodenticide because of its long-
acting effects
How long does it take for Warfarin inhibits synthesis of new fac-
anticoagulation effects to tors. While factor VII begins to degrade
emerge? within 5 hrs, peak effects are not seen
until 2–3 days.
What is the toxic dose of In patients who are not on chronic war-
warfarin? farin therapy, single acute ingestions of
warfarin do not cause clinically significant
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anticoagulation; however, small amounts

(2–5 mg) repeated over multiple days can
lead to significant anticoagulation.
What is the duration of 2–7 days

anticoagulant effect after a
single dose of warfarin?
What is the duration of anti- Weeks to months

coagulant effect after a sin-
gle dose of a superwarfarin?
How is warfarin Cytochrome P450 liver enzymes, resulting

metabolized? in numerous potential drug interactions
What drugs interfere with 1. ↑ anticoagulation – allopurinol,

the anticoagulant effect of amiodarone, cimetidine, disulfiram,
warfarin? ginkgo biloba, NSAIDS, salicylates,
sulfa
2. ↓ anticoagulation – barbiturates,
carbamazepine, nafcillin, PO
contraceptives, phenytoin, rifampin
What is the primary adverse Bleeding

effect of warfarin?
Name two nonhemorrhagic Warfarin skin necrosis and purple toe

complications of syndrome
warfarin use.
Is checking a warfarin level No, warfarin levels are not clinically use-
helpful for management of ful in the acute management of a known
an overdose? warfarin overdose. The PT/INR should
be checked; a normal PT/INR at 48 hrs
post-ingestion rules out significant poi-
soning. Warfarin and superwarfarin (i.e.,
brodifacoum) levels can be measured if
surreptitious poisoning is suspected.
Are there any specific Vitamin K1 (phytonadione) restores pro-

antidotes for warfarin duction of clotting factors by bypassing
overdose? the inhibitory effects of warfarin.
Is prophylactic vitamin K No. Prophylactic vitamin K therapy will

therapy warranted in make the 48-hr PT/INR inaccurate as a
treatment? measure of toxicity.
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How do monitoring Monitoring must continue at least 5 days

parameters change after following the last vitamin K1 dose.
antidote administration?
How is acute bleeding Transfusions with fresh whole blood or

treated in the setting of a fresh frozen plasma to replete coagula-
warfarin overdose? tion factors rapidly
How is vitamin K PO, SQ, and IV

administered?
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Chapter 3 Drugs of Abuse
AMPHETAMINES
What are amphetamines? Chemicals with structures similar to

phenylethylamine. Added side chains
promote different levels of catecholamine
and serotonin activity.
What is the mechanism of Amphetamines bind to the monoamine

action of amphetamines? transporters and ↑ extracellular levels of
the biogenic amines dopamine,
norepinephrine, and serotonin.
Which amphetamines are 1. Dextroamphetamine

used in the treatment of 2. Methylphenidate
narcolepsy and attention-
deficit hyperactivity
disorder (ADHD)?
Which amphetamines were 1. Fenfluramine

used for weight loss but 2. Dexfenfluramine
later recalled due to
cardiopulmonary toxicity
when used in combination
with phentermine?
What amphetamine began to 3,4-methylenedioxy-N-methylampheta-

be used therapeutically in mine (MDMA, “ecstasy”)
the mid-1970s after the
chemist Alexander Shulgin
introduced it to
psychotherapist Leo Zeff?
What illicit amphetamine is Methamphetamine in a smokable form

referred to as “ice”?
What is the bioavailability of Good oral absorption with predominant

amphetamines? hepatic metabolism. Urinary excretion is
favored by an acidic environment.
132
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Chapter 3 / Drugs of Abuse 133
What are the clinical signs Agitation, anxiety, AMS, mydriasis, hy-
of acute amphetamine pertension, tachycardia, diaphoresis,
intoxication? tremor, muscle rigidity (sometimes with
rhabdomyolysis), hyperthermia, seizures
What is the toxidrome for The sympathomimetic toxidrome

this constellation of
symptoms?
What are adverse effects of Anorexia, paranoia, cardiomyopathy, pul-

chronic amphetamine monary hypertension, vasculitis, aortic re-
intoxication? gurgitation, mitral regurgitation
What is an important class Benzodiazepines. Large doses may be

of drugs for counteracting needed.
the sympathomimetic effects
of amphetamines?
Amphetamine became a The Controlled Substances Act

schedule II drug with the
passage of what act in 1970?
COCAINE
How is cocaine administered Intranasal (snorting), inhalation

as a drug of abuse? (smoking), IV injection, ingestion
By which method is the Inhalation (3–5 sec)

onset of action most rapid?
Which method provides the Intranasal or other mucosal

longest duration of action? administration (60–90 min)
What is a “speedball”? IV injection of a combination of cocaine

and heroin
What is a common Free base, including “crack”

alternative form of the
hydrochloride salt?
Why is “free base” 1. Lower temperature of volatilization

preferred over the HCl salt 2. More heat-stable
for smoking?
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Which form of cocaine is Crack

considered to be most
addictive?
What is the approximate 60 min

half-life of cocaine?
In which compartment(s) is 1. Plasma

cocaine metabolized? 2. Liver
What is the mechanism of 1. Blockade of presynaptic

action of cocaine? norepinephrine, dopamine, and
serotonin reuptake centrally and
peripherally
2. Na⫹ channel blockade (neuronal and
cardiac)
What are the desired effects Euphoria and ↑ vigilance

of illicit cocaine use?
What are the acute Cerebral ischemia/infarction, intracranial

untoward effects of cocaine hemorrhage, myocardial ischemia/
use? infarction, cardiac arrhythmias,
hyperthermia, seizures, anxiety, agitation,
muscle rigidity, hypertension
What is the incidence of 5%

myocardial infarction
associated with cocaine-
induced chest pain?
What active compound is Cocaethylene

enzymatically formed when
cocaine and ethanol are co-
administered?
What is the significance of 1. Longer half-life

this compound relative to 2. Significantly ↑ risk of sudden death
cocaine? 3. Less reinforcing
4. Less euphoria
5. Smaller increase in heart rate
By what methods can recent 1. Direct blood or urine detection

cocaine use be detected? (several hrs after use)
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2. Detection of metabolites in blood or

urine (24–36 hrs after use)
3. Hair analysis (weeks to months after
use)
What drug class is Beta blockers

contraindicated for use in
the cocaine intoxicated
patient?
In the agitated, cocaine Benzodiazepines

intoxicated patient who is
manifesting
sympathomimetic overdrive,
what drug class should
initially be used in
management?
DESIGNER DRUGS
What is the definition of a A chemical substance intended for

designer drug? recreational use that results from the
modification of a legitimate
pharmaceutical agent
List some of the different 1. Narcotic derivatives

classes of designer drugs. 2. Phenylethylamine/amphetamine
derivatives
3. Tryptamine-based substances
4. Phencyclidine (PCP) analogs
5. Piperazine-based substances
6. Gamma-hydroxybutyrate (GHB)
analogs
What are some common 1. Fentanyl analogs – 3-methylfentanyl

narcotic designer drugs and and alpha-methylfentanyl (“China
their street names? White” and “Tango and Cash,”
respectively)
2. Meperidine analog – 1-methyl-4-
phenyl-4-propionoxy-pyridine (MPPP)
What is the typical triad of AMS, miosis, respiratory depression

symptoms in opioid
overdose?
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What are the side effects of Usual potency is greater than that of
the fentanyl-based designer heroin, resulting in excessive sedation
drugs? and death. Higher than usual doses of
naloxone may be needed to reverse
effects.
What unique and serious This drug is often contaminated with the
presentation can occur after chemical 1-methyl-4-phenyl-1,2,3,6-
a single use of the tetrahydropyridine (MPTP), which is me-
meperidine analog MPPP? tabolized to 1-methyl-4-phenyl-1,2,5,6-
tetrahydropyridine (MPP⫹) by
monoamine oxidase-B (MAO-B). The lat-
ter causes the destruction of the
dopamine-containing cells in the substan-
tia nigra. A parkinsonian-like syndrome
can result after even a single use. Effects
are often permanent, hence the name
“frozen addicts.”
Name some of the common 1. Methamphetamine

amphetamine-based 2. 4-Methylaminorex
designer drugs. 3. MDMA
4. 2,4-dimethoxy-4-
propylthiophenylethylamine (2C-T7)
What is “ice”? The translucent crystals of

methamphetamine in a very pure form.
In what ways can Injected, inhaled/smoked, ingested

methamphetamine be
administered?
How long can the effects of 2–24 hrs

methamphetamine last?
What are some of the Delusions, paranoia, tics, compulsive be-

undesired and dangerous havior, GI distress, anorexia, weight loss,
effects of methamphetamine coronary ischemia/infarction, stroke,
use? acute pulmonary edema, death
Mixing “ice” with what Ethanol

other commonly used drug
results in increased cardiac
and cerebrovascular
toxicity?
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What are the desired effects Euphoria, verbosity, intimacy

of MDMA?
How long do the desired 4–6 hrs

effects last?
What is the usual route of Orally ingested in tablet or capsule form

administration of MDMA?
What is the mechanism of Induces the release and blocks the

action of MDMA? reuptake of serotonin, dopamine, and
norepinephrine
What are the undesirable Hyperthermia, diaphoresis, muscle

and dangerous effects of rigidity (including trismus), rhabdomyol-
MDMA? ysis, disseminated intravascular coagula-
tion (DIC), cardiac dysrhythmias,
anorexia, hyponatremia, metabolic
acidosis
How should the drug- 1. Active cooling – cold IV fluids, misting

induced hyperthermia fans
caused by MDMA be 2. Benzodiazepines
treated? 3. If resistant to active cooling and
benzodiazepines, intubation with
paralysis may be needed to ↓ muscle
rigidity and prevent further
hyperthermia and rhabdomyolysis
(continuous EEG may be needed to
monitor for seizure activity).
What is the long-term effect Destruction of serotonergic neurons →

of MDMA use? chronic dysphoria
The tryptamine analogs Euphoria, hallucinations, disinhibition

(e.g., alpha-
methyltryptamine,
dimethyltryptamine) are
recreationally used as
psychedelics and produce
what desirable effects?
What are some of the Anxiety, insomnia, GI discomfort, muscle

undesirable effects of the rigidity (including trismus)
tryptamine analogs?
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The piperazine-based MDMA

designer drugs have similar
effects to what other drug?
What designer drug is Methcathinone

similar to the drug found in
leaves of the khat bush
(Catha edulis)?
DEXTROMETHORPHAN
For what condition is OTC antitussive

dextromethorphan used?
What is the mechanism of 1. Serotonin reuptake inhibition

action of 2. NMDA receptor antagonism
dextromethorphan?
How is dextromethorphan By the oral route. Available in liquid,

abused? pill, and caplet form. Products
containing dextromethorphan are often
combined with other agents (e.g., aceta-
minophen, chlorpheniramine). Common
slang terms include “Triple C’s,” “Dex,”
and “DXM.”
Why is dextromethorphan While dextromethorphan is often classi-

abused? fied as an opioid, the popularity of abuse
comes from the “out-of-body” experience
produced from blocking the NMDA
receptor.
To what dissociative agent is PCP

dextromethorphan
structurally similar?
Name the substance assay PCP

that cross-reacts with
dextromethorphan on many
urine drug screens.
Name two hyperthermic 1. Serotonin syndrome. The risks are

syndromes associated with especially great when the person
dextromethorphan abuse. abusing the drug is taking other pro-
serotonergic agents (e.g., SSRIs).
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2. Anticholinergic toxidrome, as
dextromethorphan is often combined
with anticholinergic agents
What electrolyte Dextromethorphan bromide may cause a

abnormality may be a clue falsely elevated chloride level, as bromide
to dextromethorphan abuse? and chloride have the same valence on
the periodic table.
Where is dextromethorphan GI tract, then crosses blood-brain barrier

absorbed? after absorption into vascular compartment
What is the half-life of 3–6 hrs

dextromethorphan?
When is the onset of 15–30 min post-ingestion

therapeutic effect?
What are the signs and Dizziness; ataxia; hallucinations (visual

symptoms of and auditory); dystonias; miosis; nystag-
dextromethorphan toxicity? mus; seizures; respiratory depression; stu-
por; coma; serotonin syndrome
How should Supportive care. Naloxone may be help-

dextromethorphan toxicity ful for CNS and respiratory depression.
be treated?
ETHANOL
Should ethanol be classified Both. It competitively inhibits alcohol

as a toxic alcohol or an dehydrogenase and may be used as an
antidote? antidote for methanol and ethylene gly-
col poisonings when fomepizole is not
available.
Action at what receptor is GABAA receptor binding and activation

responsible for the major
CNS effects of ethanol?
Is the rate of absorption Mixed drink. The fastest absorption

higher from a “straight comes from drinks containing 20%
shot” of ethanol or from a ethanol. High concentrations of ethanol
mixed drink? cause pylorospasm and delay systemic
absorption.
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Alcohol dehydrogenase Males and Pacific Rim Asians. High levels

activity is higher in what of acetaldehyde (from rapid ethanol
groups of people? conversion) are responsible for the skin
flushing seen in some people after ethanol
consumption. Pacific Rim Asians also tend
to be slow metabolizers of acetaldehyde,
leading to further accumulation.
What are the metabolites of Acetaldehyde and acetate, respectively

ethanol in the major
pathway (i.e., alcohol and
aldehyde dehydrogenases)?
What are the main Slurred speech, ataxia, nystagmus, CNS

symptoms of alcohol depression
intoxication?
Name three commonly Some cephalosporins, metronidazole,

prescribed antibiotics which nitrofurantoin
react with ethanol
metabolism similarly to
disulfiram.
What mechanism is The presence of ethanol favors conver-

responsible for ethanol- sion of pyruvate to lactate, leaving less
induced hypoglycemia? pyruvate available for gluconeogenesis.
Children, chronically malnourished alco-
holics, and binge drinkers who do not eat
are at particular risk.
Does ethanol intoxication No; however, in alcoholic ketoacidosis

alone produce an anion gap (AKA), the high anion gap is caused by
acidosis? acetoacetate, beta-hydroxybutyrate, and
lactate. Serum ethanol levels are usually
not elevated in this setting.
What antidote cures ethanol None. Caffeine and cold showers are of
intoxication? no benefit. Hemodialysis can clear serum
ethanol in life-threatening ingestions but
is seldom necessary with airway protec-
tion and supportive care.
An intoxicated patient in the While the average serum ethanol clear-

emergency department has ance is 15 mg/dL/hr, there is considerable
a measured blood alcohol individual variation. Discharge criteria
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level of 140 mg/dL. When should be based on the clinical scenario

can this patient be safely and serial assessments of the patient.
discharged?
Describe the ethanol Tachycardia, tremor, hypertension,

withdrawal syndrome. agitation. This may be followed by
hallucinations (usually tactile or visual) or
seizures. Seizures may be one of the first
signs of ethanol withdrawal.
What is the treatment for Benzodiazepines. High doses often are

ethanol withdrawal? needed.
GAMMA-HYDROXYBUTYRATE (GHB)
What was the original Anesthesia

intended indication for
GHB?
Why was GHB withdrawn Insufficient anesthesia, emergence delir-

for this indication? ium, myoclonus, bradycardia
Is GHB prescribed for any Yes. It has been FDA-approved as the

legitimate purpose? schedule III drug Xyrem®, or sodium
oxybate, for narcolepsy since 2002; how-
ever, due to both the narrow scope and
the extreme abuse potential it carries,
GHB is concurrently listed as a schedule
I drug.
What is the “street” purpose GHB is abused as a “club drug” for its
and delivery method of euphoric properties. It also may be used
GHB? for drug-facilitated sexual assault (“date
rape”) secondary to its quick action and
amnestic properties. For this purpose,
GHB often is mixed with ethanol.
What other chemicals are 1. Gamma-butyrolactone (GBL) is

converted to GHB? hydrolyzed to GHB either
spontaneously or in the blood.
2. 1,4-butanediol (1,4-BD) is oxidized by
alcohol dehydrogenase to gamma-
hydroxybutyraldehyde, which is then
metabolized to GHB by aldehyde
dehydrogenase.
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GHB is the structural analog GABA; however, GHB also appears to be

of which endogenous an endogenous neurotransmitter, pos-
neurotransmitter? sessing its own receptors in the brain.
What is the mechanism of It easily crosses the blood-brain barrier

toxicity of GHB? and exerts GABA-like CNS depressant
effects.
What are the signs and CNS and respiratory depression, apnea,
symptoms of GHB toxicity? amnesia, hypotonia, euphoria, coma,
bradycardia. Symptoms have a rapid
onset and are followed by a rapid
arousal in 6–8 hrs when the drug has
cleared.
What is the antidote? None available
What is the recommended Supportive care

hospital treatment for
suspected GHB toxicity?
Does GHB have a Yes. In heavy users, manifestations can

withdrawal syndrome? occur within hours after the last dose
and include anxiety, tremor, nausea,
vomiting, possibly delirium, hallucina-
tions, and mild autonomic instability.
Treatment of GHB withdrawal syn-
drome can be difficult and requires
large doses of benzodiazepines or barbi-
turates to control.
What are some common Easy Lay, Everclear, Fantasy, G, Griev-

street names for GHB? ous Bodily Harm, Georgia Home Boy,
Great Hormones at Bedtime, G-riffick,
Jolt, Liquid Ecstasy, Salty Water, Scoop,
Soap, Vita G, Zonked
HALLUCINOGENS
Name some commonly 1. Lysergic acid diethylamide (LSD)

abused hallucinogens. 2. MDMA (“ecstasy,” “X”)
3. Alpha-methyltryptamine (AMT)
4. Dimethyltryptamine (DMT)
5. Mescaline (Peyote)
6. Psilocybin (“Magic Shrooms”)
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What are the desired effects? “Tripping,” an altered state of perception

usually associated with auditory and
visual hallucinations. Senses are often
distorted and can be merged, a
phenomenon known as synesthesia.
How are hallucinogens Primarily ingested, although some may

abused? be smoked or injected:
1. LSD is taken on sugar cubes, blotter
paper, and microdots.
2. Psilocybin mushrooms and peyote
cactus are dried and eaten or brewed
in tea.
3. Dimethyltryptamine may be smoked,
snorted, or injected.
What is the mechanism for Pure hallucinogens bind serotonin,

these drugs? primarily 5-HT2A, activating these
receptors. Other drugs, such as anti-
cholinergics and sympathomimetics, may
cause hallucinations but are not
considered primary hallucinogens.
What are some of the Hyperglycemia, tachycardia, hyperthermia,

physical signs that have paresthesias, mydriasis, rhabdomyolysis
been associated with
hallucinogen ingestion?
What are some of the Significant variation from person-to-per-

psychotropic effects? son, but include visual and auditory hal-
lucinations, time distortion, feelings of
dissociation, synesthesia, intense color
perceptions, feelings of ecstasy or terror
Name some natural Salvinorin A (Salvia divinorum), bufote-

hallucinogens. nine (Bufo alvarius), mescaline
(Lophophora williamsii), psilocin/psilocy-
bin (Psilocybe sp.), lysergic acid hydrox-
yethylamide (Ipomoea violacea)
Name the household spice Nutmeg. The active chemical is myristicin.

capable of producing
hallucinations.
What is a “bad trip”? A terrifying or paranoid experience asso-

ciated with the use of hallucinogens,
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often associated with the environment or

mindset of the user.
How are these effects Primarily supportive with close monitor-

treated? ing of vital signs, IV fluids for rhabdomy-
olysis, and benzodiazepines for agitation.
A quiet, dark, nonstimulating environ-
ment is recommended.
INHALANTS
What are inhalants? A large group of substances whose vapors

can be inhaled to produce a “high.”
What are the general classes 1. Volatile hydrocarbons – paint thinners,

of inhalants? paints, glues, degreasers, gasoline,
felt-tip marker fluids, dry-cleaning
fluids, refrigerants
2. Nitrites – cyclohexyl nitrite, amyl
nitrite, butyl nitrite
3. Gases – nitrous oxide
What is the terminology for 1. Huffing – using an inhalant-soaked rag

the various methods of placed in the mouth or over the face
inhaling? 2. Sniffing or snorting – inhaling fumes
directly from a container through the
nose
3. Bagging – inhaling fumes from sub-
stances sprayed or deposited in a bag
What is the mechanism of While the exact mechanisms are poorly

action and onset for most understood, most inhalants appear to
inhalants? work by modulating cell membranes, ion
channels, and GABA receptors. Nitrites
differ by causing peripheral vasodilation.
Onset of inhalant action is within seconds
with effects lasting only several minutes;
thus, abusers use repeatedly over short
periods of time.
What are the signs and Slurred speech, euphoria, dizziness, hal-
symptoms of acute inhalant lucinations, delusions, ataxia, headache,
intoxication? lethargy, agitation, unconsciousness,
seizures, respiratory depression, asphyxia-
tion, coma, sudden death
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Are there long-term effects Yes. Weight loss, muscle weakness,

with inhalant use? ataxia, mood instability, depression.
Toluene and other organic solvents have
been shown to cause cerebral atrophy
and peripheral demyelination.
Chronic inhalation of what Nitrous oxide

anesthetic may produce a
peripheral neuropathy and
vitamin B12 deficiency?
Which volatile hydrocarbon Methylene chloride

is metabolized to carbon
monoxide?
Which agents may produce Nitrites

methemoglobinemia?
What are slang terms for 1. “Poppers” or “snappers” – amyl and

some common inhalants? butyl nitrite
2. “Whipits” – whipped cream aerosols
What is the term for a Sudden sniffing death syndrome (SSDS)

patient with sudden death
from inhalant use?
Describe the proposed Halogenated hydrocarbons sensitize the

mechanism of SSDS. myocardium to endogenous cate-
cholamines → ↑ risk of VF
Why may toluene abuse 1. Following acute abuse, toluene is

result in metabolic acidosis? metabolized to acidic metabolites
(i.e., benzoic and hippuric acid) that
result in an anion gap metabolic
acidosis.
2. Following chronic abuse, toluene
may induce a distal renal tubular
acidosis and subsequent non-anion
gap metabolic acidosis with
hypokalemia.
Are there any specific Generally, treatment includes supportive

antidotes or interventions? care. Symptomatic methemoglobinemia
induced by nitrites should be treated
with methylene blue.
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MARIJUANA
Marijuana is derived from Cannabis sativa

what plant?
How is marijuana consumed 1. Inhalation (smoking)

as a drug of abuse? 2. Ingestion (often baked into brownies)
By which method is the Inhalation

onset of action most rapid?
What is the predominant Delta-9-tetrahydrocannabinol (THC)

psychoactive chemical in
marijuana?
What is the mechanism of It binds to cannabinoid receptors (anan-

THC? damide and palmitoylethanolamide) to
modulate euphoric effects.
What is the origin of the Ananda is the Sanskrit word for “bliss.”
name “anandamide”? Anandamide is an endogenous
cannabinoid.
What are some common 1. Marijuana – leaves and flowers of

forms of cannabis? C. sativa
2. Hashish – concentrated resin of
C. sativa
3. Kief – marijuana mixed with tobacco
4. Bhang – marijuana and other spices
boiled in milk
5. Budder – hashish whipped with butter
What is a “joint” or Marijuana cigarette made by rolling mari-

“reefer”? juana in cigarette papers
What is a “bong”? A pipe used to smoke marijuana. Water is

commonly used to “filter” the smoke.
How can marijuana be 1. Baked goods, commonly in brownies

ingested? (“magic brownies” or “space cakes”)
2. Infused into milk or tea (“bhang”)
3. Infused into ethanol (“Green Dragon”)
What is the approximate 20–30 hrs

half-life of marijuana?
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What are the short-term Euphoria, ↑ appetite, altered time

effects of marijuana use? perception, poor short-term memory,
paranoia, lethargy
What are the signs of acute Tachycardia, orthostatic hypotension,

marijuana use? conjunctival erythema, ↓ IOP, slurred
speech, ataxia
What physical findings are “Amotivational syndrome,” obesity,

associated with chronic pulmonary disease
marijuana use?
By what methods can recent 1. Direct blood or urine detection

marijuana use be detected? (several hrs after use)
2. Detection of metabolites in blood or
urine (24–36 hrs after use)
3. Hair analysis (weeks to months after
use)
How long can marijuana be In chronic users, positive urine screens

detected in the urine? can occur for up to 1 month.
Describe the treatment of Due to low acute toxicity, few abusers

acute marijuana present with a primary complaint of mar-
intoxication. ijuana intoxication. Those that do have
adverse symptoms likely have co-inges-
tions with more toxic drugs. Treatment
consists of supportive care.
MESCALINE
What is mescaline? Mescaline is a hallucinogenic alkaloid

present in peyote that is structurally
related to amphetamines and is a 5-HT2
agonist.
What is peyote? The flesh of the spineless cactus

Lophophora williamsii, whose crowns
and seeds contain a considerable amount
of mescaline. The crowns are dried and
sold as “buttons.”
What term is sometimes Psychedelic agent

preferred over
“hallucinogen”?
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Mescaline is similar to LSD; however, mescaline is much less

what other hallucinogenic potent.
agent?
Mescaline is what structural Phenylethylamine

type of hallucinogen?
Describe the typical triad of 1. First – nausea and vomiting

peyote intoxication. 2. Second – catecholamine surge
3. Third – hallucinations and a sense of
depersonalization
Name the household Nutmeg

spice that may produce a
similar toxidromic triad
as peyote when taken in
excess.
Name the psychedelic Myristicin

chemical in nutmeg.
List the clinical features of Nausea, vomiting, abdominal pain, CNS

mescaline ingestion. stimulation, mydriasis, nystagmus,
headache, dizziness
Where is peyote found? Southwestern United States and northern

Mexico
How much mescaline does a ⬃45 mg; 6–12 “buttons” are typically
peyote button contain? taken to produce hallucinations
How much mescaline is A typical dose is 3–12 mg/kg, or

needed to produce a 200–500 mg of mescaline.
psychedelic effect?
What is the duration of The initial uncomfortable physical effects

action? may last ⬃2 hrs (GI symptoms and sym-
pathomimetic symptoms), while halluci-
nations may last 6–12 hrs.
Describe the management Supportive care. Death typically occurs

of mescaline toxicity. from behavior, not direct toxicity.
When is the use of peyote For traditional use by Native Americans

legal?
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NICOTINE
How may people become 1. Ingestion of chewing tobacco

poisoned by nicotine? 2. Ingestion of cigarettes
3. Ingestion of or dermal exposure to
nicotine-containing pesticides
4. Ingestion of or dermal exposure to
prescription nicotine-replacement
products
What is the toxic dose? Ingestion of as little as 2 mg can lead to

GI upset, but 40–60 mg can be fatal if
absorbed quickly.
Ingestion of how many Children who ingest 1 whole cigarette or

cigarettes or cigarette butts 3 cigarette butts are likely to become
is reason for concern in a symptomatic.
child?
When is the usual onset of Symptoms usually occur within 30–90

symptoms? min.
What are the symptoms of Activation of nicotinic receptors at auto-

nicotine toxicity? nomic ganglia (sympathetic and parasym-
pathetic), along with end-organ effects
(neuromuscular junction and CNS), pro-
duces nausea, vomiting, diarrhea, abdomi-
nal pain, salivation, diaphoresis, pallor, and
agitation then lethargy. Initial elevation of
heart rate, blood pressure, and respiratory
rate may occur followed by subnormal
values of each. CNS depression, muscle
fasciculations, and seizures, followed by
paralysis, may reflect severe toxicity.
How is nicotine toxicity 1. Atropine – anticholinergic agent that

treated? can be used to treat symptoms such as
bronchorrhea and cardiac depression
(due to parasympathetic excess)
What is “green tobacco Tobacco workers with direct skin contact

illness”? to moist tobacco leaves may absorb a
significant amount of nicotine and
become symptomatic.
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OPIOIDS
What are opioids? Naturally-occurring or synthetic drugs

that have opium-like activity
How do opioids exert Agonists of opioid receptors in the cen-

effects? tral and peripheral nervous systems and
the GI tract
What are the three main Delta (OP1), kappa (OP2), mu (OP3)
receptors activated by
opioids?
What are clinical effects of Analgesia, drowsiness, changes in mood

opiate administration? (often euphoria)
What triad of symptoms CNS depression, miosis, respiratory

strongly suggests opioid depression
intoxication?
Which opioids are not Tramadol, propoxyphene, meperidine

associated with miosis?
What are the Hypotension and bradycardia (may be

cardiovascular effects of mild or absent)
opioid overdose?
What are the dermatologic Flushing and pruritus (variably present)

symptoms of opioid
intoxication?
What are other respiratory Respiratory depression, bronchospasm,

effects of opioid and noncardiogenic pulmonary edema.
intoxication? Fentanyl administration may be associ-
ated with chest wall rigidity.
What are the GI effects of Nausea, vomiting, constipation

opioid intoxication?
What is the cause of most Respiratory depression resulting in anoxia

opioid-related deaths?
How do opiates cause Direct effect on brainstem respiratory

respiratory depression? centers (through mu and delta
receptors)
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What are the primary 1. 6-monoacetylmorphine

metabolites of heroin? 2. Morphine
What paralytic infection is Wound botulism (Clostridium botulinum)

associated with the use of
black tar heroin?
Which opioid has cardiac Propoxyphene and its metabolite

fast sodium channel norpropoxyphene, both of which cause
blocking properties? QRS prolongation
Which opioid has a unique Meperidine – may result in serotonin

interaction with monoamine syndrome
oxidase inhibitors (MAOI)?
What is the opioid Naloxone, which competitively binds

antagonist that is used to opioid receptors
treat acute toxicity?
What is the normal 30–60 min

elimination half-life of
naloxone?
What medical condition Renal failure

results in prolongation of
the elimination half-life of
naloxone?
What are “body packers”? Individuals who swallow wrapped packets

of illicit drugs or insert such packets into
body orifices. Most are asymptomatic but
can have acute intoxications with rupture
of the packets. If suspected, abdominal
radiographs may be obtained, but packets
present are not always radio-opaque.
Consider whole bowel irrigation with
polyethylene glycol (PEG-ELS). Surgical
indications include bowel obstruction or
intestinal perforation. Continuous infu-
sion of naloxone may be indicated with
rupture of heroin packets.
What are “body stuffers”? Individuals who swallow poorly wrapped

or un-wrapped drugs, usually in an at-
tempt to avoid arrest. There is generally
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more likelihood of becoming sympto-

matic secondary to the exposure to the
intestinal lumen.
PHENCYCLIDINE (PCP)
What is PCP? Synthetic piperadine derivative that

works as a dissociative anesthetic and is
considered a hallucinogen
Why is PCP unlike other It causes marked sympathomimetic

hallucinogens? activity and agitation in addition to
hallucinations.
What drug is structurally Ketamine

similar to PCP?
What is the mechanism of 1. Glutamate antagonism at the NMDA

action of PCP? receptor – leads to loss of pain
perception with minimal respiratory
depression
2. Reuptake inhibition of serotonin,
dopamine, and norepinephrine
3. Modulation of sigma opioid receptors
How can phencyclidine be Ingestion, injection, sniffing, smoking

administered?
What are the onset and Onset is 2–5 min with “high” at 15–30
duration of action of PCP min and duration of 4–6 hrs. Return to
when smoked? baseline may take 24–48 hrs.
What is the street name “Angel dust”

for the most common
preparation of PCP?
What is a typical dose of 1–6 mg can cause disinhibition and

PCP? hallucinations, while 6–10 mg causes
toxic psychosis.
Why is PCP often It is easy and inexpensive to make, so is

unknowingly ingested? often used as an adulterant of other
drugs. For example, a marijuana joint
may be dusted with PCP to create a
“Wicky Stick.”
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List some clinical effects of Nystagmus (horizontal then vertical or

an acute PCP ingestion. rotary), hallucinations, delusions,
agitation, hypertension, tachycardia
For which psychiatric Schizophrenia

condition may acute PCP
intoxication be mistaken?
List some medical Coma, seizure, rhabdomyolysis, renal

complications of PCP failure, hyperthermia, intracerebral
overdose. hemorrhage (due to hypertension),
trauma
Does a positive PCP urine No. Chronic users can test positive for
toxicology screen mean weeks following last use. Dextromethor-
acute ingestion? phan, diphenhydramine, and ketamine
may produce false positive urine PCP
screens.
How long after acute use is 1–5 days

PCP able to be detected in
the urine?
What is the treatment for Generally supportive. Benzodiazepines

PCP overdose? are indicated for agitation and psychosis.
Aggressive cooling may be needed for
hyperthermia.
Why are pharmaceutical Limits muscular activity and the

interventions preferred over development of rhabdomyolysis
physical restraints for
violence and agitation?
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Chapter 4 Environmental and

Industrial Toxins
ACIDS
What are some common Used in disinfectants, cleaners, glues,

acids and common uses of batteries, polish, photographic solutions,
these acids? among many others. Some of the most
common acids include acetic acid, boric
acid, carbolic acid, chromic acid, formic
acid, hydrochloric acid, oxalic acid, nitric
acid, phosphoric acid, and sulfuric acid.
How do acids cause tissue Acids (hydrogen ions) desiccate tissues

damage? by drawing water out of cells to form
hydronium ions (H3O⫹), which results
in coagulative necrosis and eschar forma-
tion. Depending upon the severity of the
exposure, eschars can prevent the deeper
penetration of acids, causing superficial
damage to the tissues.
What are some factors that pH, volume, concentration, duration of

determine the severity of an contact, titratable acid reserve
acid injury?
What types of burns are Mucosal burns to the mouth, esophagus,

typically caused by ingestion and the lesser curvature of the stomach.
of acid? Acid-induced pylorospasm may spare
the duodenum but lead to acid pooling
in the stomach and subsequent gastric
perforation.
How do acidic and alkali In mild and moderate acid burns, there is
injuries differ? less damage because acids precipitate and
coagulate, acting as a mechanical barrier
to further penetration. Severe acidic
burns can penetrate the self-limited tis-
sue barriers and cause more extensive
damage. Alkalis cause saponification of
membranes, which allows for rapid and
extensive burns through tissues.
154
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Chapter 4 / Environmental and Industrial Toxins 155
Describe the clinical 1. Upper respiratory – stridor, drooling,

presentation of an acid respiratory distress
ingestion. 2. GI – oropharyngeal pain and burns,
odynophagia, nausea, vomiting,
abdominal/chest/epigastric pain
3. Severe injury can manifest with
hypotension, metabolic acidosis,
DIC, mediastinitis
How should a patient with 1. Supportive care – give water or milk

acid ingestion be managed to dilute, especially with powder or
in the emergency granular preparations. It is important
department? to make sure the patient can swallow
without difficulty.
2. Decontamination with an NG tube
and gentle suction is controversial.
3. Endoscopic evaluation as needed
4. Emergent laparotomy for suspected
perforation
5. AVOID cathartics, neutralization,
induced-emesis, activated charcoal,
steroids
Who should undergo Anyone with stridor, pain, vomiting, or

endoscopy? drooling. Esophageal or gastric injury is
not ruled out by the absence of oral burns.
Why should hydrofluoric HF is a weak acid that easily crosses

acid (HF) burns be managed membranes and causes deeper tissue
differently than other acid damage. Fluoride ions chelate calcium
burns? and magnesium and form deposits. Dys-
rhythmias may develop secondary to
hypocalcemia or hypomagnesemia.
Treatment for superficial injuries in-
volves topical calcium gluconate gel.
Deeper wounds with systemic symptoms
may require intra-arterial calcium glu-
conate with additional IV calcium and
magnesium replacement.
How should ocular acid Copious irrigation with normal saline is

injuries be managed? the mainstay of therapy. Several liters of
irrigation are usually needed to raise the
pH back to 7.40. Fluorescein exam
should be done to confirm that a normal
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pH is achieved. An ophthalmology con-

sult is warranted for corneal involvement.
AMMONIA
What products contain Fertilizers, refrigerants, household and

ammonia? commercial cleaning solutions, explosives
Are aqueous solutions of Alkaline

ammonia acidic or alkaline?
Combination of ammonia Solutions containing chlorine or

with what compounds will hypochlorite
produce chloramine gas?
In what two forms is Gas and aqueous solution

ammonia available?
What is the mechanism of When ammonia gas contacts moist sur-

toxicity of ammonia? faces (i.e., mucous membranes), ammo-
nium hydroxide is formed, yielding a
corrosive effect. Ammonia solutions skip
the first step of dissolution in water and
are directly caustic.
On what organ systems will Integumentary, ophthalmic, respiratory

ammonia gas have its (upper ⬎ lower tract injury)
effects?
How does skin exposure Mild to severe burns depending on con-

manifest? centration and duration of contact
How much more 2.5–6 fold more concentrated. Household

concentrated are cleaning solutions contain 5% to 10%
commercial cleaning ammonia, while commercial cleaning
solutions compared to solutions contain 25% to 30%.
household versions?
Are household solutions No. They can only cause harm if a mas-
(dilute) typically associated sive amount is ingested.
with significant injuries?
What signs and symptoms Immediate pain, redness, conjunctivitis,

are seen with eye exposure lacrimation, blistering to full-thickness
to ammonia gas or solution? burns, blindness
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How does inhalation of 1. Immediate burning of nose and throat

ammonia gas present with resultant cough
clinically (in order of 2. Upper respiratory tract injury may
exposure severity)? result in airway obstruction,
presenting as stridor, hoarseness,
wheezing, and “croupy” cough.
3. Lower respiratory tract injury mani-
festing as wheezing or pulmonary
edema
What symptoms are seen Immediate oral/pharyngeal pain, which

with ingestion of ammonia may progress to dysphagia, difficulty
solutions? handling secretions, and chest/abdominal
pain. Esophageal or gastric injury is not
ruled out by the absence of oral burns.
What life-threatening event Esophageal or gastric perforation

can occur with ingestion of
concentrated solutions?
List a long-term sequela of Esophageal and/or gastric scarring caus-

ammonia ingestion. ing stricture and chronic dysphagia
How is ammonia gas 1. Remove from exposure immediately

inhalation treated? and administer supplemental O2.
2. Observe for signs of airway compro-
mise, and initiate intubation early.
3. Administer bronchodilators for
wheezing.
4. Treat pulmonary edema by avoiding
excessive fluid administration and
adding PEEP as needed to maintain
PaO2 ⱖ60–70 mm Hg.
How is ingestion of aqueous 1. Give water or milk orally to dilute the

ammonia solution treated? ammonia if early after the ingestion
and the patient is able to swallow
without difficulty.
2. Gastric suction with an NG tube may
be beneficial early after ingestion
when large amounts have been taken.
Use a small, flexible tube to avoid
worsening of mucosal injury. Never
force the tube, and only use if the
patient can tolerate it.
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3. If a solution ⱖ10% has been ingested

or if dysphagia, drooling, or pain is
present, flexible upper endoscopy is
warranted.
4. Chest and abdominal radiographs
5. AVOID induced emesis, activated
charcoal, and neutralization with acid.
How is eye exposure Copious irrigation with several liters of

treated? normal saline to lower the pH back to
7.40. Fluorescein exam should be done
after normal pH is achieved. An ophthal-
mology consult is warranted for corneal
involvement.
ANTISEPTICS AND DISINFECTANTS
Define “antiseptic.” An antimicrobial agent applied to vital tis-

sues to exert “cidal” (i.e., kills the microor-
ganism) or “static” (i.e., halts the growth of
the microorganism) effects.
Define “disinfectant.” An antimicrobial agent applied to nonliv-

ing surfaces. They may be “cidal” or
“static.”
Where is chlorhexidine 1. Dental rinses, including mouthwashes

found? 2. Skin cleansers
3. Cleaning solutions
What are the toxic effects of Irritation and corrosive injury to the oral
chlorhexidine? and esophageal mucosa may occur after
ingestion. Hepatic injury has been re-
ported following ingestion. Dermal ab-
sorption is minimal, but skin irritation
may occur.
Systemic absorption or Iodine or iodophors. These agents may

ingestion of what antiseptic cause a falsely elevated serum chloride
agent may cause a low or on some analyzers, resulting in a
negative anion gap? decreased anion gap.
Where is glutaraldehyde 1. Hospital equipment disinfectants

found? 2. Tissue preservatives
3. Topical antifungal agents
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What are the toxic effects of 1. Skin irritation

glutaraldehyde? 2. Respiratory tract irritation
3. Repeated exposure may result in
contact dermatitis.
Where is hydrogen peroxide 1. Dental products

found? 2. Skin cleansers
3. Hair products
4. Earwax irrigants
5. Industrial oxidizing solutions
How many milliliters of 100 mL

oxygen are released from
1 mL of 35% (concentrated)
hydrogen peroxide?
What are the toxic effects of Hydrogen peroxide breaks down readily
hydrogen peroxide? to water and oxygen. When ingested, the
production of oxygen gas can cause
distension, perforation, and even gas
embolization.
What specific therapies may Gastric aspiration with an NG tube may

be used to treat hydrogen help prevent gas formation and emboliza-
peroxide poisoning? tion. Hyperbaric oxygen therapy may be
used to treat gas embolization.
Where is potassium 1. Dilute antiseptics

permanganate found? 2. Swimming pool, fish tank, and well
water purification/decontamination
products
3. Industrial oxidants
What are the toxic effects of Acute toxicity is primarily a corrosive in-
potassium permanganate? jury. Secondary to strong oxidative effects,
methemoglobinemia may also occur.
What complications can Manganese toxicity characterized by

occur following chronic parkinsonian symptoms, also known as
potassium permanganate “manganese madness”
exposure?
How is hypochlorite used? 1. Household bleach (sodium

hypochlorite) contains ⬃5%
hypochlorite
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2. Industrial strength disinfectants in

20% solutions
What is the primary toxicity Corrosive injury

of hypochlorite exposure?
What are the acute effects Phenol is a caustic agent that may result
of phenol ingestion? in oropharyngeal and esophageal burns.
Systemic symptoms include seizures,
lethargy, hypotension, and coma.
Name the organomercury Mercurochrome

compound used as a topical
antiseptic.
How does mercurochrome Systemic mercury toxicity may occur after

toxicity occur? ingestion or from repeated exposure to
compromised skin.
What are the key features of Caustic injury to the stomach, including
formaldehyde ingestion? possible gastric necrosis and perforation.
Systemic absorption results in the metab-
olism of formaldehyde to formic acid, re-
sulting in an anion gap metabolic acidosis.
What are typical effects of GI (i.e., vomiting and diarrhea)

dilute antiseptic ingestions?
How is antiseptic or 1. Removal of the offending agent with

disinfectant ingestion decontamination
treated? 2. Supportive care
3. Mild irritation is self-limited, but
more corrosive agents may require
endoscopy
4. Hyperbaric oxygen (HBO) therapy for
gas emboli following hydrogen
peroxide ingestion
How is decontamination per- Dilute with milk or water

formed following acute in-
gestion of corrosive agents?
What should not be given 1. Proemetics, as they exacerbate erosive

following ingestion of injury
corrosive agents and why?
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2. Activated charcoal is contraindicated

and will obstruct endoscopic
evaluation.
How are eyes and skin 1. Remove contaminated clothing

decontaminated? 2. Irrigate with copious amounts of water
ASBESTOS
What is asbestos? Naturally occurring silicate fibers that are

chemically inert but have been impli-
cated in carcinogenesis and, once in-
haled, can remain in the lungs for a
lifetime
What type of asbestos fiber Amphibole, particularly crocidolite

is considered the most
injurious?
What is the major concern Inhalation of asbestos fibers ⬎5 ␮m can

with asbestos? lead to pulmonary fibrosis and cancer
(i.e., mesothelioma).
Why are fibers smaller than They are removed from the lungs by
5 ␮m not implicated in the macrophages.
pathogenesis of lung fibrosis
and cancer?
What populations are most Most exposure is work-related, and a high

likely to be exposed to incidence of exposure is known to occur in
asbestos? insulation workers, asbestos-cement work-
ers, shipyard workers, and plumbers.
\
What is the average time 15–20 yrs
after exposure for clinical
presentation?
List some clinical Asbestosis, pleural disease (e.g., pleural

manifestations of asbestos thickening/plaques/effusions), lung
exposure. cancer, mesothelioma (pleural and
peritoneal)
What is asbestosis? Progressive interstitial pulmonary fibro-

sis, leading to a restrictive pattern with
compromised gas exchange
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What is seen on CXR? X-ray changes are dependent on the

stage of disease; commonly seen are
small, irregular opacities in the mid and
lower lung fields, thickening of the
pleura, pleural plaques, and calcifica-
tions. Later stages may show progression
to involvement of the upper lung fields.
Why should you encourage The relative risk for development of

asbestos workers to stop lung cancer approximately doubles for
smoking? asbestos and smoking combined. The ef-
fects of this combination are synergistic.
What antidotes are available None

for asbestos exposure?
What advice would you give Emphasize avoidance of exposure. Pro-

someone who will be tective equipment should be worn to pre-
working in an asbestos vent inhalation. Although fibers are not
environment about absorbed transdermally, inhalation from
treatment? the skin may occur, so attention should be
paid to cleansing the skin after exposures.
AZIDE
How is sodium azide used It is commonly used as the propellant

commercially? agent in automobile airbags. Azide may
also be used in military explosives, as a
reagent/preservative in laboratories, and
as an herbicide/fungicide.
What is the route of toxicity Inhalation, ingestion, dermal, IV

for sodium azide? (uncommon route)
How is sodium azide Metabolized hepatically, then excreted

eliminated? renally
What is the mechanism of Azide inhibits the function of cytochrome

toxicity of sodium azide? C oxidase by binding irreversibly to the
heme moiety in a process similar to that
of cyanide, thereby inhibiting the forma-
tion of ATP.
What are acute effects of Hypotension, dysrhythmias, pulmonary

sodium azide toxicity? edema, headache, syncope, CNS depres-
sion, nausea, vomiting, diarrhea
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What is the clinical presen- Hypotension, tachypnea, conjunctival

tation of an inhalation erythema, nasal mucosal irritation,
exposure? pulmonary edema, respiratory arrest
Which is the most Hypotension

commonly reported effect,
irrespective of route of
exposure?
What metabolic abnormality Anion gap metabolic acidosis

is expected to be present
after exposure?
Are enhanced elimination No

methods available for
sodium azide?
Is a specific antidote No
available for sodium azide?
What precautions should be Azides are converted to hydrazoic acid

taken when treating in acidic environments; exposure to
patients? vapors from emesis may result in
bystander toxicity. Hydrazoic acid
appears to have similar anti-metabolic
properties to azide. Contact of azides
with metals may result in spontaneous
explosion.
What treatments should Supportive care

be undertaken for patients
who have ingested
sodium azide?
BENZENE
What is benzene? A volatile aromatic hydrocarbon that is

widely used as a solvent in industrial
processes and can be found in a variety of
plastics, dyes, rubbers, and pesticides. It
is also a byproduct in the burning of or-
ganic compounds and is therefore a com-
ponent of cigarette smoke.
How are people exposed to Usually by inhalation or ingestion, but

benzene? dermal absorption is possible
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What is the clinical Acute toxicity is similar to other solvent

presentation of a person syndromes, including dizziness, nausea,
with acute benzene vomiting, headache, possible seizures, and
poisoning? coma. Benzene may also result in acute
hemolysis. Dermal exposure may result in
chemical burns. Inhalation or aspiration
can lead to chemical pneumonitis, poten-
tially progressing to ARDS.
What are the symptoms of Long-term benzene exposure is known to

chronic exposure? cause bone marrow suppression and
hematologic pathology, including aplastic
anemia, myelodysplastic syndromes, and
leukemia. Benzene is a known carcinogen
(IARC group I). Effects on human fertility
are unknown, but menstrual irregularities
and ovary shrinkage have been reported.
Secondary to the carcinogenic risk, work-
place exposure is limited to 0.5 ppm per
8-hr day.
Describe the mechanism of Benzene is metabolized in the liver, pri-

toxicity. marily by cytochrome P450. This forms
multiple metabolites including benzene
oxide, phenol, and reactive oxygen
species. These metabolites are directly
cytotoxic and may form protein and DNA
conjugates that promote carcinogenicity.
What is the antidote? None. Additionally, hemodialysis and

hemoperfusion are ineffective.
What is the recommended Supportive care. Consider placement of

treatment? an NG tube with aspiration of gastric
contents if the patient presents promptly
after benzene ingestion. Oxygen is the
preferred treatment for acute solvent
exposure. Avoid sympathomimetics, as
benzene may cause myocardial sensitiza-
tion to catecholamines.
What tests should be Check a CBC with differential to evalu-

ordered? ate for hemolysis or bone marrow effects.
Reticulocyte count may also be useful if
anemia is found. Electrolytes, LFTs, and
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RFTs should be ordered. Order a CXR

as needed for evaluation for potential
pneumonitis. Urine phenol levels are
useful to monitor for or detect chronic
exposure. Acute exposures may be con-
firmed by blood testing for benzene and
its metabolites.
BORIC ACID, BORATES, AND BORON
How toxic are boron, boric Borates, boranes, and boric acid are
acid, and borates? chemical compounds of the element
boron. Generally, borates and boric acid
have low toxicity, usually developing after
repeated exposures. Boranes are much
more toxic and may produce both acute
and chronic poisoning.
What are the routes of Exposure to boric acid is primarily

exposure? through the oral route; however,
repeated contact with abraded or
compromised skin may result in toxicity.
Boranes may be toxic through ingestion,
inhalation, or dermal exposure.
What is the mechanism of Unknown

toxicity of borates?
How is boric acid speculated It is likely a metabolic poison.

to cause toxicity?
Where are boric acid and Pesticides (e.g., roach powder), skin
borates found? lotions, medicated powders
Where can boranes be Boranes are primarily used in the

found? commercial/industrial setting. They are
found in herbicidal and bactericidal
agents, in fuels, and in various
manufacturing processes.
What are the adverse effects Mucous membrane irritation, nausea,

of boric acid and borates? intractable vomiting, diarrhea, abdomi-
nal pain, and skin erythema. Seizures,
alopecia, and renal failure have also
been reported.
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Describe the typical skin Diffuse erythema that involves the palms
finding associated with boric and soles, which later desquamates, and is
acid toxicity. described as a “boiled lobster” appearance
What is the characteristic Blue-green

color of diarrhea and emesis
produced by boric acid
ingestion?
What other ingestion may Copper sulfate

cause a similar emesis
finding?
Describe the toxicity of Acute inhalation primarily produces pul-

borane exposure. monary irritation; however, pulmonary
edema may occur. CNS depression and
seizures have been reported as have car-
diac and hepatic toxicity. Concentration
and personality changes, along with he-
patic and renal damage, may occur after
chronic exposure.
What methods can be used Predominantly by history. Blue-green

to detect boric acid, borates, color of diarrhea or emesis may be help-
or borane exposure? ful. Serum/blood levels are not widely
available and are of little clinical utility.
How are these exposures 1. Antiemetic therapy with nonsedating

managed? agents
2. Fluid and electrolyte repletion
3. Treat seizures with benzodiazepines.
4. Local wound care for potential skin
exfoliation
5. Evaluate for hepatic or renal damage.
Are there any available There are no antidotes. Hemodialysis is

antidotes or enhanced effective and may be considered after
elimination methods? large exposures.
BROMATES
What are the common forms Potassium bromate and sodium bromate
of bromate?
What is potassium bromate 1. Flour enhancer in the baking

commonly used for? industry
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2. Neutralizing solution for cold wave

home hair permanents and professional
solutions
What are the signs and 1. GI distress (i.e., nausea, vomiting,

symptoms of acute bromate diarrhea)
poisoning? 2. CNS depression
3. Anemia from intravascular hemolysis
4. Acute renal failure (acute tubular
necrosis), which may be irreversible
5. Sensorineural hearing loss
(irreversible)
What hematological effects Methemoglobinemia and hemolysis, sec-

may bromates cause? ondary to their oxidizing ability
Chronic exposure to Renal cell carcinoma

bromates is thought to
cause what cancer?
What are useful tests when CBC, ABG with co-oximetry to evaluate
evaluating a bromate-toxic for methemoglobinemia, electrolytes,
patient? BUN, creatinine, audiometry to evaluate
for hearing loss
How should bromate 1. Supportive care

ingestions be treated? 2. Consider gastric lavage with 2%
sodium bicarbonate to prevent the
formation of hydrobromic acid.
3. Consider administration of IV sodium
thiosulfate.
4. Consider early hemodialysis in large
ingestions.
In theory, what does the Reduces bromate to bromide (less toxic)

sodium thiosulfate do?
BROMIDES
What are some of the Brompheniramine, dextromethorphan,

pharmaceutical agents in halothane, pancuronium, pyridostigmine,
which bromide may be scopolamine
found?
Historically, how was As a sedative and antiepileptic agent

bromide used?
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By what mechanism does Displacement of chloride ions in cellular

bromide exert its processes
physiological effects?
Acute ingestion of bromide Severe GI distress and CNS depression

causes what signs and
symptoms?
What laboratory Pseudohyperchloremia

abnormality may be found
with bromide toxicity?
Elevated bromide levels will Because bromide resembles chloride,

do what to the anion gap? it may falsely elevate the chloride on
some analyzers and may decrease the
anion gap.
What is “bromism”? Neurologic and dermatologic changes

seen with chronic bromide intoxication
What are the neurological Behavioral changes (e.g., depression,

features of “bromism”? dementia, delirium), psychosis, hallucina-
tions, tremor, ataxia, slurred speech,
hyperreflexia, lethargy
What are the dermatological 1. Acneiform eruptions on face and

features of “bromism”? upper trunk (most common)
2. Erythema nodosum-like lesions on the
lower extremities
3. Pemphigus-like vesicles
4. Morbilliform dermatitis
What is another name for Bromoderma

the dermatological features
of “bromism”?
Why are activated charcoal 1. Bromide is rapidly absorbed.

and other GI 2. Charcoal does not bind bromide.
decontamination methods
not useful for bromide
ingestions?
How is bromide eliminated By the kidney – providing exogenous

from the body? chloride may help clear bromide from
the body.
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What enhanced elimination 1. IV normal saline to optimize chloride

methods are effective for repletion
bromide? 2. IV furosemide may be helpful to
enhance excretion but has not been
shown to improve clinical outcome.
3. Hemodialysis is effective but reserved
for severe intoxication.
CAMPHOR
What is camphor? Volatile aromatic compound (essential oil)

initially isolated from the Cinnamomum
camphora tree
What are the major uses of 1. Liniments and decongestant

camphor? ointments
2. Plasticizers
3. Preservatives in pharmaceuticals and
cosmetics
4. Mothballs
What are the signs and Initially, GI complaints (e.g., nausea and
symptoms of camphor vomiting), tachycardia, confusion, agita-
intoxication, and how long is tion. Eventually, CNS and respiratory
the onset of action? depression and seizures may develop.
Camphor may be evident on the breath.
Onset of toxicity is rapid, usually within
1 hr of exposure.
Describe the manifestations Prolonged exposure may result in dermal

of dermal toxicity. and mucous membrane irritation and
mild burns. Systemic toxicity may result
from large mucous membrane exposure.
What is the mechanism of Largely unknown. Camphor may halt cel-

camphor toxicity? lular respiration or interact with cell
membrane channels.
What oral doses of camphor As little as 1 g of camphorated oil may

may be toxic in adults and cause severe toxicity.
children?
How are patients with Primarily supportive care. Seizures

camphor toxicity managed? should be managed initially with
benzodiazepines.
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Does activated charcoal or Activated charcoal has unknown efficacy,

hemodialysis have any role and caution should be used secondary to
in managing toxic camphor the risk of aspiration. Hemodialysis is not
exposures? expected to be beneficial.
CARBON DISULFIDE
What is carbon disulfide? A volatile industrial solvent that readily

evaporates when exposed to air. It also
may be known as carbon bisulfide,
carbon sulfide, or dithiocarbonic
anhydride.
What are common uses and 1. Cellophane, rubber, and rayon

sources of carbon disulfide? production
2. Insecticides/fumigants
3. Common laboratory solvent
4. Disulfiram metabolite
What are possible routes of Inhalation, ingestion, absorption (dermal,

exposure to carbon disulfide? ocular, mucous membranes)
What is the most common Inhalation

route of exposure?
What is the mechanism of Mechanisms are largely unknown.

toxicity of carbon disulfide? Dithiocarbamates, which chelate zinc
and copper, are produced from metabo-
lism of carbon disulfide. Carbon disul-
fide also binds sulfhydryl, amino, and
hydroxyl groups. These effects may be
partially responsible for the neurotoxic-
ity seen with exposure. Finally, carbon
disulfide inhibits dopamine beta-hydrox-
ylase and interferes with catecholamine
metabolism.
What is the approximate Immediate, though carbon disulfide is

onset of action following an rapidly metabolized
acute exposure to carbon
disulfide?
What are symptoms of an CNS excitation, followed by CNS

acute, high-level carbon depression (which may be profound),
disulfide exposure? psychosis, mania, delirium, respiratory
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depression progressing to failure,

eye/skin irritation
What symptoms are Peripheral neuropathy (predominantly of

consistent with a chronic, the lower extremities), fatigue, headache,
low-level carbon disulfide personality changes, and memory loss are
exposure? most commonly reported. Extrapyramidal
symptoms (EPS) and atypical parkinson-
ism are also frequently reported. Other
possible findings include optic neuritis,
hearing loss, fatty liver degeneration, ath-
erosclerosis, blood dyscrasias, dermatitis,
renal damage, and reproductive problems.
What additional symptoms Irritation of the GI tract with associated

are associated with an abdominal pain, nausea, and vomiting
ingestion exposure?
What additional symptoms 1. Severe mucous membrane and skin

are associated with a dermal irritation, possible partial- and full-
exposure? thickness burns
2. Ocular irritation with potential for
corneal burns
What additional symptoms Upper respiratory tract irritation and

are associated with an bronchospasm
inhalational exposure?
How is a carbon disulfide No specific diagnostic test. Diagnosis re-

exposure detected? lies on history and supportive presentation
and is not based on blood/urine testing.
Are there any drugs or No. Management is supportive.

antidotes effective at treating
a carbon disulfide exposure?
What are the treatments 1. Placement of an NG tube for

indicated for an acute aspiration of gastric contents is
exposure? appropriate for patients presenting
promptly after liquid ingestion.
2. Copious irrigation for dermal and
ocular exposures
3. Oxygen and bronchodilators may be
needed for inhalational exposures.
4. Otherwise, general supportive care
is indicated.
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Are there any secondary Only in those exposed to liquid carbon

contamination risks to disulfide, who may contaminate care
healthcare providers? providers through direct contact or vapor
off-gassing
CARBON MONOXIDE
What is carbon A gas generated by the incomplete com-

monoxide (CO)? bustion of organic (carbon containing)
compounds
Why is CO so dangerous? Odorless, colorless, tasteless, nonirritating
What are common sources 1. Gas appliances

of CO exposure? 2. Charcoal grills
3. Combustion engine exhaust
(e.g., automobiles, boats)
4. Smoke from any type of fire
5. Cigarettes
How much stronger is CO’s 240 times greater

affinity for hemoglobin than
oxygen?
CO’s uptake into the body 1. Concentration of CO inspired

is dependent upon what 2. Patient’s minute ventilation
factors? 3. Duration of exposure
What is the elimination 1. ⬃320 min with room air (21% oxygen)
half-life of CO when 2. ⬃90 min with 100% oxygen at 1
breathing room air, 100% atmosphere
oxygen, and under 3. ⬃20 min under HBO at 3 atmospheres
hyperbaric oxygen (HBO)?
In what direction does CO To the left

shift the oxyhemoglobin
dissociation curve?
Besides hemoglobin, 1. Cytochrome oxidase

where else does CO bind 2. Myoglobin (both skeletal and cardiac)
in the body?
What are the clinical signs Headache, nausea, vomiting, fatigue,

and symptoms of CO dizziness, confusion, dyspnea, ataxia,
intoxication? chest pain, syncope, seizure, coma,
dysrhythmia, hypotension, death
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What syndrome can Delayed neuropsychiatric sequelae

manifest days to weeks
following a significant
exposure to CO?
Would a CO poisoned Both would be normal

patient with normal
respirations have a high,
low, or normal pulse
oximetry? Blood gas
PaO2?
What hemoglobin type binds Fetal hemoglobin

CO strongest?
Name three chemical 1. Cyanide

asphyxiants. 2. Carbon monoxide
3. Hydrogen sulfide
Typical hospital co-oximetry 1. Oxyhemoglobin

measures what 4 types of 2. Deoxyhemoglobin
hemoglobin? 3. Methemoglobin
4. Carboxyhemoglobin
Which would provide an Either

accurate assessment of the
CO concentration, an
arterial blood gas or a
venous blood gas?
What is the primary treat- Oxygen

ment for CO intoxication?
What are the proposed 1. Increases the amount of oxygen

mechanisms of HBO’s dissolved in the blood
efficacy for CO poisoned 2. Dissociates CO from all heme moieties
patients? 3. Causes cerebral vasoconstriction,
thereby ameliorating reperfusion
injury
4. Impairs leukocyte adherence
HBO should be considered 1. A history of loss of consciousness

for patients with what 2. Severe neurologic findings (e.g., coma
clinical findings? or seizures)
3. Persistent findings despite 100%
oxygen therapy
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4. Symptomatic pregnancy
5. CO level ⬎40%
CARBON TETRACHLORIDE
What is the mechanism of Carbon tetrachloride (CCl4) metabolism

carbon tetrachloride through the cytochrome P450 system
toxicity? creates free radicals that cause nephro-
toxicity and hepatotoxicity. Similar to
halogenated hydrocarbons, carbon tetra-
chloride may produce CNS depression
and sensitize the myocardium to endoge-
nous catecholamines.
How is carbon Primarily as a reagent in the production

tetrachloride used? of other chemicals. Use has been limited
secondary to the toxicity of this com-
pound. It was formerly used in fire extin-
guishers, as a fumigant, and as a solvent
for dry cleaning.
What substance can Ethanol particularly increases hepa-

potentiate the nephrotoxic totoxicity. These effects are further
and hepatotoxic effects of pronounced with long-term use.
carbon tetrachloride?
What are the routes of Inhalation, ingestion, dermal

exposure for carbon
tetrachloride?
How is carbon tetrachloride 1. Nearly half of the absorbed carbon

metabolized and excreted? tetrachloride is excreted unchanged
via the lungs.
2. The remainder is metabolized to the
trichloromethyl free radical via the
cytochrome P450 enzyme system
(primarily via 2E1).
Carbon tetrachloride may Chloroform (Cl3CH)

be partially metabolized to
what anesthetic agent?
What are signs and Irritation of mucous membranes/eyes/skin,

symptoms of exposure to nausea, vomiting, confusion, dizziness,
carbon tetrachloride? headache, cardiac dysrhythmias due to
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increased myocardial sensitivity to

catecholamines, CNS depression
What is the potential delay 1–4 days

to onset of hepatotoxicity
and nephrotoxicity?
Name the hepatic zone most Zone 3 (centrilobular)

prone to damage from
carbon tetrachloride.
What is considered a lethal Ingestion – as little as 5 mL may be

level of exposure? lethal
Inhalation – air concentrations as low
as 160–200 ppm may be lethal
How can exposure to carbon For occupational purposes, levels may

tetrachloride be detected? be obtained in urine, blood, and expired
air, though they are of minimal clinical
utility. Abdominal x-rays may show this
radiopaque substance when ingested. A
history of exposure associated with a
consistent clinical picture remains the
cornerstone of diagnosis.
Is carbon tetrachloride a Possibly (IARC Group 2B)

human carcinogen?
Why is epinephrine Increased myocardial sensitivity to cate-

relatively contraindicated cholamines after carbon tetrachloride ex-
after acute carbon posure may lead to cardiac dysrhythmias.
tetrachloride exposure?
What can be used to treat N-acetylcysteine (NAC) may help pre-

carbon tetrachloride vent hepatic and renal damage after ex-
exposure? posure. Otherwise, treat supportively.
Is gastric lavage with an Yes, if the patient presents promptly after

NG tube indicated after exposure.
ingestion of carbon
tetrachloride?

procedures of proven
clinical benefit?
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CAUSTICS
What is a caustic agent? An agent that causes corrosive injury upon

tissue contact. Although other agents can
cause corrosive injury, acids and alkalis are
the predominant agents in this class.
What are examples of 1. Acids – hydrochloric acid (toilet bowl

caustic agents? cleaner), sulfuric acid (drain cleaner
and automobile battery fluid),
phosphoric acid (metal cleaner)
2. Alkali – sodium or potassium
hydroxide (drain cleaner, hair relaxer),
calcium hydroxide (wet cement),
sodium hypochlorite (bleach),
ammonium hydroxide
What is the fundamental 1. Acidic agents donate protons in an

chemistry behind caustic aqueous solution.
agents? 2. Alkali (or basic) agents accept protons
in an aqueous solution.
What is the pathology Acids cause coagulation necrosis. This

associated with an injury may cause eschar formation, limiting
secondary to acid exposure? penetration and further damage.
What is the pathology Alkalis cause liquefaction necrosis. This

associated with an injury can result in extensive penetration.
secondary to alkali exposure?
What are the toxic routes of Inhalation, ingestion, dermal, ocular

exposure?
What are common signs and Oral/abdominal/chest/throat pain, vomit-

symptoms after a caustic ing, drooling, dysphagia, coughing and
ingestion? stridor, possibly progressing to airway
obstruction
What are the clinical Mucous membrane irritation, stridor,

manifestations of an bronchospasm, pulmonary edema
inhalational injury?
Why is it dangerous to mix It will produce and release chloramine

ammonia and bleach fumes, resulting in pneumonitis.
(sodium hypochlorite)?
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What are the clinical Pain, erythema, and blistering. Ocular

manifestations of a dermal exposure can cause corneal ulceration
or ocular injury? and opacification → blindness.
How should a caustic 1. A small amount of water or milk can

ingestion be managed? be given to dilute the agent; however,
care must be taken to avoid inducing
vomiting, as this will reexpose tissues
and may cause aspiration.
2. Assess for any airway compromise.
3. Careful nasogastric aspiration of liquid
caustics can be attempted.
4. Endoscopy if indicated
5. Surgical consultation for any signs of
perforation
Should a neutralizing agent No. There is a risk of the exothermic

be given? neutralization reaction, causing a thermal
injury.
What are the indications for Any patient presenting with an oral
endoscopy? injury, vomiting, drooling, dysphagia,
stridor, or dyspnea
How long after an exposure In mildly symptomatic patients,

should endoscopy be endoscopy is commonly performed
performed? between 12 and 48 hrs. Before 12 hrs,
the burns may not have fully developed,
and after 48 hrs, there is increased risk
of perforation. In anyone with potential
airway compromise, endoscopy should
be performed emergently.
How are esophageal burns Grade 0 – normal esophagus

graded? Grade 1 – edema and hyperemia involving
mucosa without sloughing or ulceration
Grade 2a – noncircumferential loss of
mucosa, variable loss of submucosa with
possible extension into muscularis. Some
muscularis remains viable, and
periesophageal tissues are not injured.
Grade 2b – all the findings in 2a but
circumferential
Grade 3 – Grade 2 findings plus deep
ulceration, friability, eschar formation,
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perforation; entire esophageal wall is

necrotic with possible extension to
periesophageal tissues
What is the purpose of For prognosis. Grading the lesions

endoscopy? predicts the likelihood of stricture devel-
opment. Grade 0 and 1 lesions do not
cause strictures, while grade 2b lesions
can result in strictures in 71% of cases,
and grade 3 lesions will cause strictures
in almost 100% of cases.
Are steroids indicated to This is disputed. Theoretically, steroids

prevent strictures? can prevent strictures by limiting the
inflammatory process; however, strong
evidence of effectiveness is lacking, and
steroid therapy can mask symptoms of
perforation and infection. In animal
models, steroids resulted in increased
mortality.
How would you treat an 1. Remove patient from the

inhalational injury due to environment.
chlorine gas? 2. Treat bronchospasm with beta
2-adrenergic agonists.
3. Nebulized sodium bicarbonate may
relieve symptoms.
How would you treat dermal Immediate copious irrigation. Ocular

or ocular burns? burns should be irrigated for ⱖ15 min,
and pH should be measured to deter-
mine need for additional irrigation. Due
to extensive penetration, alkali burns may
require extensive irrigation.
CHLORATES
In what chemical forms are Usually in the form of salts, with sodium
chlorates usually found? chlorate (NaClO3) and potassium
chlorate (KClO3) being the most
common. These are strong oxidizing
agents.
In what products can 1. Herbicides

chlorates be found? 2. Used in the production of explosives,
matches, and fireworks
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What are the initial The chlorate ion is a strong mucosal

presenting symptoms of irritant and causes nausea, vomiting,
acute chlorate ingestion? diarrhea, and abdominal pain, usually
within 1–4 hrs after ingestion.
What are the most serious 1. Intravascular hemolysis

clinical features of chlorate 2. Methemoglobinemia that can lead to
ingestion? cyanosis, dyspnea, and coma
3. Acute renal failure
4. DIC
What lab abnormalities can Hemolytic anemia, elevated methemo-

be found in acute chlorate globin levels (⬎10%), elevated serum
ingestions? creatinine, hyperkalemia secondary to
gross hemolysis and renal failure
Why might an ECG be To evaluate for signs of hyperkalemia,

helpful in a chlorate-toxic such as peaked T waves, widened QRS,
patient? and PR prolongation
What procedure can be Chlorates are freely dialyzable, and

performed to help enhance hemodialysis is recommended in severe
chlorate elimination? toxicity, especially in the presence of
coexisting renal failure. This therapy may
prevent life-threatening hemolysis.
Is there an antidote for Some case reports advocate the use of

chlorate toxicity? sodium thiosulfate, either PO or IV
(2–5 g in 200 mL of 5% sodium
bicarbonate), which may inactivate the
chlorate ion, although supportive therapy
remains the mainstay of treatment.
Should methemoglobinemia Yes; however, methemoglobinemia from

caused by chlorate chlorate ingestion may be poorly respon-
ingestion be treated with sive to methylene blue. One proposed
methylene blue? mechanism for this is that chlorates may
inhibit G6PD, an enzyme necessary for
the production of NADPH, which is re-
quired for the reduction of methemoglo-
bin by methylene blue.
CHLORINE
How is chlorine used Chlorine has multiple purposes,

commercially? including chemical manufacturing
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(e.g., plastics, pesticides, solvents);

disinfection; bleaching; sewage treat-
ment; and water purification (including
swimming pools).
What is the name of the Bertholite

chlorine gas agent used by
the military in World War I
for chemical warfare?

toxicity for chlorine?
What is the mechanism of Chlorine is a very caustic and irritating

toxicity for chlorine? substance. Contact with water on dermal
or mucosal surfaces produces hydrochlor-
ous and hydrochloric acid, resulting in
oxidative and corrosive damage.
At what concentration of 1 ppm

chlorine gas will effects
begin to occur?
What are acute effects of 1. Inhalation – nasal and oropharyngeal

chlorine toxicity? irritation, wheezing, cough,
rhinorrhea, respiratory distress,
syncope
2. Ingestion – burn injuries to
oropharynx/esophagus/gastric mucosa,
dysphagia, drooling, possible
hematemesis, and esophageal/gastric
perforation
3. Dermal – irritation of
skin/eyes/mucosa, burn injuries
Is a specific antidote Nebulized sodium bicarbonate may be

available for chlorine? beneficial in acute inhalational exposure.
While chemical neutralization is
normally not recommended, the large
surface area of the lungs dissipates heat
quickly; consequently, no thermal injury
appears to occur.
Are laboratory tests Electrolyte studies may reveal hyper-

available for specific levels chloremia and acidosis. An ABG may be
of chlorine exposure? needed to assess for hypoxia. Obtain a
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CXR as needed for evaluation of pneu-

monitis and pulmonary edema.
What emergency measures 1. Remove patient from exposure.

should be taken for patients 2. Provide supplemental humidified
who inhale chlorine? oxygen.
3. Bronchodilators for respiratory
distress symptoms (e.g., wheezing)
4. Nebulized sodium bicarbonate should
be considered.
5. The patient may need intubation for
impending respiratory failure.
What emergency measures Have the patient drink modest amounts

should be taken for patients of water. Gastric aspiration with an NG
who ingest chlorine? tube may be useful for patients with
liquid exposures presenting promptly
after ingestion. Patients may need
endoscopic studies to assess for mucosal
damage.
What emergency measures Remove contaminated clothing, and

should be taken for patients irrigate the skin with water to remove any
who experience dermal remaining chlorine.
exposure to chlorine?

methods available for
chlorine?
CHLOROFORM
What are the physical Colorless liquid with a sweet odor

properties of chloroform
(Cl3CH)?
How was chloroform As an anesthetic agent

first used?
What are other names for Trichloromethane, trichloroform, freon

chloroform? 20, formyl/methane trichloride,
methenyl/methyl trichloride
What is chloroform 1. Refrigerant and aerosol propellants

used for? 2. Extractant solvent for rubber,
resins, oils
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3. Chemical analysis
4. General solvent for industrial products
What are the modes of Ingestion, inhalation, dermal

exposure?
What is the concern with Corneal injury

ocular liquid exposure?
What are the main effects of Initially, mucous membrane irritation.

acute inhalation? With increased doses, CNS depression,
CV depression, and cardiac dysrhyth-
mias may occur.
What are the effects of Hepatic and renal damage

chronic inhalation?
Describe the mechanism of Hepatic metabolism (primarily CYP450-

hepatic and renal injury. 2E1) of chloroform generates free
radicals such as phosgene (Cl3CO) that
damage proteins and nucleic acids.
What are the clinical effects Nausea, vomiting, ataxia, headache,

of ingestion? progressing to CNS depression.
Dysrhythmias due to sensitization of the
myocardium may occur, as may hepatic
and renal damage.
What is the effect of Skin irritation, dermatitis, and defatting

cutaneous exposure? of the skin may occur.
Why do patients require Due to delayed hepatic and renal effects

close observation after an up to 48 hrs post-exposure
exposure?
What is the therapy for 1. Removal from the source and

acute exposure? decontamination.
2. NG tube aspiration may be used if
the patient presents soon after
ingestion.
3. N-acetylcysteine (NAC) has been
used to help reduce hepatic and renal
damage, but efficacy data is limited.
4. Supportive care is otherwise
indicated.
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CYANIDE
What are some sources of 1. Ingestion of cyanide salts (e.g.,

cyanide exposure? potassium cyanide (KCN), sodium
cyanide (NaCN))
2. Smoke inhalation (e.g., produced by
the burning of plastics)
3. Acetonitrile (e.g., found in artificial
nail remover and metabolized to
cyanide)
4. Pits or seeds from fruit in the Prunus
species (e.g., apricots, cherries,
peaches) contain amygdalin, which
releases cyanide when ingested.
5. Cassava root
6. Sodium nitroprusside
What is the mechanism of Cyanide inhibits multiple enzymes. The

cyanide toxicity? most important toxic action is inhibition
of cytochrome oxidase. Cyanide binds to
cytochrome a3, blocking oxygen utiliza-
tion in the last step of cellular respiration.
This causes a shift from aerobic to anaer-
obic metabolism, depleting ATP and
causing lactic acidosis.
What are the potential Ingestion, dermal, inhalation, parenteral

routes of exposure?
What is considered a toxic Oral – 200 mg of either the potassium or

dose of cyanide? sodium salt is potentially lethal
Inhalation – ⬎110 ppm over 30 min is
life-threatening, while ⱖ270 ppm is
immediately fatal
What are the signs and 1. CNS – anxiety, agitation, confusion,

symptoms of cyanide lethargy, and headache initially, with
toxicity? possible rapid onset of seizures
and coma
2. GI – abdominal pain, nausea, vomiting
3. Skin – cherry-red color (due to
increased oxygen saturation of
cutaneous venous hemoglobin) is
classically described, although not
often seen
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4. CV – initial hypertension, which can

progress to cardiac arrest heralded by
bradycardia and hypotension
5. Respiratory – initial tachypnea
followed by bradypnea or apnea
(CNS-mediated); acute lung injury
also can occur
What changes are seen on 1. ↑ lactate

lab tests? 2. ↓ pH
3. ↑ venous oxygen saturation (due to ↓
tissue extraction)
4. Elevated anion gap metabolic
acidosis
How quickly does onset of Inhalation – within minutes

symptoms occur? Ingestion – minutes to hours. Onset is
delayed when metabolism to cyanide is
required.
What does a cyanide 1. Amyl nitrite pearls to be crushed and

antidote kit include? inhaled
2. Sodium nitrite to be administered IV
3. Sodium thiosulfate to be
administered IV
How does the antidote 1. The nitrites induce methemo-

kit work? globinemia. Because cyanide has a
higher affinity for methemoglobin
than cytochrome oxidase, cyanide will
leave the mitochondria, allowing for
resumption of oxidative
phosphorylation.
2. Sodium thiosulfate acts as a
sulfhydryl donor. This helps the
enzyme Rhodenase convert cyanide
into thiocyanate, which is eliminated
in the urine.
What other antidote is Hydroxocobalamin

available for treating
cyanide poisoning?
How does it work? Combines with cyanide to form

cyanocobalamin (vitamin B12). This is
nontoxic and renally eliminated.
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What advantages does 1. It does not induce methemoglo-

hydroxocobalamin have? binemia, so it is safe to administer to
victims of smoke inhalation.
2. It does not cause hypotension
(possible with nitrites).
Does hydroxocobalamin Yes. Although it is a safe antidote, it will

have any adverse effects? cause red discoloration of the skin,
mucous membranes, and urine. This
typically resolves in 48 hrs. The
discoloration of the serum may interfere
with several laboratory tests.
Is activated charcoal Although cyanide is poorly adsorbed by

effective in treating cyanide activated charcoal, the lethal dose of
ingestion? cyanide is quite small and may be suffi-
ciently bound by a 1 g/kg dose. Gastric
lavage is controversial due to risk of sec-
ondary exposure of healthcare workers.
DETERGENTS
What are detergents? Amphipathic compounds (having both

hydrophilic and hydrophobic ends) that
reduce the surface tension of water,
acting as surfactants
How are detergents used? Household uses are most familiar, includ-
ing laundry- and dish-cleaning agents, as
well as surface-cleaning solutions. Some
mouthwashes also contain detergents.
List four chemical 1. Nonionic

classifications of detergents. 2. Anionic
3. Cationic
4. Amphoteric
What is the basic mechanism Detergents act as irritants, adversely

of toxicity? affecting the skin, the mucosa of the GI
tract, and the eyes.
Which of these types is Cationic surfactants, which have been

considered the most toxic? reported to be corrosive at concentra-
tions ⬎7.5% and cause hematemesis,
abdominal pain, and inability to swallow
secretions. Large ingestions can cause
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systemic toxicity (i.e., hypotension, CNS

depression, seizures, coma).
What other potentially toxic Sodium hypochlorite (bleach), bacterio-

agents can household static agents, enzymes
detergents contain besides
the actual detergent?
Which household detergent Automatic dishwasher detergents have a

is particularly dangerous? high alkalinity and can cause severe cor-
rosive injury.
What respiratory effects can Aspiration can cause chemical pneumoni-

occur due to detergent tis and pulmonary edema. Also, inhala-
ingestion? tion of powdered detergent can cause
edema of the vocal cords and epiglottis.
What metabolic disturbances Hypocalcemia and hypomagnesemia

occur with ingestions of (phosphates bind divalent cations)
phosphate-containing
products?
How is detergent ingestion 1. Supportive care is generally sufficient.

treated? 2. Any patient who vomits should be
observed for at least 6 hrs for signs of
aspiration.
3. Endoscopic evaluation of upper GI
tract may be needed for persistently
symptomatic patients who have
ingested automatic dishwasher
detergent or cationic detergents with
concentrations ⬎7.5%.
Are there any techniques to A small amount of water or milk can be

reduce toxicity? given orally for dilution if the patient can
take the liquid without difficulty. Such
liquids should never be forced and could
potentially increase aspiration risk.
What can be used to Aluminum hydroxide

specifically bind phosphate
in the GI tract?
How should eye exposure be Flush with copious amounts of water or

handled? saline for 15–20 min. If corneal injury is
expected, consult ophthalmology.
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Granular detergents and automatic

dishwasher detergents have a greater
chance of causing injury.
DIMETHYL SULFOXIDE (DMSO)
What is dimethyl sulfoxide 1. Industrial solvent

(DMSO), and where might it 2. Used in organic synthesis, as a metal-
be encountered industrially? complexing agent, and as a paint
stripper
3. Found in hydraulic fluid and
antifreeze
Are there any approved Yes, as a bladder instillate for the treat-
medical uses for DMSO? ment of interstitial cystitis. It is also used
as a vehicle for certain medications and is
effective topically in treating extravasation
injury from certain antineoplastic agents.
What is the mechanism of Unknown, but may cause mast cell

toxicity of DMSO? degranulation with histamine release.
DMSO spilled on the skin or clothing
may carry other toxic substances
transdermally.
What are the clinical effects Common symptoms include skin rash
seen with toxic exposure to and urticaria, irritation of mucous
DMSO? membranes/eyes/respiratory tract, garlic
odor to breath, nausea, and headache.
Following intravascular administration,
hemolysis may occur. CNS depression
has been reported. As DMSO is an
efficient solvent, dermal exposure to this
chemical may result in toxicity
characteristic of any solute present.
Are there any specific tests No. Diagnosis relies principally on history.
helpful for diagnosis?
What treatments are 1. No specific antidotes exist. Manage-

available for DMSO toxicity? ment is supportive.
2. Rapid decontamination is important,
as DMSO is readily absorbed
transdermally.
3. Enhanced elimination methods are of
no proven clinical benefit.
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DIOXINS
What is the most common Dietary ingestion; however, absorption

route of exposure to dioxins may also occur through dermal and
in the United States? inhalational exposure.
What are the major food Meat, fish, dairy

sources of dioxin
contamination?
What is a dioxin? A member of a group of 75 distinct

chemicals known as chlorinated dibenzo-
p-dioxins that consist of two benzene
rings connected by two oxygen atoms.
The remaining binding sites bind up to
4–8 chlorine atoms. They are lipid solu-
ble compounds and bioaccumulate; they
also tend to persist in the environment.
How are dioxins formed? 1. Combustion of polychlorinated

compounds (e.g., PVC, plastic)
2. Exhaust from diesel engines
3. Waste from coal-burning power plants
4. Production of chlorinated organic
solvents
5. Component of cigarette smoke
6. Municipal waste processing
What are some infamous 1. German – Ludwigshafen BASF

environmental disasters that accident in 1953
involved dioxins? 2. Netherlands – Amsterdam Philips-
Duphar Facility explosion in 1963
3. Japan – Yusho disease (rice oil) in 1968
4. England – Coalite explosion in 1973
5. Italy – Seveso Meda ICMESA plant
disaster in 1976
6. Taiwan – Yu-Cheng disease (rice oil)
in 1979
7. Vietnam – “Operation Ranch Hand”
in the Vietnam War from 1962–1971
In what tissue type are Adipose tissue, due to high lipophilicity

dioxins most heavily
concentrated?
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What are potential health Carcinogenicity (IARC Group 1), hepato-

effects of dioxin exposure? toxicity, immunotoxicity, cytochrome P450
induction, reproductive and developmen-
tal abnormalities, dermatological lesions
How are dioxins speculated Bind the aryl hydrocarbon receptor,

to cause their effects? which helps to regulate gene expression
and other regulatory proteins
What is the minimum toxic 0.1 ␮g/kg

dose in humans?
What are acute symptoms of Myalgias, mucous membrane irritation,

dioxin toxicity? nausea, and vomiting are reported,
although acute toxicity is limited, as no
deaths from acute exposure have been
reported.
What are late clinical effects Chloracne (pathognomonic), hirsutism,

of dioxin toxicity? hyperpigmentation, peripheral neuropa-
thy, porphyria cutanea tarda, elevated
triglycerides, liver cytochrome enzyme
induction
What is chloracne? Cystic acneiform lesions, predominantly

on the face and upper body, that may
occur 1–3 weeks after exposure to dioxins
and related compounds and may last for
decades
What substance, designed as Olestra®

a fat substitute, can
substantially increase the
fecal excretion of dioxins?
What vitamins may be of Vitamins A and E

benefit in high doses
following dioxin toxicity?
What is the name of the “Agent Orange” (2,4,5-T, a chlorophe-

infamous dioxin-containing noxy herbicide)
herbicide used by the
United States during the
Vietnam War?
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Who is a famous victim of Viktor Yushchenko, a Ukranian politician

dioxin poisoning? who was poisoned by 2,3,7,8-tetra-
chlorodibenzo-p-dioxin (TCDD)
DISK BATTERIES
What are disk batteries? Also called button batteries, they are flat,
smooth, and typically 8–25 mm in diame-
ter. They are commonly used in watches,
hearing aids, and calculators.
What chemicals do disk Alkaline sodium or potassium

batteries contain? hydroxide, plus a heavy metal
(lithium, mercury, zinc)
Why is ingestion of a disk If stuck in the esophagus, mucosal

battery an emergency? damage may begin almost immediately
with associated morbidity and mortality
reported.
How do ingested disk 1. Pressure necrosis

batteries cause tissue 2. Electrical current
damage? 3. Leakage of alkaline corrosives
Does heavy metal poisoning No. The amount of heavy metal content
occur if a disk battery is too low to cause significant toxicity.
fragments in the GI tract?
Should emesis be induced in No. This is unlikely to cause expulsion of

patients who have ingested the battery and may lead to esophageal
disk batteries? perforation, aspiration, or other
complications.
What imaging is done in Plain radiographs of the entire respira-

patients with suspected disk tory and GI tracts
battery ingestion?
What is the treatment for a Emergent endoscopic battery removal

battery located in the
esophagus?
What is the treatment for a Asymptomatic patients may be allowed

battery located past the 10 days for passage before further imag-
esophagus? ing or treatment is needed.
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How long does spontaneous Most pass within 7 days; every stool must
passage of the battery take be examined for presence of the battery.
once past the stomach?
Can a retained disk battery Yes. Burns can occur within hours, and
cause esophageal perforation has occurred in as few as
perforation? 6 hrs.
ETHYLENE DIBROMIDE
What is ethylene dibromide? A colorless substance with a sweet chlo-

roform-like odor. It is a liquid at room
temperature, having a vapor pressure
similar to that of water.
What are common uses of Formerly used as an additive in leaded

ethylene dibromide? gasoline. It is used as a pesticide and fumi-
gant, although its use was banned in the
U.S. in 1984. It is still used as a solvent, a
chemical intermediate, and a gauge fluid.
What are possible routes of Inhalation (vapor is heavier than air

exposure to ethylene leading to accumulation), ingestion,
dibromide? absorption (dermal, ocular, mucous
membranes)
What is the mechanism of It is an alkylating agent that causes

toxicity of ethylene inhibition of DNA activity. Also, hepatic
dibromide? metabolism of ethylene dibromide leads
to production of free radicals and
cytotoxic metabolites.
What are possible clinical 1. Dermal – erythema, edema,

effects of an ethylene blistering
dibromide exposure? 2. Ocular – chemical conjunctivitis
3. Pulmonary – cough, bronchospasm,
pulmonary edema, acute lung injury
4. GI – abdominal pain, nausea,
vomiting, diarrhea
5. Systemic – it has general anesthetic
properties resulting in mental status
changes that can cause sedation
progressing to coma. Also, it can cause
metabolic acidosis, coagulation
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abnormalities, and hepatic and renal

failure.
What is the expected onset Often immediate; however, development

for symptoms? of dermal ulcers and pulmonary edema
may be delayed for 2–3 days.
When working with or It will penetrate protective clothing, in-

responding to spills of cluding rubber, neoprene, and leather.
ethylene dibromide, what
chemical property must be
considered?
How is an ethylene 1. Reliable history of exposure with

dibromide exposure consistent signs and symptoms
detected? 2. Expired air, blood, or tissue detection
is possible but not useful.
3. Serum bromide levels can confirm an
exposure but do not predict clinical
course.
Are there any drugs or There is no proven antidote. Dimercaprol

antidotes effective in an and acetylcysteine have been suggested
ethylene dibromide for use, but there is no supporting data.
exposure?
What treatments are 1. NG aspiration may be considered for

indicated for an ingestion recent ingestions.
exposure? 2. Activated charcoal is only indicated in
the alert, cooperative ingestion patient.
What treatments are Remove clothing and decontaminate as

indicated for a dermal or needed. Irrigate ocular exposures imme-
ocular exposure? diately with saline or water for 15 min.
What treatments are Administer supplemental oxygen, treat

indicated for an inhalation bronchospasm with inhaled beta 2-adren-
exposure? ergic agonists, and observe for develop-
ment of pulmonary edema.
ETHYLENE GLYCOL
What is the most common Engine coolant (antifreeze), not to be

source of ingestion of confused with gas line antifreeze, which
ethylene glycol? likely contains methanol
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What are the early signs of Signs of inebriation – altered metal sta-
acute ethylene glycol tus, nystagmus, ataxia, slurred speech
toxicity?
Does the urine of a patient Not necessarily. Although fluorescein is

poisoned with antifreeze frequently added to antifreeze to aid in
fluoresce under a mechanics’ search for leaks, observer
woods lamp? interpretation and even the presence
of urine (or gastric content) fluores-
cence are highly variable. Treatment
decisions should be based on history and
clinical indication of ethylene glycol
poisoning.
What finding in the urine Presence of calcium oxalate crystals

should raise your suspicion
of ethylene glycol poisoning
in the appropriate clinical
setting?
Ethylene glycol is Glycoaldehyde, glycolic acid, glyoxylic

metabolized to what acid, and oxalic acid. The latter three
clinically significant contribute to clinical acidosis. Glycolic
compounds? What is the acid can lead to a false elevation in serum
significance of each? lactic acid when using some methods of
analysis. Oxalic acid is responsible for
urine calcium oxalate crystal formation,
acute renal failure, and hypocalcemia
(and its sequelae).
What is the rate limiting Conversion of glycolic acid to

step in oxalic acid glyoxylic acid
production?
What metabolic state is High anion gap metabolic acidosis

expected from ethylene
glycol poisoning?
Can a patient with a normal No. Ethylene glycol, but not its metabo-
osmolar gap be ruled out for lites, contributes to the osmolar gap. Late
significant toxicity? in metabolism, when no parent compound
is present, the osmolar gap may be nor-
mal. It is at this time that the anion gap
should be elevated. Also, due to individual
variations in normal serum osmolarity, a
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gap may appear “normal” but still hide a

significant ethylene glycol level.
How do you correct for Using the standard formula for a calcu-
concomitant ethanol lated serum osmolarity (Osmc), the blood
intoxication when concentration of ethanol (mg/dL) divided
calculating the osmolar gap? by 4.6 (molecular weight of ethanol
divided by 10 to correct for units) must
also be added in to correctly calculate the
osmolar gap:
BUN glucose
Osmc ⫽ 2[Na⫹] ⫹ ⫹
2.8 18
ethanol
⫹
4.6
From the osmolar gap, how Multiplying the osmolar gap by 6.2 (eth-
do you estimate the ylene glycol’s molecular weight divided
concentration of ethylene by 10) will give a rough estimate of the
glycol (in mg/dL) of a ethylene glycol level in mg/dL.
suspected ethylene glycol
intoxicated patient?
What role do calcium Calcium oxalate crystals primarily deposit

oxalate crystals play in in the kidney, resulting in renal failure,
ethylene glycol toxicity? but also may deposit in other tissues such
as the brain and spinal cord. This may re-
sult in neurologic deficits.
What “antidotes” are Fomepizole or ethanol administration

used in the medical
management of ethylene
glycol toxicity?
What enzyme do these Alcohol dehydrogenase

medications inhibit?
At what ethanol level is the 100 mg/dL

metabolism of ethylene
glycol by alcohol
dehydrogenase completely
inhibited?
When should fomepizole or Therapy should continue until serum eth-

ethanol be discontinued? ylene glycol concentrations are
⬍20 mg/dL.
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Once alcohol dehydrogenase Ethylene glycol is cleared by the kidneys

is inhibited, how are with a half-life of ⬎17 hrs.
ethylene glycol and its
metabolites eliminated?
What is the definitive Hemodialysis

therapy for ethylene glycol
intoxication?
What are the indications for Consensus opinion supports hemodialysis

hemodialysis in ethylene if metabolic acidosis, end-organ toxicity, or
glycol poisoning? renal failure is present. A serum ethylene
glycol level ⬎50 mg/dL or high osmol gap
are relative indications for hemodialysis.
The ultimate decision should be based on
physician judgment.
What theoretical adjunctive Thiamine and pyridoxine may aid in con-

therapies may prevent verting glyoxylic acid to metabolites less
toxicity in ethylene glycol toxic than oxalic acid.
poisoned patients?
ETHYLENE OXIDE
What is ethylene oxide? A colorless, flammable, and highly reac-

tive gas. It is used to sterilize medical
equipment and in the production of eth-
ylene glycol, surfactants, and polyesters.
Does it have an odor? Yes, it has a sweet, ether-like odor; how-

ever, it can cause olfactory fatigue, limit-
ing one’s ability to smell it. As a result,
smell does not provide adequate expo-
sure warning.
What is the mechanism of It is an alkylator of protein and DNA that

toxicity of ethylene oxide? has general anesthetic properties.
What are possible routes of Inhalation, ingestion (unlikely, as ethyl-

exposure to ethylene oxide? ene glycol is a gas at room temperature),
absorption (dermal, ocular, mucous
membranes)
Are there any contamination People can be exposed through direct

risks to healthcare contact while sterilizing equipment, clean-
providers? ing spills, or opening packaged supplies.
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What is the approximate Immediate local and systemic symptoms

onset of action after an are possible; however, respiratory and
acute exposure to ethylene neurologic symptoms may be delayed for
oxide? hours following inhalation.
What are possible effects of Neurological symptoms range from

an acute ethylene oxide drowsiness, confusion, ataxia, and
exposure? headache to seizures, coma, and death.
Ethylene oxide is a potent irritant and
will cause irritation of the eyes, nose,
and throat. It may also cause bron-
chospasm and delayed pulmonary
edema.
What effects are possible Ethylene oxide liquid can cause frostbite,
with dermal exposure? and contact with aqueous solutions can
cause erythema, edema, vesiculation, and
desquamation; this can be delayed for
hours.
Why is allergic sensitization Repeat patient contact with ethylene

an important concern in an oxide-sterilized medical equipment may
ethylene oxide exposure? result in sensitization, causing an acutely
life-threatening allergic reaction.
What systemic effects are Cardiac dysrhythmias

possible after an exposure to
an ethylene oxide/freon
mixture?
How is an ethylene oxide Diagnosed clinically with a reliable his-

exposure detected? tory of exposure and consistent signs and
symptoms
How is an ethylene oxide 1. Remove the patient from the

exposure managed? environment. Rescue personnel
should wear personal protective
equipment, including self-contained
breathing apparatus (SCBA) if
necessary.
2. Patients must be decontaminated by
removing clothing and washing
exposed skin.
3. Thoroughly irrigate affected eyes,
assess visual acuity, and examine for
corneal injury.
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4. Treat significant skin exposures with

appropriate burn care.
5. There is no proven antidote.
Treatment is supportive.
What additional treatments 1. Administer supplemental oxygen.

are indicated for an 2. Treat bronchospasm with a
inhalation exposure? bronchodilator.
3. Anticipate and treat pulmonary
edema.
What are the possible effects Sensory and motor peripheral neuropa-
of chronic exposure? thy, cataracts, and increased risk of
leukemia. Exposure may also be respon-
sible for birth defects and spontaneous
abortion.
FLUORIDES
What are some of the most 1. Hydrofluoric acid (HF) – used in glass
common products which and silicon etching
contain fluoride? 2. Chrome cleaning agents (ammonium
bifluoride)
3. Toothpaste (sodium
monofluorophosphate)
4. Insecticides
5. Dietary supplements (sodium fluoride)
By what routes can patients 1. Ingestion – corrosive effects causing

be exposed to fluorides? nausea, vomiting, and abdominal pain.
Fluoride is also passively absorbed
from the GI tract, leading to systemic
toxicity.
2. Dermal – irritation, edema, pain,
potential systemic absorption
3. Ocular – corrosive injury
4. Inhalation – respiratory tract irritation,
potential systemic absorption
How does dermal exposure There may be a delay of hours before

to a dilute HF solution or symptom onset. Patient can develop
ammonium bifluoride significant pain despite a normal exam.
present? Progressive erythema, followed by
blanching and possibly necrosis, can
develop. The pain is excruciating, and
deep tissue injury can result.
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What are the mechanisms of 1. Direct binding to divalent cations

fluoride toxicity? (i.e., calcium and magnesium), which
can lead to hypocalcemia or
hypomagnesemia
2. Interference with enzyme systems,
including the Na-K-ATPase, which
may lead to hyperkalemia, and
enzymes involved in the oxidative
phosphorylation, which leads to ATP
depletion and cell death
3. Concentrated HF will cause
coagulation necrosis in addition to the
systemic effects of absorbed fluoride.
What GI signs and symptoms Nausea, vomiting, abdominal pain,

are most commonly seen hematemesis, dysphagia
with fluoride toxicity?
What neurologic effects are Clinical manifestations of hypocalcemia

most commonly seen with (e.g., muscle spasms, tremors, headache,
fluoride toxicity? seizures, hyperreflexia)
What CV effects are most 1. Effects of

commonly seen with hypocalcemia/hypomagnesemia
fluoride toxicity? (i.e., prolonged QT interval)
2. Effects of hyperkalemia (i.e., peaked
T waves, widened QRS complex, AV
nodal block, bradycardia)
3. Ventricular tachycardia and
ventricular fibrillation
What is the estimated toxic 5–10 mg/kg

dose for fluoride ingestion?
What studies should be 1. Serum calcium, magnesium, and

performed on patients with potassium levels to monitor for
suspected fluoride toxicity? hypocalcemia, hypomagnesemia, and
hyperkalemia
2. Serial ECGs to look for prolongation
of the QT interval (i.e., hypocalcemia)
and/or peaked T waves
(i.e., hyperkalemia)
Is it possible to check a Yes, it is possible to check both serum

fluoride level? and urine fluoride levels, but these tests
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are not readily available in most

hospitals.
How do you treat systemic 1. Correct electrolyte abnormalities with

fluoride poisoning? IV preparations of calcium and
magnesium.
2. Correct acidosis with sodium
bicarbonate.
3. Hemodialysis can be considered for
critically ill patients that are refractory
to other forms of treatment.
What measures should be 1. Gastric emptying via NG aspiration

taken after an oral ingestion may be considered.
of HF or ammonium 2. Administer calcium carbonate,
bifluoride? magnesium/aluminum-based antacids
or milk to bind the fluoride in the
stomach.
3. Endoscopy is indicated for any clinical
suspicion of corrosive injury.
How is a dermal exposure 1. Thorough irrigation with water or

treated? saline
2. Topical calcium gel should be applied
(7 g of calcium gluconate added to
150 mg of sterile water-based
lubricant)
3. For pain refractory to above
treatment, SQ, regional IV
infusion, or intraarterial infusion
of calcium gluconate may be
effective.
Can calcium chloride be No. It can cause tissue toxicity.

used as a substitute for
dermal application,
infiltration, or infusion?
How should an ocular 1. Immediate irrigation for at least

exposure be treated? 15 min with saline or water
2. Irrigation with a weak (1%–2%)
calcium gluconate solution may be
beneficial.
3. Ophthalmology consultation should be
considered.
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What therapy may be Nebulized 2.5% calcium gluconate

beneficial after an
inhalational exposure to HF?
How much fluoride is 1 mg of fluoride per gram of toothpaste.

contained in toothpaste? Toothpaste contains sodium monofluo-
rophosphate which has low solubility and
is generally less toxic.
How should ingestion of Fluoride salts will be converted to HF

toothpaste, fluoride rinse, or upon entering the stomach. This can
fluoride supplements be cause local irritation and systemic absorp-
treated? tion. Ingestions estimated to have ⬎5
mg/kg should be treated with oral admin-
istration of milk or other sources of cal-
cium or magnesium.
Who may be considered for Asymptomatic patients who have ingested

discharge from the hospital ⬍3 mg/kg of fluoride and who have been
after fluoride ingestion? observed for 6 hrs post-ingestion.
FLUOROACETATE
What is fluoroacetate used Formerly a rodenticide in common use in

for? the U.S., this compound is now prohib-
ited except for use as a coyote poison (to
protect cattle and sheep). It is still used
outside the U.S. for its original purpose.
It is commonly known as “Compound
1080” or sodium monofluoroacetate
(SMFA).
What is/are the route(s) of Inhalation and ingestion

intoxication?
What is the mechanism of It poisons the Krebs cycle. Fluoroacetate

toxicity? (in place of acetic acid) combines with
coenzyme A to form fluoroacetyl CoA.
The latter undergoes conversion to
fluorocitrate (by citrate synthase), which
subsequently occupies the citrate binding
site on aconitase, rendering this enzyme
inactive and compromising aerobic
metabolism. Urea metabolism is also
hindered due to the inability to make
intermediates such as glutamate.
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What are the signs and Initial symptoms include nausea,

symptoms of fluoroacetate vomiting, diarrhea, and abdominal pain.
toxicity? CNS manifestations and life-threatening
CV manifestations follow, including agita-
tion, seizures, coma, hypotension, and
dysrhythmias.
What laboratory Increased anion gap metabolic acidosis

abnormalities are commonly with high lactate levels. Hypocalcemia
associated with and hypokalemia may also occur.
fluoroacetate toxicity?
What is the mechanism Citrate, the substrate immediately

behind fluoroacetate- upstream from the inhibited
induced hypocalcemia? enzyme (aconitase), accumulates and
is freely available to bind nearby
calcium ions.
What is the recommended Supportive care. Consider activated

treatment? charcoal and gastric lavage if available
within 1 hr post-ingestion.
v
Are there any antidotes? Ethanol and glycerol monoacetate have
both been studied in animal models as
potential suppliers of acetate to
competitively inhibit the action of citrate
synthase on monofluoroacetyl-CoA;
however, human data is limited.
FORMALDEHYDE
List some common sources Automobile exhaust, tobacco smoke,

of formaldehyde. fertilizers, foam insulation, burning wood,
disinfectants
What is formalin? Formaldehyde aqueous solution; it

commonly also contains methanol
What are two common uses 1. As a disinfectant

of formalin? 2. As an embalming fluid (effects tissue
fixation)
What is the metabolic Formic acid

byproduct and serum
marker of toxicity following
formaldehyde ingestion?
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What acid-base disorder Anion gap metabolic acidosis

may result from
formaldehyde ingestion?
What are the physical effects 1. Exposure to formaldehyde gas can

of prolonged or excessive cause irritation of eyes/skin/mucous
formaldehyde exposure? membranes with associated sneezing,
laryngospasm, bronchospasm, and
noncardiogenic pulmonary edema.
2. It is a potent caustic causing
coagulation necrosis. When ingested,
it can cause rapid and significant GI
injury, including ulceration, bleeding,
and perforation.
3. CNS depression can develop and
progress to coma. Hypotension and
shock can develop secondary to GI
injury and profound acidosis.
What measures may aid in Dilution with water may reduce local
reducing injury from acute injury, and gastric aspiration may lessen
formaldehyde ingestion? systemic absorption.
How is formaldehyde 1. Supportive care

toxicity treated? 2. Folinic acid to help convert formic
acid to nontoxic metabolites (carbon
dioxide and water)
3. IV sodium bicarbonate to treat
metabolic acidosis
4. Fomepizole or ethanol should be
administered if there is suspicion of a
significant co-ingestion of methanol.
5. Hemodialysis will remove formic acid,
formaldehyde, and methanol.
6. Endoscopy is indicated to evaluate
caustic injury.
What are the indications for Development of metabolic acidosis

dialysis following
formaldehyde intoxication?
FREONS AND HALONS
What is freon? Freons are a type of halogenated

hydrocarbon, and they are a subclass of
chlorofluorocarbons (CFC). They are
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colorless, odorless, and noncorrosive. They

have historically been used as refrigerants,
aerosol propellants, solvents, and as
polymer intermediates in plastic
manufacturing. Although their production
has been stopped, freon is still available in
older air-conditioners and refrigerators,
and there is a considerable stockpile.
How does the primary Primarily through refrigerator and air-

exposure to freon occur? conditioner leaks, which can cause
absorption or inhalation of freon. Also, it is
commonly inhaled intentionally as a drug
of abuse.
How is freon metabolized? Freon is rapidly absorbed through the

skin or by inhalation and rapidly excreted
through exhalation. It is not metabolized
by the lungs or kidneys.
What toxic effects do freons 1. Dermal/ocular – low concentration

have? exposure can cause ocular/mucosal
irritation. Skin contact with liquid
freon or with freon escaping from a
pressurized container can cause
frostbite. Systemic absorption can
cause CNS depression, headache,
confusion, and dysrhythmias.
2. Inhalation – pulmonary irritation,
bronchospasm, pulmonary edema
3. Freon is neither a carcinogen nor a
teratogen.
By what mechanisms can 1. Mucosal irritation

freon cause pulmonary 2. Freons can produce toxic gases (i.e.,
edema? phosphine and chlorine) when heated
or by decomposition.
How do freons cause They sensitize the myocardium to en-

dysrhythmias? dogenous catecholamines, predisposing
the patient to tachydysrhythmias and
ventricular fibrillation.
How do freons induce AMS Both as an asphyxiant (by displacing

and coma? oxygen) and through a general anesthetic
effect
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How do you manage 1. Remove patient from the source.

patients with a freon 2. Provide oxygen and respiratory
exposure? support, if needed.
3. A calm environment should be
provided, and adrenergic agents
should be avoided.
4. GI decontamination is not warranted.
5. Treat frostbite with warm water
immersion, tetanus prophylaxis, and
analgesia.
What is halon? A halogenated hydrocarbon, also known

as bromochlorodifluoromethane, used in
fire protection systems
How are individuals exposed When fire protection systems are acti-
to halon? vated, halon is released as a gas. It is also
abused as an inhalant.
What is the clinical Similar to freon, with bronchospasm,

presentation of a halon lightheadedness/euphoria, CNS depres-
exposure? sion, and palpitations. Fatalities can occur
secondary to dysrhythmias or asphyxiation.
What is the management of Same as for freon exposures

a patient exposed to halon?
What poisonous gas can be Phosgene

produced when halon is
heated?
GASES (IRRITANT)
What are irritant gases? Gases that result in mucous membrane

irritation on exposure, producing a
characteristic syndrome of pharyngeal,
nose, throat, and eye burning.
Where do people encounter Industrial settings, structure fires,

toxic irritant gases? hazardous materials spills, certain house-
hold cleaning products
How should irritant gases be By water solubility:

classified? 1. High solubility – ammonia, chlorine,
formaldehyde, hydrogen chloride,
nitric acid, sulfur dioxide
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2. Low solubility – nitric oxide, nitrogen

dioxide, phosgene
What is the “warning The amount of initial irritation the gas

property” of an irritant gas? causes. Gases with high warning
properties tend to result in lower patient
exposure, as patients flee the irritating
effects.
Name the gases that are Chlorine and chloramine gas

formed from the common
mistake of mixing
household bleach and
ammonia.
What are the effects of high Immediate irritation of the

solubility gases? mucous membranes of the eyes, nose,
and throat
What are the effects of low Because these gases are less soluble to
solubility gases? the upper airway mucosa, they can
be inhaled into the pulmonary alveoli
and cause delayed-onset pulmonary
toxicity.
What are the common signs Conjunctivitis, rhinitis, burns, dry cough,
of exposure to high wheezing, odynophagia
solubility gases?
What are the complications Pulmonary edema (commonly delayed)

of exposure to low solubility and damage to the lower respiratory
gases? epithelium
Are there long-term Usually not; however, some gases

complications of irritant gas (i.e., nitrogen dioxide, phosgene) may
exposure? predispose to bronchiolitis obliterans
and COPD.
What is the treatment for 1. Remove the victim from the

irritant gases? exposure.
2. Observe the patient for delayed
sequelae.
3. Maintain the airway, with intubation if
necessary.
4. Assess pulmonary status with CXR,
ABG, and PFTs.
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GLYCOL ETHERS
What are glycol ethers? A class of industrial compounds that are

used in solvents; industrial and home
cleaners; topical coatings (i.e., lacquers,
paint thinners, latex paints);
semiconductor manufacturing; and
automotive antifreeze and brake fluids.
Examples include diethylene glycol,
ethylene glycol monobutyl ether, and
ethylene glycol monomethyl ether.
How does exposure typically Ingestion, inhalation, dermal absorption

occur?
What pivotal role have The misuse of diethylene glycol

glycol ethers played in (DEG) in 1937 in the drug “Elixir
pharmaceutical regulation? Sulfanilamide” marketed by a Tennessee
company, caused the deaths of over
100 people, many of them children,
in 15 states. This disaster led to the
passage of the 1938 Food, Drug, and
Cosmetic Act, which allowed the Food
and Drug Administration (FDA) to
regulate drugs and cosmetics. Addition-
ally, safe labeling and premarket testing
were required prior to mass-market
sales.
How are glycol ethers Although knowledge of exact pathways is

metabolized? limited, glycol ethers appear to be pre-
dominantly metabolized in the liver, with
some metabolism through alcohol and
aldehyde dehydrogenase.
What is the clinical Generally, acute exposure may manifest as

presentation of a patient nausea, vomiting, and abdominal pain fol-
with acute glycol ether lowed by metabolic acidosis, renal toxicity,
toxicity? and CNS depression/neurotoxicity. Hepa-
totoxicity may also occur.
What are the signs and Renal failure appears to be a prominent

symptoms of chronic glycol feature. Neurologic abnormalities,
ether toxicity? including lethargy/CNS depression,
progressive paralysis, and seizures, may
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occur. Bone marrow suppression has

also been reported.
What three features 1. Renal failure

characterized DEG toxicity 2. Metabolic acidosis
in the 2006 Panamanian 3. Symmetric ascending paralysis
outbreak?
What is the mechanism of Not fully understood. DEG and/or its

toxicity of DEG? metabolite, hydroxy-ethoxyacetic acid,
may cause the majority of the toxicity.
What is the management of 1. Gastric aspiration with an NG tube

patients with glycol ether may be beneficial if the patient
poisoning? presents immediately after ingestion.
2. 4-methylpyrazole (fomepizole) is
currently of unknown efficacy, as it is
typically not apparent whether the
metabolites or the parent compound
cause the majority of the toxicity.
3. After DEG exposure, patients with
early hemodialysis appear to have the
best outcome. This may also apply to
other glycol ethers.
4. Otherwise, general supportive care is
indicated.
HYDROCARBONS
What are hydrocarbons? Organic compounds primarily containing

carbon and hydrogen atoms. They are
derived from plants, oils, animal fats,
petroleum, natural gas, and coal and are
used as solvents, degreasers, fuels, and
lubricants.
How are patients poisoned 1. Ingestion – GI absorption of aliphatic

by hydrocarbons? hydrocarbons is limited, and systemic
toxicity typically is absent. Aromatic,
halogenated, or otherwise substituted
hydrocarbons are more prone to cause
systemic absorption and symptoms.
Both pose an aspiration risk.
2. Inhalation (fumes) – may cause CNS
depression
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3. Dermal/ocular – cause local irritation

and potential systemic absorption
4. Injection (SQ, IM, IV) – may result in
localized necrosis, pneumonitis
What are their mechanisms 1. Disruption of the alveolar surfactant

of toxicity? layer following aspiration → alveolar
collapse, V/Q mismatch, and hypoxia.
Also, direct pulmonary injury causes
pneumonitis and pulmonary edema.
Hydrocarbons of low viscosity (e.g.,
gasoline, kerosene, mineral seal oil,
furniture polish) pose a higher risk of
aspiration as compared to high-
viscosity hydrocarbons (e.g., motor oil,
petrolatum jelly, mineral oil).
2. Systemic intoxication (often after
absorption of lipid-soluble solvents) will
cause inhibition of neurotransmission
and, thus, a general anesthetic effect.
3. Sensitization of the myocardium to
endogenous catecholamines, resulting
in dysrhythmias
4. Subcutaneous inflammation,
“defatting,” and liquefaction necrosis
Which clinical entity causes Aspiration. Only a small amount is

the most morbidity and necessary to cause significant pulmonary
mortality? injury.
What factors increase the Physical properties of the hydrocarbon

risk of aspiration? ingested (i.e., low viscosity and low sur-
face tension) and a history of coughing,
gagging, or vomiting.
How will hydrocarbon Patients usually will develop coughing or

aspiration present? choking within 30 min and may have a
rapid progression of symptoms, manifest-
ing with tachypnea, abnormal breath
sounds, hypoxia, pulmonary inflamma-
tion/edema, and potentially respiratory
failure. These can worsen over several
days. If a patient is observed for 6 hrs
without development of respiratory symp-
toms, a significant aspiration is unlikely.
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Is a CXR taken on No. Radiographic changes can be

presentation to the ED after delayed for up to 24 hrs. Also,
a possible hydrocarbon radiographic recovery will lag behind
ingestion useful for clinical recovery.
prognosis?
How should hydrocarbon 1. Administer supplemental oxygen.

aspiration be treated? 2. Treat bronchospasm with inhaled beta
2-adrenergic agonists.
3. Maintain a low threshold for
endotracheal intubation and positive
pressure ventilation.
Should prophylactic Routine use is not indicated. Abnormal

antibiotics be administered lung auscultation, fever, leukocytosis,
for pneumonitis? and abnormal radiographic findings are
often presenting findings of simple
hydrocarbon pneumonitis. Antibiotics
should be considered with a rise in
temperature or white cell count
occurring 24 hrs post-exposure.
Should prophylactic steroids No

be administered for
pneumonitis?
What clinical effects are Nausea, vomiting, and hematemesis can

seen after a hydrocarbon be seen. Certain hydrocarbons pose a risk
ingestion? for systemic absorption.
What GI decontamination For agents with little or no systemic

should be performed for absorption (e.g., kerosene or furniture
hydrocarbon ingestions? polish), GI decontamination should not be
performed, as it will increase aspiration
risk without affecting toxicity. For
systemically absorbed hydrocarbons or
those containing toxins, decontamination
must be considered. NG aspiration of a
liquid ingestion is reasonable, as is
administration of activated charcoal.
Ensure a well-protected airway.
How are injection injuries 1. Proper wound care, analgesia, and

managed? tetanus immunization as indicated
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2. Surgical debridement to remove

necrotic tissue and limit hydrocarbon
exposure must be considered. A hand
surgery consult is mandatory for
patients who have injured themselves
with a high-pressure injector (e.g.,
grease gun), as tracking through
fascial planes can lead to extensive
injury and loss of function.
HYDROGEN SULFIDE
What is hydrogen A colorless, toxic gas typically formed by

sulfide (H2S)? bacterial decomposition of proteins or
during many industrial processes
What does hydrogen sulfide Rotten eggs

smell like?
Does the absence of the No. Hydrogen sulfide causes olfactory

distinctive odor of hydrogen nerve fatigue at concentrations of 100–150
sulfide mean that it is not ppm, and the ability to perceive this odor
present? can subsequently be extinguished.
What are some occupations Agriculture, petroleum industry, sewer

at risk for hydrogen sulfide workers, leather tanning, rubber industry,
exposure? mining (coal)
Hydrogen sulfide exerts its Binds to the cytochrome oxidase a3, thus
clinical effects by what inhibiting oxidative phosphorylation
mechanism?
How does hydrogen sulfide Lactic acidosis due to anaerobic

poisoning result in an anion metabolism
gap acidosis?
What other gas can cause Cyanide can cause a similar “knock down”
similar symptoms to phenomenon. Methane is also found in
hydrogen sulfide poisoning? sewer gas but has a slower onset.
What are the signs and Ocular and respiratory tract irritation can
symptoms associated with be noticed at levels of 50–100 ppm. Pro-
early, mild hydrogen sulfide longed exposure to these levels can cause
toxicity? reversible corneal ulcerations (“gas eye”)
and possibly irreversible corneal scarring.
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As levels rise to ⬎250 ppm, there is risk

of developing pulmonary edema.
When hydrogen sulfide Systemic toxicity, including:

concentrations reach ⬎500 1. CNS – headaches, confusion,
ppm, what effects may be dizziness, seizures, coma
seen? 2. GI – nausea and vomiting
3. CV – chest pain, bradycardia,
dysrhythmias, hypotension
Above what level can ⬎700 ppm

hydrogen sulfide cause
immediate death upon
inhalation?
What is the most important Move the victim(s) to fresh, uncontami-

treatment for victims of nated air. It is important never to at-
hydrogen sulfide poisoning? tempt a rescue unless rescue personnel
are wearing a self-contained breathing
apparatus (SCBA).
How else can hydrogen 1. Provide 100% supplemental oxygen.

sulfide poisoning be 2. Consider methemoglobin induction
treated? with nitrites (i.e., amyl nitrite and/or
sodium nitrite).
3. Consider hyperbaric oxygen treatment.
In theory, how does Hydrogen sulfide will preferentially bind

methemoglobin help treat methemoglobin to form sulfmethemoglo-
hydrogen sulfide poisoning? bin. This will remove hydrogen sulfide
from cytochrome oxidase a3.
In reality, what limits the Hydrogen sulfide has a rapid onset of

usefulness of action and is only present in the blood for
methemoglobin? a short period of time.
Is sodium thiosulfate No. It provides no benefit.

indicated for hydrogen
sulfide poisoning?
IODINE
What different forms of 1. Iodine – a divalent molecule (I2), also

iodine exist? known as elemental iodine or
molecular iodine. It is corrosive due
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to its cytotoxic and oxidant

properties.
2. Iodide – negative ion (I-) of iodine
that is nontoxic
3. Iodophors – iodine complexed to a
carrier agent. These are less toxic, as
the release of the corrosive elemental
iodine is limited. Betadine® (povidone-
iodine) is a well-known iodophor.
Where is iodine commonly Contrast dye, Betadine® (povidone-io-

found in healthcare dine solution), expectorants, iodoform
settings? gauze, vaginal irrigants, Lugol’s solution
How much free iodine is In a bottle of 10% Betadine®, there will

available in a typical be ⬃1% free iodine.
Betadine® solution?
What clinical manifestations These are primarily related to corrosive

can be seen after an injury and can include vomiting,
ingestion of iodine? abdominal pain, diarrhea, and GI
bleeding. This can lead to hypovolemia,
shock, and edema of the pharynx and
glottis, possibly requiring intubation.
What other routes of 1. Topical exposure can cause corrosive

exposure are possible? injury to the eyes or skin. Repeated or
prolonged topical exposure can lead to
systemic absorption and toxicity.
2. Inhalation of iodine vapor can cause
bronchospasm and pulmonary edema.
How does chronic exposure Chronic exposures can cause hyperthy-

to iodine differ from acute roidism, hypothyroidism, or goiter forma-
toxicity? tion. Contact dermatitis and other hyper-
sensitivity reactions involving the salivary
glands and skin can be seen.
What laboratory findings are 1. Hyperchloremia – due to iodine’s

seen in iodine toxicity? interference with some chloride assays
2. Lactic acidosis
3. Elevated iodine levels – toxic levels
can range from 7,000–60,000 ␮g/dL
(normal iodine levels range from
5–8 ␮g/dL)
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4. Elevated thyroid function tests

(particularly in chronic exposures)
Describe the management 1. Supportive care for most cases of

of iodine toxicity from Betadine® ingestion
ingestion. 2. Significant volumes of ingestion may
require NG tube aspiration
3. The toxicity from iodine found in
Betadine® can be minimized by using
cornstarch, starchy food, milk, or
sodium thiosulfate to convert iodine to
iodide.
4. Endoscopy is indicated if corrosive GI
injury is suspected.
5. Hemodialysis is effective at removing
iodine although not indicated in those
with intact renal function.
6. Hypovolemia and shock may require
aggressive fluid resuscitation.
What color is the aspirate Blue-green

following a Betadine®
ingestion when mixed with
cornstarch?
ISOCYANATES
What are isocyanates? Liquid compounds that can volatilize

when exposed to air and are commonly
used in the production of polymers and
other chemicals including foams, paints,
fabrics, insulation, and pesticides.
What are usual routes of Inhalation and absorption (skin or

exposure to isocyanates? mucous membranes)
What is the approximate Usually immediate; however, symptoms

onset of action following an may be delayed up to 6 hrs.
acute exposure to
isocyanates?
What are symptoms of an Isocyanates are strong irritants causing

acute isocyanate exposure? ocular, dermal, and airway burning, as
well as dyspnea with cough and wheez-
ing. Patients may progress to acute lung
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injury and noncardiogenic pulmonary

edema.
Are there any long-term After chronic low-level exposures, patients

effects of isocyanate may develop reactive airway disease.
exposure? Following acute poisonings, patients may
develop pulmonary hypersensitivity and
chronic eye irritation.
What are the treatments Decontamination with copious irrigation

indicated for an inhalation for dermal and ocular exposure. Respira-
exposure? tory symptoms should be treated sympto-
matically with oxygen and nebulized beta
2-adrenergic agonists, as needed.
What is the mechanism of Not well established but likely through

isocyanate toxicity? direct irritation and involvement of cell-
mediated immunity pathways
Does cyanide poisoning No. Cyanide is not released through

result from isocyanates? breakdown or metabolism of isocyanates.
Which industrial disaster led The Union Carbide Plant disaster in

to over 2500 deaths Bhopal, India (1984)
following a community-wide
methyl isocyanate gas leak?
ISOPROPANOL
In what products is Rubbing alcohol (70% concentration),

isopropanol (isopropyl industrial solvents, window cleaners,
alcohol) found? antiseptic and disinfectant agents
Which is more intoxicating, Isopropanol is 2 to 3 times more

isopropanol or ethanol? intoxicating.
Why doesn’t isopropanol Isopropanol is a secondary alcohol that

cause an anion gap acidosis is oxidized to a ketone, and not acidic
like other toxic alcohols? metabolites.
What is the metabolite of Acetone

isopropanol?
Does isopropanol cause an Yes, both isopropanol and its metabolite,

elevated osmolar gap? acetone, increase the gap.
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What is the classic clinical 1. CNS depression

triad of isopropanol 2. Fruity breath odor
ingestion? 3. Ketosis without metabolic acidosis
What is a GI complication of Gastritis, possibly hemorrhagic in nature

isopropanol ingestion?
What are the signs and Inebriation, vomiting, abdominal pain,

symptoms of isopropanol respiratory depression, hypotension
ingestion?
Why is activated charcoal Because of the rapid absorption of

not useful for isopropanol isopropanol
ingestion?
How do you treat 1. Airway evaluation and management

isopropanol ingestions? 2. IV crystalloid for hypotension
3. Consider hemodialysis (rare)
When is hemodialysis In the setting of unresponsive hypoten-

indicated for isopropanol sion or continued clinical deterioration
toxicity?
METALDEHYDE
What is metaldehyde? A cyclic polymer of acetaldehyde
How is metaldehyde chiefly Primarily as a slug and snail poison but

used in the U.S.? may also be found in some camping fuels
What are the metabolites of Acetaldehyde and acetone

metaldehyde?
Describe the mechanism of Largely unknown; however, acetaldehyde

toxicity. appears to have some role.
What is the toxic dose? 100 mg/kg can result in convulsions;

⬎400 mg/kg can be fatal.
How will metaldehyde Within 3 hrs of ingestion, toxicity may

poisoning present? initially resemble a disulfiram reaction
(i.e., acetaldehyde toxicity) with flushing,
nausea, vomiting, and diarrhea. Larger
doses can result in ataxia, lethargy,
myoclonus, hyperthermia, and seizures.
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What metabolic Anion gap metabolic acidosis

derangements are found
with ingestion?
How should metaldehyde Supportive treatment. Ondansetron may

poisoning be treated? be used to alleviate nausea and vomiting.
Benzodiazepines are utilized for seizures
initially.
METHANOL
What are the common Windshield washer fluid, model airplane

sources of methanol? or racing fuel, solid camping or chafing
cooking fuel, automobile fuel line an-
tifreeze. In industry, methanol is com-
monly used as a solvent.
What are the routes of Ingestion is most common, but exposures

exposure to methanol? via inhalation (i.e., “huffing” and indus-
trial accidents) have been reported.
What are common signs of Similar to ethanol, methanol produces

acute methanol intoxication? inebriation. Signs and symptoms include
nystagmus, slurred speech, ataxia, and
altered metal status.
What clinical features are “Snowfield” vision or complete blindness

unique to methanol (may be the source of the adage “blind-
poisoning? drunk”). Optic disc hyperemia or pallor
may be observed along with central sco-
toma. Hypodense basal ganglion lesions
may be observed on neuroimaging.
Methanol is metabolized by Formaldehyde and formic acid

alcohol dehydrogenase and
aldehyde dehydrogenase to
what respective compounds?
What metabolic state is High anion gap metabolic acidosis with

expected from methanol minimal lactate elevation
poisoning?
Does methanol intoxication Yes. Methanol contributes to serum

produce an elevated osmolarity and is, therefore, expected to
osmolar gap? produce an elevated gap; however, due to
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variations in normal serum osmolarity, a

normal gap does not rule out toxicity.
How do you correct for Using the standard formula for a calcu-
concomitant ethanol lated serum osmolarity (Osmc), the
intoxication when blood concentration of ethanol (mg/dL)
calculating the osmolar gap? divided by 4.6 (molecular weight of
ethanol divided by 10 to correct for
units) must also be included to correctly
calculate the osmolar gap:
BUN glucose
Osmc ⫽ 2[Na⫹] ⫹ ⫹
2.8 18
ethanol
⫹
4.6
From the osmolar gap, how Multiplying the osmolar gap by 3.2
do you estimate the concen- (the molecular weight of methanol di-
tration of methanol in mg/dL vided by 10) will give a rough estimate.
of a suspected methanol-
intoxicated patient?
What are the “antidotes” for Fomepizole or ethanol administration

management of methanol
toxicity?
What enzyme is inhibited by Alcohol dehydrogenase

these medications?
At what ethanol level is the 100 mg/dL

metabolism of methanol by
alcohol dehydrogenase
completely blocked?
When should fomepizole or Therapy should continue until serum

ethanol be discontinued? concentrations are ⬍20 mg/dL.
Once alcohol dehydrogenase Methanol has little renal elimination and is

is inhibited, how are cleared primarily via respiratory vapor (T1/2
methanol and its metabolites ⫽ 30 ⫺ 54 hrs). Methanol and formic acid
eliminated? can be removed by hemodialysis.
What are the indications for Consensus opinion supports

hemodialysis in methanol hemodialysis if metabolic acidosis, end-
poisoning? organ toxicity, or renal failure is present.
A serum methanol level ⬎25 mg/dL or a
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high osmol gap are relative indications

for hemodialysis. The ultimate decision
should be based on physician judgment.
What cofactor can be added Folinic acid may speed the formation of
to aid in methanol nontoxic metabolites.
metabolism?
METHEMOGLOBINEMIA INDUCERS
How is methemoglobin Ferrous (Fe2⫹) iron in hemoglobin is

formed? oxidized to ferric (Fe3⫹) iron.
What is the normal 1%. Although RBCs are continuously

methemoglobin exposed to oxidizing agents, there are
concentration in blood? enzymes which reduce methemoglobin to
hemoglobin in order to prevent
methemoglobin accumulation.
What are these enzymes? 1. NADH methemoglobin reductase –

⬎95% of methemoglobin reduction
2. NADPH methemoglobin reductase –
⬍5% of methemoglobin reduction
What characteristics do They are oxidizing agents.

substances that cause
methemoglobinemia share?
What drugs classically cause 1. Antibiotics – trimethoprim,

methemoglobinemia? sulfonamides, dapsone
2. Local anesthetics – cetacaine,
benzocaine
3. Antimalarials – chloroquine,
primaquine
4. Phenazopyridine
5. Nitrites – amyl nitrite, sodium nitrite
6. Silver nitrate
7. Nitroglycerin
What substances cause Nitrates (well-water, prepackaged foods),

methemoglobinemia? aniline dyes, chlorates, bromates, nitric
and nitrous oxide
How does methemoglo- Methemoglobin does not bind oxygen

binemia decrease oxygen to the oxidized heme molecules. In
delivery? addition, methemoglobin will shift the
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oxyhemoglobin dissociation curve to the

left, making the remaining normal heme
molecules less likely to release oxygen.
Why is pulse oximetry Methemoglobin interferes with absorp-

unreliable in patients with tion of light by the oximeter probe, caus-
methemoglobinemia? ing it to be inaccurate. Oxygen saturation
readings on pulse oximetry will not drop
below ⬃85% even with methemoglobin
elevations ⬎70%.
What device measures A co-oximeter, which directly determines

oxygen saturation in methemoglobin levels
the presence of
methemoglobinemia?
What signs and Although individual variations may be

symptoms occur with significant, the following is a guide:
methemoglobinemia?
\ Level 10%–15% – cyanosis may become
evident and is unresponsive to supple-
mental oxygen, symptoms are only minor
if present
Level 20% – exertional dyspnea, fatigue,
headache, dizziness, tachycardia
Level ⬎45% – confusion, metabolic
acidosis, lethargy, seizures, coma
Level near 70% – potentially fatal
What simple bedside 1. Bubble 100% oxygen through a tube

tests can detect with patient’s blood – if it remains
methemoglobinemia? dark, methemoglobin may be
present.
2. Blow supplemental oxygen onto filter
paper with a few drops of patient’s
blood – if it does not change color,
methemoglobin may be present.
What is the first-line Methylene blue

antidote for
methemoglobinemia?
How does methylene Acts as an electron transfer intermediate

blue work? for NADPH methemoglobin reductase.
This greatly increases its activity.
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Which precautions should 1. Do not administer to patients with

be considered when known G6PD deficiency. G6PD-
administering deficient patients have low NADPH
methylene blue? concentrations and, therefore,
methylene blue will be ineffective.
2. Methylene blue, itself, can induce
methemoglobinemia in excessive
doses (⬎5 mg/kg) and can result in
subsequent hemolysis.
What are alternative treat- Hyperbaric oxygen and exchange

ments for patients unre- transfusion
sponsive to methylene blue?
Does a patient need to No. Infants ⬍4 months old have reduced

be exposed to a NADH methemoglobin reductase activity
xenobiotic to develop and can develop methemoglobinemia
methemoglobinemia? secondary to a variety of insults, including
diarrheal illness, dehydration, acidosis, and
small amounts of oxidizing agents.
METHYL BROMIDE
What is methyl bromide? An extremely toxic fumigant gas used in

pest control, as a soil sterilant, and as a
chemical reagent. Secondary to its poten-
tial environmental and human toxicity, its
use is being phased out.
What is the cellular Not fully understood, but appears to

mechanism of toxicity of alkylate DNA and proteins → cell death
methyl bromide?
What are the two most Inhalation and dermal

common routes of exposure
to methyl bromide?
What property of methyl It is denser than air and, therefore,

bromide makes humans collects in low-lying areas. It may also
susceptible to exposure? collect in and around clothing,
predisposing to dermal absorption.
Why is a warning indicator It lacks irritative properties, so lethal

added to methyl bromide exposures can occur without warning.
preparations?
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What substance is added to Chloropicrin, a lacrimator

methyl bromide to serve as
a “warning” indicator?
Describe the effects of May result in localized skin irritation and

dermal exposure. breakdown. Erythema, dermatitis, and
vesiculation have been reported in areas
of contact. Systemic effects may manifest
after dermal exposure.
What are the effects of Airway irritation, cough, and dyspnea may
acute methyl bromide occur upon exposure. Initially, the irrita-
inhalation? tive symptoms are attributed to the
chloropicrin. Primary pulmonary manifes-
tations of methyl bromide include pneu-
monitis, acute lung injury, and possibly
pulmonary hemorrhage. Systemic effects
also are common following inhalation.
What are acute systemic Systemic effects usually manifest as

effects of methyl bromide nausea, vomiting, headache, confusion,
toxicity? CNS depression, tremor, and ataxia.
Severe poisoning may result in seizures
and coma.
What chronic effects may be Chronic effects may emerge from both
seen with methyl bromide chronic low-level exposure and as seque-
exposure? lae of acute poisoning. Patients may pres-
ent with neuropathy, ataxia, dementia, vi-
sual disturbances, personality changes, or
seizures. Unfortunately, these symptoms
are long-lasting and often irreversible.
Are any laboratory tests No specific labs are helpful. Bromide

useful for evaluation? levels are difficult to obtain and are very
nonspecific. Recommended testing
would include general labs to evaluate
organ system function and to rule out
other items on the differential diagnosis.
Describe the treatment of Decontamination is important, as methyl

methyl bromide poisoning. bromide can accumulate in clothing and
poses a further risk to the patient and
caregivers. Treatment is otherwise
supportive.
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METHYLENE CHLORIDE
What is another name for Dichloromethane

methylene chloride?
What is its major use? Primarily used as a solvent for chemical

reactions. It is also used as an aerosol
propellant, degreaser, and paint stripper.
What metabolite of Carbon monoxide. Hepatic biotransfor-

methylene chloride may mation of methylene chloride occurs via
contribute to systemic two pathways:
toxicity? 1. Mixed function oxidase system of
cytochrome P450 yields conversion to
CO (primary route)
2. Cytosolic transformation (glutathione
transferase-dependent) during which
formaldehyde and formic acid
intermediates are produced (low-
affinity, high-capacity route).
What is the mechanism of Dissolves fats, destroying epithelial cells.

toxicity of methylene It also causes CNS depression and may
chloride? sensitize the myocardium to endogenous
catecholamines.
What are the modes of toxic- Inhalation, ingestion, dermal

ity for methylene chloride?
What are the clinical Nausea, vomiting, dysrhythmias, CNS de-

manifestations of an acute pression, seizures, pulmonary congestion,
methylene chloride hypotension, respiratory arrest
exposure by inhalation?
What are manifestations of Corrosive burns to GI mucosa, nausea,

ingested methylene vomiting, CNS depression, dysrhythmias,
chloride? renal and liver impairment, pancreatitis
What labs should be used to Serial carboxyhemoglobin concentrations

monitor patients who have with co-oximetry, CBC, lipase, elec-
ingested methylene chloride? trolytes, liver and kidney function tests
What methods are available NG tube aspiration, if patient presents

to decrease absorption of promptly after ingestion
ingested methylene chloride?
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Are methods available to No

increase elimination of
methylene chloride?
What emergency treatments 1. Remove patient from exposure.

should be provided to 2. Administer 100% oxygen.
exposed patients? 3. Airway management and cardiac
monitoring for dysrhythmias
4. Treat seizures with benzodiazepines.
How is an increased 100% oxygen is the treatment of choice

carboxyhemoglobin
concentration treated?
How is an acute lung injury Initially, 100% oxygen is used. Bron-

from methylene chloride chodilators are used for respiratory
treated? distress symptoms (e.g., wheezing).
Aggressive airway management may
be necessary.
How is a dermal exposure Removal of all clothing and copious irri-

treated? gation of the skin with water
MOTHBALLS
What two chemicals are 1. Naphthalene (now rarely used)

used to create mothballs? 2. Paradichlorobenzene
Which of these chemicals is Naphthalene. Paradichlorobenzene rarely

more hazardous? causes toxicity.
What essential oil was for- Camphor

merly used in mothballs but
has since been abandoned
due to its high toxicity?
How do mothballs function? Sublimation to a gas that is toxic to moths

(and humans at high levels)
What physical effects indi- Eye/nose/throat irritation, headache,

cate excessive inhalation? confusion
What are clinical Initial acute symptoms are primarily GI.

manifestations of In larger ingestions, lethargy and seizures
naphthalene ingestion? may occur. Delayed methemoglobinemia
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and hemolysis can occur after even a sin-

gle mothball is ingested.
Describe the mechanism of Metabolites of naphthalene are potent oxi-

hemolysis and dizers. Oxidation of ferrous iron hemoglo-
methemoglobinemia. bin produces methemoglobin. Patients
with G6PD deficiency are at increased
risk for oxidative stress.
What laboratory tests are Hemoglobin level, lactate dehydrogenase,

useful for mothball indirect bilirubin, and peripheral blood
exposure? smear may help diagnose hemolysis.
Methemoglobin levels may be obtained
from co-oximetry.
What are the effects of Paradichlorobenzene is primarily

paradichlorobenzene nontoxic. Mucous membrane irritation
toxicity? may occur, as hydrochloric acid is
produced when paradichlorobenzene
decomposes.
What treatments are of 1. IV hydration or transfusion if

benefit in acute mothball hemolysis occurs
ingestion? 2. Methylene blue for symptomatic
methemoglobinemia; use caution
when administering to G6PD-
deficient patients
Is activated charcoal effec- Effective for naphthalene, unnecessary

tive in acute ingestion? for paradichlorobenzene
Which type of mothball Camphor

floats in fresh water?
Which type of mothball has Paradichlorobenzene

a green flame when burned?
What foods should be Milk and foods high in fats/oils due to

avoided following mothball enhancement of absorption
ingestion?
NITRITES
How are nitrites commonly 1. Ethyl, amyl, and butyl nitrites are
used? used as air fresheners and can be
abused as inhalants.
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2. Sodium and amyl nitrites are used as

cyanide antidotes.
3. Nitrites are also used in the curing
and preservation of foods.
What are the physiological Vasodilation and methemoglobinemia, re-

effects of nitrites? sulting in functional anemia and hypoxia
How do nitrites cause Nitrites oxidize ferrous (Fe2⫹) iron to

methemoglobinemia? ferric (Fe3⫹) iron in heme. This results in
the inability of that heme molecule to
bind oxygen appropriately.
How do overdoses of nitrites Flushing, headache, hypotension, tachy-

present? cardia, cyanosis
What tests can diagnose A nitrite dipstick can be used to detect

nitrite overdose? nitrites in serum. ABG with co-oximetry
will detect methemoglobinemia.
What treatments should be 1. Supportive care

used for nitrite toxicity? 2. Methylene blue to treat symptomatic
methemoglobinemia; use caution in
patients with G6PD deficiency
3. Fluids and vasopressors may be
needed for hypotension.
NITROGEN OXIDES
What are nitrogen oxides? Various oxidized species of nitrogen. The

most common forms are nitric oxide
(NO); nitrogen dioxide (NO2); and
nitrous oxide (N2O).
What role does NO play in NO serves as one of the few gaseous

the body? signaling molecules, acting on the
endothelium to produce vasodilation.
From what sources might Environmental air pollution, smoke from

someone be exposed to structure fires, gasoline and propane en-
nitrogen oxides? gine exhaust, welding fumes, fermenting
grain fumes
What is “silo filler’s” Delayed-onset pulmonary toxicity experi-

disease? enced by farm workers who, upon en-
trance into a poorly ventilated silo, are
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exposed to high concentrations of nitro-

gen dioxide produced by fermenting
grain. Symptoms are characterized by
dyspnea, cough, and hypoxia with possi-
ble wheezes and rales on exam.
Describe the mechanism of On contact with respiratory tract mucosa,

nitrogen oxide toxicity. nitrogen oxides react to form nitrous and
nitric acids, along with other reactive ni-
trogen species. These products cause
both caustic injury and oxidative stress to
the pulmonary mucosa.
What are the medical and 1. Treatment of pulmonary hypertension

industrial uses of nitrogen by selective dilation of pulmonary
oxides? vasculature
2. Treatment of neonatal respiratory
distress syndrome
3. Manufacture of related chemicals
(i.e., nitric acid, nitrosyl halides) and
bleaching of rayon
What acute findings can be Airway irritation and bronchospasm,

caused by nitrogen oxide causing dyspnea and hypoxia. Patients
poisoning? may develop noncardiogenic pulmonary
edema, and methemoglobinemia may
occur (rarely).
What chronic pulmonary Pulmonary fibrosis and brochiolitis

conditions may develop after obliterans
nitrogen oxide exposure?
What happens to NO in the Quickly reacts with hemoglobin to form

bloodstream? nitrosylhemoglobin, which is subse-
quently oxidized to methemoglobin
Are there any tests No. The most likely indicator would be a
recommended to detect history of exposure. Pulse oximetry, CXR,
nitrogen oxide poisoning? and pulmonary function tests are indi-
cated, as is ABG with co-oximetry to as-
sess concomitant methemoglobinemia.
What treatments should 1. Airway monitoring with intubation/

be performed in the ventilatory assistance, as necessary
event of nitrogen oxide
poisoning?
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2. Humidified oxygen and inhaled beta 2-

adrenergic agonists for bronchospasm
3. Corticosteroids have no role in acute
treatment.
4. Copious irrigation of mucous mem-
branes and eyes with water or saline,
if exposed
5. Methylene blue for symptomatic
methemoglobinemia
Name some common sources Surgical anesthesia, compressed gas con-

of N2O. tainers (e.g., whipped cream, cooking
spray), automotive nitrous systems
What is a “whipit”? A prepackaged cartridge filled with N2O,

which is inhaled by an abuser for its
euphoric effects
What CNS receptor does It is a rapidly acting NMDA receptor

N2O target? antagonist.
What is the most common Asphyxia (inadequate O2 supplied

cause of death from acute with N2O)
N2O exposure?
What are the common Confusion, dizziness, euphoria, CNS

clinical manifestations of depression, syncope. Acute toxicity is
acute toxicity? commonly related to asphyxia.
What essential vitamin is Vitamin B12 (required for normal DNA

inactivated by chronic and myelin synthesis)
exposure?
List the clinical manifes- Bone marrow suppression (i.e., mega-

tations of chronic N2O loblastic anemia, thrombocytopenia,
toxicity. leukopenia) and peripheral neuropathy
What studies are helpful in CBC, vitamin B12 and folic acid levels,
suspected N2O toxicity? nerve conduction study, homocysteine
and methylmalonic acid levels
How might a chronic N2O Manifestations of vitamin B12 deficiency

abuser be identified? (e.g., anemia and peripheral neuropathy)
with elevated homocysteine and methyl-
malonic acid levels but normal vitamin
B12 and folate levels.
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What treatments are avail- Supportive care with attention to airway

able for managing acute management
toxicity?
How is chronic N2O toxicity Effects typically reverse 2–3 months

treated? after discontinuing exposure. Bone mar-
row suppression may be treated with
folinic acid.
NONTOXIC AND MINIMALLY TOXIC HOUSEHOLD

PRODUCTS
Are there any nontoxic No. Any substance can be toxic given a
substances? large enough exposure. It is the job of the
healthcare provider to determine if an ex-
posure has a minimal risk of causing harm.
What information must be 1. Accurate identification of the product,

available before determining with complete ingredients from the
an ingestion to be minimally package label or other current
toxic? reference
2. A reasonable estimate of the maximum
amount ingested
3. Description of the symptoms being
experienced
4. Whether an ingestion of the suspected
substance in the amount ingested has
been reported to cause any significant
adverse effects
What are some pitfalls that 1. Brand name products can have several
must be avoided when formulations, and older versions may
evaluating risk of toxicity of have more toxic ingredients.
a household product? 2. Some products can pose a choking risk
even though there is minimal systemic
toxicity (e.g., silica gel packs).
3. There are many “sound-alike”
products – obtain the exact spelling of
the product.
4. It is possible that toxic substances
have been stored in containers meant
for another benign substance.
5. Failure to determine if there has been
chronic exposure to the substance
6. Not considering the possibility of
co-ingestions
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7. Not inquiring about underlying

medical issues
Why is it important to Household products tend to have low con-

accurately determine centrations of their toxic components. For
whether a product, such as example, household bleach contains ⬍5%
bleach, is meant for sodium hypochlorite, and household am-
household use or obtained monia has 3% to 10% ammonia hydroxide
from an industrial setting? and will usually not cause significant cor-
rosive damage unless large quantities are
ingested. In contrast, industrial strength
products are often significantly more con-
centrated and may cause serious injury.
Hair straighteners contain Sodium hydroxide (1%–3%)

what highly caustic
chemical?
Ingestion of household Significant caustic injury and potentially

hydrogen peroxide dilutions life-threatening systemic oxygen emboli
(⬍9%) is usually nontoxic;
however, commercial-
strength hydrogen peroxide
is readily available. What
complications can its
ingestion cause?
Long-term ingestion of 1 g Hypokalemia

of licorice can result in what
electrolyte disturbance?
By what mechanism does Exhibits mineralocorticoid activity through

the glycyrrhizic acid in its inhibition of 11-beta-hydroxysteroid
licorice work? dehydrogenase, which normally inactivates
cortisol
OXALIC ACID
What are the forms of Solution and salts

oxalic acid?
For what is oxalic acid used? Bleaches, metal and wood cleaners, rust
removers, leather tanning
Name some plants that Sorrel, unripe star fruit, rhubarb leaves
contain soluble oxalic acid.
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What are the modes of Inhalation, ingestion, cutaneous, ocular

exposure?
Describe the symptoms of Primarily irritation and burning; how-

cutaneous or ocular ever, corrosive injury may occur in large
exposure. exposures.
What are the concerns with 1. Airway irritation and burns

large inhalational 2. Chemical pneumonitis
exposures? 3. Pulmonary edema
What are some symptoms of Initially, muscular weakness and tetany

systemic oxalic acid toxicity? followed by possible cardiac dysrhythmias
or seizures. Renal failure, focal neuro-
logic deficits, or paralysis may result sec-
ondary to deposition of calcium oxalate
crystals.
What is the mechanism of Oxalic acid binds divalent metals, pre-

systemic oxalic acid toxicity? dominantly calcium. In the body, cal-
cium oxalate crystals are formed and may
precipitate in tissue and in the vascula-
ture (most often the kidneys, brain, and
spinal cord).
Describe ECG findings that Hypocalcemia may result in QT

may be present following prolongation.
oxalic acid ingestion.
What laboratory tests are Electrolyte and magnesium levels to eval-

helpful after oxalic acid uate for hypocalcemia and hypomagne-
exposure? semia. BUN and creatine to evaluate
renal function. Urinalysis may show large
amounts of calcium oxalate crystals.
What is the treatment for 1. Oral calcium salts (i.e., calcium chlo-
systemic ingestion? ride, calcium gluconate, or calcium
carbonate) may bind oxalic acid in the
stomach and prevent absorption.
2. IV calcium solutions should be used to
treat systemic hypocalcemia.
3. Aggressive hydration is warranted to
avoid formation of calcium oxalate
crystals in the renal tubules.
4. Monitor for dysrhythmias and
seizures.
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PENTACHLOROPHENOL AND DINITROPHENOL
What are the uses of Historically, pentachlorophenol (PCP) has

pentachlorophenol? been used widely in insecticides, fungi-
cides, and herbicides; however, PCP is no
longer publicly available and is restricted
to use as a wood preservative for utility
poles, railroad ties, and wharf pilings.
What are the uses of Dinitrophenol (DNP) has been used as a

dinitrophenol? pesticide, herbicide, and fungicide, as
well as in the manufacture of certain
types of dyes, explosives, and
photograph-developing chemicals.
What illegal (in the U.S.) Use as a weight loss supplement

and dangerous use of DNP
has made it more readily
available to consumers?
What is the mechanism of Disruption of cellular respiration by un-

toxicity of PCP and DNP? coupling oxidative phosphorylation, re-
sulting in decreased ATP production and
generation of excess heat. DNP also oxi-
dizes hemoglobin to methemoglobin.
Are PCP and DNP Based upon animal studies, the Environ-
carcinogenic? mental Protection Agency (EPA) has
classified PCP as a probable human car-
cinogen, although human studies have
not confirmed this claim. Minimal animal
studies exist to support DNP as a car-
cinogen, so the EPA has not classified
DNP as a potential carcinogen.
What are the major routes Inhalation, ingestion, dermal

of exposure to
pentachlorophenol and
dinitrophenol?
How does acute PCP or Nausea, vomiting, headache, and

DNP overdose present? lethargy, progressing to hyperthermia,
seizures, and CV collapse. In addition,
DNP may cause methemoglobinemia,
hepatomegaly, liver failure, kidney fail-
ure, and yellowish skin discolorations.
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How does chronic PCP and Profuse sweating, fever, tachycardia,

DNP toxicity present? and tachypnea are hallmarks of both
acute and chronic exposure. In addition,
chronic exposure may result in weight
loss, flu-like symptoms, and in rare
instances, damage to bone marrow.
Chronic DNP exposure is also associated
with lens changes, including glaucoma
and cataracts.
What metabolic abnormality High anion gap metabolic acidosis

is expected after PCP and
DNP toxicity?
How is the diagnosis of PCP Positive diagnosis is made based on a

or DNP overdose made? history of exposure and consistent clinical
findings. PCP or DNP exposure should be
considered in the presence of an
unexplained uncoupling syndrome
(e.g., tachycardia, tachypnea, hyperther-
mia, high anion gap metabolic acidosis).
Blood levels are not easily obtained and
are not indicative of the severity of PCP or
DNP poisoning; therefore, they should not
be used in diagnosis or management.
What treatments should be 1. Supportive care

performed in the event of 2. Aggressive cooling (both external and
PCP or DNP overdose? internal) may be needed to address
extreme hyperthermia secondary to
the uncoupling process.
3. IV fluid replacement as appropriate to
prevent dehydration and circulatory
collapse
PERCHLOROETHYLENE
What is another name for Tetrachloroethylene, PCE, Perc

perchloroethylene?
What is its major use? Primarily used in industry as a solvent, a

dry cleaning chemical, and a degreaser
How is perchloroethylene Hepatically metabolized, then renally

eliminated? excreted
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What is the mechanism Like other chlorinated hydrocarbons, per-

of toxicity of chloroethylene acts as an anesthetic. The
perchloroethylene? resulting CNS and respiratory depression
may quickly lead to death. There is very
high CNS penetration. Also, perchloroeth-
ylene potentiates the pro-arrhythmic prop-
erties of catecholamines.
What metabolite may Trichloroethanol – a similar metabolite of

contribute to its CNS chloral hydrate
depressant effect?
What are the modes Inhalation, ingestion, dermal

of toxicity for
perchloroethylene?
What are the potential Airway irritation, headache, dizziness,

clinical manifestations of an nausea, vomiting, CNS depression, car-
acute perchloroethylene diac dysrhythmias, elevated liver enzymes
exposure by inhalation?
What are possible mani- Nausea, vomiting, diarrhea, abdominal

festations of ingested pain, hepatotoxicity, CNS depression,
perchloroethylene? cardiac dysrhythmias
What labs should be used to LFTs and RFTs, ABG, ECG, CXR
monitor perchloroethylene
patients?
What are the effects of Perchloroethylene is listed as a probable

chronic exposure? carcinogen in humans (IARC Group 2A)
and is a known carcinogen in animals. It
also may result in hepatotoxicity.
Where are the predominant The air and ground water near industrial
environmental sources of and waste sites
perchloroethylene?
Are methods available to One study found increased elimination of

increase elimination of ingested perchloroethylene via hyperven-
perchloroethylene? tilation.
What methods are available Placement of an NG tube to suction if

to decrease absorption of the patient presents promptly after
ingested perchloroethylene? ingestion of liquid
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What emergency treatments 1. Administer 100% oxygen, and aggres-

should be provided to sively manage the airway, especially
exposed patients? for those with aspiration pneumonia
2. Intubation may be required for those
with inhalational exposures showing
respiratory depression.
3. Mechanical ventilation for pulmonary
edema
4. Cardiac monitoring for dysrhythmias
How is a dermal exposure Remove all clothing, and irrigate the skin
treated? with copious amounts of water.
PHENOL
What is phenol? Phenol (carbolic acid) is a caustic agent

with potent antiseptic properties.
How can phenol be Appears as a transparent, light pink liquid

identified? with a characteristic aromatic odor
In what other compounds 1. Cigarette smoke

can phenol be found? 2. Disinfectants
3. Oral/throat hygiene and anesthetic
products in the form of lozenges,
throat sprays, and mouthwashes
4. Pharmaceutical preservatives in some
analgesic compounds, vaccines, and
antivenom preparations
5. Skin products, such as lotions and nail
cauterizers
6. Solvents
7. Wood preservatives
Can phenol still be found as Yes, but it is now uncommon. In histori-

a preservative associated cal preparations, glucagon was commonly
with glucagon? paired with a diluent preserved with phe-
nol that was used in the reconstitution of
glucagon powder. The concentration was
only toxic to patients who were receiving
multiple large dosages of glucagon, as oc-
curs in the treatment of beta-adrenergic
and calcium channel blocker overdoses.
What is phenol’s mechanism Rapid protein denaturation, cell wall

of toxicity? disruption, and coagulation necrosis
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What are the pharmacoki- 1. Absorption – lipid-soluble, rapidly

netics of phenol? absorbed through all routes
2. Distribution – VD is very large
(actual value is unknown)
3. Elimination – renal, half-life is
0.5–5 hrs
4. Lethal dose – ⬎1 g in adults. If a high
concentration is used, death can occur
within minutes.
What is ochronosis? A discoloration of collagenous tissue

following prolonged dermal exposure
to phenol
In dark-skinned individuals, Depigmentation

what unsightly condition
may occur following
prolonged dermal exposure
to phenol?
What are the typical 1. Inhalation – coughing, stridor, distinct

patterns of clinical effects aromatic odor to breath, chemical
following inhalational and pneumonia, respiratory arrest
GI exposure? 2. Ingestion – abdominal pain caused by
corrosive burns, nausea, vomiting,
diarrhea, hematemesis, hematochezia
3. Both routes of exposure may progress
to systemic toxicity characterized by
AMS, hypotension, dysrhythmias,
seizures, and death.
How does “phenol Anorexia, brown urine, headache,

marasmus,” or chronic myalgias, salivation, vertigo, weight loss
phenol toxicity present?
Is there a specific antidote No

available to reverse phenol
toxicity?
What dermal Flushing with copious amounts of

decontamination procedures water is controversial. Studies have
are beneficial? demonstrated that water irrigation may
enhance the absorption of phenol
through the skin by enlarging the
surface contact of phenol with the skin;
however, water is typically the only
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irrigant available. As a result, the follow-

ing is recommended: immediately re-
move all contaminated clothing, irrigate
with copious amounts of water, and (if
available) swab with a 50% solution of
polyethylene glycol (PEG-300 or
PEG-400).
Should endoscopy be Yes, in patients with GI symptoms

included in the patient’s following oral ingestion
treatment regimen?
PHOSPHINE AND PHOSPHIDES
What is the difference Phosphine is a poisonous gas. The solid

between phosphine and phosphide releases phosphine when ex-
phosphide? posed to moisture (including gastric acid).
What different types of 1. Calcium phosphide – used in welding

phosphide exist? and in flares
2. Zinc phosphide – used as a rodenticide
3. Indium phosphide – used in
semiconductor manufacturing
4. Aluminum phosphide – used in food
and grain fumigation (potent inhibitor
of Aspergillus species)
What smell is associated Odor is similar to decaying fish.

with phosphine gas?
Describe how these agents Solid phosphide pellets (zinc phosphide)

are used as rodenticides. are placed in likely rodent locations
(i.e., “mole holes”). Contact with mois-
ture or ingestion produces toxic phos-
phine gas.
What is the mechanism of Phosphine is a metabolic poison, blocking

phosphine toxicity? electron transport.
What are the symptoms of Dyspnea, hyperpnea, cough, dizziness,

phosphine gas toxicity? headache, vomiting, pulmonary edema,
acute lung injury
What are the symptoms of Ingestion will more likely lead to sys-
phosphide ingestion? temic symptoms. Nausea, vomiting, and
diarrhea may initially occur. Symptoms of
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phosphine gas toxicity occur subsequently

due to secondary inhalation. Progression
to seizures and multi-organ system failure
may occur.
How is phosphine toxicity Based on clinical history and associated

diagnosed? symptoms. No blood level available.
Is there a risk to healthcare Yes. Bystander toxicity may result due

staff when caring for a to off-gassing from gastric contents.
patient who has ingested a Use caution!
phosphide?
PHOSPHORUS
What are the allotropes of 1. White phosphorus, also known as

elemental phosphorus? yellow phosphorus
2. Red phosphorus
3. Black phosphorus
Which allotrope is the White phosphorus

most toxic and is also
combustible?
What is the ignition 30°C (86°F) in moist air. It may, there-

temperature of white fore, spontaneously combust in varying
phosphorus? atmospheric conditions.
What is the byproduct of Phosphoric acid. This may result in pul-

white phosphorus oxidation monary symptoms along with ocular and
(combustion)? dermal irritation.
What is the toxic oral dose? Fatal oral dose for white phosphorus is
⬃1 mg/kg
In what products is Fireworks/pyrotechnics, military ammu-

phosphorus used? nition, production of methamphetamine,
organophosphorus compounds, match
pads, fertilizer
What are the potential Inhalation, dermal, ocular, ingestion

routes of exposure?
What is the cellular White phosphorus is a metabolic poison,

mechanism of white disrupting electron transport.
phosphorus toxicity?
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Describe the toxicity of White phosphorus can cause both chemi-

dermal exposure. cal and thermal burns.
What are the effects of Mucosal injury with nausea, vomiting, and
acute oral phosphorus diarrhea may be followed by a quiescent
toxicity? phase progressing to renal, hepatic, and
cardiac toxicity.
Chronic inhalational Mandibular necrosis, also known as

exposure of white “phossy jaw”
phosphorus may lead to
what complication?
What methods can be used History of exposure. Hypocalcemia may

to detect phosphorus occur, and phosphorus levels are variable
exposure? and of limited utility. Spontaneous com-
bustion of phosphorus in emesis or stools
may result in a “smoking” appearance.
Describe the treatment of Solid phosphorus on clothing or skin

phosphorus toxicity. should be covered in water to prevent
combustion. Ocular contamination should
be treated with irrigation. Supportive care
is the mainstay of treatment.
PHTHALATES
What are phthalates? Dialkyl or alkyl aryl esters of 1,2-

dibenzenecarboxylic (phthalic) acid that
are used in industry as “plasticizers” to
make vinyl compounds more pliable
Where are phthalates Cosmetics; plastic wrap; food packaging;

commonly found? medical devices (e.g., blood bags, PVC
tubing, disposable syringes); building ma-
terials; industrial materials (e.g., rocket
fuel, agricultural fungicides, solvents)
How does phthalate expo- Leaching from the parent material (e.g.,
sure commonly occur? PVC tubing)
What are the 4 primary 1. Inhalation – off-gassing of PVC

routes of exposure causing flooring, leaching from intubation
phthalate toxicity? tubing, occupational exposure
2. Ingestion – food packaging/wrap,
water supplies, children’s plastic toys
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3. Dermal – clothing, personal care and

beauty products, occupational exposure
4. Injection
How do acute phthalate Acute toxicity of phthalates is generally

toxicities typically present? low. Early symptoms are route-dependent
and include bronchitis, airway irritation,
pulmonary dysfunction, dermatitis, and
possible hepatitis. In severe poisonings,
late symptoms can include stupor, convul-
sions, and coma for those phthalates that
cross the blood-brain barrier.
What is the principle Dilution (specific to route of exposure)

treatment for acute and removal from the source
phthalate toxicities?
Are phthalates water Low molecular weight phthalates are water

soluble? soluble; however, the hydrophobicity of
high molecular weight phthalates causes
them to partition into lipids (e.g., adipose
tissue) with limited water solubility.
What is the most common Di(2-ethylhexyl)phthalate (DEHP)

phthalate to which people
are exposed?
Which known DEHP Mono(2-ethylhexyl)phthalate (MEHP)

metabolite is thought to be
responsible for DEHP’s
toxicity?
What are the concerns of While data is limited, there are concerns
chronic phthalate poisoning? over hepatocarcinogenicity, testicular le-
sions and atrophy, infertility (in both gen-
ders), teratogenicity, and thyroid toxicity.
POLYCHLORINATED BIPHENYLS (PCBS)
What are polychlorinated Synthetic chlorinated organic compounds

biphenyls (PCBs), and where previously used for insulating electrical
might they be encountered? equipment and as components of inks,
lubricants, and hydraulic fluid. Their pro-
duction and use has been banned in the
U.S. since the 1970s due to environmen-
tal and carcinogenic concerns.
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How does the oxidation and Oxidized PCBs and those with more
chlorination state of these chlorine are more toxic.
compounds affect their
toxicity?
What are the modes of toxic Secondary to their marked lipophilic na-
exposure to PCBs? ture, PCBs may be absorbed by ingestion,
dermal exposure, or by inhalation. They
subsequently bioaccumulate in fat stores
following repetitive exposure.
What are the clinical Acute toxicity predominantly results in ir-

effects seen with toxic ritation of eyes, skin, and throat. Chronic
exposure to PCBs? toxicity is more problematic secondary to
teratogenic effects. Exposure may result
in elevated hepatic enzymes, chloracne,
and increased risk or carcinoma (IARC
Group 2A). Maternal exposure may also
result in fetal developmental
abnormalities.
Are there any specific tests No. Diagnosis relies principally on his-
helpful for diagnosis? tory but may be supported by the pres-
ence of chloracne in association with oth-
erwise unexplained elevated liver
enzymes.
Is there a specific antidote No specific antidotes exist. Management

available in the treatment of is supportive.
PCB toxicity?
What substance, designed as Olestra®

a fat substitute, can
potentially increase the fecal
excretion of PCBs?
RADIATION (IONIZING)
What is radiation? Radiation is the transfer of energy in the

form of particles or waves. It is also
known as electromagnetic radiation
(EMR), a self-propagating wave in space
with electric and magnetic components.
EMR can be classified into types accord-
ing to the energy of the wave.
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What are the classifications Radio waves, microwaves, infrared radi-

of EMR in order of ation, visible light, ultraviolet radiation,
increasing energy? x-rays, gamma rays, cosmic rays
What is ionizing radiation? Ionizing radiation is a particle or wave

containing enough energy (⬎30 eV) to
remove an electron from the outer shell
of an atom. It is released from an unsta-
ble atom that has an unequal number of
electrons and protons, causing too much
energy in the nucleus. This unstable
atom releases excess energy in the form
of radiation in order to achieve stability.
What are sources of ionizing 1. Alpha-particles, containing 2 protons

radiation? and 2 neutrons each. They travel
only a few cm in air and are stopped
by a thin film of water, paper, and
the cornified epithelial layer of the
skin.
2. Beta-particles are electrons that travel
approximately 20 cm in air. They can
penetrate the cornea and lens of the
eye and several centimeters into
the skin.
3. Gamma/x-rays can travel great
distances in air and are highly
energetic, removing electrons form
their orbits. They can easily penetrate
deep tissue to cause both acute and
chronic organ injury. They can only be
stopped by many feet of concrete or
dense metals such as lead.
4. Neutrons are particles with no charge,
and they do not occur during natural
nuclear reactions. They are produced
during nuclear fission and by
radiotherapy beams. They can cause
damage from direct collision with
other atoms and also by causing
previously stable atoms to be
radioactive. Highly penetrating and
difficult to stop, the combination of
water, paraffin, and oil must be used
to shield them.
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Are alpha- and beta- No. They can be incorporated into the
particles of no concern body after being ingested, inhaled, or
because they are stopped so absorbed through wounds. They can
easily externally? then transmit a great amount of energy
over short distances throughout the
body.
What is radioactivity? A term used to describe the spontaneous

decay or disintegration of an unstable
atom. Different radioactive materials
decay, or lose their strength, over
different periods and are measured
in half-lives (T1/2).
How is radiation measured? The two fundamental units are the Curie
(Ci) and Becquerel (Bq). They reflect the
number of disintegrations of the nuclei
per second.
How is a radiation dose The Roentgen (R) is a measure of the

measured? ionization of air caused by ionizing radia-
tion and cannot be used to describe dose
to tissue. When radiation interacts with
tissue energy, it is deposited, and the tra-
ditional unit is the Radiation Absorbed
Dose (rad). The SI unit for dose is
termed the gray (Gy), with a conversion
of 100 rad ⫽ 1 Gy. Since the degree of
energy transferred to tissue can vary by
type of radiation (alpha imparting more
energy than beta internally), the effective
dose or extent of damage done to that tis-
sue also varies. The Roetgen Equivalent
Man (rem) is the unit of effective dose
actually absorbed, taking biological ef-
fects into account. The rem and rad are
related by the formula:
rem ⫽ [rad][Quality Factor]
The SI unit for rem is the Sievert (Sv),
with a conversion of 100 rem ⫽ 1 Sv.
Do all tissues respond the No. Equal absorbed doses from different
same to equal doses of kinds of radiation do not necessarily pro-
radiation? duce the same biological effect.
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What are the most radiosen- Cells with a high turnover rate – lympho-
sitive mammalian tissues? cytes, spermatagonia, hematopoietic tis-
sues, gastrointestinal epithelial cells
What are the most radiore- CNS, muscle, bone

sistant mammalian tissues?
What damage does ionizing Two theories exist to explain the manner
radiation cause to biological in which radiation causes damage to a cell:
systems? 1. Indirect – the radiation transfers its
energy to a nonbiologic molecule such
as water, converting the water
molecule to a free radical. This highly
reactive molecule then causes damage
to biologic molecules. Indirect effects
are believed to be more common with
most types of radiation.
2. Direct – the radiation transfers its
energy directly to a biologic molecule,
causing damage without an
intermediate.
What are major cell targets 1. Membranes – damage to proteins

of radiation damage? leads to alteration in the permeability
of the membrane, resulting in leakage
of catabolic enzymes from lysosomes
2. Cytoplasm – irradiated proteins can
be inactivated, but the cell can
produce more proteins as long as the
genetic material coding for the protein
is still intact
3. Nucleus – DNA damage is the most
devastating to a cell. If the damage
is repaired accurately, the cell will
continue to function; however, if
the damage is not repaired or the
repair is incomplete, the cell may
be functionally impaired or
neoplastic changes may be induced
through damage to regulatory or
operator genes.
What are possible exposure 1. External irradiation – when all or part

routes of ionizing radiation? of the body is exposed to penetrating
radiation
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2. External contamination – the physical

presence of radiation or radioactive
material on the surface of the body
3. Internal contamination – when
radioactive material enters the body
through the digestive tract, airways, or
wounds. Radioactive materials are
distributed throughout the body and
are incorporated. Location can vary
depending on chemical properties
(e.g., I-131 is taken up by the thyroid
during ablation therapy and utilized
just as stable I-127).
4. Combined exposures – mixtures of the
above
Is a patient who is exposed No

to external irradiation a
hazard to healthcare
workers?
What are the principles of 1. Prevent internal contamination

external decontamination? 2. Reduce total patient exposure
3. Reduce attendant exposure
4. Prevent contamination of facility
5. Reduce skin exposure
Has a healthcare provider Healthcare providers have NEVER been

ever been injured by a hurt caring for contaminated patients.
contaminated patient? The highest recorded dose was 14 mrem,
measured by an ED provider caring for a
contaminated patient.
What are the decontam- 1. Remove patient’s clothing.

ination procedures? 2. Wash patient with detergent and
water, or have them shower.
3. Above steps are 95% effective.
How are wounds treated? Any wound shall be assumed to be con-

taminated. Following each wound-specific
treatment below, all wounds should be
covered to prevent cross-contamination
from other areas of the body.
1. Lacerations – gentle irrigation with
copious amounts of water or saline,
collect and save wound drainage
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2. Foreign bodies – remove if clinically

indicated, be sure to mark and save
for later analysis
3. Puncture wounds – can be handled
by simple scrubbing, do not mutilate
tissue to decontaminate
(incision/coring)
4. Thermal/chemical burns – normal
burn care, some radionucleides may
be absorbed and trapped in the eschar
that will be removed later during
routine burn care
5. Orifices – if possible, the patient
should rinse the mouth with copious
amounts of water, save all irrigation
fluids for analysis
6. Ocular wounds – treat like any other
eye exposure, primary consideration
is given to locating and removing any
foreign bodies. Secondary
consideration is given to chemical
contaminants, which unlike
radioactivity, can cause immediate
damage to the eye.
Is there a difference in Delivering the same total dose of radia-

acute vs. chronic exposure tion at a much lower dose rate over a
of the same dose? long period of time allows tissue repair to
occur. There is a consequent decrease in
the total level of injury that would be ex-
pected from a single dose of the same
magnitude delivered over a short period
of time.
What is Acute Radiation Effects from high-dose radiation that de-

Syndrome (ARS)? velop over a period of hours to months
after exposure to ⬎0.7 Sv. Clinical effects
of ARS are divided into several distinct
stages and phases based on time and
organ systems affected. The stages based
on time are the Prodrome, Latent, Mani-
fest illness, and Recovery or Death. The
phases based on the clinical picture are
the Hematopoietic, GI, and CNS/CV
Syndromes, and are in order of increas-
ing dose rate.
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What is the hematopoietic Results from exposures of doses ⬎0.7 Sv

syndrome? (or 100–800 Rem)
1. Prodrome – nausea, vomiting, anorexia
with an onset of 3–24 hrs, severity
increases with dose
2. Latent – mostly asymptomatic, except
for mild weakness, hair/weight loss
around 14 days; circulating cell lines
become depleted
3. Manifest illness – bone marrow
atrophy with reduced circulating
blood cell numbers, hemorrhage and
infection around 3–5 weeks
4. Treatment – prophylactic oral
absorbable quinolone antibiotics to
sterilize gram-negative gut flora,
adding amoxicillin-clavulanate or
cefixime for gram-positive coverage. If
bleeding develops, transfusions of
irradiated blood, blood products, and
platelets should be administered.
Consider CMV, HSV, fungal, PCP
prophylaxis if appropriate. If the bone
marrow does not recover sponta-
neously, it can be stimulated with
growth stimulation factors, or
transplantation may be required.
Are there any useful The absolute lymphocyte count is the

laboratory tests for the most useful indicator of dose received. A
hematopoietic syndrome? 50% drop in lymphocytes within 24 hrs
indicates significant radiation injury.
What is the GI syndrome? Exposure to radiation in the 7–30 Sv

(or ⬎800 rem) can cause damage to mu-
cosal epithelial and crypt cells lining the
GI tract. The hematopoietic syndrome
occurs concurrently, as the doses are well
above those required to produce severe
bone marrow depletion.
1. Prodrome – severe nausea/vomiting,
possibly watery diarrhea and cramps,
onset 1–4 hrs
2. Latent – malaise and weakness, onset
5–7 days
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3. Manifest illness – return of severe

vomiting, diarrhea with fever,
progression towards bloody diarrhea,
shock, and death
4. Treatment – consists of replacing
fluid and electrolytes, antibiotics for
infection, in addition to all the
treatment required for the severe
hematopoietic syndrome. Despite
intensive treatment, patients are
likely to die.
What is the CNS/CV Doses above 30 Sv (or ⬎300 rem) will

syndrome? lead to damage to the relatively radiore-
sistant CNS and CV system. Most of the
damage is to radiosensitive vascular com-
ponents supplying blood to the CNS. The
heart and great vessels are more radiore-
sistant than the capillaries.
1. Prodrome – rapid development
(usually within 1 hr) of severe nausea
and vomiting, confusion, ataxia, and
prostration
2. Latent – a short period of a few hrs at
most
3. Manifest illness –return of nausea,
vomiting, and diarrhea. Confusion,
seizures, AMS, respiratory distress,
hypotension, and death will follow
within a few hrs to days.
4. Treatment – despite the
aforementioned treatments, this
syndrome is essentially fatal
What are permissible annual 1. General public – 0.5

radiation dose limits (rem)? 2. Occupationally exposed pregnant
female – 0.5 (over term of pregnancy)
3. Radiation and emergency workers – 5
4. Lifesaving exposure limit – 25
Are we exposed to natural, Yes. The average American is exposed to

background radiation in 360 mrem (3.6 mSv) per year of back-
the U.S.? ground radiation composed of the types
listed below (mrem):
1. Cosmic – 28
2. Terrestrial – 29
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3. Radon – 200
4. Medical – 53
5. Commercial products – 10
6. Internal – 39
7. Other – 1
What are typical exposures 1. Head/neck radiographic – 20

from diagnostic 2. Cervical spine – 20
radiographic exams (mrem)? 3. Chest – 8
4. Upper GI series – 245
5. Barium enema – 406
6. CT (head and body) – 111
7. Dental – 10
8. Lumbar spine – 127
9. Hip – 83
What are commercial and/or 1. Smoke detector – 0.008

other sources of radiation 2. Nuclear power – 0.01
(mrem/yr)? 3. Computer screen – 0.1
4. Watching TV – 1
5. Airline trip from New York to Los
Angeles – 2
6. Cigarettes, 1 pack/day – 7,000
7. Astronauts – 36,000
SMOKE INHALATION
What is the composition of Smoke is a composite of vapors, gases,

smoke? heated air, and small solid and liquid
particles.
What is soot? Aerosolized carbonaceous particulate

matter
How are toxic combustion 1. Simple asphyxiants – carbon dioxide

products classified? Give 2. Irritants – hydrogen chloride, acrolein,
examples of each. phosgene, nitrogen oxides
3. Chemical asphyxiants – carbon
monoxide, hydrogen cyanide,
hydrogen sulfide
How do the different 1. Simple asphyxiants – displace oxygen

combustion products cause from the airways
toxicity? 2. Irritants – may cause direct corrosive
effects, free radical production, and
immune-mediated effects
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3. Chemical asphyxiants – interfere with

systemic oxygen utilization
What are some toxic 1. Hydrogen cyanide – hydroxocobalamin

products produced in fires and sodium thiosulfate. Sodium and
and their antidotes? amyl nitrite should be used with
caution in smoke inhalation secondary
to worsening methemoglobinemia.
2. Methemoglobinemia – methylene blue
3. Carbon monoxide – high-flow oxygen
What is the most important Airway management with early endotra-

part of management in cheal intubation, as needed. Patients may
smoke inhalation victims? decompensate quickly secondary to
increased airway resistance from intralu-
minal debris, mucosal edema, and
bronchospasm.
What delayed pulmonary Acute lung injury and ARDS

complications may occur
following smoke inhalation?
What diagnostic tests ABG analysis with co-oximetry to assess

should be included in for acidosis, carboxyhemoglobin, and
management? methemoglobin. An elevated lactic acid
may help diagnose cyanide poisoning.
CXR will evaluate for pulmonary infil-
trates or edema.
What problems can The nitrite components of the kit produce

accompany the use of the methemoglobinemia, which may worsen
traditional cyanide kit (amyl the functional anemia if the patient has
nitrite, sodium nitrite, coexisting carbon monoxide poisoning.
sodium thiosulfate) when
treating cyanide poisoning
in a smoke inhalation
victim?
STRYCHNINE
What is strychnine? An alkaloid derived from the seeds of the

Strychnos nux-vomica tree, indigenous to
South East Asia and Australia. The pure
form is an odorless, bitter, white crys-
talline powder.
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Where has strychnine been 1. Old rodenticides, laxatives, and

found in the past? homeopathic tonics that are no longer
in use
2. As an adulterant in illicit drugs such as
heroin and cocaine
How quickly is strychinine Rapidly absorbed by the GI mucosa with

absorbed following onset of symptoms in 15–45 min
ingestion?
How is strychnine 80% hepatic and 20% renal; elimination

eliminated? half-life ⫽ 10–16 hrs
What strychnine dose is Any dose should be considered poten-

considered lethal? tially serious, but any single ingestion of
1–2 mg/kg or a serum level of ⬎1 mg/L is
considered lethal.
What is strychnine’s Competitive antagonism of inhibitory

mechanism of toxicity? spinal cord glycine receptor, resulting in
neuronal excitability with consequent
skeletal muscle spasm
How does strychnine toxicity 1. Episodic, simultaneous tonic flexor

clinically present? and extensor muscle contraction with
alternating periods of relaxation.
2. Opisthotonus
3. Full consciousness, though severe
poisoning can cause respiratory
insufficiency and lactic acidosis, which
can cause CNS depression.
4. “Risus sardonicus,” facial grimacing
often accompanied by trismus
Are these muscle contrac- No. They originate in the spinal cord,
tions considered seizures? not the cerebral cortex. Consciousness is
not impaired, no postictal period will be
observed, and patients should have rec-
ollection of the event.
Are there any special Any type of intense environmental or

considerations for this type sensory stimuli can potentiate an episode
of toxicity? of muscle contractions. It is very impor-
tant to keep the patient in a dimly lit,
quiet environment.
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What are the complications 1. Rhabdomyolysis with resultant

of a strychnine overdose? myoglobinuria and acute renal failure
2. Hyperthermia due to excessive muscle
activity
3. Lactic acidosis
4. Respiratory arrest
What infection can mimic Tetanus, which acts by inhibiting glycine

strychnine poisoning? release. Tetanus has similar signs and
symptoms, although it develops more
slowly.
What is the primary goal of Supportive care – airway protection and

treatment? control of muscle contractions
What methods are effective 1. Benzodiazepines to reduce muscular

at managing the symptoms hyperactivity. Barbiturates are second-
of strychnine toxicity? line agents.
2. Paralysis with nondepolarizing
neuromuscular blockade and intubation
if symptoms are refractory to treatment
3. Active cooling if the patient is
hyperthermic
4. IV hydration to prevent renal failure
secondary to rhabdomyolysis
Is there a specific antidote? No
Are there any specific 1. Do not induce vomiting or use gastric

decontamination/elimination lavage. Besides aspiration risk, there is
procedures that have proven the risk of potentiating an episode of
to be effective or are muscle contractions.
contraindicated? 2. Acidification of urine and diuresis are
not effective.
3. Activated charcoal will bind strychnine
and is effective if given soon after
ingestion.
SULFUR DIOXIDE
What is sulfur dioxide? An irritant gas

Where might sulfur dioxide Released from natural fires, automobiles,
be encountered? paper manufacturing plants, power plants
fueled by oil or coal, metal smelting
facilities. In addition, it can be used as a
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food preservative, a disinfectant, a refrig-

erant, and a water dechlorination agent.
What is the mechanism of Contact with moist surfaces (e.g., eyes,

toxicity of sulfur dioxide? mucosa) yields sulfurous acid, which
causes intense irritation, induces bron-
choconstriction, and alters mucous secre-
tion in the respiratory tract. Direct con-
tact with liquid sulfur dioxide freezes
exposed tissues.
How did sulfur dioxide gain It is a major component of acid rain.

its notoriety?
What are the clinical effects Rapid onset of irritation of mucous mem-
seen with toxic exposure to branes/eyes/skin/respiratory tract, dyspnea
sulfur dioxide? due to bronchoconstriction and pulmonary
edema, nausea, vomiting. Pulmonary symp-
toms may be delayed. Liquid sulfur dioxide
causes frostbite injuries upon contact and
may result in corneal necrosis, and possible
blindness, following ocular exposure.
Are there any specific tests No. Diagnosis relies principally on history
helpful for diagnosis? of exposure with consistent symptoms.
What treatments are 1. No specific antidotes exist.

available for sulfur dioxide Management is supportive.
toxicity? 2. Removal of the agent is important,
through decontamination and physical
relocation. Irrigate skin and eyes with
copious water.
3. Treat frostbite injury from liquid
sulfur dioxide as a thermal burn.
4. Enhanced elimination methods are of
no proven clinical benefit.
TOLUENE
What is toluene? Highly volatile aromatic hydrocarbon
How is toluene used? 1. Solvent for paints, lacquers

2. Gasoline additive
3. Found in explosives, glues, dyes
4. Abused as an inhalant
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What are the effects of Dizziness, ataxia, headache, nausea, vom-

acute inhalation? iting, euphoria
Describe the primary Enhances the activity of the GABA

mechanism of action. receptor and may inhibit the NMDA
receptor
What is the primary method Abuse occurs though inhalation, with

of abuse? “huffing” (i.e., placing a solvent-soaked
rag over the mouth and nose and inhal-
ing); “bagging” (i.e., inhaling the solvent
from a bag); and sniffing (i.e., inhaling
the solvent directly from the container)
being the primary methods.
What are signs of chronic 1. Weight loss, muscle weakness, ataxia,

toluene abuse? mood instability, depression
2. Progressive irreversible
encephalopathy
3. Renal tubular acidosis
4. Peripheral neuropathies
Are there any ways to 1. Most levels are noncontributory

monitor toluene levels during initial stabilization of a patient.
during intoxication? 2. Toluene levels may be measured from
venous blood. Hippuric acid levels can
be obtained from urine samples.
What are two important 1. CPK (creatinine kinase) – rhabdomy-

parameters to monitor in olysis is common in chronic users
exposures? 2. Electrolytes – severe hypokalemia,
hypophosphatemia, and both anion
gap and non-anion gap metabolic
acidosis may occur. Bicarbonate
therapy should be avoided in these
patients because of hypokalemia.
How does toluene produce Metabolites of toluene include benzoic

an anion gap metabolic acid and hippuric acid, which contribute
acidosis? to the acidosis.
What is the mechanism of Toluene and its metabolite hippuric acid

non-anion gap acidosis? may cause a renal tubular acidosis similar
to the distal (or type 1) variety, with
potassium wasting and hyperchloremia.
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What interventions and 1. All patients should be decontaminated

monitoring are indicated and placed on cardiac and respiratory
with toluene exposure? monitoring.
2. Basic labs such as CBC, electrolytes,
ABG, chest radiograph, creatinine
kinase, and urinalysis should be
obtained.
3. Metabolic abnormalities usually
resolve within a few days of
discontinuing the exposure.
TRICHLOROETHANE AND TRICHLOROETHYLENE
What are trichloroethane Chlorinated hydrocarbons that are typi-

(TCA) and trichloroethylene cally used as solvents
(TCE)?
Name some products in Due to their solvent properties, these

which these agents are agents are found in degreasers, glues/
found. adhesives, and paint removers. They
were formerly found in dry cleaning solu-
tions and typewriter correction fluid.
What are the potential Inhalation, ingestion, dermal

routes of toxic exposure?
What is the mechanism of Multiple mechanisms have been de-

toxicity responsible for CNS scribed, including GABAA stimulation
depression? and inhibition of voltage-sensitive cal-
cium channels.
Why might these agents be They have properties similar to inhala-

abused? tional anesthetics and, when inhaled,
may produce dizziness, ataxia, and
euphoria.
What key features of All have the metabolite trichloroethanol,

metabolism are shared a GABAA agonist that contributes to the
between TCE, TCA, and the CNS depressant effects
commonly used sedative,
chloral hydrate?
What chemical property Lipid solubility

facilitates its anesthetic
action?
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What are the clinical effects Inhalation or ingestion may produce

following an acute ataxia, dizziness, nausea, vomiting,
exposure? headache, confusion followed by
lethargy, seizures, dysrhythmias, and
coma. Delayed hepatic and renal injury
may occur.
How do these agents exert Chlorinated hydrocarbons may cause my-

their CV effects? ocardial depression by altering the my-
ocardial cell membrane bilayer. They also
sensitize the myocardium to endogenous
catecholamines, resulting in dysrhyth-
mias.
Which of these two agents TCE

was associated with
trigeminal neuralgia?
What is “degreaser’s flush”? Exposure to TCE may cause inhibition

of aldehyde dehydrogenase, leading to a
disulfiram-like reaction following
ethanol exposure.
What are the dermal effects Both agents are solvents, and contact
of exposure? with the skin may cause defatting and
dermatitis.
Are these two agents TCE is probably carcinogenic in humans

considered carcinogens? (IARC Group 2A), whereas TCA is not
classifiable as to carcinogenicity to hu-
mans based on the available evidence
(IARC Group 3).
How is a toxic exposure History of exposure and clinical effects.

diagnosed? The parent compounds can be measured
in expired air, blood, and urine. The
urine can be tested for trichloroacetic
acid, a metabolite of both of these agents.
Describe the method of Treatment is primarily supportive. Der-

treatment. mal decontamination consists of copious
irrigation with soap and water. Care
should be used when administering cat-
echolamines due to the possibility of in-
ducing dysrhythmias.
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Chapter 5 Heavy Metals
ALUMINUM
List sources of aluminum 1. Dermal exposure – antiperspirants,

exposure. cosmetics
2. Ingestion – contaminated water, food
containers, cooking utensils, antacids
3. Inhalation – mine workers, processors
of aluminum silicate
4. Parenteral – total parenteral nutrition
(TPN) solutions, IV drug abuse,
dialysis patients
How is aluminum eliminated Renally. The body absorbs ⬍1% of in-

from the body? gested aluminum, and the kidneys readily
eliminate it.
Describe the typical Patients can present with encephalopa-

presentation of aluminum thy, microcytic hypochromic anemia,
toxicity. and/or osteodystrophy. Acute toxicity is
rare and presents with abdominal pain,
vomiting, confusion, dysarthria, my-
oclonus, asterixis, seizure, and coma. Car-
diomyopathy has been reported.
What are the mechanisms of 1. Interference with synaptic transmission

toxicity for aluminum? 2. Oxidative damage
3. Localization to bone with inhibition of
calcium and phosphorus turnover
4. Disruption of parathyroid function
The findings on blood Lead

smears mimic poisoning
with which other metal?
How does aluminum cause 1. Impaired heme metabolism, including

anemia? ↓ Hgb synthesis
2. Hemolysis
3. Impaired iron metabolism and
transport
256
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Chapter 5 / Heavy Metals 257
What is dialysis Encephalopathy induced by aluminum in

encephalopathy? renal failure patients undergoing dialysis.
This typically results from the use of alu-
minum-containing phosphate binding
agents or aluminum-contaminated water
(softened or untreated). The encephalopa-
thy is partially due to aluminum inhibition
of dihydropteridine reductase.
What is osteomalacic dialysis Aluminum reduces vitamin D activity on

osteodystrophy? bone → ↓ deposition of calcium in
osteoid and subsequent osteomalacia.
Hypercalcemia results. Bone pain, patho-
logical fractures, and proximal myopathy
may subsequently be seen.
Does vitamin D reverse this No. This disease is resistant to vitamin D

condition? therapy as long as aluminum is present
because aluminum blocks the action of
vitamin D.
What is Shaver’s disease? Aluminum dust exposure may lead to

pulmonary complaints consisting of dys-
pnea, coughing, substernal chest pain,
weakness, and fatigue. A pneumoconio-
sis can be seen with CXR findings con-
sisting of bilateral lace-like shadowing,
more frequent in the upper halves and
lung root.
Are serum aluminum levels Not routinely, as they only reflect the
helpful in the diagnosis of amount in the blood. Because most of
aluminum toxicity? the aluminum is deposited in bone and
liver, these studies may not reflect the
true body burden of aluminum.
What is the preferred Deferoxamine

chelating agent for
aluminum toxicity?
How can serum aluminum Deferoxamine draws aluminum from

levels be helpful? bone into the intravascular space where it
may be quantified by blood testing. This
effect may take several days.
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How is the definitive Iliac crest bone biopsy

diagnosis made?
How is aluminum toxicity 1. Avoid further exposure.

treated? 2. Optimize renal function.
3. Chelation therapy with deferoxamine,
in combination with hemodialysis or
hemofiltration. Hemodialysis alone
will not significantly reduce body
burden, as it only removes the
aluminum in the intravascular space
while leaving the bone deposits to
leach out over time.
Why is aluminum phosphide Aluminum phosphide is used as a roden-

so toxic? ticide. Its toxicity is due to liberation of
phosphine gas in the body. This will
inhibit oxidative phosphorylation and
hinder ATP production. The resulting
clinical effects include abdominal pain,
vomiting, hypotension, pulmonary
edema, renal failure, and CV collapse.
ANTIMONY AND STIBINE
What is antimony? Antimony is classified as a “metalloid”

and is similar to arsenic in toxicity. Anti-
mony is one of the oldest known medical
“remedies,” being used for epilepsy, lep-
rosy, and leishmaniasis. It also has signifi-
cant historical use as a poison. Today, it is
still used in many industrial processes,
often as an alloy, in flame-retardant ma-
terial, and in antiprotozoal medications.
What antimony compound Tartar emetic (antimony potassium tar-

was once used as a trate). This compound is a potent emetic
medicinal “cure-all”? that is no longer used secondary to its
considerable toxicity.
What are some of the more 1. Used in the production of rubber

common applications of 2. Incorporated in plastics to act as a
antimony? flame retardant
3. Used in metal alloys as a hardening
agent and to prevent corrosion
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4. Used in paints and dyes to provide color

5. Used in the production of safety
matches
6. Found in certain antiparasitic
medications
Which is more toxic, Trivalent

pentavalent or trivalent
antimony?
What are the two most Inhalation and ingestion

common routes of antimony
poisoning?
What is the mechanism of Although the definite mechanism is not

antimony toxicity? known, it is theorized that antimony acts
by binding to sulfhydryl groups, which
thereby inactivates certain enzymes. Anti-
mony also acts as a direct irritant to
mucous membranes.
Concerning inhalation, what 0.5 mg/m3 8-hour time-weighted average.

air level of antimony is Levels ⬎50 mg/m3 are considered to be
considered to be the life-threatening.
workplace limit?
What symptoms are seen Nausea, vomiting, headache, weakness,

with exposure to elevated pneumonitis, anorexia, oropharyngeal ir-
levels of antimony dust / ritation / bleeding, pruritic and pig-
fumes? mented skin pustules (antimony spots),
conjunctivitis
Are fatalities from antimony No, they are rare. There are several re-
poisoning common? ported cases of sudden death in individuals
exposed to antimony, presumably from a
cardiotoxic effect. Antimony has also been
implicated as a possible carcinogen (anti-
mony trioxide – IARC classification 2B),
contributing to some mortality.
Describe the toxic effects of 1. Severe nausea, vomiting, and diarrhea

acute antimony ingestion. (often hemorrhagic in nature)
2. Abdominal pain
3. Hepatitis or renal insufficiency may
occur
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Name the ECG abnormality QTc prolongation

that may occur secondary to
antimony toxicity.
What laboratory findings are 1. ↓ RBC count

observed with antimony 2. ↑ LFTs, BUN, creatinine
exposure? 3. Pancytopenia has been reported.
4. RBCs and Hgb in urine
What are antimony spots? Pruritic papules progressing to pustules

occurring most frequently in areas of
sweating
Are any laboratory tests 1. Serum antimony levels are available

used to quantify antimony but are rarely used because they are
exposure? unreliable.
2. Urine antimony levels ⬎2 mg/L are
considered abnormal. Exposure to air
concentrations ⬎0.5 mg/m3 will
increase urine levels but cannot be
used to accurately quantify exposure
levels.
What is the treatment for 1. Remove the patient from the

antimony toxicity? exposure.
2. Gastric lavage may be considered if
the patient presents promptly to the
emergency department.
3. Patients may need large volume fluid
resuscitation secondary to massive GI
fluid loss.
4. Monitor and replace electrolytes as
needed.
5. There is no role for activated charcoal,
as it does not effectively bind
antimony.
Is there any antidote for There is no specific antidote. Based on

antimony toxicity? animal studies, chelation with agents
such as dimercaprol (BAL), DMSA, and
DMPS are expected to be beneficial,
but human data proving their efficacy is
limited.
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Is hemodialysis an option? No. Dialysis is not effective at removing

antimony.
What is stibine? Antimony hydride (SbH3) is a colorless

gas which is produced when antimony-
containing compounds are heated or
treated with acid. Stibine smells strongly
of rotten eggs.
Where might exposure to During mining operations or industry

stibine occur?
What is the mechanism of Stibine causes the hemolysis and is an

stibine toxicity? irritant gas which can affect the CNS.
What air level of stibine is 0.1 ppm per 8-hour time-weighted aver-
considered the workplace age. Levels ⬎5 ppm are considered to be
limit? life-threatening.
What symptoms and Nausea, vomiting, headache, weakness,

conditions can be seen with jaundice, hemolysis, hemoglobinuria,
stibine inhalation? renal failure
What laboratory findings are Anemia with elevated RFTs, CPK, LDH,
observed with stibine bilirubin, hemoglobinuria
exposure?
What is the treatment for 1. Remove the patient from the

stibine exposure? exposure.
2. Supplemental oxygen
3. Blood transfusions in cases of massive
hemolysis
4. IV fluids and bicarbonate for
rhabdomyolysis
5. Exchange transfusions may be
necessary in some cases of massive
hemolysis.
Is there any antidote for No. Chelation therapy is not thought to

stibine toxicity? be effective.
Is there any way to enhance No. Hemodialysis and forced diuresis

the elimination of stibine? are not effective at reducing stibine
levels.
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ARSENIC AND ARSINE
What are some sources of 1. Groundwater

arsenic? 2. Wood preservatives
3. Semiconductors
4. Smelting/soldering
5. Animal feed
6. Pesticides
7. Moonshine
8. Folk / alternative medicines
9. Used therapeutically for acute
promyelocytic leukemia
What is arsine? Arsine (AsH3) is a colorless, nonirritating

gas with a garlic odor formed when metal
alloys containing arsenic are exposed to
acid. In addition, it is formed as a
byproduct of semiconductor production,
metal refining, soldering, and galvanizing
operations.
What is lewisite? A gaseous arsine derivative that has been

used as a chemical warfare agent. It
causes severe eye, skin, and airway irrita-
tion, possibly progressing to necrosis.
In the United States, what Arsenic – ingested through contaminated

are the major sources of food or water. Inorganic arsenic is taste-
accidental arsenic and less and odorless and is readily absorbed
arsine exposures? by the GI tract and mucosa.
Arsine – unintentional inhalation by
workers in industrial settings
Can arsenic intoxication While blood and urine tests may register
occur due to consumption of positive, the arsenic found in seafood /
seafood? shellfish is organic in the form of arseno-
betaine, which is nontoxic and easily ex-
creted. Organic arsenic is also found in
several antiparasitic medications.
What is the mechanism of Once absorbed, the trivalent (arsenite)

toxicity of arsenic? form of arsenic will inhibit key compo-
nents of cellular metabolism, including
the pyruvate dehydrogenase complex and
the alpha-ketoglutarate dehydrogenase
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complex → ↓ ATP production. Pentava-

lent arsenic (arsenate) is metabolized to
arsenite and will independently disrupt
oxidative phosphorylation by substituting
for inorganic phosphate. Other mecha-
nisms include oxidative damage and di-
rect mucosal irritation (causing GI ulcer-
ation and respiratory tract / skin cancers).
It is thought to disable DNA repair.
What is the mechanism of The primary effect of arsine is profound

toxicity of arsine? hemolysis with resultant anemia. An in-
crease in intracellular calcium caused by
a reaction product of arsine binding to
heme is thought to be responsible. Renal
tubular damage results from the deposi-
tion of hemoglobin, and severe hemolysis
can disrupt oxygen delivery.
What is the clinical Phase 1 (within hours) – profound gas-

presentation of acute troenteritis (cholera-like) with resultant
arsenic intoxication? nausea, vomiting, watery diarrhea, and
abdominal pain. The GI fluid losses, plus
diffuse third spacing of fluids, lead to
tachycardia, hypotension, and possibly
hemodynamic collapse. Metabolic acido-
sis, rhabdomyolysis, and renal failure may
occur.
Phase 2 (after 1 to 7 days) – initial GI
symptoms and hypotension may resolve
in 24 to 48 hrs. This presents with cardio-
vascular compromise, including conges-
tive cardiomyopathy, cardiogenic and
noncardiogenic pulmonary edema. The
QT interval may increase, potentially
causing torsade de pointes. During this
phase, encephalopathy with delirium, agi-
tation, or coma may develop, as may ele-
vated transaminases and proteinuria.
Phase 3 (after 1 to 4 weeks) – begins with
a sensorimotor peripheral neuropathy. Ini-
tially, it presents with painful dysesthesias
in a stocking-glove pattern. Ascending sen-
sory and motor deficits will ensue, possibly
leading to quadriplegia and respiratory
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failure. Pancytopenia with basophilic stip-

pling of RBCs may be seen in this phase.
What dermatologic signs are A diffuse maculopapular rash, desquama-

seen with acute arsenic tion of the palms and soles, periorbital
poisoning? edema, and herpetic-like lesions. Mees’
lines or white transverse striae on the
nails may be observed 4 to 6 weeks post-
ingestion.
What is the clinical Dermatological signs become more

presentation of chronic prominent and include darkened skin
arsenic intoxication? with hypopigmented areas, hyperkerato-
sis, brittle nails, and Mees’ lines. Periph-
eral neuropathy, headache, and confusion
may also be apparent. Peripheral vascular
disease (Blackfoot disease), hypertension,
and malignancy can be caused by chronic
arsenic exposure.
What is the clinical There are no immediate symptoms dur-

presentation of acute arsine ing exposure. After a delay of 1 to 24 hrs,
intoxication? nonspecific symptoms including nausea,
vomiting, abdominal cramping, fatigue,
headache, and chills will present. Hemol-
ysis occurs, resulting in hematuria, renal
failure, flank pain, and he-
patosplenomegaly. Jaundice may be seen
by day 2, and cardiovascular collapse has
been reported. The classic triad is ab-
dominal pain, jaundice, and dark urine.
Although rare, what is the Nonspecific constellation of anemia,

clinical presentation of nausea, vomiting, headache, dyspnea,
chronic arsine intoxication? weakness
How are arsenic levels Atomic absorption spectrophotometry on

measured? blood, urine, hair, or nail samples. Blood
testing is unreliable due to rapid clear-
ance, although urine testing is accurate
with levels peaking 1 to 2 days post-
exposure. Hair and nail levels remain ele-
vated for 6 to 12 months, depending on
individual growth and removal patterns.
A 24-hour urine collection is the pre-
ferred method of testing for arsenic.
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Does an elevated arsenic No. Organic arsenic from seafood can

level definitely confirm cause an elevated urine arsenic without
arsenic poisoning? causing toxicity. Also, contamination of
hair samples is not uncommon.
How is the diagnosis of Arsenic – history of exposure with other-

arsenic or arsine overdose wise unexplained systemic manifestations
made? including severe GI distress, peripheral
neuropathy, and possible cardiac conduc-
tion problems. Elevated urine levels can
help confirm the diagnosis.
Arsine – rapid onset of hemolysis, hemo-
globinuria and ↓ urine output with a his-
tory of potential occupational exposure to
arsine
What is the treatment for 1. Supportive care, including aggressive

arsenic intoxication? IV hydration
2. Avoid phenothiazine antiemetics, as
these may further prolong the QT
interval.
3. For large, recent ingestions, consider
gastric lavage. Activated charcoal is
ineffective.
4. Cardiac monitoring for 48 hrs
5. Chelation therapy with IV unithiol
(analog of dimercaprol) is indicated
for large oral overdose. If venous
access or unithiol are unavailable,
administer IM BAL. Oral chelation
with succimer or unithiol may be used
once vitals stabilize and GI distress
abates.
What is the treatment for 1. Remove patient from toxic

arsine intoxication? environment, including removal of
clothes and copious irrigation of skin.
2. Supportive care
3. Chelation is ineffective.
BARIUM
What barium compounds Any soluble barium salt, most commonly

are harmful to humans? barium chloride, barium carbonate, bar-
ium peroxide, barium nitrate, and barium
chlorate
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Is there any danger from No. These contain barium sulfate, which
barium-containing is insoluble and, therefore, has minimal
radiological contrast systemic absorption.
agents?
How do barium compounds Ingestion and inhalation of dust contain-

enter the body? ing barium compounds
What are the possible 1. Intentional ingestion

etiologies of barium toxicity? 2. Occupational exposures
3. Accidental ingestion, either due to
substitution of a soluble barium salt
(e.g., barium carbonate) for barium
sulfate in radiological contrast, or
eating contaminated food
What industrial processes 1. Barium mining and refining

can lead to exposure to 2. Manufacturing – glass, matches,
barium compounds? explosives, paint, rubber products
3. Combustion of fossil fuels
4. Found in rodenticides and depilatory
products
What is the mechanism of Competitive antagonism of potassium

toxicity of barium? efflux channels → ↑ intracellular potas-
sium levels and extracellular hypokalemia
→ ↑ membrane potential → cellular
depolarization and subsequent paralysis
Does barium toxicity cause No. Toxicity is associated with hy-

hypomagnesemia? pokalemia but not hypomagnesemia.
What are the acute Initial symptoms are abdominal cramp-

symptoms of barium ing, nausea, vomiting, and watery diar-
ingestion? rhea. Within minutes to hours, patients
can develop ↑ muscle tone manifested as
rigidity, myoclonus, and trismus, followed
by weakness progressing to flaccid paraly-
sis. Patients can suffer lactic acidosis,
rhabdomyolysis, renal failure, respiratory
arrest, and cardiac arrest.
What are the cardiac effects 1. Hypertension due to vasoconstriction

following high-dose barium may be seen initially.
ingestions?
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2. ECG findings include QRS widening,

U waves, AV dissociation, ventricular
ectopy, torsade de pointes, and VF.
How is barium poisoning Diagnosis is based on a history of expo-

diagnosed? sure, combined with the triad of severe
hypokalemia, GI distress, and weakness.
No routine test is available, but levels can
be obtained for confirmation.
Does the degree of muscle No. The barium level more accurately
weakness correlate with the reflects the degree of muscle weakness.
degree of hypokalemia?
How is acute barium 1. Potassium administration for those

poisoning treated? with significant hypokalemia
2. Oral administration of sulfates (e.g.,
sodium sulfate, magnesium sulfate) can
cause precipitation of soluble barium,
as barium sulfate limits absorption.
3. Hemodialysis can be considered to
treat refractory hypokalemia.
4. Anticipate airway compromise and the
need for mechanical ventilation.
What is baritosis? A benign, reversible pneumoconiosis that

results from inhalation of barium
Does barium bioaccumulate No

like other heavy metals?
BERYLLIUM
What is beryllium? A light metal often used in the telecom-

munication and aerospace industries sec-
ondary to its strength and conductive
properties
How does beryllium enter 1. Inhalation of dust or fumes containing

the body? beryllium or beryllium compounds
2. Through compromised skin
What are the most likely Occupational exposure, natural occur-

sources of inhaled rence, tobacco smoke
beryllium?
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What industrial processes 1. Beryllium mining, refining, alloy

can lead to exposure to production, machining, reclamation
beryllium compounds? 2. Manufacturing – electronic devices,
telecommunications, aerospace
industry
3. Combustion of fossil fuels
What are the acute effects Acute berylliosis, also known as acute
of inhalation of high levels beryllium disease
of beryllium?
What are the signs and Acute respiratory effects are those of
symptoms of acute chemical pneumonitis, including airway
berylliosis? irritation, cough, chest tightness, and dys-
pnea; this may progress to pulmonary
edema, cyanosis, tachycardia, anorexia,
and general malaise. Acute exposure may
also produce dermal effects, including
dermatitis, ulceration, and granulomas.
Describe the treatment of Pulmonary symptoms are treated with

acute berylliosis. systemic corticosteroids along with oxy-
gen and respiratory support, as needed.
What are the effects of Chronic beryllium disease (CBD), or

chronic exposure to chronic berylliosis, is a T-cell-mediated
beryllium-containing dust? immune reaction in the respiratory sys-
tem as a result of chronic beryllium expo-
sure. It is characterized by the formation
of pulmonary and extrapulmonary granu-
lomas (noncaseating). These can mimic
sarcoidosis and tuberculosis.
What test has been A beryllium-specific in vitro lymphocyte

developed to establish if a proliferation test
person is at risk for CBD?
What are the symptoms of Progressive pulmonary disease that may

CBD? be restrictive or obstructive in nature.
The disease usually manifests as increas-
ing cough and shortness of breath. Sys-
temic symptoms are likely to occur and
include anorexia, weight loss, fatigue, and
arthralgias. In severe disease, the patient
may develop pulmonary hypertension
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and cor pulmonale. CBD may also have

dermal manifestations, including nodular
granulomas and chronic dermatitis.
What is the treatment for 1. Oxygen therapy

CBD? 2. Glucocorticoids may be beneficial, but
data on efficacy is limited.
Is beryllium a carcinogen? Epidemiological studies are highly sug-

gestive that beryllium is a cause of can-
cer, particularly lung cancer. It has an
IARC Group 1 classification.
What are the federal limits 1. EPA – industrial release of 0.01 ␮g/m3
for beryllium exposure? of air, averaged over 30 days
2. OSHA – 2 ␮g/m3 of workplace area
for an 8-hour workday
BISMUTH
How does bismuth typically Ingestion

enter the body?
How is bismuth typically Bismuth may be found in fire detection

used? devices, ceramic glaze, hunting shot,
medications, and cosmetics.
What are the most likely Bismuth-containing medications

sources of ingested bismuth?
What bismuth compounds 1. Bismuth subsalicylate (Pepto-Bismol

are commonly found in and Kaopectate) – used for GI upset
drugs? and diarrhea
2. Bismuth subgallate (Devrom) – used
for ostomy care
3. Bismuth subcitrate (Pylera) – used for
treatment of H. pylori
How was bismuth historically Injection for treatment of syphilis prior to

used in medicine? advent of antibiotics
What are the signs and Acute toxicity is typified by abdominal

symptoms of acute bismuth pain, nausea, and vomiting, along with
poisoning due to a oliguric renal insufficiency secondary to
significant ingestion? acute tubular necrosis.
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What are the signs and The key finding in chromic bismuth toxi-
symptoms of chronic city is progressive myoclonic en-
bismuth poisoning? cephalopathy. This is characterized by
poor coordination, loss of memory,
changes in behavior, dysarthria, myoclonic
jerks, and progressive lethargy. Chronic
toxicity may also produce renal failure.
What gingival findings may Blue-black discoloration of the gumline

be present in chronic (bismuth lines)
bismuth exposure?
What is the mechanism of While the mechanism is not fully known,

bismuth toxicity? bismuth is thought to bind sulfhydryl
groups, altering enzymatic and protein
function.
How is bismuth poisoning 1. History of exposure

usually diagnosed? 2. Blood or urine testing is available to
confirm exposure, but levels have not
been correlated with outcome.
3. Abdominal x-ray may detect
radiopaque material.
4. Salicylate level should be obtained in
the case of bismuth subsalicylate
exposure.
How is bismuth poisoning 1. Primarily with supportive care

treated? 2. Benzodiazepines may be used for
myoclonic activity.
3. BAL and 2,3-dimercapto-1-
propanesulfonic acid (DMPS) have
been used with some success as
chelating agents; however, data
regarding their efficacy is limited.
CADMIUM
How does cadmium typically Inhalation and ingestion

enter the body?
What are the most likely 1. Occupational exposure

sources of inhaled 2. Cigarette smoke
cadmium? 3. Burning of fossil fuels
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In what industries are 1. Mining and smelting

workers most likely to be 2. Production of batteries (Ni-Cd)
exposed to cadmium? 3. Welding and soldering
4. Production of pigments, plastics, and
other synthetics
At what doses has inhaled 1. Concentrations ⬎1 mg/m3 of air are

cadmium been found to be likely to cause symptoms
harmful? 2. Concentrations ⬎5 mg/m3 of air are
likely lethal
How does acute inhalational 1. Respiratory – cough, wheezing,

cadmium poisoning present dyspnea, possible pulmonary edema
clinically? 2. Systemic – fever, chills, weakness
3. GI – nausea, vomiting
4. Other – chest pain, headache, metallic
taste
For what disease is acute Metal fume fever

cadmium poisoning
sometimes mistaken?
How is poisoning from Supportive care. There is no proven role

inhalation of cadmium for chelation therapy, and chelators, such
treated acutely? as BAL, worsen toxicity.
What is the most common Contaminated water and food (particu-

source of ingested cadmium? larly shellfish, liver, and kidney meats)
How is acute poisoning from GI distress (e.g., nausea, vomiting, diar-

ingested cadmium salts rhea, abdominal pain), hypotension,
likely to present clinically? metabolic acidosis. Pulmonary edema
and facial / pharyngeal edema have been
reported.
How is poisoning from Supportive care. Aggressive fluid resusci-

ingested cadmium usually tation may be needed.
treated?
What are the effects of Renal disease is a common finding, ini-

chronic exposure to tially manifesting as proteinuria. Chronic
cadmium? lung disease may develop following in-
halational exposure. Osteomalacia, osteo-
porosis, and bone pain may result from
disturbances in calcium homeostasis.
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Neurologic abnormalities, such as Parkin-

sonian symptoms, have been reported.
What environmental “Itai-Itai” or “ouch-ouch” disease oc-

cadmium disaster curred in Japan in the 1950s. It was
highlighted the pathologic named for the severe bone pain and
bone changes produced by pathologic bone fractures incurred by pa-
this disease? tients who had the misfortune of eating
food and drinking water contaminated
with cadmium from mining runoff.
Is cadmium classified as a Cadmium is associated with lung cancer

carcinogen? and is classified as IARC Group 1.
What is the mechanism of Cadmium binds to sulfhydryl groups, af-

toxicity for cadmium? fecting protein and enzyme function. It
may also mimic calcium in cellular proce-
sses and interfere with cell-cell adhesion.
How is suspected cadmium 1. Blood tests may help determine

exposure confirmed? exposure, but concentrations have
limited utility in management.
2. Urine protein, along with serum BUN
and creatinine assays, can determine
extent of renal damage.
What limits has the federal 1. EPA – ⱕ5 ppb cadmium in drinking

government placed on water
allowable workplace 2. FDA – ⱕ15 ppm cadmium in food
exposure? colors
3. OSHA – 100 ␮g/m3 of workspace per
8-hour time-weighted average (TWA)
workday (cadmium fumes),
200 mg/m3 of workspace per 8-hour
TWA workday (cadmium dust)
CHROMIUM
What are the three most Elemental chromium (Cr0), trivalent

common oxidation states of chromium (Cr3⫹), hexavalent chromium
chromium? (Cr6⫹)
Which oxidation state of Cr6⫹, though at high levels, Cr3⫹ may be

chromium is believed to be harmful as well
harmful to humans?
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Which oxidation state of Cr3⫹, required for metabolism of glucose

chromium is an essential and fat
nutrient?
How does chromium enter Ingestion, inhalation, dermal exposure

the body?
Which method of exposure Inhalation. Cr6⫹ is most efficiently ab-

is most harmful? sorbed through the lungs.
What are the most common 1. Cr3⫹ – food and drinking water
sources of chromium? 2. Cr6⫹ – chromium dust, usually an
occupational exposure
In which industries is one Mining, steel production, welding,

most likely to be exposed to chrome plating, chrome pigment
chromium? production
What is the estimated fatal 50–70 mg/kg

dosage of soluble chromium
salts?
Describe the mechanism of Cr6⫹ has a substantial oxidizing potential.

Cr6⫹ toxicity. It is corrosive to mucous membranes, the
airway, skin, and GI tract. Significant se-
quelae come from its ability to oxidize
DNA, resulting in cellular apoptosis and
mutagenic effects.
How does acute ingestion of 1. Burns and ulceration of mouth,

harmful amounts of Cr6⫹ pharynx and upper GI tract
present clinically? 2. Abdominal pain, nausea and vomiting,
often hemorrhagic in nature
3. Possible renal, pancreatic, and hepatic
damage
How does acute inhalational Airway irritation, including oropharyngeal

toxicity of Cr6⫹ present burning, rhinnorhea, cough, and dyspnea,
clinically? with a possible progression towards pul-
monary edema
What are “chrome holes”? Perforations in the nasal septum and/or

dermal ulcerations secondary to chronic
Cr6⫹ exposure
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What are the manifestations Chronic airway irritation, nasal septal per-
of chronic Cr6⫹ inhalation? forations, chronic cough, dyspnea, reactive
airway disease, restrictive lung disease
Is Cr6⫹ a carcinogen? Yes. Cr6⫹ is a widely recognized

carcinogen and has an IARC Group 1
classification.
How does skin exposure to Acute exposure induces skin irritation and
Cr6⫹ manifest? ulceration. Contact dermatitis or ulcera-
tions may occur through repeat exposures.
Are any labs useful in Chromium levels can confirm exposure,

chromium exposure? but levels may be difficult to interpret
and are of little clinical utility. Elec-
trolytes, CBC, BUN, creatinine, transam-
inases, and urinalysis should be checked
to evaluate effects of toxicity.
How is acute exposure to 1. Supportive care

Cr6⫹ treated? 2. Dermal or ocular decontamination
may be needed.
3. Aggressive fluid resuscitation may be
needed.
4. N-acetylcysteine may be effective in
increasing the excretion of chromium,
although human data is limited.
5. Animal studies suggest ascorbic acid
may help reduce Cr6⫹ to Cr3⫹,
thereby limiting its absorption, but
human data is limited.
What limits has the federal 1. EPA – ⱕ100 ppb Cr3⫹ and Cr6⫹ in
government placed on drinking water
workplace chromium 2. OSHA – 500 ␮g/m3 of Cr3⫹
exposure? compounds and 52 ␮g/m3 of Cr6⫹
compounds in the workplace per
8-hour time-weighted average workday
COBALT
Where is cobalt most In industry to produce heat-resistant

commonly used? super alloys, which are used in the fabri-
cation of jet engines. It is also an impor-
tant component of some magnets.
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What are the medicinal uses 1. Source of radiotherapy for cancer

of cobalt? 2. To label vitamin B12 when employed
in the Schilling test (used to diagnose
intrinsic factor deficiency)
3. Manufacture of medical prostheses
4. Cobalt dichloride (CoCl2) has (rarely)
been given orally to patients for the
treatment of refractory anemia
(induces an erythropoietic response).
Is cobalt toxicity common? No. It is exceedingly rare, as cobalt and

its salts are relatively nontoxic by inges-
tion. Most cases of cobalt toxicity are re-
lated to occupational skin exposure and
inhalation of cobalt dust.
Who is at risk for cobalt 1. Hard metal workers (e.g., tungsten-

inhalation toxicity? carbide industry)
2. Diamond workers (e.g., diamond
polishing)
3. Chemical refinery workers
What are the effects of 1. Hypersensitivity-induced asthma

cobalt inhalation? 2. Interstitial lung disease (i.e., fibrosing
alveolitis)
Describe the treatment of 1. Remove the patient from the exposure.

cobalt inhalation. 2. Treat asthma with conventional
measures (e.g., beta 2-adrenergic
agonists).
3. Annual medical evaluation, including
CXR, CBC, and thyroid function tests
What are the effects of skin 1. Allergic contact dermatitis

exposure to cobalt? (erythematous maculopapular type)
2. Rare cases of orofacial granulomatosis,
which has been described in association
with delayed hypersensitivity
What is the treatment of 1. Remove the patient from the exposure,

cobalt skin exposure? and remove excess cobalt from the skin.
2. Treat with traditional remedies for
allergic contact dermatitis.
3. Skin patch testing with 1% CoCl2 may
be done to confirm sensitivity.
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What is considered a toxic Inhalation by experimental animal

inhalational dose of cobalt? studies for 3 years indicated that
20 mg/m3 of cobalt-containing dust
resulted in granulomatous changes and
pulmonary fibrosis.
What are the symptoms Ingestion of cobalt salts may produce

associated with acute cobalt abdominal pain, nausea, vomiting, and
ingestion? diarrhea. Polycythemia has also been
reported.
Is there any treatment for 1. Supportive care is the primary

acute cobalt ingestion? treatment.
2. Chelation with calcium disodium
EDTA has proven successful in animal
studies.
3. N-acetylcysteine may improve both
urinary and fecal excretion of cobalt,
although data on human exposures is
limited.
What is cobalt-beer In the 1960s, cobalt salts were added to

cardiomyopathy? beer to act as a foam stabilizer. Some
heavy drinkers were estimated to have
consumed up to 10 mg of cobalt per
day, which was associated with the onset
of an atypical cardiomyopathy. Clinical
symptoms included acute-onset, left-
sided heart failure, followed by right-
sided heart failure, cardiomegaly, hy-
potension, and cyanosis. Mortality rate
was estimated to be 30% to 50%. Al-
though it was never definitively shown
that cobalt was responsible, when cobalt
was removed from the brewing process,
no new cases of associated cardiomyopa-
thy developed.
COPPER
Who is at risk for copper 1. People who live near or work at

toxicity? copper-producing facilities, such as
mines, smelters, or refining
facilities
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2. People with copper pipes or who are

drinking from / cooking with copper-
lined vessels
3. Vineyard workers exposed to copper
sulfate and hydrated lime
4. Exposure to algaecides, herbicides,
wood preservatives, pyrotechnics,
ceramic glazes, electrical wiring,
welding, or brazing with copper alloys
Describe the mechanism of Copper is a transition metal and is capa-

copper toxicity. ble of generating oxidative stress. Effects
on epithelia and mucous membranes are
irritative and corrosive in nature. Redox
reactions contribute to the majority of
systemic copper toxicity, including renal
and hepatic damage with hemolysis.
What is the clinical Ingestion (salts) – severe GI irritation,

presentation of acute copper resulting in abdominal pain, nausea,
toxicity? vomiting, and diarrhea. Hematemesis is
common. Oxidative damage contributes to
renal and centrilobular hepatic injury. He-
molysis is common after copper salt inges-
tion. The combination of these symptoms
may lead to intravascular volume deple-
tion, lethargy, and CV collapse.
Inhalation (fumes) – airway irritation,
cough, dyspnea, chest pain, fever,
pneumonitis
What is characteristic about Blue-green in color

the emesis seen with copper
toxicity?
What is chalcosis? Penetration of metallic copper into

cornea / vitreous humor resulting in con-
junctivitis, eyelid edema, granulomas,
and retinal detachment
What is Indian childhood Chronic copper toxicity, and subsequent

cirrhosis? cirrhosis, that developed in children who
drank copper-contaminated milk due to
the storing of milk in brass containers
(leaching of copper)
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What is vineyard sprayer’s The development (Portugal, 1960s) of

lung? granulomas, pulmonary fibrosis, and lung
cancer in workers who utilized a fungi-
cide vineyard spray consisting of copper
sulfate.
Describe the manifestations Wilson’s disease is an inherited disorder

of chronic copper poisoning. of copper metabolism that may result in
behavioral and movement disorders; it is
not a true exogenous copper poisoning,
however. Little data exits on chronic ex-
ogenous copper poisoning. Most cases
occur in the developing world in children
exposed to copper-contaminated milk or
water. In these cases, progressive hepatic
cirrhosis is reported.
Chronic inhalational exposure may
result in pulmonary fibrosis. Associations
have been made between chronic
copper inhalation and adenocarcinoma
of the lung, hepatic angiosarcoma, and
hepatic cirrhosis.
Is copper a carcinogen? While copper has been associated with

hepatic angiosarcoma and adenocarci-
noma of the lung, the IARC does not
include copper in the list of known
carcinogens.
What labs are useful in the CBC, electrolytes, BUN, creatinine,

initial presentation of acute transaminases, fractionated bilirubin,
toxicity? type and screen for severe hemolysis.
Serum or whole blood copper levels may
aid in sub-acute management of copper
toxicity but are unlikely to influence
acute management.
How is toxic copper 1. Aggressive fluid resuscitation and

ingestion treated in the electrolyte repletion for massive GI
emergency department? fluid losses
2. Blood transfusion for severe
hemolysis
3. BAL chelation therapy is likely
beneficial in severe poisoning,
although data is limited.
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How is toxic copper Inhalational exposure is generally self-

inhalation treated in the limited. Supportive care with oxygen and
emergency department? nebulized beta 2-adrenergic agonists is
indicated.
Describe the treatment for Removal from the source of exposure is

chronic exogenous copper the primary treatment. Chelation
poisoning. therapy and other modalities that are
used to treat Wilson’s disease have not
been studied for exogenous copper
exposure.
GALLIUM
What are the common uses In semiconductors, metal alloys, and

of gallium? high temperature thermometers. Med-
ically, gallium is used for radiologic
studies. It has also been used to treat
arthritis and has been studied for use in
treating hypercalcemia and certain
cancers.
Describe the manifestations While data is limited, gallium appears to

of ingestional or inhalational have low toxicity through either route.
gallium exposure.
What form of gallium is Salt forms (e.g., gallium nitrate, gallium

used therapeutically? citrate) are used for radiological studies.
How is gallium administered IV

therapeutically?
What are the acute Primarily nausea and vomiting

symptoms of parenteral
gallium nitrate toxicity?
What is the major adverse Renal toxicity

effect of acute gallium
nitrate toxicity?
What therapy is needed to Fluid therapy and osmotic diuresis

prevent or minimize acute
renal failure with gallium
nitrate toxicity?
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What electrolyte Hypocalcemia and hypophosphatemia.

abnormalities may be Bicarbonate may also be reduced during
expected with gallium acute toxicity.
nitrate toxicity?
What is the toxic dose of Unknown. Patients using other nephro-

gallium? toxic drugs (e.g., aminoglycosides), may
have nephrotoxicity with lower doses of
gallium.
What is the mechanism of While the mechanism is not fully known,

toxicity of gallium? hypocalcemia is caused by inhibited bone
resorption.
How is gallium eliminated? Renally
How should a gallium Supportive treatment. Aggressive fluid

overdose patient be treated? hydration and osmotic diuresis is war-
ranted to prevent acute renal failure.
Also, electrolyte disturbances may need
to be corrected.
GERMANIUM
What is germanium used for 1. Semiconductor material for transistors

in industry? 2. Camera lenses
3. Precious metal alloys
What is the major risk with Inhalation injury

industrial exposure?
Describe the effects of Airway / eye / mucous membrane irrita-

inhalational germanium tion, along with cough and possible
exposure. dyspnea
What are the symptoms of Germane gas acts similarly to arsine and
germane gas (GeH4) stibine gas, producing acute hemolysis.
inhalation? CV, renal, and hepatic dysfunction may
also occur.
Describe the symptoms of Acute toxicity appears to be low. Mani-

oral germanium exposure. festations may include nausea, vomiting,
and abdominal pain.
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What are the manifestations Chronic ingestion of germanium is more

of chronic germanium problematic. Renal insufficiency, myopa-
exposure? thy, and transaminitis are the most com-
monly reported symptoms. Deaths have
been reported from chronic germanium
supplementation.
Who is most likely to Those taking germanium health supple-

develop germanium toxicity? ments (i.e., HIV patients)
How is germanium Renally

excreted?
What is the treatment for Removal from the source of exposure and
germanium toxicity? supportive care
GOLD
Is gold exposure toxic? Yes, on a chronic level
Who is at risk for gold Patients being treated for rheumatoid

toxicity? arthritis with gold compounds
What gold compound is used Gold sodium thiomalate

to treat rheumatoid
arthritis?
What are the most common Dermatitis and renal disease

manifestations of gold
toxicity?
How does gold toxicity Integumentary complaints are common,

present? ranging from skin erythema to severe
exfoliative dermatitis. Similar reactions
are noted on the mucous membranes.
Chronic exposure may produce a gray-
blue pigmentation of the skin and
mucous membranes, especially in sun-
exposed areas. Thrombocytopenia,
aplastic anemia, encephalitis, peripheral
neuronitis, hepatitis, and pulmonary infil-
trates have all been reported, but tend to
be rare findings.
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What is chrysiasis? A permanent dermatological condition

caused by the chronic ingestion of gold.
This consists of a skin pigmentation that
is uniformly grayish blue and is usually
limited to sun-exposed portions of the
body. It may involve the conjunctivae but
usually spares the oral mucosa.
What is a nitroid reaction? An uncommon reaction that can occur

minutes after gold injection and consists of
a sensation of warmth and skin flushing
How are the kidneys Proteinuria, microscopic hematuria, and

affected by gold toxicity? membranous glomerulonephritis may
occur. All are reversible with cessation of
treatment.
What is the treatment? Cessation of gold compound therapy with

symptomatic care
If conservative treatment Antihistamines and glucocorticoids can be

fails, what is the next step? used to treat skin and mucous membrane
lesions. Dimercaprol, N-acetylcysteine,
and D-penicillamine have all been shown
to enhance elimination of gold from the
body but are rarely used and have not
been demonstrated to improve patient
outcome.
IRON
What are the clinical uses of As a nutritional supplement, notably

iron? used for treating anemia and in prenatal
vitamins
How do you calculate the [Total # of tablets][weight (mg)

amount of iron ingested per per tablet][% elemental Fe per tablet]
unit of body weight? [patient weight (kg)]
How much elemental iron 1. Ferrous gluconate (12%)

does each formulation 2. Ferrous lactate (19%)
contain? 3. Ferrous sulfate (20%)
4. Ferrous chloride (28%)
5. Ferrous fumarate (33%)
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What is the toxic dose of ⱖ10 mg/kg – GI effects

iron? ⱖ40 mg/kg – systemic effects possible
⬎60 mg/kg – potentially lethal
How is iron normally 10% enters mucosal cells of the small

absorbed and utilized by the bowel where it is bound by ferritin (stor-
body? age molecule). Transferrin carries iron to
the liver, where it is stored until needed
for biosynthesis. Unneeded iron is elimi-
nated when the intestinal cells slough off.
This limits absorption.
How does iron exert its toxic 1. Local GI effects are due to corrosion
effects on the body? and include hemorrhagic necrosis,
perforation, and infarction.
2. The local corrosive effect on the GI
mucosa causes unregulated passive
absorption of iron.
3. Systemic effects are mediated by free
radical-induced tissue damage. The
excess iron, unbound to transferrin,
will cause oxidative damage to
multiple organ systems.
4. Anion gap metabolic acidosis, due to
disruption of oxidative phosphorylation,
and hypovolemia secondary to third-
spacing of fluids. The generation of
protons from conversion of ferric iron
to ferrous iron is life-threatening.
5. Coagulopathies may manifest due
to iron-mediated inhibition of
proteases necessary in the hemostatic
pathway.
How does acute iron Stage 1 (30 min to 6 hrs) – GI symptoms

overdose present? of nausea, vomiting, abdominal pain,
and diarrhea. This can progress to
hematemesis and hematochezia.
Stage 2 (4–12hrs) – referred to as the
latent stage. GI symptoms resolve,
giving the impression of improvement;
however, hypoperfusion and metabolic
acidosis are developing. Patients will
appear lethargic and have tachycardia or
metabolic acidosis.
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Stage 3 (12–24 hrs) – rapid clinical

decline, progressing to severe metabolic
acidosis and shock. Accompanied by
possible coagulopathy, coma, and
multisystem organ failure. Death due to
iron intoxication occurs most frequently
during this stage due to circulatory
collapse and acidosis.
Stage 4 (12–96 hrs) – hepatotoxicity
due to absorbed iron causing oxidative
damage resulting in periportal hepatic
necrosis. Can result in hepatic failure.
Stage 5 (2–4 weeks) – late scarring of the
GI tract, causing pyloric obstruction,
bowel obstruction, or hepatic cirrhosis
Do all patients experience No, many patients will not. Some will
all five stages? only suffer GI distress. Those with
large ingestions can progress to stage 3
within several hours. Also, there is
no universal agreement on the number
of stages or the times assigned to
those stages.
How is the diagnosis of iron 1. History is most important.

overdose made? 2. If patient denies overdose but
suspicion is high, abdominal
radiograph can locate radiopaque iron
tablets in the stomach. Significant
ingestion is unlikely in the presence of
a normal abdominal x-ray and a lack of
GI symptoms.
3. Serum iron levels – significant toxicity
with levels ⬎500 ␮g/dL
When should a serum iron Ideally, at 2 to 6 hrs post-ingestion when

level be drawn? serum levels peak. Due to redistribution,
serum levels drawn more than 8 to 12 hrs
post-ingestion do not reflect the total
body burden.
Should you wait for a serum No. Treat the patient according to their
iron level before initiating clinical situation.
treatment?
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Is the total iron-binding No. Also, in the past it was believed that
capacity (TIBC) useful for a WBC ⬎15,000 and a serum glucose
determining toxicity? ⬎150 mg/dL would correlate with a
serum iron ⬎300 ␮g/dL. Recent studies
do not support this.
What treatments should be 1. Supportive care with particular

performed for iron toxicity? attention paid to aggressive hydration
2. Whole bowel irrigation should be
considered if iron tablets are visible on
abdominal x-ray.
3. Chelation therapy with deferoxamine is
indicated for shock, AMS, metabolic
acidosis, or a serum iron ⬎500 ␮g/dL.
Ensure hemodynamic stability prior to
deferoxamine administration, as
hypotension is common with this agent.
4. Avoid activated charcoal, as it is
ineffective and potentially harmful
(can exacerbate GI effects).
Ipecac is no longer Vomiting and GI upset are useful in pre-

recommended in the routine dicting if a toxic amount has been in-
treatment of any poisoning, gested. Ipecac will cloud the clinical
but why is it particularly ill- picture.
advised after an iron
ingestion?
LEAD
What is the mechanism of Lead binds sulfhydryl groups, which

lead toxicity? interferes with enzymes and structural
proteins. Lead also chemically resembles
calcium. It appears to interfere with cal-
cium homeostasis and calcium-dependent
signaling and metabolic pathways. This
includes disrupting mitochondrial
processes and interfering with the cellu-
lar second messenger signaling cascade.
What are common sources 1. Lead-based paint

of lead exposure? 2. Contaminated soil
3. Water contaminated by lead-based
plumbing
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4. Emissions created by leaded gasoline

(less common in United States due to
EPA regulations)
5. Lead dust and fumes in the industrial
setting
6. Food stored in lead-soldered cans
7. “Moonshine” whisky
8. Firearms training or bullet cartridge
reloading
Which occupations have the Those involving burning, cutting, or weld-

highest risk of lead ing of lead or lead-containing materials
exposure?
What are the routes of 1. Inhalation (most rapid)

exposure? 2. Ingestion (absorption is facilitated by
young age and diet deficient in
calcium, iron, and/or zinc)
3. Transdermal (least efficient, but
organic absorption ⬎ inorganic
absorption)
What are the general signs Severe (whole blood lead level (BLL)
and symptoms of toxic lead ⬎100–150 ␮g/dL) – encephalopathy (i.e.,
exposure in adults? coma, seizures, delirium, signs of ↑ ICP),
foot / wrist drop, abdominal pain (lead
colic), vomiting, anemia, nephropathy
Moderate (BLL ⬎80 ␮g/dL) – headache,
memory loss, fatigue, irritability, insom-
nia, ↓ libido, muscle pain / weakness, ab-
dominal pain, anorexia, weight loss,
nephropathy (if chronic exposure), mild
anemia
Mild (BLL ⬎40 ␮g/dL) – fatigue, moodi-
ness, hypertension, ↓ interest in everyday
activities
Are children more or less More sensitive. The “classic” adult symp-
sensitive to lead exposure? toms tend to develop at lower BLLs.
What subtle clinical Constipation and abdominal pain

presentation of lead
poisoning is easy to dismiss
as “normal” childhood
behavior?
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What age group is most 1 to 6 years old

severely affected by lead
poisoning?
What is the concern with Lead affects neurocognitive develop-

even mildly elevated BLLs ment, and BLLs seem to inversely corre-
in children? late with IQ.
How is lead detected in the A BLL is the best way to detect and
body? measure the amount of lead in the body.
Capillary BLLs are often used for screen-
ing but may be easily contaminated from
external sources. Venous BLLs should be
drawn to confirm elevated capillary
BLLs.
What other laboratory tests A CBC may show a microcytic anemia

may be useful in the with basophilic stippling on peripheral
assessment of lead-poisoned blood smears. Erythrocyte protopor-
patients? phyrin levels may be elevated as a result
of the inhibition of key enzymes in the
heme biosynthetic pathway.
Does ingested lead show up Yes, recently ingested lead, such as paint
on x-ray? chips or solid objects, can be detected on
x-ray.
What other radiographic Dense radiopaque metaphyseal lines

evidence may help with the (“lead lines”), especially at the wrists and
diagnosis? knees, may indicate chronic lead expo-
sure in children.
What is the current “action” 10 ␮g/dL. Close observation, education,

level defined by the CDC and follow-up evaluation should be
for pediatric lead exposure? arranged for children with confirmed
BLLs at or above this level.
How is symptomatic lead 1. Two options are available – chelation

poisoning treated? with CaNa2EDTA and dimercaprol
(BAL) for severe poisoning with
encephalopathy or with succimer
(DMSA) PO for patients able to
tolerate oral medication. Consultation
with a toxicologist is recommended due
to the complexity of this treatment.
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2. Consider whole bowel irrigation if

lead foreign bodies can be visualized
in the GI tract on radiograph.
3. Endoscopic removal is indicated for
lead foreign bodies retained in the
stomach or esophagus.
4. Surgical removal is indicated if the
lead object poses the threat of
prolonged retention.
At what BLL do current 45 ␮g/dL

recommendations advise
starting chelation therapy in
asymptomatic children?
What is another essential Patient or parent education on sources of

component of management lead in the environment and physician
for patients with elevated follow-up. An environmental survey may
BLLs? be necessary and will depend on local
health department regulations.
Should retained lead foreign Current evidence suggests removal of

bodies in tissue (e.g., only those foreign bodies that are
bullets) be removed? bathed in fluid (such as synovial fluid
or CSF). Tissue foreign bodies tend
to cause fibrosis and do not cause
significant or long-term elevations in
lead levels.
LITHIUM
What is the ionic charge of Lithium is an alkali metal in Group 1 of

lithium? the periodic table. It has a single valence
electron, which it readily loses to become
the positively charged cation Li⫹.
What important elements Sodium and potassium

share a similar valence with
lithium?
Lithium is usually Lithium carbonate (Li2CO3). Lithium cit-

administered orally as a salt rate and lithium orotate are also used.
in combination with what
anion?
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What is the mechanism of While exact mechanisms are unknown,

action of lithium? lithium appears to modulate the release
of serotonin and norepinephrine.
What are four medical 1. Bipolar disorder

indications for lithium use? 2. Depression (often in combination with
antidepressants)
3. Prevention of migraine and cluster
headaches
4. Treatment of thyroid storm in patients
with iodine allergy
What are four nonmedical 1. Batteries

uses of lithium? 2. Mixed with alloys of aluminum,
cadmium, and copper to make aircraft
parts
3. Lithium chloride (LiCl) is a
dessicant.
4. Lithium hydroxide (LiOH) is used to
scavenge carbon dioxide in
submarines and spacecraft, forming
lithium carbonate.
Use of lithium, especially Serotonin syndrome

in combination with
other serotonergic
agents, may lead to
what hyperthermic
syndrome?
What are four groups of 1. Diuretics

medications that can 2. NSAIDs
increase the risk of lithium 3. Tetracyclines
toxicity? 4. Phenytoin
What are the clinical Initial findings manifest as GI symptoms,

findings of acute lithium including nausea, vomiting, and diarrhea.
toxicity? This is followed by CNS symptoms, in-
cluding tremor, nystagmus, fasciculations,
ataxia, hyperreflexia, lethargy, seizures,
and coma.
What model of distribution The two compartment model

helps explain the delayed
CNS findings?
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What ECG findings occur 1. Flattened or inverted T-waves

with lithium toxicity? 2. ST depression
What are the signs of CNS symptoms predominate and include

chronic lithium toxicity? fatigue, ↓ concentration, dysarthria, and
ataxia, as well as acute toxicity findings
such as tremor, seizures, and coma.
What is the most common Nephrogenic diabetes insipidus

renal complication of
chronic lithium therapy?
What serum lithium 0.7–1.2 mg/dL

concentration is considered
therapeutic?
How is lithium eliminated Renally

from the body?
What is the effect of The kidney confuses lithium for sodium,

hyponatremia or dehydration and while trying to retain sodium, will
on lithium clearance? also reabsorb lithium.
What is the effect of a high A decreased anion gap may be seen with
serum lithium concentration lithium toxicity because lithium is an un-
on the anion gap? measured cation that may induce renal
retention of chloride or bicarbonate,
which are both measured anions.
What is the role of activated It is a poor binder of lithium and is not

charcoal in the treatment of useful in isolated lithium ingestion; it
lithium toxicity? should be given if there is a possibility of
a recent co-ingestion.
Describe the treatment for 1. Optimize fluid and electrolyte

acute lithium toxicity. (especially sodium) status to increase
renal excretion of lithium
2. Whole bowel irrigation may be used
to limit absorption.
3. Dialysis may be considered for severe
neurotoxicity, but forced diuresis plays
no role in treatment.
What is the treatment for Similar to that of acute toxicity; however,

chronic lithium toxicity? since CNS tissue concentrations are
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likely to be higher and neurologic symp-

toms are likely to be more prominent,
hemodialysis should play a greater role in
treatment.
What is the role of dialysis Lithium is freely dialyzable; however,

in lithium toxicity? secondary to the two-compartment
model of distribution, slow equilibration
between the tissue and blood compart-
ments may cause fluid and electrolyte
shifts and require multiple runs of dialy-
sis. Continuous renal replacement ther-
apy may be a better option. Neither
method has been conclusively demon-
strated to improve outcome. Hemodialy-
sis is indicated for severe neurotoxicity,
renal failure, and an inability to tolerate
sodium repletion. Other indicators for
dialysis, such as blood lithium concentra-
tion, are less fixed, and clinical judgment
should prevail.
MANGANESE
What is manganese? Trace element that serves as a cofactor

for many enzymes, including superoxide
dismutase
What is manganese used for? Alkaline batteries, some pesticides, decol-

orizing glass, fuel additive
Who is most likely to Welders, miners, dry-cell battery

experience manganese manufacturers
exposure?
What are the most common Inhalation and ingestion

routes of exposure?
What organ is most severely The brain

affected by manganese
exposure?
How is manganese excreted Biliary elimination

from the body?
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What chronic disease is Hepatic cirrhosis. Manganese levels are

associated with elevated increased secondary to decreased elimi-
manganese levels? nation from the body.
What is the mechanism of Largely unknown; however, toxicity may

manganese toxicity? be related to alterations in iron or other
essential element metabolism.
What are the signs and Personality changes, memory loss, and
symptoms of manganese parkinsonian symptoms. These symptoms
neurotoxicity? are progressive and often debilitating. Psy-
chosis and hallucinations have also been
reported with high manganese levels,
often referred to as “manganese madness.”
Describe the classic walk A high-stepping, toe walk known as “cock

associated with manganese walk” or “Hehnestritt,” which was named
toxicity. after its resemblance to a German sol-
dier’s high-step march
What disease does Parkinson’s disease

manganese toxicity mimic?
How does neuroimaging In acute manganese toxicity, lesions ap-

differ in manganese toxicity pear in the basal ganglia on T1 imaging.
versus Parkinson’s disease? In Parkinson’s disease, lesions are con-
centrated in the substantia nigra.
What are sources to test for Blood levels are commonly used, but
manganese levels? urine levels are also available. As man-
ganese is rapidly cleared from the body,
neither method detects remote exposure.
What is the treatment for 1. Supportive care with removal from the
manganese toxicity? exposure source
2. Carbidopa / levodopa has variable
efficacy in symptomatic improvement.
3. Chelation therapy may ↓ blood
manganese levels but appears to do
little to alter the course of the disease.
MERCURY
What are the three primary 1. Elemental (metallic)

forms of mercury? 2. Inorganic
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3. Organic (most commonly

methylmercury)
What are the primary routes 1. Elemental – inhalation

of toxic exposure from each 2. Inorganic – ingestion or dermal
form of mercury? absorption
3. Organic – ingestion or dermal
absorption
By what physiologic Reacts with sulfhydryl groups, phospho-

mechanism does mercury ryl groups, amide groups, and carboxyl
primarily cause toxicity? groups, causing nonspecific inhibition
of enzymes, transport proteins, and
structural proteins. Inorganic mercury
also has a corrosive effect on the
GI tract.
What catecholamine- Pheochromocytoma. Mercury inhibits

secreting tumor derived S-adenosyl-methionine, ultimately pre-
from chromaffin cells does venting catecholamine catabolism and
mercury toxicity mimic? causing sympathomimetic signs and
symptoms.
List some common sources Thermometers, sphygmomanometers,

of mercury exposure. folk remedies, seafood, burning fossil
fuels, mercury mining/smelting, manufac-
turing chlorine, electrical equipment,
gold mining, dental amalgams
What sea animals have the Shark, swordfish, mackerel, tuna, tilefish,
potential for crab
bioaccumulation of high
levels of methylmercury?
How does the acute Fever, chills, nausea, vomiting, abdomi-

inhalation of elemental nal cramping, diarrhea, ↓ vision, metallic
mercury vapors present taste. Pulmonary edema or chemical
clinically? pneumonitis may develop.
What are the clinical None. Only an extremely small amount

manifestations of elemental of elemental mercury is absorbed from
mercury ingestion (i.e., the GI tract. If it becomes trapped in the
thermometer-based)? GI tract (e.g., within a diverticula or ap-
pendix), however, mercury absorption
can be increased.
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Is it dangerous to spill Yes. A spill in a confined space can lead

elemental mercury? to significant levels of airborne mercury,
resulting in chronic inhalation. It is espe-
cially important to avoid vacuuming
the spill.
What are the clinical Oropharyngeal pain, hematemesis, hema-

manifestations of inorganic tochezia, intestinal necrosis, renal failure,
mercury ingestion? shock
What are the clinical Primarily CNS manifestations –

manifestations of organic dysarthria, ataxia, constriction of visual
mercury ingestion? field, hearing impairment, paresthesias.
The onset is usually insidious, and effects
are permanent.
What are the manifestations Tremor, gingivostomatitis, hypersalivation,

of chronic mercury toxicity? abnormal neuropsychiatric manifestations.
Renal dysfunction ranging from protein-
uria to nephritic syndrome may result.
What is erethism? Erethism is the psychiatric constellation

of chronic mercury toxicity, consisting of
irritability, anxiety, insomnia, and patho-
logical shyness.
What is acrodynia? Also called “pink’s disease,” it is a rare

reaction to mercury toxicity in children,
manifesting as painful pink discoloration
of the hands and feet accompanied by
sweating, hypertension, neurological
changes, photophobia, and a peeling
rash.
What body fluids prove most Elemental and inorganic – whole blood
accurate when measuring levels in acute exposure, urine levels in
levels of toxic mercury? chronic exposure
Organic – whole blood levels (limited
renal elimination)
What pharmacological Inorganic – chelation with PO succimer

therapies are available for (DMSA) or IM BAL if unable to tolerate
mercury toxicity? oral medications. DMPS is an IV compat-
ible derivative of BAL, but is not FDA-
approved in the United States.
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Elemental and organic – oral succimer

and N-acetylcysteine (organic mercury).
Oral penicillamine is available, but pro-
found GI side effects limit its usefulness.
Avoid BAL when treating for these two
types of mercury poisoning, as there are
animal studies indicating that it can cause
redistribution of mercury to the brain.
Are activated charcoal or Yes. These should be considered for

gastric lavage effective in acute ingestion of inorganic or organic
acute ingestion? mercury.
Can dialysis increase the No; although, it may become necessary if

rate of mercury elimination? renal failure results from intoxication.
MOLYBDENUM
What is molybdenum? An essential trace element necessary for

the catabolism of purines and the sulfur-
containing amino acids cysteine and
methionine
What is the role of Used in heat-resistant steel alloys, weld-

molybdenum in industry? ing, pigments, and some fertilizers
Which enzymes require 1. Xanthine dehydrogenase (used for

molybdenum as a cofactor? purine metabolism to uric acid)
2. Xanthine oxidase (a form of xanthine
dehydrogenase)
3. Sulfite oxidase (located in
mitochondria, catabolizes cysteine and
methionine, converts sulfite to sulfate)
4. Aldehyde oxidase (pyrimidine
catabolism and biotransformation of
xenobiotics)
How is molybdenum carried Bound to alpha-macroglobulin and ad-

in the bloodstream? sorbed to RBCs
How is molybdenum In urine and bile

excreted?
How does molybdenum Over-ingestion of dietary supplements

poisoning usually occur?
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Describe the features of oral While data is limited, acute toxicity from
molybdenum exposure. oral exposure appears to be low. Chronic
toxicity may induce xanthine oxidase and
increase uric acid production, leading to
the development of gout. Toxicity may
also result in a hypochromic microcytic
anemia.
What are the manifestations Inhalational exposure may produce a

of inhalational molybdenum syndrome similar to metal fume fever,
exposure? characterized by headache, arthralgias,
myalgias, weakness, fatigue, cough, and
diarrhea.
What is the treatment for Supportive care

molybdenum poisoning?
NICKEL
What is the most common Nickel dermatitis

disorder following nickel
exposure?
What organ systems are Skin, pulmonary, neurologic, hepatic

affected by systemic nickel
toxicity?
Name two types of nickel 1. Primary – an eczematous allergic

dermatitis. reaction following direct contact.
Erythematous papules and vesicles
may progress to lichenification.
2. Secondary – widespread rash caused
by ingestion, transfusion, inhalation, or
implanted medical devices /
orthodontic appliances
Primary nickel dermatitis is Type IV hypersensitivity

an example of what type of
immune reaction?
Which nickel compound Nickel carbonyl

most commonly causes
acute, generalized nickel
toxicity?
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What is nickel carbonyl? A highly volatile liquid compound used in

nickel refining and petroleum processing
Name the two metabolites of 1. Carbon monoxide

nickel carbonyl. 2. Elemental nickel
Describe the manifestations Initial symptoms after inhalational expo-

of acute nickel carbonyl sure often produce nonspecific respiratory
exposure. complaints, including airway irritation,
cough, and dyspnea. Nausea, weakness,
and headache may develop, as may chemi-
cal pneumonitis. Severe symptoms of in-
halational or ingestional exposure include
myocarditis, ARDS, and cerebral edema.
What are the effects of Chronic airway irritation and mucosal

chronic nickel exposure? atrophy may occur along with the devel-
opment of reactive airway disease and
pulmonary fibrosis. Nickel is listed as an
IARC Group 1 carcinogen and is associ-
ated with nasal and pulmonary carcino-
genesis with long-term exposure.
What are the recommended OSHA – ⬍0.007mg/m3 per 8-hour time-

limits in workplace nickel weighted average workday
carbonyl exposure?
What are the recommended 1. Exposure avoidance

treatments for nickel 2. Topical steroids
dermatitis? 3. Oral antihistamines
4. Avoidance of exposure to stainless
steel (controversial)
What are the recommended 1. Removal from the source and general
treatments for acute, supportive care
generalized nickel toxicity? 2. For liquid ingestion with prompt
presentation to the ED, gastric
aspiration with an NG tube may be
attempted.
3. Chelation with diethyldithiocarbamate
may also be warranted for severe
poisoning.
What is diethyldithiocarba- A chelation agent with purported efficacy

mate (DDC)? for nickel toxicity. While animal studies
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and human case reports appear to show

some benefit with its use, no conclusive
evidence is available to support its effi-
cacy; however, it is still considered the
chelator of choice for nickel toxicity.
PLATINUM
In what form are toxic levels The antineoplastic drugs cisplatin, carbo-
of platinum most often platin, and oxaliplatin
ingested?
What are common side Primarily GI – nausea, vomiting, diarrhea

effects of platinum-
containing drugs?
What are the common end- 1. Renal dysfunction (cisplatin)

organ manifestations of 2. Auditory impairment
platinum toxicity? 3. Peripheral sensory neuropathy
4. Myelosuppression (carboplatin)
What determines the Nephrotoxicity

maximum dosing of
cisplatin?
What determines the Myelosuppression

maximum dosing of
carboplatin?
With what pathological 1. Acute tubular necrosis (distal

processes are cisplatin’s convoluted tubule)
nephrotoxicity associated? 2. Chronic interstitial nephritis
3. Renal tubular abnormality (e.g.,
acidosis, hypokalemia,
hypomagnesemia)
What are the primary goals 1. Renal protection

in the treatment of a 2. Platinum elimination
cisplatin overdose?
What treatments help 1. IV normal saline 1–3 mL/kg/h for 6 to

achieve these primary goals? 24 hrs
2. Osmotic diuresis with an appropriate
diuretic (e.g., mannitol). Furosemide
may potentiate ototoxicity.
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3. Plasmapheresis initiated immediately

after overdose
4. Sodium thiosulfate can limit
nephrotoxicity if given after an
overdose.
What role does hemodialysis None. Hemodialysis has not been proven
play in treating cisplatin effective in treating platinum / cisplatin
overdose? overdose.
What symptoms are Loss of proprioception and vibration

associated with cisplatin sense with relative preservation of pain
neurotoxicity? and temperature sensation
What fluid and electrolyte 1. Hypomagnesemia

disturbances are associated 2. Hypokalemia
with cisplatin toxicity? 3. Hypocalcemia (secondary to
hypomagnesemia)
4. Syndrome of inappropriate anti-
diuretic hormone secretion (SIADH)
What is the primary hemato- Thrombocytopenia

logical disturbance seen
with carboplatin toxicity?
Is there another route of Yes. Platinum is used in multiple industrial

exposure which causes settings. Inhalation of platinum by workers
toxicity secondary to can lead to sensitization and development
platinum? of dermatitis and bronchospasm.
RARE EARTHS
What are the rare earth A group of metals that includes the lan-
elements? thanoids (except promethium, plus scan-
dium and yttrium) – lanthanum (La),
cerium (Ce), praseodymium (Pr),
neodymium (Nd), samarium (Sm), eu-
ropium (Eu), gadolinium (Gd), terbium
(Tb), dysprosium (Dy), holmium (Ho), er-
bium (Er), thulium (Tm), ytterbium (Yb),
lutetium (Lu), scandium (Sc), yttrium (Y)
What are the main industrial/ Professional and motion picture lighting,
medical uses of the rare glass production, manufacture of other
earth elements? metals, electronic devices (e.g., micro-
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phones, speakers, television tubes),

magnets, nuclear power technology,
portable x-ray devices, other radiographic
imaging
In general, how dangerous Generally, the rare earths are of low to

is exposure to the rare earth moderate toxicity. Few are radioactive
metals? (see below), and few are associated with
risks following exposure during medical
procedures.
Which rare earth metal is Ytterbium. Compounds of ytterbium can

considered highly toxic? be irritating to the skin and eyes, and
may cause birth defects following expo-
sure during pregnancy.
Which rare earth metals are 1. Europium

radioactive? 2. Scandium has a radioactive isotope
(Sc-46)
3. Promethium (technically not a “rare
earth”)
In what medical setting is Gadolinium is contained in the contrast

the rare earth element medium used in MRI.
gadolinium used?
What medical condition has Nephrogenic systemic fibrosis

been linked to gadolinium
exposure through MRI
contrast agent?
SELENIUM
What are common Pigments and dyes, gun-bluing solution

commercial uses of (selenious acid), electronics
selenium?
What are medical uses of 1. Selenium sulfide is used to treat

selenium-containing pityriasis versicolor, scalp dandruff,
compounds? and seborrheic dermatitis of the scalp.
2. Selenium is used as an OTC dietary
supplement.
Which selenium compound Selenious acid. ⬃15 mL of gun-bluing

is most toxic? solution may be fatal.
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Describe the mechanism of Little is known about the mechanism of

selenium toxicity. toxicity. Selenious acid produces corro-
sive injury to the GI tract. Selenium may
also produce systemic oxidative stress in
overdose; it may disrupt cellular respira-
tion and/or cause interference with pro-
tein synthesis.
How does dermal, ocular, or Select selenium compounds (i.e., sele-

inhalational selenium nious acid, selenium dioxide, and sele-
exposure manifest? nium oxychloride) cause corrosive
injury. Corresponding symptoms include
ocular or dermal erythema, pain, and
caustic burns. Pulmonary findings
after inhalation include airway
irritation, cough, dyspnea, and chemical
pneumonitis.
What are symptoms of acute Severe GI distress with nausea, vomiting

selenious acid ingestion? and diarrhea. This may progress to
lethargy, hypotension, and multisystem
organ failure. Ingestion of selenium salts
may present similarly, but symptoms tend
to be less severe.
Describe the symptoms of Hair and nail abnormalities, including

chronic selenium exposure. brittleness and discoloration, are com-
mon. Skin erythema, blistering, and pe-
ripheral neuropathy may also occur.
What breath odor is Garlic

associated with selenium
ingestion?
What is the nail finding that Red pigmentation of the nail beds or
can occur with selenium Mees’ lines (transverse lines on the nails)
toxicity?
How is selenium toxicity Whole blood, serum, and urine selenium

diagnosed? levels can be measured; however, these
levels are not well correlated with degree
of exposure or prognosis. Other labora-
tory evaluation should be determined by
the degree of toxicity and the speculated
organ systems involved.
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What is the treatment for Supportive care is the primary treatment.

oral selenium toxicity? For patients presenting promptly after
selenious acid ingestion, gastric aspiration
with an NG tube may be beneficial.
What treatments may be In addition to copious irrigation, a topi-

helpful for dermal or ocular cally applied 10% sodium thiosulfate
injury? solution may help reduce corrosive
selenium dioxide to elemental selenium,
which is benign.
SILVER
What are some common 1. Colloidal silver (elemental silver in

sources of silver? suspension) solutions found in alter-
native medicine dietary supplements
2. Electrical components
3. Photography
What are the medical uses Silver has natural antimicrobial proper-
of silver? ties and, historically, was widely used for
this purpose. Today, its use is more lim-
ited; it is commonly used as topical burn
cream (silver sulfadiazine) and as a chem-
ical cautery agent (silver nitrate).
What are the uses of silver 1. Silver oxide is used to prepare other
oxide and silver nitrate? silver compounds and is the cathode
in silver oxide batteries (often used in
watches).
2. Silver nitrate is used as an
antimicrobial in neonatal
conjunctivitis, as a cauterizing agent,
and in dentistry to assist in healing
ulcers of the mouth. It is also used as
a histological stain and in electron
microscopy.
What are the most common Mucosal irritation from exposure to silver
acute manifestations of oxide and silver nitrate
silver toxicity?
Describe the systemic In very large ingestions or in intravenous

manifestations of acute dosing, silver has been shown to cause he-
silver toxicity. patic, cardiac, neurologic, and hematologic
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abnormalities; however, silver is consid-

ered to be essentially nontoxic.
Name the most common Argyria

dermatologic manifestation
of chronic silver exposure.
What is argyria? Local or generalized gray or blue-gray

skin discoloration due to silver deposition
within the skin from ingestion of elemen-
tal silver or silver compounds. Usually,
ingestion is because of the touted antimi-
crobial properties of silver.
Is this condition reversible? No, it is permanent. There is no known

effective chelator.
What are the deleterious Cosmetic discoloration may lead to psy-

effects of argyria? chological stress. Otherwise, no harmful
health effects are known.
THALLIUM
What is thallium? It is a soft, gray, malleable metal that

oxidizes when exposed to air. Thallium
salts are extremely toxic, tasteless,
odorless, and will dissolve completely
in water, making it popular among
poisoners.
Historically, what was the As a rat poison and insecticide, but its
most common use of use in the United States has ceased be-
thallium? cause of its high toxicity to humans
Are there other uses for Yes. It is used in manufacturing lenses,

thallium? semiconductors, infrared detectors, and
alloys (due to its anticorrosive
properties).
What is its mechanism of Exact mechanism is unclear. It may cause

toxicity? energy depletion by interfering with the
Krebs cycle, glycolysis, and oxidative
phosphorylation. Also, it may form com-
plexes with sulfhydryl groups on en-
zymes, inhibiting function.
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Which is more toxic, highly Highly water-soluble compounds

water-soluble compounds or (e.g., thallous acetate, thallic chloride)
compounds with low water are more toxic than those with low
solubility? solubility (e.g., thallic oxide, thallous
iodide).
How does acute thallium Thallium poisoning can result in many

toxicity present? nonspecific clinical effects. This makes
diagnosis difficult. GI complaints are
often noted first and include abdominal
pain and diarrhea, followed by constipa-
tion. Vomiting can occur but is usually
not a major symptom. The most reliable
early diagnostic feature of thallium poi-
soning is an extremely painful, rapidly as-
cending peripheral neuropathy. This can
take from several days to 2 weeks to de-
velop. Other neurological symptoms in-
clude weakness, tremor, cranial nerve
palsies, optic neuropathy, seizures, coma,
and death. Cardiac manifestations in-
clude hypertension, tachycardia, and non-
specific ST and T wave changes.
What is a distinctive feature Hair loss with hyperpigmentation of the

of chronic thallium toxicity? hair root; however, do not wait for this
finding to consider thallium poisoning, as
it may not be noticed for days to weeks
and is not always present
What other dermatological Mees’ lines, or transverse white lines

finding can be seen? across the nails. These will not be noted
for at least 2 weeks.
What is the classic picture of Gastroenteritis, painful peripheral neu-

thallium toxicity? ropathy and subsequent alopecia
What radiological adjunct Abdominal x-ray. As thallium is ra-

can be used to support acute diopaque, plain films may be useful in
thallium toxicity? acute ingestions. The sensitivity is not
known if radiographs are obtained after
symptoms develop.
What test can confirm the A 24-hour urine thallium level

diagnosis?
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What is the antidote to Prussian blue (ferric ferrocyanide,

thallium toxicity? Radiogardase)
What is its mechanism? Binds thallium ions and interrupts the

enterohepatic recycling of thallium
What chelators are Penicillamine and diethyldithiocarba-

contraindicated in thallium mate, as they may augment CNS
toxicity? redistribution
What are other means to Activated charcoal

augment elimination of
thallium from the body?
What distinguishes thallium Arsenic poisoning has more pronounced

poisoning from arsenic GI symptoms, particularly copious diar-
poisoning? rhea. Aresnic may also cause pancytope-
nia, whereas thallium does not.
TIN
What is tin most widely used Plating steel cans for food preservation and
for? as a protective coating for other metals
What special properties It is not easily oxidized and resists corro-

make tin great for storing sion because it is protected by an oxide
food? film.
What are other uses of tin? Tin alloys are used in making bronze, sol-
dering materials, and dental fillings, and it
is found in toothpaste, perfumes, soaps,
and additives. Organic tins may be used as
fungicides, pesticides, and bactericides.
What is the most common Ingestion of foods contaminated with tin

route of tin exposure? compounds, especially large amounts of
those stored in tin for long periods of
time and in low pH conditions
What are other routes of Inhalation of tin-containing particles or

exposure? contact with the skin and mucous
membranes
What are the effects of tin Acutely, tin salts and organotins produce
inhalation? irritation of mucous membranes and the
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upper airway. Cough, dyspnea, and bron-

chospasm may develop.
What is stannosis? A pneumoconiosis caused by chronic in-

halation of inorganic tin
Describe the toxic Ingestion of tin salts primarily produces

manifestations of tin GI symptoms, including nausea, vomiting,
ingestion. diarrhea, abdominal pain, and possible he-
matemesis. Usually, large amounts are
needed to produce significant toxicity.
Do tin compounds cause Organotins may cause corrosive skin in-

dermal toxicity? jury, often presenting as erythema or der-
matitis. Some organotin compounds may
be dermally absorbed.
Describe the neurotoxicity Organic tin compounds are associated with

associated with organotins. CNS disease (e.g., delirium, encephalopa-
thy, cerebral edema, cerebellar dysfunc-
tion) and peripheral polyneuropathy.
Which types of organotins Triorganotins, including trimethyltin and

are most associated with triethyltin
toxicity?
What is the treatment for tin Inhalational exposure should be managed

toxicity? with oxygen and beta 2-adrenergic
agonists, as needed. Ingestion of tin
compounds is managed primarily with
supportive care.
VANADIUM
In what industries is Iron and steel industries, mining and pro-

vanadium found? cessing of ores, production of chemical
catalysts, boiler and furnace mainte-
nance, pacemaker battery manufacturing
What is the most common Vanadium pentoxide

type of vanadium exposure?
What is the usual route of Inhalation of fine particulate matter. Di-

toxicity? rect ingestion is rare, and toxicity through
this route appears to be limited.
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How is vanadium excreted? 91% in the urine, 9% in the feces
What are the signs and Mucosal irritation, cough, wheezing, dys-
symptoms of acute pnea, and possible green-black discol-
inhalational toxicity? oration of the tongue. Conjunctivitis may
also be present secondary to ocular vana-
dium dust exposure.
What are the long-term None. Airway disease is typically re-

effects of vanadium versible, and no long-term changes in
exposure on the lungs? pulmonary function tests are seen.
What are the effects of Data is limited on oral exposures. Diar-

vanadium ingestion? rhea, along with abdominal cramping, ap-
pears to be a common manifestation.
Nausea and vomiting may also occur.
What is unique about Vanadate (pentavalent vanadium) is one

pentavalent vanadium? of the most potent known inhibitors of
the Na-K-ATPase pump.
Does vanadium exposure Vanadium is listed as a “possible human

pose a long-term health carcinogen,” with an IARC classification
risk? of Group 2B.
What is the treatment of Supportive care, with oxygen and beta

vanadium toxicity? 2-adrenergic agonists as needed for pul-
monary symptoms
ZINC
What is the typical use of Galvanizing steel and iron to prevent

metallic zinc? corrosion
What industries are Metal alloy manufacturing, petroleum re-

associated with exposure to fineries, paint and pigment manufactur-
zinc? ing, cosmetics, woodworking, embalming,
dentistry, military smoke bomb manufac-
turing, topical ointments in medicine
What zinc compound is most Zinc oxide

widely used?
What zinc compounds are Zinc oxide and zinc chloride

associated with toxicity?
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What zinc compound is used Zinc phosphide

as a common rodenticide?
What is the most common Ingestion of products containing zinc, fol-

route of exposure? lowed by inhalation of dust and fumes
containing zinc compounds. Dermal and
mucous membrane exposure comes from
aerosolized zinc compounds or topical
ointments containing zinc.
What metal is the most Zinc.

common cause of metal
fume fever?
What is metal fume fever? A flu-like, febrile syndrome that may

occur after inhaling fumes from heated
metals. This typically occurs during
welding.
What are the signs and Toxicity can present similarly to other
symptoms associated with corrosive metal salt exposures. Nausea,
acute oral zinc toxicity? vomiting, diarrhea, hematemesis, and
mucosal erosion have been reported.
Describe the manifestations Dermal or inhalational exposure to corro-

of dermal and inhalational sive zinc compounds generally produces
exposure. symptoms of local irritation. Pulmonary
symptoms include airway irritation,
cough, dyspnea, and chemical pneumoni-
tis. Dermal exposure may produce der-
matitis, erythema, and ulcerations.
Describe the effects of Anemia and myelodysplastic syndrome

chronic zinc toxicity. have been reported after long-term expo-
sures. Both are reversible upon cessation
of exposure. The pathogenesis is likely re-
lated to zinc-induced copper deficiency.
Are zinc levels useful for Zinc levels may help confirm toxicity in
patient management? cases of chronic exposure. Collection
methods should be meticulous, as con-
tamination can easily occur. Zinc and
copper levels should be obtained to-
gether, as elevated zinc may cause copper
deficiency. Zinc levels are unlikely to be
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helpful in acute poisoning because of the

significant delay in receiving results.
What is the management for 1. Supportive care. Metal fume fever is

acute zinc toxicity? self-limiting.
2. Pulmonary symptoms may be treated
with oxygen and beta 2-adrenergic
agonist therapy.
3. Aggressive fluid resuscitation may be
needed following oral exposure, as GI
losses may be significant.
4. Endoscopy for evaluation of the extent
of corrosive injury.
METAL FUME FEVER
What is metal fume fever? A febrile illness that develops after expo-
sure to metal oxides
What is the route of Inhalation of “fumes” that contain partic-

exposure? ulate metal oxides
What metal oxide is most Zinc oxide

strongly associated with
metal fume fever?
What environments are Occupations that involve the welding,

associated with metal fume melting, or cutting of metal, specifically
fever? galvanized or zinc-coated steel
What is the mechanism of The exact mechanism is not known but is

toxicity? suspected to be immune-mediated.
What are the signs and Flu-like symptoms including fever, chills,
symptoms? headaches, cough, dyspnea, fatigue, and
myalgias that typically resolve within 36
hrs. Symptoms usually occur within 6 hrs
of exposure.
Are there any helpful WBCs may be elevated. CXR is normal.

laboratory tests?
What are other names for Monday morning fever, brass foundry
metal fume fever? workers ague, brass chills, smelter shakes,
zinc chills
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Why is it called “Monday After repeated exposure, patients develop

morning fever”? a transient resistance to developing
metal fume fever but rapidly become
re-sensitized after cessation of exposure.
Workers commonly develop symptoms
again when returning to work after hav-
ing the weekend off.
What is the antidote? There is no antidote. After removal

from the source, the symptoms are self-
limiting. Treatment is supportive and
aimed at symptomatic relief.
How is metal fume fever Polymer fume fever is a similar flu-like

different from polymer illness developing after inhalation of
fume fever? fumes from fluorinated polymers. Unlike
metal fume fever, patients with polymer
fume fever are more likely to develop
pneumonitis and acute lung injury. Infil-
trates may be apparent on CXR. These
patients do not develop the progressive
acclimation that is characteristic of metal
fume fever.
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Chapter 6 Pesticides
FUNGICIDES
What are dithiocarbamates? Commonly used fungicides. Unlike N-

methyl carbamates, dithiocarbamates
have no anticholinesterase activity.
By what mechanisms do 1. Mucosal irritants

dithiocarbamates cause 2. Metabolism produces carbon
toxicity? disulfide, causing headache, delirium,
and encephalopathy.
3. Many of the dithiocarbamates will
inhibit aldehyde dehydrogenase. This
may cause a disulfiram reaction
(tachycardia, hypotension, vomiting,
tremor) if ethanol is ingested after
exposure.
What neurological condition Parkinsonism. This is caused by either

is caused by chronic chronic carbon disulfide exposure or toxi-
exposure to maneb city from the manganese component.
(manganese ethylene-bis-
dithiocarbamate)?
What are organochlorine Also known as substituted aromatic

fungicides? fungicides. Important members of this
class include pentachlorophenol, which
is used as a wood preservative, and
hexachlorobenzene.
What is the mechanism of Uncoupling of oxidative phosphoryla-

toxicity for tion, inducing a hypermetabolic state
pentachlorophenol? with fever, diaphoresis, tachypnea,
tachycardia, and metabolic acidosis.
As toxicity progresses, patients can
develop AMS, coma, rigidity, seizures,
and death.
How can human exposure Ingestion, inhalation, dermal. A number

occur? of infants were exposed to diapers and
311
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linens treated with pentachlorophenol

and developed significant toxicity,
including hepatosplenomegaly.
What condition can Porphyria cutanea tarda, hepatomegaly,

hexachlorobenzene cause? and hypertrichosis
What are organotin Alkyl and aromatic derivatives of tin that

compounds? are used as fungicides, preservatives for
paints and fabrics, and antifouling agents
for ships
What toxic effects do 1. Tributyltin – potent skin and eye

organotins have? irritant, exposure can cause burns
2. Triphenyltin – also a dermal irritant,
can cause headache, nausea, vomiting,
blurred vision, and seizures.
Hepatotoxicity is possible.
3. Trialkyltin – will readily cross the
blood-brain barrier and cause
neurotoxic effects, including tremor,
headache, weakness, and paralysis
4. All organotins – immunotoxicity with
decreased lymphoid tissue weight,
lymphopenia, and altered immune
function has been observed after
organotin exposure in animal studies.
What clinical presentation Corrosive effects on the GI tract. Ingestion

can be seen after ingestion may cause greenish blue emesis, abdomi-
of a copper salt? nal pain, hematemesis, melena, hepatotox-
icity, hemolysis, and methemoglobinemia.
What are examples of Vinclozolin and iprodione

dicarboximide fungicides?
What is the mechanism of Antagonistic binding at androgen recep-

toxicity of dicarboximides in tors → ↓ protein synthesis for genes that
humans? require androgen binding for expression
What are the effects of Hypospadias and cryptorchidism

prenatal exposure?
What are examples of Captan, folpet, captafol

phthalimide fungicides?
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Chapter 6 / Pesticides 313
What is another major use Synthesis of amines in the plastics

of phthalimides? industry
What is the mechanism of Inhibition of the cytochrome P450 system

toxicity of phthalimides?
What is the most commonly Reversible dermatitis

reported effect of
phthalimide toxicity?
What are the prenatal There is concern they may be terato-

effects of phthalimides? genic, causing CNS and musculoskeletal
defects. Phthalimides are analogs of
thalidomide.
What are examples of Azoxystrobin, pyraclostrobin,

strobilurins? trifloxystrobin
What is the mechanism of Inhibition of complex III of the oxidative

action of strobilurins? respiratory system in mitochondria
What are the effects of Dermatitis and conjunctivitis predomi-

strobilurin exposure? nate. Patients can also suffer upper
airway irritation, chest pain, or nausea
after aerosol exposure. Strobilurins are
not considered teratogenic.
HERBICIDES
CHLOROPHENOXY
What are chlorophenoxy A group of synthetic plant hormones, used

herbicides? as commercial and household herbicides,
that selectively target broad-leaf plants
What is the prototypical Dichlorophenoxyacetic acid (2,4-D)

chlorophenoxy herbicide?
In what clinical situation is Intentional ingestion

chlorophenoxy herbicide
toxicity usually seen?
Through what route does Intestinal absorption (⬎90% of chemical

2,4-D most efficiently enter ingested is absorbed). Transdermal
the bloodstream? absorption is low.
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What increases dermal Sunscreen

absorption of 2,4-D?
What organ system is the CNS

primary target of 2,4-D?
What are symptoms of Marked irritation of the eyes, nose, and

exposure to 2,4-D? throat potentially lasting for days
Describe the manifestations Oropharyngeal burning followed by

of 2,4-D toxicity following nausea, vomiting, and diarrhea. AMS,
ingestion. lethargy, and seizures may occur, along
with cardiac dysrhythmias, in severe
poisoning.
What abnormal laboratory 1. Elevated CPK

values are associated with 2. Myoglobinuria (with possible renal
toxic 2,4-D exposure? dysfunction)
3. Metabolic acidosis
4. Mild to moderate hepatic
transaminase elevation
Can elimination of 2,4-D be Both urinary alkalinization and hemodial-

enhanced? ysis have been studied in 2,4-D poison-
ing, but neither treatment has been
shown to improve patient outcome.
What chlorophenoxy 2,4,5-trichlorophenoxyacetic acid

herbicide used during the (2,4,5-T), also known as “Agent Orange.”
Vietnam War has been The role of 2,4,5-T in long-term health
linked to chronic health problems is still uncertain but may be
problems? related to chemical contaminants, such as
dioxins, and not the parent compound.
DIQUAT
What is diquat? A fast-acting, nonselective herbicide
How is diquat used? Applied directly to leaves and grass and is

inactivated upon contact with soil
Who has access to diquat? No formal license is required for use

in the United States. It is found in
several commercially available gardening
products.
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What are the major routes Ingestion, inhalation, transdermal

of entry to the systemic (poorly)
circulation for diquat?
In what organ is diquat Kidney. Ingestion can lead to renal

concentrated? failure.
How does diquat toxicity Following ingestion, there is no pul-

differ from that of monary involvement in diquat poisoning,
paraquat? as long as the patient does not aspirate.
Paraquat, on the other hand, causes pul-
monary injury.
With what pathological Renal failure

conditions is diquat ingestion
primarily associated?
What are the initial GI distress (i.e., nausea, vomiting,

symptoms associated with abdominal pain) predominates, although
diquat ingestion? symptoms vary in intensity with the dose
ingested.
What are signs of diquat Corrosive GI injury, renal failure,

ingestion? myonecrosis, agitation, seizures, coma.
Unlike paraquat, diquat does NOT cause
pulmonary fibrosis.
How is diquat poisoning 1. History of exposure is most helpful.

diagnosed? 2. Oral mucosal burns that may have a
pseudomembranous appearance of the
soft palate
3. CXR to rule out aspiration
4. Plasma and urine diquat levels are
available from the chemical
manufacturer.
What laboratory values are 1. Electrolytes, BUN, and creatinine to

helpful in poisoning? assess for renal dysfunction
2. CPK to evaluate for myonecrosis
How is diquat ingestion 1. Supportive care

treated? 2. Dermal and ocular decontamination
through copious irrigation
3. Gastric aspiration with an NG tube
may be indicated for early patient
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presentation. Administer activated

charcoal, bentonite, or fuller’s earth if
available and if the patient is able to
swallow without difficulty (i.e., no
signs of caustic injury).
What other treatments have Charcoal hemoperfusion or hemodialysis

been suggested for diquat has been suggested in some reports,
poisoning? but no definitive scientific evidence is
available.
PARAQUAT
What is paraquat? A fast-acting, nonselective herbicide used

for killing unwanted grass and weeds
How is paraquat used? After topical application to weeds and

grass, it distributes within the plant
tissue, interrupting photosynthesis and
generating free radicals. Paraquat is
inactivated upon contact with soil.
Who has access to paraquat? A license for use is required in the

United States, so it is not often used for
home gardening applications.
What is the mechanism of Generation of free radicals with subse-

paraquat toxicity? quent damage to proteins, DNA, and cell
membranes
What are the major routes Ingestion, inhalation, transdermal (poorly)

of entry to the systemic
circulation for paraquat?
In what organs is paraquat 1. Lungs – selective alveolar cell uptake

most highly concentrated? → necrosis and proliferation of
connective tissue
2. Kidney
3. Liver
4. Muscle
How is paraquat Active transport by the polyamine uptake

concentrated in lung tissue? pathway keeps lung concentrations high.
What is a lethal oral dose of 2 to 4 g of 20% solution (10 to 20 mL for

paraquat? an adult or 4 to 5 mL for a child)
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What are the initial Nausea, vomiting, abdominal pain,

symptoms of paraquat oropharyngeal pain. Symptoms vary in
ingestion? intensity with the dose ingested.
What are signs of paraquat 1. Hours to days post-ingestion –

ingestion? corrosive injury to oropharynx and GI
tract, renal failure, myonecrosis
2. Several days post-ingestion –
progressive pulmonary fibrosis →
respiratory failure (the major cause of
death)
How is paraquat poisoning 1. History of exposure is most helpful.

diagnosed? 2. Oral mucosal burns with a
pseudomembranous appearance of the
soft palate
3. CXR
4. Plasma and urine paraquat levels are
not readily available but can be
obtained through the product
manufacturer.
How is paraquat ingestion 1. Gastric aspiration with an NG tube

treated? should be attempted for patients
presenting within a few hours
post-ingestion.
2. Dermal and ocular decontamination,
as needed, through copious irrigation.
3. Consider administration of activated
charcoal, fuller’s earth, or bentonite if
the patient lacks significant signs of GI
injury and presents early after
ingestion.
What treatment is Oxygen, as it increases the production of

contraindicated for paraquat free radicals
poisoning?
What other treatments have Cyclophosphamide and methylpred-

been suggested for paraquat nisolone may improve outcomes in
poisoning? paraquat-poisoned patients, but no con-
clusive evidence is available to support
their efficacy. Charcoal hemoperfusion
and hemodialysis may also improve out-
come if initiated early, but data on effi-
cacy is limited. As paraquat has extreme
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toxicity and few treatment modalities are

available, aggressive decontamination,
as well as responsible use of the above
unproven therapies, may be the patient’s
best option.
OTHER
What is the most widely Roundup® brand weed killer

used herbicide in the
United States?
What is the active Glyphosate

ingredient in Roundup?
How does glyphosate Inhibition of plant-specific enzymes,

inhibit plant growth? resulting in disruption of aromatic amino
acid production
What “inactive Surfactant, specifically polyoxyethyle-

ingredients” are present in neamine (POEA), which is included to
glyphosate-containing allow passage through the waxy coating
herbicides that may of leaves and is more toxic (lower LD50)
contribute to toxicity? than isolated glyphosate. Because
glyphosate targets a plant-specific
enzyme, Roundup’s adverse effects
described in humans are due to the
accompanying surfactant.
Through what route are Ingestion (often intentional). Direct oral

glyphosate preparations mucosal injury is followed by adverse
most toxic? effects on CV, respiratory, renal, and
hepatic function in select cases.
What are signs and Vomiting, diarrhea, oropharyngeal corro-

symptoms of glyphosate sive injury, metabolic acidosis, cardio-
toxicity? genic shock, cardiac dysrhythmias
How should glyphosate Supportive care and decontamination.

ingestion be treated? Consideration may be given to gastric
suction with an NG tube if the patient
presents promptly after ingestion.
What is atrazine? A commonly used, nonselective herbicide

in the chlorotriazine class
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In what commonly used Ortho Weed and Feed, Scott’s Bonus

brands of home-use Type S, Attrex, Atratol
herbicides can atrazine be
found?
Through what route is Ingestion. Transdermal and mucous

atrazine most toxic? membrane absorption is minimal.
What reported clinical AMS, GI hemorrhage, metabolic

effects are associated with acidosis, hypotension. As with glyphosate-
atrazine-containing containing compounds, effects from
herbicide toxicity? atrazine-containing compounds are
thought to be mediated by other “inactive
ingredients,” such as surfactant.
How should atrazine Supportive care with elective considera-

ingestion be treated? tion for gastric aspiration by NG tube.
Particular care should be taken to avoid
pulmonary aspiration of the product, as
many of the atrazine-containing products
also contain a hydrocarbon solvent.
How is sodium chlorate used It is nonselective and may be applied to

as an herbicide? the plant or the soil, where it may remain
for years. It is also used to remove
moisture from crops before harvest.
What is the mechanism of Oxidation of a necessary plant enzyme

toxicity of sodium chlorate complex, rendering it inactive
in plants?
Describe the mechanism of Oxidation of heme complex (Fe2⫹ →

toxicity of sodium chlorate Fe3⫹), creating methemoglobin. Oxida-
in humans. tive stress may also result in intravascular
hemolysis secondary to RBC membrane
disruption.
Through what route is Ingestion. While it may cause irritation to

sodium chlorate most toxic? the skin and mucous membranes, it does
not have significant dermal or mucous
membrane absorption.
What are the early signs and GI distress (i.e., vomiting, diarrhea,
symptoms of sodium abdominal pain)
chlorate ingestion?
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What are the later signs of Manifestations of hypoxia and hemolysis,

sodium chlorate ingestion? including cyanosis, shock, cardiac dys-
rhythmias, hyperkalemia, renal failure,
AMS, respiratory failure, acidosis, and
jaundice. These manifestations may be
delayed up to 48 hrs.
What is the treatment for 1. Supportive care is the primary

sodium chlorate ingestion? treatment.
2. Methylene blue for symptomatic
methemoglobinemia
3. Blood transfusions may be necessary
for severe hemolysis.
What is the herbicidal Acts as a glutamate analog, incorporating

mechanism of action of itself into plant proteins and interfering
glufosinate? with glutamine synthetase. This results
in toxic ammonia levels, as the plant is
unable to metabolize this substance.
What is the mechanism of 1. Disruption of ammonia catabolism,

toxicity of glufosinate in yielding elevated levels. Alternative
humans? metabolic pathways are available in
humans, however, so small exposures
may remain asymptomatic.
2. Inhibition of glutamate dehydrogenase
→ ↓ GABA → seizures and AMS
What are signs and Nausea, vomiting, AMS, respiratory

symptoms of glufosinate depression, ataxia, seizures. Rarely,
toxicity? diabetes insipidus has been reported.
When do signs and GI effects occur almost immediately;

symptoms of glufosinate however, AMS may be delayed up to
toxicity become clinically 8 hrs, and seizures may be delayed up to
apparent? 24 hrs. Initial GI symptoms may be
related to surfactant toxicity.
How is glufosinate toxicity 1. Supportive care

treated? 2. Consider gastric aspiration with an
NG tube if patients present promptly
after ingestion.
3. Hemodialysis may also be considered
for severe exposures but has not been
definitively shown to improve outcomes.
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INSECTICIDES
CARBAMATES
What are the common Aldicarb, carbaryl (Sevin), pirimicarb

carbamate insecticides? (Aphox, Rapid), propoxur (Baygon),
trimethacarb (Landrin)
What is the mechanism of Bind to a serine hydroxyl residue at the

action of carbamates? active site of the acetylcholinesterase
(AChE) enzyme → active site is blocked
→ ACh breakdown ceases → ACh accu-
mulates in the synapse → excessive
cholinergic stimulation
Does “aging” occur with No. Carbamates bind to AChE reversibly,

carbamates? and aging does not occur (unlike
organophosphates, which do cause aging).
What is a common DUMBELS

mnemonic used to Defecation
remember the cholinergic Urination
signs and symptoms of Miosis
carbamate poisoning? Bronchorrhea / Bronchospasm /
Bradycardia
Emesis
Lacrimation
Salivation
Does this list include all the No, it only includes muscarinic effects.
possible effects of The excess cholinergic stimulation will
carbamate poisoning? also stimulate nicotinic receptors, causing
effects at the motor end plate (e.g., fasci-
culations, weakness, paralysis) and sym-
pathetic ganglia (e.g., tachycardia, HTN).
What routes of exposure are All routes of contact

possible with carbamates?
Do carbamates penetrate Poorly; thus, patients with carbamate

the CNS? exposure have less CNS toxicity (rare
seizures and coma) than patients with
organophosphate exposure. However,
patients may develop CNS effects
secondary to hypoxia caused by bron-
chospasm and bronchorrhea.
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What are treatments for 1. Removal from exposure source and

acute carbamate exposure? clothing (avoid secondary exposure of
healthcare workers)
2. Copious dermal irrigation with soap
and water for cutaneous exposures
3. Consider activated charcoal for GI
exposure.
4. Protect the patient’s airway if
necessary (use a nondepolarizing
paralytic for RSI).
5. Atropine to resolve bronchospasm and
pulmonary secretions
6. Pralidoxime is not indicated in pure
carbamate poisoning, as AChE
poisoned by carbamates does not
undergo aging. It is reasonable to
consider administration of pralidoxime
to a patient presenting with
cholinergic symptoms if the exact
agent is not known.
ORGANOCHLORINES
What are the common Chlorobenzilate, dicofol (Kelthane),

organochlorine insecticides? dienochlor (Pentac), endosulfan, lindane
(Kwell), dichlorodiphenyltrichloroethane
(DDT)
What is the mechanism of 1. Disrupts normal axonal transmission,

toxicity of organochlorines? likely by opening sodium and
potassium channels
2. Antagonizes GABA-mediated
inhibition in the CNS → a
hyperexcitable state in the CNS and
PNS
What are the potential Acute exposure causes CNS stimulation,

clinical effects following resulting in paresthesias, ataxia, tremor /
acute organochlorine myoclonus, nausea, vomiting, and seizures.
exposure / toxicity?
What routes of toxicity are Ingestion, inhalation, dermal

possible with
organochlorines?
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How are organochlorines Most are metabolized by the liver and

metabolized and excreted? induce hepatic microsomal enzyme sys-
tems. Also, many are eliminated fecally,
with some agents undergoing enterohep-
atic and enteroenteric recirculation.
What are the treatments for 1. Removal from exposure source and
an acute organochlorine clothing (avoid secondary exposure of
exposure? healthcare workers)
and water for cutaneous exposures.
3. Cholestyramine (a nonabsorbable bile
acid) may ↑ fecal elimination.
Are there chronic health Extended exposure may produce chronic

effects from neurologic effects, including tremor,
organochlorines? weakness, and ataxia. These effects were
prominent among factory workers in-
volved in the manufacture of the
organochlorine chlordecone in Hopewell,
Virginia; this became known as the
“Hopewell epidemic.”
What topical pediculicide is Lindane

contraindicated in children
secondary to its ability to
cause seizures?
Name the organochlorine DDT

that is credited for saving
millions of lives worldwide
and whose inventor won
the Nobel Prize for his
contribution to world
health.
What is the name of the Rachel Carson’s Silent Spring

book that highlighted the
adverse effects of DDT,
coined the term biocides,
and whose publication
resulted in the subsequent
ban on DDT use in the
United States?
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ORGANOPHOSPHATES
What are the common Acephate (Orthene), azinphos-methyl

organophosphate (OP) (Azinphos, Guthion), chlorphoxim
insecticides? (Baythion-C), chlorpyrifos (Dursban,
Lorsban), diazinon, dimethoate (Cygon,
DeFend), disulfoton (Di-Syston), etho-
prop (Mocap), fenamiphos (Nemacur),
fenitrothion (Sumithion), fenthion
(Baytex), malathion (Fyfanon, Cythion),
methamidophos (Monitor), methidathion
(Supracide), methyl parathion (Penncap-
M), naled (Dibrome), oxydemeton-
methyl (MSR), phorate (Phorate,
Thimet), phosmet (Imidan), profenofos
(Curacron), terbufos (Counter)
What is the mechanism of Bind to a serine hydroxyl residue at the

toxicity of active site of the acetylcholinesterase
organophosphates? (AChE) enzyme → active site is blocked
→ ACh breakdown ceases → ACh accu-
mulates in the synapse → excessive
cholinergic stimulation
What is a common DUMBELS

mnemonic used to Defecation
remember the cholinergic Urination
signs and symptoms of OP Miosis
poisoning? Bronchorrhea / Bronchospasm /
Bradycardia
Emesis
Lacrimation
Salivation
possible effects of The excess cholinergic stimulation will
organophosphate poisoning? also stimulate nicotinic receptors, causing
culations, weakness, paralysis) and sym-
pathetic ganglia (e.g., tachycardia, HTN).
List the target organs of OP CNS – agitation, AMS, seizures, coma

exposure and the associated Eyes – miosis, lacrimation
clinical effects. Mouth – salivation
Lungs – ↑ bronchial secretions,
bronchospasm
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CV – tachycardia / bradycardia, QT inter-

val prolongation
GI – diarrhea, emesis, ↑ motility
GU – urinary incontinence
Sweat glands – diaphoresis
Adrenals – ↑ catecholamines
Neuromuscular junction – fasciculations,
weakness, paralysis
What is the mechanism of Within the first 5 min, seizures appear to

seizures from OP exposure? be due to cholinergic overstimulation,
and atropine can abort or prevent
seizures. After 5 min, other changes are
noted, including a decrease in brain nor-
epinephrine, an increased glutaminergic
response, and the activation of NMDA
receptors. At this point, both atropine
and benzodiazepines are needed.
Why might seizure activity Nicotinic effects can progress from

be missed in an OP- fasciculations to flaccid paralysis, result-
poisoned patient? ing in nonconvulsive seizures. Any
comatose OP-poisoned patient should
be treated with benzodiazepines, as well
as atropine, with emergent EEG
monitoring.
What routes of exposure are All routes

possible with OPs?
What are the Absorption, peak effect, half-life, and

pharmacokinetics of OP elimination kinetics vary dramatically
exposure? based on the specific OP, as well as on
the route, dose, and rate of exposure
(acute vs. chronic). For this reason,
patients exposed to OP insecticides
should be observed closely for at least
8 hrs after exposure for delayed effects.
What are treatments for 1. Removal from exposure source and

acute OP exposure? clothing (avoid secondary exposure of
healthcare workers)
and water for cutaneous exposure
3. Consider activated charcoal for GI
exposure.
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4. Protect the patient’s airway, if

necessary (use a nondepolarizing
paralytic for RSI).
5. Atropine titrated to the drying of
pulmonary secretions and resolution
of bronchospasm
6. Pralidoxime – 1–2 g IV over 10 min,
repeated in 1–2 hrs. Alternatively, a
bolus of 30 mg/kg, followed by an
infusion of 8 mg/kg/hour, is advocated
by the WHO.
7. Benzodiazepines to prevent and treat
seizures
8. ECG to assess for QT prolongation
Why should one use a The effect of succinylcholine can be

nondepolarizing markedly prolonged due to inhibition of
neuromuscular blocker if plasma pseudocholinesterase.
intubating an OP-poisoned
patient?
Is tachycardia a No. The tachycardia may actually improve

contraindication to atropine due decreased activation of preganglionic
use in an acute OP nicotinic sympathetic nerve terminals,
exposure? decreased release of norepinephrine from
the adrenal glands, and alleviation of
dyspnea and hypoxia.
How does pralidoxime OPs form a covalent bond with the

work? active site of AChE, preventing break-
down of ACh. Pralidoxime is attracted to
the active site of AChE, and its nucle-
ophilic oxime moiety will attack the
phosphate atom of the OP. This will dis-
place it from the active site, reactivating
the enzyme.
What is “aging”? “Aging” occurs when the OP forms an

irreversible covalent bond with the AChE
enzyme after losing an alkyl side chain.
This permanently inactivates the AChE
enzyme. This can take from ⬍1 hour to
several days, depending on the particular
OP. Pralidoxime will have no effect on an
aged AChE complex.
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Why is it important to Once aging occurs, the patient will not

prevent aging? regain vital functions, such as muscle
strength or respiratory drive, until new
enzyme is synthesized. This may take
weeks to months.
What lab test can confirm Measurement of the activity of erythrocyte

OP exposure? AChE and plasma pseudocholinesterase.
Results are usually not available quickly
enough to affect clinical decisions and are
used only to confirm the diagnosis.
What is “intermediate Development of profound muscle weak-

syndrome”? ness 24–96 hrs after exposure to OPs. It
occurs after resolution of the initial
cholinergic syndrome. Patients present
with weakness of neck flexion, cranial
nerve palsies, and proximal muscle weak-
ness. Respiratory muscle weakness may
also occur, leading to respiratory insuffi-
ciency requiring intubation. Fasciculations
and cholinergic signs will be absent.
How is intermediate There is no specific antidote. Atropine is

syndrome treated? not effective. With appropriate supportive
care, recovery will occur in 5 to 18 days.
Some experts believe adequate treatment
with pralidoxime can prevent this.
What is OP-induced delayed A rare disease characterized by leg

polyneuropathy? cramping followed by progressive weak-
ness and paralysis of the extremities
(lower more than upper) that begins 1 to
4 weeks after OP exposure. The mecha-
nism of this disease is thought to be
related to phosphorylation and “aging” of
a protein called neuropathy target
esterase. As the condition progresses,
flaccid paralysis can be replaced by
hypertonicity with a spastic gait.
PYRETHRINS AND PYRETHROIDS
What are pyrethrins? Active extracts from the Chrysanthemum

plant. They are degraded by sunlight and
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are commonly found in pediculicidal

shampoos.
What are pyrethroids? Synthetic analogues of pyrethrins. In

comparison to pyrethrins, pyrethroids
carry greater potency and have longer
half-lives.
Explain the two groups of Type 1 – no cyano group. Examples

pyrethroids. include allethrin, cyfluthrin (Baythroid),
and permethrin (Ambush, Dragnet, Nix,
Pounce, Raid).
Type 2 – does contain a cyano group.
Examples include cypermethrin
(Barricade, Cymbush, Cynoff, Demon),
deltamethrin, and fenvalerate.
What is the mechanism of Disrupt sodium channel inactivation →

action of pyrethrins / prolonged depolarization → rapid paralysis
pyrethroids? of the insect nervous system. Humans are
relatively resistant to these agents because
of our ability to rapidly metabolize them.
What are the routes of Ingestion, inhalation, dermal. Dermal

absorption of pyrethrins / absorption of pyrethroids can cause local
pyrethroids? paresthesias. Ocular exposure can cause
pain, tearing, and photophobia.
What are the signs and 1. Anaphylactic reactions are most

symptoms of acute pyrethrin common.
exposure? 2. Inhalation may cause bronchospasm
or induce an asthma attack.
3. Pyrethrins generally do not cause
significant systemic toxicity.
What group is at particular Those with a ragweed allergy

risk for an allergic reaction
from pyrethrin exposure?
What are the differences in 1. Type 1 – fine tremor, twitching and

clinical effects between type hyperexcitability, possibly leading to
1 and type 2 pyrethroids? hyperthermia
2. Type 2 – hypersalivation, seizures,
choreoathetosis, and sympathetic
activation
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Why are type 2 pyrethroids They cause a greater delay in sodium chan-
more toxic? nel closure, producing a more sustained
depolarization. They also inhibit chloride
influx through the GABA receptor.
What are treatments for 1. Skin decontamination with soap and

acute pyrethrin / pyrethroid water (avoid secondary exposure to
exposure? healthcare providers)
2. GI decontamination with activated
charcoal for recent ingestions
4. Standard allergic reaction therapy (i.e.,
antihistamines, epinephrine, steroids)
5. Bronchodilators for bronchospasm /
wheezing
6. Protect the patient’s airway, if necessary.
As with all pesticides, aspiration
pneumonitis due to the hydrocarbon
vehicle is possible, in addition to the
effects of the individual toxins.
Pyrethroid toxicity mimics Organophosphates. Type 2 pyrethroid

the effects of what other toxicity can result in hypersalivation,
toxic agent? seizures, and hypertension, resembling
an acute organophosphate poisoning.
OTHER
Where is N,N- Insect repellant

diethyltoluamide (DEET)
commonly found?
What is the mechanism of In theory, it blocks insect antennae

action of DEET on insects? receptors, which are used to locate hosts.
How does DEET toxicity Ingestion or prolonged exposure on cov-

occur? ered or damaged skin
What are the signs and 1. Mild skin irritation from prolonged
symptoms of DEET toxicity? dermal exposure
2. Nausea and vomiting following
ingestion
3. Hypotension and tachycardia have
been reported with heavy dermal or
oral exposure.
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4. Rarely, CNS depression, coma,

seizures, and respiratory failure
with excessive dermal or oral
exposure
What is the treatment for 1. Removal from exposure source and

acute DEET toxicity? clothing
2. Copious irrigation with soap and water
for cutaneous exposures
What is fipronil? A broad-spectrum insecticide that antag-

onizes GABA receptors preferentially in
insect nervous systems
Describe the effects of CNS depression, vertigo, weakness, and

fipronil toxicity. seizures have been described; however,
human overdose data is limited.
What are avermectins? As a group, these agents interact

with both GABA and glutamate
channels, resulting in paralysis of the
target insect. Abamectin, ivermectin,
and emamectin are commonly used
insecticides.
Describe the manifestations Coma and respiratory arrest have

of avermectin toxicity. been reported, although human data
is limited.
How does imidacloprid Nicotine receptor agonism. It is used as

cause toxicity? an insecticide and as a flea repellant.
What are the effects of While human data is limited, animal

imidacloprid toxicity? studies have shown effects of nicotine
poisoning, including vomiting, muscle
fasciculations, weakness, and paralysis.
Symptoms in humans may also be
related to solvents included in the
product.
What is the general 1. Supportive care is the primary

treatment for these treatment.
insecticides? 2. Benzodiazepines for seizures
3. Dermal decontamination should be
performed, if indicated.
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RODENTICIDES
ALPHA-NAPHTHYLTHIOUREA (ANTU)
For what purpose is alpha- As a rodenticide, sometimes used specifi-

naphthylthiourea (ANTU) cally against Norway rats. It was used
used? widely in Britain in the 1940s and 1950s,
but its use has now been all but aban-
doned because of the use of coumarin-
derived rodenticides.
What are the manifestations Toxicity appears to be limited, as no

of acute ANTU toxicity? deaths have been reported following
acute exposure. Following ingestion,
patients may develop tracheobronchial
hypersecretion requiring intubation.
Can exposure to ANTU While ANTU has been associated with

result in carcinogenesis? bladder carcinoma, especially when
contaminated with beta-naphthylamine,
no definitive evidence exists that it is
carcinogenic. Therefore, it has an IARC
Group 3 classification.
What organ is primarily Lungs. Overall, ANTU is relatively selec-

affected by ANTU poisoning? tive for causing pulmonary symptoms.
Describe the mechanism of In animal studies, ANTU appears to

ANTU toxicity. damage pulmonary capillaries, leading to
pulmonary edema and pleural effusions.
What are the signs and Dyspnea, rales, cyanosis, and pulmonary
symptoms of ANTU edema / effusion may result after
poisoning? inhalation.
What are symptoms of Antithyroid activity and hyperglycemia

chronic ANTU exposure? have been reported.
Describe the management Supportive care. There is no specific

of acute ANTU exposure. treatment.
ANTICOAGULANTS
What is the mechanism of Inhibit the enzymes vitamin K 2,3-epoxide

action of the coumarin- reductase and vitamin K quinone reduc-
derivative rodenticides? tase, decreasing the availability of reduced
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vitamin K1. Reduced vitamin K1 is neces-

sary to activate (by carboxylation) the vita-
min K-dependent clotting factors II, VII,
IX, X, and proteins C and S. Depletion of
the clotting factors will cause coagulopathy.
What are the symptoms of All are related to inappropriate hemor-

rodenticide anticoagulant rhage – gingival hemorrhage, sponta-
overdose? neous ecchymosis, hematuria, epistaxis,
GI bleeding, intracranial hemorrhage
Are overdoses with No. An increase in PT will not occur until

anticoagulant rodenticides active factors are decreased to 25% of
symptomatic immediately? normal. The factor with the shortest half-
life is factor VII (t1/2 ⫽ 5 hrs); therefore,
at least 3 half-lives (or 15 hrs) must pass
before there is a detectable change in the
measured PT (or calculated INR).
Do all rodenticides that are No. Long-acting anticoagulant rodenti-

coumarin-based have cides called “superwarfarins” are
equivalent toxicity to commonly used (e.g., brodifacoum,
warfarin? bromadiolone, coumafuryl, difenacoum).
What is an important “Superwarfarins” are lipophilic and have

chemical property of greater potency and longer half-lives than
“superwarfarins,” and what does warfarin. Typical half-lives of 42 to
is a clinical consequence of 51 days have been reported in humans,
this property? with some cases of anticoagulation lasting
up to 1 year.
Does a single accidental No. There must be repeated ingestions

ingestion of a “warfarin over a period of time or a massive inges-
only” rodenticide usually tion to cause clinically significant antico-
produce bleeding? agulation. An accidental exposure is
rarely clinically significant. In contrast,
ingestion of a “superwarfarin” rodenticide
can produce coagulopathy following a
single ingestion.
What are some important PT is the best test to identify anticoagu-

laboratory tests for assessing lant effect. PTT and thrombin time
a patient with rodenticide may be useful to evaluate for other
anticoagulant poisoning? causes of coagulopathy. Specific assays
for “superwarfarin” molecules exist and
can be ordered to confirm the diagnosis.
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What are the antidotes to 1. Vitamin K1 – phytonadione

rodenticide anticoagulant 2. FFP or whole blood to replace
poisoning? clotting factors in patients with active
bleeding
3. Recombinant activated factor VII can
be considered.
Should vitamin K1 be given No. It should only be given if the patient

to every patient who has develops significant prolongation of
ingested a “superwarfarin”? their PT, which may be delayed up to
48 hrs. If there is no elevation in the
INR after 48 hrs, the patient will not
develop toxicity and will not need
treatment. The administration of
vitamin K1 prior to the development of
coagulopathy can mask the toxicity and
commit the patient to long-term
vitamin K1 treatment.
Are all forms of vitamin K No, only the K1 form is effective.

effective at reversing the K3 (menadione) and K4 are provitamins
toxicity from coumarin- which are slowly converted to the
derived rodenticides? active form and are not effective as
antidotes.
CHOLECALCIFEROL
What is another name for Vitamin D3. This is the same chemical
cholecalciferol? produced when 7-dehydrocholesterol in
the skin is exposed to sunlight.
What is the major clinical Hypercalcemia

consequence of
cholecalciferol overdose?
Why is cholecalciferol used To induce hypercalcemia, resulting in

in rodenticides? death from metastatic calcifications in
multiple organ systems
How is cholecalciferol 1. Hepatic – converts cholecalciferol to

metabolized? 25-hydroxyvitamin D
2. Renal – converts 25-hydroxyvitamin D
to 1,25-dihydroxyvitamin D (calcitriol)
3. Intracellular – calcitriol binds to its
receptors → ↑ intestinal calcium
absorption
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When do the clinical 2 to 8 days following exposure. Data in

manifestations of human exposure is limited; however, no
cholecalciferol overdose cases of severe toxicity or death have
become apparent? been reported in the literature.
What are the clinical 1. GI – constipation (most common GI

manifestations of complaint), anorexia, acute pancreatitis
hypercalcemia? 2. Renal – ↓ concentrating ability, acute
renal insufficiency, nephrolithiasis
3. CV – shortened QT interval, HTN
(due to renal insufficiency ⫹
peripheral vasoconstriction)
4. Musculoskeletal – weakness
What laboratory studies are Electrolytes, including calcium, magne-

essential for evaluation? sium, and phosphorus. A normal calcium
level at 48 hrs essentially excludes toxic
ingestion. BUN and creatinine are help-
ful to evaluate renal function.
What are some treatments 1. Standard treatments for hypercalcemia

for acute cholecalciferol (i.e., IV fluids and loop diuretics to
ingestion? enhance renal calcium excretion)
2. Phosphate PO forms a nonabsorbable
calcium-phosphate complex in the gut.
3. Calcitonin → ↑ renal calcium
excretion and ↓ bone resorption
4. Bisphosphonates interfere with
osteoclast activity and inhibit bone
resorption.
5. Hemodialysis may be indicated for
patients with renal failure or for
severe toxicity.
SODIUM MONOFLUOROACETATE (1080)
By what other names is Compound 1080, SMFA

sodium monofluoroacetate
known?
Is SMFA available as a In 1972, it was banned as a rodenticide

rodenticide in the United due to its high toxicity. Since that time,
States? this ban has undergone several court
challenges, resulting in limited availabil-
ity for licensed pest control operators.
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Other than as a rodenticide, It is used today for coyote control. A

where can SMFA exposure commercially available “toxic collar” con-
occur? taining SMFA is placed on a sheep. The
poison is released when the sacrificial
sheep is attacked.
What are the main routes of Ingestion or inhalation

SMFA toxicity?
How does SMFA cause It poisons the Krebs cycle. Monofluoroac-

poisoning? etate (in place of pyruvate) combines with
coenzyme A to form fluoroacetyl CoA. The
latter undergoes conversion to fluoroci-
trate (by citrate synthase), which subse-
quently occupies the citrate binding site on
aconitase, rendering this enzyme inactive
and compromising aerobic metabolism.
What are some clinical Initial symptoms include nausea,

manifestations of SMFA vomiting, and abdominal pain. These are
poisoning? followed by signs of organ system dys-
function, including agitation, hypoten-
sion, dysrhythmias, seizures, and coma.
What specific laboratory 1. High anion gap metabolic acidosis

abnormalities are associated 2. Elevated lactate
with SMFA poisoning? 3. Hypokalemia and hypocalcemia may
be present.
Describe the treatment of Treatment is primarily supportive.

SMFA poisoning.
Is there an antidote for Both ethanol and glycerol monoacetate

SMFA poisoning? have been studied as possible treatments.
These agents supply acetyl-CoA to com-
petitively inhibit the action of SMFA.
Neither agent has definitely been shown
to improve patient outcome.
STRYCHNINE
What is strychnine? An alkaloid, occasionally used as a

rodenticide, that is extracted from the
seeds of the strychnine tree (Strychnos
nux-vomica). Use has been limited in
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modern times; however, historically this

poison was widely used in medicinal
tonics, as a rodenticide, and for criminal
poisonings.
How does strychnine cause Glycine receptor antagonism in the spinal

poisoning? cord, resulting in failure of normal
inhibitory signals
What are some signs and Painful generalized muscle spasms that
symptoms of strychnine may resemble tonic seizures and are
poisoning? often triggered by external stimuli. Early
in the poisoning, patients have a normal
mental status, although later may develop
AMS secondary to the complications of
profound rigidity. Consequences of pro-
longed muscle spasm include rhabdomy-
olysis, lactic acidosis, myoglobinuria, and
renal failure.
Name the bacterial illness Tetanus (tetanospasmin)

that may be confused with
strychnine poisoning.
What is opisthotonus? Extreme arching of the back that occurs

as a result of back muscle spasms. This
finding can be seen in both tetanus and
strychnine poisoning.
What is “risus sardonicus”? The grimace produced as a result of con-

tracted facial muscles. This is also seen in
both tetanus and strychnine poisoning.
How long after ingestion do 15–60 min post-ingestion

symptoms occur?
How does strychnine 1. Ingestion – accidental, suicidal,

poisoning occur? homicidal
2. Recently, there are reports of
strychnine poisoning occurring as a
result of contaminated street drugs.
How can strychnine Blood, urine, and gastric aspirate levels

poisoning be detected? are available but are not likely helpful in
the acute setting.
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What other laboratory Electrolytes, CPK, and renal function

values are useful in tests to monitor for acidosis, rhabdomyol-
strychnine poisoning? ysis, and renal failure.
How does death occur from Hypoxia, following generalized muscle

strychnine poisoning? spasm with respiratory muscle dysfunction
Is there a specific antidote No. Treatment is aimed at relieving mus-

for strychnine poisoning? cle spasm. Initially, this consists of ben-
zodiazepines and opioids. For severe
symptoms, muscle paralysis with a non-
depolarizing agent may be necessary.
Hyperthermia from profound muscle
hyperactivity may be treated with mist-
ing or cooling blankets.
VACOR (PNU)
What is another name for N-3-pyridylmethyl-N’-p-nitrophenyl urea

Vacor? (PNU). Vacor contains 2% PNU. It is
also known as pyrimil.
What does it look like? Yellow-green powder, may resemble

corn meal
What are the 2 main clinical 1. DM (insulin-dependent)

conditions that occur with 2. Autonomic dysfunction
Vacor poisoning?
How does Vacor cause DM? 1. Disrupts nicotinamide metabolism,

causing abnormalities in pentose
phosphate and, therefore, interfering
with RNA metabolism and resulting in
destruction of pancreatic islet beta
cells (responsible for insulin secretion)
2. Substitutes for nicotinamide in NAD
and NADPH, interfering with
oxidoreductase reactions
How do patients present Within hours of ingestion, patients can

after Vacor poisoning? present with DKA, peripheral neuropa-
thy, and autonomic neuropathy. The
autonomic neuropathy can cause severe
orthostatic hypotension, impotence, ↓
sweating, urinary retention, constipation,
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and dysphagia. Transient hypoglycemia is

possible before hyperglycemia and is due
to insulin release from damaged pancre-
atic cells.
Is Vacor available? Was withdrawn by the manufacturer in

1979; however, occasional poisonings are
still reported
What are common symptoms Similar to those commonly recognized in

in patients with Vacor DKA, including nausea, vomiting,
overdose? blurred vision, polyuria, thirst, abdominal
pain, generalized weakness and chills
What are common findings 1. Hyporeflexia

on examination of the 2. ↓ vibration and light touch sensation
peripheral nervous system in the extremities
in the patient with Vacor 3. Paresthesias
poisoning? 4. Fine tremor
Do patients recover after Fatalities have occurred secondary to

Vacor poisoning? DKA, GI perforation, and dysrhythmias.
If a patient survives, they will likely be left
with insulin-dependent DM and treat-
ment-resistant orthostatic hypotension.
Is there an antidote to Possibly. Niacinamide (vitamin B3) has

Vacor? been used; however, a parenteral form of
niacinamide is no longer available and
now must be substituted with niacin. This
is less effective and can cause vasodila-
tion and impaired glucose tolerance, both
of which exacerbate the effects of Vacor
poisoning. Early administration is essen-
tial for clinical benefit.
Why is Vacor poisoning It is a mechanism for the biological induc-

important? tion of insulin-dependent DM, and expo-
sure closely mimics the natural disease.
OTHER
What is red squill? A plant (Urginea maritime) that

contains cardiac glycosides (scilliroside)
in the bulb
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How does red squill kill Causes cardiac glycoside poisoning,

rodents? resulting in pulmonary edema
What is different about Humans vomit upon ingesting the toxin

rats and humans that due to its potent emetic effect; rats are
contributes to the selective unable to do so.
toxicity of red squill in
rodents?
Thallium is used as a Painful peripheral neuropathy and

rodenticide in countries alopecia
outside the United States.
What are common symptoms
of significant thallium
poisoning?
In the past, arsenic was 1. Pentavalent arsenic can substitute for

commonly used as a phosphorus during glycolysis, forming
rodenticide in the United an unstable intermediate at a critical
States. What are 4 ATP-generating step.
mechanisms by which 2. Binds to sulfhydryl groups, inhibiting
arsenic causes poisoning? numerous enzymes (e.g., succinate
dehydrogenase, a key enzyme in the
citric acid cycle)
3. Production of reactive oxygen species,
causing direct injury to a variety of
tissues
4. Interference with gene expression, cell
signal transduction, and apoptosis
A patient presents with Yellow (or white) phosphorus

garlic odor, oral burns,
phosphorescent (luminous in
the dark) “smoking” feces,
and vomiting following the
ingestion of a rodenticide.
What agent has caused the
toxicity?
Is red phosphorous No
poisonous?
What is the clinical Classically described in 3 stages:

presentation after white Stage 1 – oral burns, nausea, vomiting,
phosphorus poisoning? abdominal pain, and possibly diarrhea
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occur within minutes to hours post-

ingestion. CV collapse or dysrhythmias
may occur.
Stage 2 – apparent recovery during this
period of systemic absorption
Stage 3 – multi-system organ failure after
several days
What are 2 metal phosphides 1. Zinc phosphide

that are used as rodenticides? 2. Aluminum phosphide
What does zinc phosphide Decaying fish

smell like?
Zinc phosphide is used as a Phosphide (P3⫺) becomes phosphine

rodenticide. Is it the zinc or (PH3) upon exposure to moisture or
the phosphide that is stomach acid and is responsible for the
responsible for the toxicity? toxic effects. The zinc does not con-
tribute to its toxicity.
How does phosphine cause Phosphine may block cytochrome c oxi-

toxicity? dase of the electron transport chain. It
also causes free radical generation and
resultant lipid peroxidation.
What are some common 1. GI – profuse vomiting and abdominal

clinical manifestations of pain within 10–30 min
phosphide poisoning? 2. Respiratory – cough, excessive sputum
production, tachypnea, pulmonary
edema
3. CV – palpitations, tachycardia,
hypotension, QRS interval
prolongation, dysrhythmias (i.e., atrial
fibrillation, VT, VF)
4. Endocrine – metabolic acidosis
5. CNS – seizures, coma
Is there an antidote for No. Therapy is supportive. Administering

metal phosphide poisoning? sodium bicarbonate to decrease gastric
acidity and lessen phosphine production
has been considered but is of unproven
benefit.
What is tetramine? A rodenticide, also called tetramethylene

disulfotetramine. It is an odorless, tasteless
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powder that dissolves easily in water. It

has been banned worldwide, but poison-
ing continues to be reported in China,
Hong Kong, and the United States.
What is its mechanism of Noncompetitive GABAA receptor antago-

toxicity? nism → blocks Cl⫺ influx → cells are
more prone to depolarization
How can patients be Inhalation and ingestion

exposed to tetramine?
What clinical manifestations Onset – 10 to 30 min post-ingestion

does it cause? Mild poisoning – nausea, vomiting,
abdominal pain, lethargy, headache,
weakness
Severe poisoning – refractory seizures,
coma, and death within hours
What is the treatment for 1. Decontaminate patients by removing

tetramine poisoning? clothes and cleaning them with soap
and water.
2. Activated charcoal may be given if the
patient has a well-protected airway.
3. Treat seizures aggressively with
benzodiazepines, barbiturates, and
pyridoxine.
4. Hemoperfusion or hemofiltration may
be effective.
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Chapter 7 Chemical Agents of

Terrorism
BOTULINUM TOXIN
What is botulinum? Any one of eight serologically distinct,

heat-labile exotoxin heterodimer proteins
(labeled A, B, C1, C2, D, E, F, G), of
which only A, B, E, and (rarely) F cause
illness in humans
What produces botulinum? The anaerobic, spore-forming, gram-

positive bacillus Clostridium botulinum
What are the modes of Ingestion, inhalation, parenteral

transmission that may be
utilized by terrorists /
criminals?
What is the LD50 of .001 microgram per kilogram

botulinum toxin?
Is there an antidote to Yes, a trivalent (A, B, E) antitoxin from

botulinum? the CDC and a heptavalent antitoxin
from the U.S. Army. Contact the CDC or
local state health department to arrange
antidote delivery and assist with confir-
matory testing.
What is the onset time for Highly variable—symptoms may appear

an acute botulinum as early as 2 hrs post-ingestion, with most
poisoning? patients developing symptoms between
10–72 hrs. In some cases, signs and
symptoms may not be noticed for up to
8 days. The delay and variability can
make identifying a source difficult.
What is the mechanism of Toxin is endocytosed by the nerve → light

toxicity of botulinum? chain of botulin proteolytically cleaves var-
ious SNARE proteins → prevents synaptic
vesicle fusion with the presynaptic nerve
terminus → nerve cannot release ACh,
thereby interrupting neurotransmission
342
13486_CH07.qxd 10/31/08 12:20 PM Page 343
Chapter 7 / Chemical Agents of Terrorism 343
What symptoms occur with Presenting symptoms follow a stereotypi-

acute botulinum poisoning? cal pattern of descending weakness:
1. Cranial nerve dysfunction manifested
as dysphagia, diplopia, and dysarthria
2. On exam, ptosis, gaze paralysis, and
facial palsy are most often noted.
3. Inhibition of muscarinic cholinergic
function can cause dry mouth,
mydriasis, and constipation.
4. It progresses as a descending motor
paralysis affecting the upper limbs,
then the lower limbs.
5. In severe cases, the intercostals and
diaphragm are affected, possibly
necessitating mechanical ventilation.
6. Ingested botulinum may also cause GI
symptoms, including nausea, vomiting,
constipation, and less commonly,
diarrhea that typically precedes
neurological symptoms.
How does inhalational In a similar fashion to food-borne botu-

botulism present? lism. The time-course for inhalational
botulism is poorly understood, due to the
small number of cases; however, the
onset is believed to occur in about 3 days.
What might lead you to There are several clues that should raise
suspect that there has been suspicion:
an intentional release of 1. A large number of patients
botulinum toxin? 2. Multiple clusters without an
identifiable source
3. Groups of patients who share a
common geographic connection
4. Outbreaks involving the rare types C,
D, E, F, or G
What role does botulinum Botulin oxidizes rapidly upon atmospheric

toxin play in biological exposure, rendering it harmless. Poisoned
warfare? air is considered breathable in roughly
1 day. There are no documented warfare
uses in history; however, it is the most
toxic naturally occurring protein in the
world, and there is concern that it could
be used as an agent of terror.
13486_CH07.qxd 10/31/08 12:20 PM Page 344
How is acute poisoning with 1. Supportive care, with attention to

botulinum toxin treated? airway protection and ventilatory
support
2. Botulinum antitoxin is the definitive
treatment. This will be empiric, based
on clinical suspicion, as no rapid
confirmatory tests will be readily
available. Consider antitoxin
administration in any patient with a
clinical presentation suspicious for
botulism, particularly when a group of
2 or more presents with suggestive
symptoms.
INCAPACITATING AGENTS
What is an incapacitating An agent that transiently impairs an indi-

agent? vidual in a non-lethal manner by disrupt-
ing the CNS and/or PNS
What are some common Anticholinergic agents, ultra-potent

classes of incapacitating opioids, aerosolized benzodiazepines
agents?
What anticholinergic agent 3-quinuclidinyl benzilate (QNB or BZ)

is an incapacitating agent?
What are ultra-potent Typically fentanyl derivatives (e.g., car-

opioids? fentanil, remifentanil) designed to inca-
pacitate through sedation
How are these agents Exposure occurs through inhalation after

typically used? these agents are aerosolized. Clinical ef-
fects are those of the opioid toxidrome,
including miosis and CNS and respiratory
depression.
What is the onset of action Rapid, generally within minutes

of ultra-potent opioids?
During what hostage The Moscow Theater, Russia 2002

situation were ultra-potent
fentanyl derivatives likely
used to subdue captors?
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What are the effects of These agents produce the sedative-

aerosolized hypnotic toxidrome. Symptoms include
benzodiazepines? CNS depression with possible respiratory
depression after large exposures. While
data is limited, effects are expected to
be produced rapidly after inhalational
exposure.
What prevalent hallucinogen LSD, a potent hallucinogen in the ergot-

has been studied for use as amine family that is active in ␮g quanti-
an incapacitating agent? ties. It may be absorbed by ingestion,
transdermally, or through mucous mem-
branes. Effects typically begin within 1 hr
and may last up to 8 to 12 hrs.
INCENDIARY AGENTS
What are incendiary agents? Compounds used, primarily by the mili-

tary, to burn / destroy supplies, equip-
ment, ordnance, and structures
What are the main types of Thermite, magnesium, white phosphorus,

incendiary agents? and gelled hydrocarbons (e.g., napalm)
are the most common types.
What is thermite, and what Mixture of powdered aluminum and iron

are some of the oxide. Upon ignition, it burns at
characteristic injuries it ⬎2500°C (4500°F). Molten particles of
causes? iron may lodge in the skin, causing deep
tissue burns.
What is a typical injury from Magnesium burns at ⬎2000°C (4200°F).

a magnesium burn? Deeply embedded magnesium fragments
may produce magnesium dihydroxide and
localized hydrogen gas, resulting in tissue
necrosis.
What are some important It may spontaneously ignite upon expo-

chemical characteristics of sure to air. Oxygen must be excluded
white phosphorus? from the agent (i.e., with water or a wet
cloth) in order to stop the burning.
How does ingested white White phosphorus is a metabolic poison,

phosphorus result in disrupting electron transport. A large ex-
toxicity? posure to embedded particles may result
in systemic toxicity.
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Describe the treatment of Patients with retained particles on skin or

white phosphorus burns. clothing should have those areas covered
with water prior to mechanical debride-
ment. Treatment should otherwise follow
standard burn therapy.
What is napalm, and what Napalm is a gelled form of gasoline which

secondary exposure should is more stable and burns longer than nor-
be considered in patients mal gasoline. Burning napalm gives off
with napalm burns? CO, so this secondary exposure must be
considered in patients with napalm burns.
What other considerations Blunt or penetrating trauma may be

should be observed in present, as these agents are typically
patients exposed to deployed with explosives.
incendiary agents?
What type of dressing Oily or greasy dressings. The element is

should you avoid using on a lipid-soluble and can penetrate the tissues.
white phosphorus burn?
IRRITANTS
What are irritant gases? Gases that cause irritation to the respira-
tory tract. Effects may be immediate or
delayed depending on the water solubil-
ity of the gas.
What 2 broad 1. Highly water soluble (e.g., chlorine,

categorizations are used for sulfur dioxide, ammonia)
irritant gases? 2. Poorly water soluble (e.g., nitrogen
dioxide, ozone, phosgene)
What are the effects of Because they are highly water soluble,
highly soluble irritant gases? they cause immediate airway irritation
upon contact with moist tissue.
What are the effects of Effects on the pulmonary mucosa take

poorly soluble irritant time to develop due to the low water
gases? solubility of these gases. Delayed onset
pulmonary edema is often seen.
Exposure to these gases is typically
prolonged, as there is no initial irritation
to warn of their presence.
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What is the typical Irritation of nose, throat, eyes, and skin,

presentation of a patient manifesting as oropharyngeal burning,
exposed to a highly soluble cough, and dyspnea
irritant gas?
Describe the mechanism of Generate caustic substances and free

irritant gas toxicity. radicals on contact with airway mucosa
Describe the treatment of 1. Removal from the source with dermal

irritant gas exposure. decontamination, if necessary.
2. Oxygen, nebulized bronchodilators,
and airway support, as needed.
3. Nebulized sodium bicarbonate may
be beneficial after chlorine gas
exposure.
4. Observe for delayed sequelae
following exposure to gases of low
water solubility.
What are lacrimating Lacrimators (tear gas) are primarily used

agents? for riot control and self-protection. They
produce irritation of the eyes, skin, and
airway.
Name some different types Chloroacetophenone (CN, aka “mace”),

of tear gas. chlorobenzalmalononitrile (CS), and
capsaicin, also known as pepper spray.
Rarely, CS and CN may cause
bronchospasm, pulmonary edema, and
skin vesication.
What are the general effects Eye and airway irritation, lacrimation,
of lacrimators? blepharospasm
Describe the treatment for Removal from exposure, followed by skin

lacrimator exposure. and eye irrigation
NERVE AGENTS
What are nerve agents? Organophosphate (OP) chemical

weapons
What is the mechanism of AChE inhibition. Covalent bonding to a

action of nerve agents? serine hydroxyl residue on the active
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site of the AChE prevents ACh hydroly-

sis, resulting in accumulation of ACh in
the synapse and an exaggeration of the
typical action mediated by the postjunc-
tional structure (e.g., neuron, gland,
myocyte). This causes excessive cholin-
ergic stimulation.
What are the G-series nerve Tabun (GA), sarin (GB), soman (GD),
agents? cyclosarin (GF)
What are the V-series nerve VE, VG, VM, VX

agents?
What are the physical The term nerve gas is misleading; nerve
properties of G- and agents are in fact liquids at room
V-series nerve agents? temperature and must be aerosolized
or evaporated to be used effectively as
an inhalation agent. The vapors are
heavier than air and, therefore, will
remain close to the ground and settle
in low-lying areas. They have different
degrees of volatility. For example,
sarin evaporates as readily as water,
while VX evaporates 1,500 times more
slowly.
What makes the V-series They are persistent agents, resistant to

nerve agents so dangerous? degradation and removal (even by surfac-
tants), so toxic concentrations can remain
for weeks to months, long after their ini-
tial release.
What are the physical Volatile liquids at room temperature,

properties of G-series and varying from colorless to brown and from
V-series nerve agents? odorless to fruity-smelling
What are the Novichok Stable and safe-to-handle binary solid

nerve agents? versions of nerve agents that were devel-
oped in the Soviet Union and Russia be-
tween 1970 and 2000.
What are the routes of Inhalation and dermal

exposure to nerve agents?
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What is the LD50 of GB? Inhalation – 75–100 mg/min/m3

Dermal – 1700 mg
What is the onset of action Inhalation – seconds to minutes (dose

for an acute nerve agent dependent)
exposure? Dermal – 20 to 30 min after large expo-
sures, otherwise may be delayed up to
18 hrs
What are the signs and DUMBELS

symptoms of an acute nerve Defecation
agent exposure, along with Urination
the mnemonic used to Miosis
remember the cholinergic Bronchorrhea / Bronchospasm /
signs and symptoms of OP Bradycardia
poisoning? Emesis
Lacrimation
Salivation
possible effects of nerve The excess cholinergic stimulation will
agent poisoning? also stimulate nicotinic receptors, causing
culations, weakness, paralysis) and gan-
glia (e.g., tachycardia, HTN).
List the target organs of CNS – agitation, AMS, seizures, coma

nerve agent exposure and Eyes – miosis, lacrimation
the associated clinical Mouth – salivation
effects. Lungs – ↑ bronchial secretions, bron-
chospasm
CV – tachycardia / bradycardia, QT inter-
val prolongation
GI – diarrhea, emesis, ↑ motility
GU – urinary incontinence
Sweat glands – diaphoresis
Adrenals – ↑ catecholamines
Neuromuscular junction – fasciculations,
weakness, paralysis
What is the most reliable Miosis

physical exam finding for
volatilized nerve agent
poisoning?
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How is the presentation of Inhalational – onset within seconds to

an inhalational exposure minutes. With a small vapor exposure,
different from that of a miosis, rhinorrhea, and slight bron-
dermal exposure? chospasm will be seen. This will progress
to marked dyspnea with obvious secre-
tions as the exposure continues. Those
with large exposures will progress to
AMS, generalized fasciculations, seizures,
paralysis, and apnea.
Dermal – exposure to liquid nerve
agents may have delayed effects (dose
dependent). Contact with the skin will
cause localized sweating and possibly
fasciculations of the underlying muscles.
Later, patients will experience nausea,
vomiting, diarrhea, generalized
sweating, and fatigue. With larger
exposures, progression to AMS, seizures,
generalized fasciculations, ↑ secretions,
paralysis, and apnea will occur. Unlike
vapor exposure, a dermal exposure will
delay the development of miosis. The
delayed presentation and lack of miosis
can make the diagnosis of a nerve agent
exposure difficult.
What is the mechanism of Within the first 5 min, seizures appear to

seizures from OP/nerve be due to cholinergic overstimulation,
agent exposure? and atropine can abort or prevent
seizures. After 5 min, other changes are
noted, including a decrease in brain
norepinephrine, an increased
glutaminergic response, and the activa-
tion of NMDA receptors. At this point,
both atropine and benzodiazepines are
needed.
Why might seizure activity The nicotinic effects can progress from
be missed in an OP/nerve fasciculations to flaccid paralysis, result-
agent-poisoned patient? ing in nonconvulsive seizures. Any
comatose patient who experiences this
type of exposure should be treated with
benzodiazepines, as well as atropine, with
emergent EEG monitoring.
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Is there an antidote for an Yes. Atropine and related anticholinergic

acute nerve agent drugs will antagonize excess cholinergic
poisoning? transmission and compete with ACh.
Pralidoxime chloride (2-PAM) serves to
reactivate AChE and restore normal
cholinergic function. These must be given
immediately in order to be effective.
How does pralidoxime Nerve agents form a covalent bond with

(2-PAM) work? the active site of AChE, preventing
breakdown of ACh. 2-PAM is attracted to
the active site of AChE, and its nucle-
ophilic oxime moiety will attack the phos-
phate atom of the nerve agent. This will
displace it from the active site, reactivat-
ing the enzyme.
What is “aging”? “Aging” occurs when the nerve agent

forms an irreversible covalent bond with
the AChE enzyme after losing an alkyl
side chain, rendering the enzyme perma-
nently inactive. This can take from ⬍1 hr
to several days, depending on the partic-
ular agent. Pralidoxime will have no ef-
fect on an aged AChE complex.
Why is it important to Once aging occurs, the patient will not

prevent aging? regain vital functions, such as muscle
strength or respiratory drive, until new
enzyme is synthesized. This may take
weeks to months
How fast does aging occur Depends on the agent. For example,
after nerve agent poisoning? soman rapidly and permanently disables
AChE in 2 to 6 min, whereas sarin and
VX age more slowly, with aging half-lives
of 5 hrs and 48 hrs, respectively.
What lab test can confirm Measurement of the activity of erythro-

nerve agent exposure? cyte AChE and plasma pseudo-
cholinesterase. Results are usually not
available quickly enough to affect clinical
decisions and are used only to confirm
the diagnosis.
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What is the treatment for 1. Removal from exposure source and

nerve agent poisoning? removal of clothing (avoid secondary
exposure of healthcare workers)
and water for liquid exposure
3. Protect the patient’s airway, if
necessary (use a non-depolarizing
paralytic for RSI)
4. Atropine titrated to the drying of
pulmonary secretions and resolution
of bronchospasm
5. 2-PAM: 1–2 g IV over 10 min, repeated
in 1 to 2 hrs. Alternatively, a bolus of
30 mg/kg, followed by an infusion of
8 mg/kg/hr, is advocated by the WHO.
6. Benzodiazepines to prevent and treat
seizures
What is a Mark I kit? A set of auto-injectors which deliver 2 mg

of atropine and 600 mg of 2-PAM. There
is also a separate auto-injector that will
deliver 10 mg of diazepam.
How is it used? The auto-injectors are designed to deliver

medication through protective clothing.
For patients with significant poisoning,
immediate administration of three Mark I
kits is recommended (1,800 mg of 2-
PAM). The diazepam auto-injector should
also be used for anyone with significant
symptoms. If an IV has been established,
it is preferable to use this route.
How much atropine is Typical total dose required ranges from

usually needed to treat 5–20 mg; however, similar to OP insecti-
nerve agent poisoning? cide poisonings, there are reports of larger
doses (up to 200 mg) of atropine having
been used to treat nerve agent casualties
Is tachycardia a No. The tachycardia may actually

contraindication to atropine improve due to decreased activation of
use in an acute OP preganglionic nicotinic sympathetic nerve
exposure? terminals, decreased release of
norepinephrine from the adrenal glands,
and alleviation of dyspnea and hypoxia.
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What is the goal of atropine Drying of pulmonary secretions

therapy? (reflected by improved oxygenation)
and relief of bronchospasm (reflected
by ease of breathing/ventilation).
Atropine will likely not improve
miosis or skeletal muscle paralysis;
therefore, reversal of these effects
is not a therapeutic endpoint.
Attempting to reverse these findings
with atropine can result in
anticholinergic toxicity.
What is the prognosis of a Without rapid antidote treatment, death

weapons-grade, acute nerve will occur within minutes.
agent poisoning?
Just how potent is VX? Extremely potent. A droplet of VX

⬍20% of the size of the Lincoln
Memorial on the back of a penny has
the potential to kill the average human
within 30 min if placed on unbroken
skin.
PHOSGENE
What is phosgene? Also called carbonyl chloride, it is a col-

orless gas or liquid at ⬍8°C (46°F) that
smells like “freshly mown hay” or “green
corn.”
Where is phosgene used? In the production of dyes, resins, phar-

maceuticals, and pesticides. It was used
as a gaseous warfare agent during WWI,
where it was responsible for 80% of poi-
son gas fatalities.
Why was phosgene so It is heavier than air and, therefore,

effective? will settle and accumulate in low-lying
areas such as trenches. Also, because of
its low water-solubility, it is not as
irritating to the upper airways as
some irritant gases. This will allow vic-
tims to remain in a contaminated area
for a prolonged period, increasing
exposure.
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What is the most common Phosgene gas may be produced when

method of phosgene chlorinated organic compounds (e.g.,
exposure? freon, household solvents, paint removers,
dry-cleaning fluids) are heated. Occupa-
tional exposure can occur when welding
metals are cleaned with these agents.
What is the mechanism of Pulmonary irritation, causing a chemical

toxicity of phosgene? pneumonitis with inflammation of the
small airways and alveoli. Leakage of
serum into the alveolar spaces may even-
tually lead to noncardiogenic pulmonary
edema.
What are the symptoms of At high concentrations, it can cause im-

phosgene exposure? mediate-onset symptoms of eye irritation,
cough, reflex hypoventilation, and apnea.
Delayed-onset symptoms are due to in-
flammation of the bronchial and alveolar
structures and development of pul-
monary edema. This is characterized by
progressive dyspnea, potentially leading
to respiratory failure.
What must be remembered May take up to 12 to 24 hrs to develop;

about the time-to-onset of therefore, patients with a suspected phos-
pulmonary edema in gene exposure must be observed for 24 hrs
phosgene exposure (and
other poorly water-soluble
irritants)?
Does the characteristic odor No. The odor threshold is too high to af-
afford adequate warning? ford adequate warning properties. Also,
phosgene can cause olfactory fatigue.
Does significant immediate No. The degree of delayed toxicity de-

irritation portend a bad pends on the concentration and duration
outcome? of exposure; therefore, lack of immediate
irritation may in fact be more dangerous,
as the victim may not leave the contami-
nated area.
What can be used to predict The latency period until the development
outcome? of pulmonary edema. Shorter latency ⫽
greater exposure and poorer prognosis
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What part(s) of the airway Lower respiratory tract and lung

are most affected by parenchyma
phosgene inhalation?
What is the treatment for 1. Removal from environment (including

phosgene poisoning? contaminated clothing)
2. Wash contaminated skin, and flush
eyes if there is ocular exposure.
3. Supportive care. Have low threshold
for endotracheal intubation and PPV.
Use as large an endotracheal tube as
possible, as frequent suctioning may
be required.
4. Nebulized beta 2-adrenergic agonists
can reduce bronchospasm.
Is there an antidote for No, although administration of steroids is

phosgene exposure? recommended.
3-QUINUCLIDINYL BENZILATE
What is 3-quinuclidinyl Odorless, nonirritating anticholinergic

benzilate (QNB)? psychomimetic classified as a schedule 2
military hallucinogenic incapacitating
agent (NATO code ⫽ BZ)
Why is QNB considered an QNB is a potent anticholinergic agent

incapacitating agent? that produces delirium at low doses.
What is the mechanism of Systemic competitive inhibition of ACh

toxicity of QNB? at postsynaptic and postjunctional mus-
carinic receptor sites
What are the routes of 1. Inhalation (particulate aerosol)

exposure to QNB? 2. Percutaneous absorption (particulate
immersion)
What is the onset time of an 1 to 4 hrs, usually with peak effects at

acute QNB exposure? 8 hrs
What are the symptoms of Synonymous with an anticholinergic

an acute QNB exposure? response—dry mucous membranes,
mydriasis, tachycardia, urinary retention,
flushing, delirium
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What is the reported Symptoms may not resolve for 2 to 4 days.

duration of effect of QNB?
Are any laboratory tests No

helpful for diagnosis?
Is there an antidote to Physostigmine can be used to reverse

QNB? anticholinergic symptoms; however,
repeat doses may be necessary due to
QNB’s extended half-life in comparison
to physostigmine.
What are the treatment 1. Supportive care is the primary

recommendations for an treatment.
acute QNB exposure? 2. Decontamination for dermal
exposures
4. Physostigmine may be used to reverse
anticholinergic symptoms.
What is “Agent 15”? An anticholinergic glycolate

incapacitating agent possessed by the
Iraqi military during the Gulf War. It was
found to be similar (or possibly identical)
to QNB.
RICIN
What is ricin? A toxalbumin found in castor beans (Rici-

nus communis). When purified, it is a
white, water-soluble powder.
How is ricin’s heterodimeric It has a 〉 chain that allows for cellular

structure important to its entry by binding to galactose-containing
function? receptors on the cell membrane, and an
A chain that causes toxicity.
What is the mechanism of Ricin’s A chain inhibits protein synthesis

toxicity of ricin? by depurinating an adenine base of the
60S ribosomal subunit. This prevents
binding of elongation factor 2 (EF2) and
subsequently stops protein translation by
RNA polymerase.
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By what routes can ricin Ingestion, inhalation, parenteral

cause toxicity?
What limits ricin’s oral Poor GI absorption. This is especially

toxicity? true of whole castor beans. Ricin is found
within the seed coat and the bean must
be chewed to release significant toxin.
How toxic is ricin after an Estimated lethal oral dose ⫽ 1–20 mg/kg
oral ingestion? (~8 castor beans)
What are the symptoms Primarily GI (i.e., vomiting, diarrhea,

associated with acute oral abdominal pain, oropharyngeal irritation).
ricin poisoning? Patients can have electrolyte
abnormalities or develop shock due to
dehydration or GI hemorrhage.
Multisystem organ failure with hemolysis,
renal failure, LFT abnormalities, and
AMS can occur.
What is the average onset of 4 to 6 hrs. Presentation beyond 10 hrs

action for acute ricin post-ingestion is unlikely.
poisoning?
What is the prognosis of oral ⬍5% mortality

ricin poisoning?
How toxic is ricin after Far more toxic than with oral exposure.
parenteral exposure? In mice, the LD50 is ~5–10 ␮g/kg.
What is the presentation After a delay of up to 12 hrs, the patient

after parenteral exposure? will present with nonspecific symptoms,
including fever, malaise, headache,
nausea, or abdominal pain. There may be
inflammation or erythema at the injection
site. The patient can develop laboratory
abnormalities such as elevated WBC,
transaminases, amylase, CPK, and
creatinine. Death secondary to
multisystem organ failure can occur.
How does an inhalation 4 to 8 hrs post-exposure, patients can

exposure present? present with fever, cough, nausea,
arthralgias, chest tightness, shortness of
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breath, and pulmonary edema. Fatalities

are due to respiratory failure. Symptom
onset may be delayed for 24 hrs.
How long can ricin If death has not occurred in 3 to 5 days,

poisoning symptoms persist? the patient will often recover; however,
full recovery may take weeks.
How do you treat a patient 1. Removal from exposure (including

after ricin exposure? clothing) with soap and water
decontamination before entry into a
healthcare facility. Use PPE if
entering a potentially contaminated
environment.
2. For oral exposures, activated charcoal
should be given.
3. Supportive care with aggressive IV
fluid administration and electrolyte
repletion. Dialysis is ineffective.
4. Pulmonary edema may require
intubation and PPV.
For how long should a Oral exposure: if asymptomatic for

patient be observed 12 hrs, patient may be discharged with
following an exposure? instructions to return immediately for any
respiratory symptoms
Dermal exposure: observe for 12 hrs, as
absorption may occur through
compromised skin
Symptomatic patients must be admitted
and observed for development of
hypovolemia, hemolysis/anemia, renal
failure, or hepatotoxicity.
Is there an antidote for No; however, the U.S. military has

ricin? developed a vaccine.
What is ricin’s role in It is listed as a schedule 1 controlled

biological warfare? substance and given the military symbol
W. Although considered relatively
inefficacious due to its rapid atmospheric
oxidation (∼3 hrs), it is easily obtained
and has no antidote.
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Has ricin been used as an 1. WWI – United States investigated as a

agent of biological warfare bullet coating
in the past? 2. WWII – United States investigated as
a cluster bomb component
3. Georgi Markov – Bulgarian dissenter,
was assassinated in 1978 with injection
of encapsulated ricin
4. Terrorist groups – Ansar al-Islam and
Al Qaeda have tested weaponized
ricin since 2000
What other toxalbumin- Jequirity beans (Abrus precatorius) are

producing bean is similar to used ornamentally and as rosary beads.
castor beans? Abrin is the specific toxalbumin found in
this plant and has properties similar to
ricin (reportedly more potent).
TRICHOTHECENE MYCOTOXINS
What are trichothecene A group of toxins produced as

mycotoxins? byproducts of fungal metabolism. T-2
is a specific trichothecene that is
regarded as the most toxic of this
group. While T-2 acts primarily as a
vesicant, it may also exert systemic
effects.
Can T-2 mycotoxin be used Yes. “Yellow rain” incidents occurring in

as a chemical warfare agent? Southeast Asia in the 1970s have been
controversially linked with T-2 myco-
toxin. During these exposures, T-2 toxin
was allegedly dispersed by aircraft.
What are the routes of T-2 Inhalation, ingestion, dermal

mycotoxin exposure?
What was the route of Ingestion. Multiple natural outbreaks of

alleged T-2 mycotoxin GI illness related to T-2 have been re-
exposure that occurred in ported throughout the world. Typically,
past nonmilitary outbreaks? these outbreaks are related to consump-
tion of moldy wheat or corn that laid
unharvested over the winter and was
collected the following spring.
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What is the mechanism of T-2 binds the 60S subunit of eukaryotic

toxicity of T-2 mycotoxin? ribosomes and obstructs peptidyl
transferase activity, thereby
interrupting the RNA translation
process. This results in the
blockade of RNA, protein, and
DNA synthesis.
Which tissues are most Rapidly dividing cells (e.g., GI epithe-

affected by systemic T-2 lium, bone marrow)
mycotoxin poisoning?
What are the signs and Dermal/ocular exposure – skin and eye
symptoms of T-2 mycotoxin irritation, erythema and blistering,
exposure? possibly progressing to tissue necrosis
Inhalation – oropharyngeal irritation,
rhinorrhea, epistaxis, dyspnea, cough,
blood-tinged sputum
Inhalation/ingestion – nausea, vomiting,
abdominal cramps, diarrhea. GI bleeding
is likely, and delayed leukopenia may
develop.
Can T-2 mycotoxin exposure Yes, within minutes to days, depending

be fatal? on dose and route
Is there an antidote for T-2 No

mycotoxin?
What is the primary Decontamination and supportive care.

treatment for T-2 mycotoxin Granulocyte colony stimulating factor
ingestion? (G-CSF) may be of benefit to treat
neutropenia.
VESICANTS
What is a vesicant? Blister agent characterized for its use in

chemical warfare
What are the different 1. Sulfur mustards (H, HD, HT, HL)
types of vesicants (military 2. Nitrogen mustards (HN-1, HN-2,
designations in HN-3)
parentheses)? 3. Lewisite (L)
4. Phosgene (CG)
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What is a mustard agent? Sulfur mustard is an alkylating chemical

that was originally used as a weapon in
WWI. It is a liquid at room temperature
but may readily vaporize in warm
environmental conditions. Sulfur mustard
agent may be weaponized as a liquid or
aerosol. Distilled mustards are usually
clear, odorless hydrophobic liquids at
room temperature. Impurities or mustard
mixtures typically develop a pale
yellow/amber to brown color (i.e., look
like mustard) and a mustard, garlic, or
horseradish smell. Nitrogen mustards are
newer agents that have been used for
medical purposes, but not in weapon
form.
Describe the mechanism of Mustard is an alkylating agent, causing

mustard toxicity. damage to DNA and cellular proteins.
After topical exposure, damage occurs to
the dermal-epidermal junction, causing
vesicle/bullae formation and skin
sloughing. Secondary to the alkylation of
DNA, systemic manifestations may
include bone marrow suppression.
What is Lewisite? An organic arsenical compound

developed for use as a vesicating weapon.
Pure Lewisite is a clear, odorless, oily
liquid; however, impure Lewisite can
turn completely black and faintly smells
of geraniums.
What is the chemical Largely unknown; however, toxicity

mechanism of Lewisite appears to result from the depletion of
toxicity? glutathione and from the interaction of
arsenic with sulfhydryl groups
Is phosgene a vesicant? While it may cause intense skin irritation,

it does not result in skin vesiculation;
therefore, it is not a true vesicant.
What are the primary sites Eyes, skin, and respiratory tract
of vesicant action?
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How are vesicants able to Ingestion, inhalation, dermal absorption.

produce systemic symptoms? They are lipophilic, and are thus readily
(and rapidly) absorbed through
epithelia.
What is the onset of action Depends on specific compound and route:

for a vesicant exposure? Mustard – usually 2 to 48 hrs after contact
exposure, with gradual escalation in
severity
Lewisite – immediate
How do acute vesicant With severe irritation and decomposition

exposures typically present? of exposed tissues:
Skin – erythema, dermatitis, edema,
extreme vesiculation
Ocular – conjunctivitis, edema, corneal
degradation, photosensitivity, blindness
Mucous membranes – mucous
hypersecretion, laryngitis, bronchitis,
hemorrhage
Respiratory – dyspnea, pulmonary edema
GI – nausea, vomiting, diarrhea
What are Lewisite-specific “Lewisite-shock” – hypotension

symptoms in an acute secondary to capillary damage and
exposure? subsequent third spacing of fluids
What are the sub-acute and Infection, COPD, hepatic/renal

chronic risks of vesicant dysfunction, bone marrow suppression,
exposure? immune dysfunction (mustards),
carcinogenesis
What treatment is 1. Rapid decontamination

recommended for an acute 2. Neutralization if available
vesicant exposure? 3. Supportive care
Are antidotes to vesicants 1. Mustards – povidone-iodine may help

available? to neutralize
2. Lewisite – British anti-Lewisite (BAL)
chelates Lewisite, forming a stable
5-membered ring
What is the mortality rate ⬍5% mortality reported in WWI;

for acute vesicant exposure? however, large surface area (⬎50%)
concentrated contact exposures can be
fatal
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Are any vesicants used 1. Mustard gas (HD) for psoriasis

therapeutically? (discontinued)
2. HN-1 for wart removal (discontinued)
3. Mustine (HN-2) and a variety of non-
weaponized nitrogen mustards for
cancer chemotherapy
VOMITING AGENTS
What emetics are used as 1. Diphenylchloroarsine (DA or Clark I)

chemical warfare agents? 2. Diphenylcyanoarsine (DC or Clark II)
3. Diphenylamine(chloro)arsine (DM, or
adamsite)
What are other names for Sneezing gases, harassing agents, human
this group of agents? repellants
How are these agents used 1. Non-lethal riot control

as weapons? 2. Emesis induces removal of PPE to
enhance exposure to other chemical
agents
How are these agents As smoke or droplet aerosols

typically deployed?
When aerosolized, how does Odorless, yellow-green vapor

adamsite gas look and smell?
Historically, when have 1. Used by Germany during WWI

these agents been employed 2. Stockpiled by Japan in WWII
for warfare?

exposure?
When do clinical symptoms After several minutes

manifest after exposure?
How might this latency Patients are initially unaware of the

affect the toxicity of these exposure and fail to leave the environment
agents? before significant absorption occurs.
What are the signs and Initially, mucosal irritation with

symptoms of acute rhinorrhea, tearing, and coughing. This is
exposure? followed by nausea, vomiting, diarrhea,
abdominal pain, and headache.
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Can these agents be lethal? Rarely. Death can occur with significant
exposures, particularly in enclosed
spaces.
What is the treatment for Decontamination and supportive care

toxic exposures to vomiting
agents?
OTHER
When considering exposure Biologic weapons

to chemical weapons, what
other exposures must one
also consider?
What are some examples of 1. Anthrax spores (Bacillus anthracis)

biologic weapons? 2. Plague (Yersinia pestis)
3. Tularemia (Franciscella tularensis)
4. Small pox (Variola)
5. Hemorrhagic fever viruses (e.g.,
Ebola, Marburg)
What are some similarities 1. Typically vaporized/aerosolized for

between chemical and dissemination
biologic weapons? 2. Dissemination is weather-
dependent.
3. PPE is required when handling.
What are some differences Biologic agents:

between chemical and 1. Are usually slower-acting, tasteless,
biologic weapons? and odorless, and are thus harder to
identify early
2. Can mimic endemic diseases
(e.g., plague still found in United
States, inhalation exposure to anthrax
during flu season)
3. Decontamination less important
because of delayed presentation
4. Isolation usually more important to
stop spread
What is another name for “Wool-sorter’s disease” because wool

anthrax? workers often contracted the cutaneous
form of anthrax via spores from the
sheep’s wool.
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What are the types of 1. Inhalational anthrax

anthrax exposures? 2. Cutaneous anthrax
3. Gastrointestinal anthrax
What are the signs and Initial fever, malaise, fatigue, cough, and
symptoms of inhalational mild chest pain, progressing to respira-
anthrax? tory distress and even hemorrhagic medi-
astinitis, sepsis, and meningitis
What is the classic Black eschar with surrounding edema

cutaneous manifestation of after inoculation through compromised
dermal exposure to anthrax? skin
What clinical syndrome Pneumonic plague, occurring 2 to 3 days

occurs after exposure to after inhalation; patient experiences fever
aerosolized plague? with cough / hemoptysis and sepsis, pro-
gressing to respiratory distress and CV
collapse.
What is bubonic plague? Vector-borne endemic plague that occurs

after exposure to infected fleas and is
characterized by buboes (painful
adenopathy) with fever and fatigue
What precautions must be Respiratory isolation with droplet precau-

employed when a patient is tions (highly contagious)
suspected of having plague?
What are the characteristics Macules which elevate to form papules,

of the skin lesions that vesicles, and pustules
develop with smallpox?
Where are the lesions most Extremities and face, may also see oral
prominent? lesions
What are the extradermal Fever, malaise, nausea, vomiting,

manifestations of smallpox? myalgias
What is aflatoxin? Mycotoxins produced predominately by

Aspergillus spp. The Iraqi military was
known to possess weaponized aflatoxin
during the first Gulf War. Aflatoxins are
of lower potency than trichothecene my-
cotoxins but may cause both acute and
chronic disease.
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Chapter 8 Natural Toxins
AMPHIBIANS
What are amphibians? Vertebrate ectothermic (cold-blooded)

animals that live part of their life in
the water and part on land. This
taxonomic class includes frogs, newts,
salamanders, and caecelians (worm-like
creatures).
What are some poisonous 1. Poison dart frogs (Phyllobates genus)

amphibians? 2. Atelopid frogs
3. Western newts (Taricha genus)
4. Red-spotted newt (Notophthalmus
viridescens)
5. Bufo toads – cane toad (Bufo
marinus); Colorado River toad (Bufo
alvarius), also called the Sonoran
Desert toad
What are toxic components 1. Bufotenine – a tryptamine produced in

of Bufo toad venom? the parotid gland of the toad; has been
speculated to cause hallucinations
(unlikely, as it does not cross the
blood-brain barrier)
2. Bufodienolide – cardioactive steroids
that will inhibit Na-K-ATPase
3. 5-methoxydimethyl tryptamine –
secreted by Bufo alvarius and is a
potent hallucinogen
How can a Bufo toad Licking/eating the toad. Also, consuming

poisoning occur? products containing toad venom may
cause poisoning. Inhaling or smoking
the venom of Bufo alvarius can cause
hallucinations.
What laboratory drug assay Detectable digoxin level, as the bufo-

may be abnormal in Bufo dienolide cross-reacts with the digoxin
toad poisoning? immunoassay
366
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Chapter 8 / Natural Toxins 367
How can Bufo toad Digoxin Fab fragments have been suc-
poisoning be treated? cessfully used in treating overdoses in
patients with bufodienolide poisoning
presenting with elevated digoxin levels.
What is the most toxic dart Golden poison dart frog (Phyllobates
frog? terribilis), found along the Saija River of
Colombia
Where do “dart frogs” get South American Indians were historically

their name? known for rubbing their blowgun darts
on the backs of these frogs to make poi-
sonous darts.
What is one of the main Batrachotoxins, which bind with high

toxic substances found in affinity to voltage-gated sodium channels
poison dart frogs? and maintain them in an open state →
irreversible depolarization → paralysis
and cardiac dysrhythmias
What toxin is found in All produce a toxin identical to

Atelopid frogs, western tetrodotoxin, which is most commonly as-
newts, and red-spotted sociated with pufferfish. When referring
newts? to newts, tetrodotoxin is often called
tarichatoxin, from the genus Taricha to
which these animals belong.
What is the mechanism of Blocks neuronal voltage-gated sodium

action of tetrodotoxin? channels → blocks transmission by pre-
venting sodium flux. This is the opposite
mechanism of batrachotoxins from the
poison dart frog.
ARTHROPODS
BLACK WIDOW SPIDERS

Where (geographically) are Latrodectus species are found in temper-
black widows (Latrodectus ate and tropical regions of the world. In
mactans) found? the United States, they are found through-
out the lower 48 states and Hawaii.
What types of environments Dark, secluded places (e.g., woodpiles,

does the black widow barns, beneath stones)
prefer?
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What are the distinguishing The female is shiny, black, and 8–10 mm
features of the female black with a red hourglass mark on the ventral
widow? surface of its rounded abdomen. Females
have large fangs capable of penetrating
human skin, unlike the male spiders.
What are the characteristics 1. “Bull’s eye-like” erythematous region

of a black widow bite? surrounding puncture marks (fades
within 12 hrs)
2. Often painless locally since the venom
lacks human cytotoxic properties
What is the major toxic Alpha-latrotoxin

component of black widow
venom?
What is the mechanism of Alpha-latrotoxin → presynaptic neuronal

toxicity of alpha-latrotoxin? Ca2⫹ influx → exocytosis of neurotrans-
mitters (including ACh, norepinephrine
and dopamine) → muscle spasm and
sympathomimetic toxidrome
What are the signs and Initial signs may be minimal with little or
symptoms of systemic no pain at the bite site. Mild erythema
toxicity? and localized swelling may then be no-
ticed around the bite. As symptoms
progress, pain develops from the bite site
proximally, along with HTN and tachy-
cardia. Nausea and vomiting may be
present. Lower extremity bites often re-
sult in intense abdominal pain, whereas
upper extremity bites often result in se-
vere chest pain, both of which may re-
semble surgical or other pathologic
processes.
What is lactrodectism? The general syndrome of pain and cate-

cholamine surge that develops following
envenomation
What are the subcategories 1. Hypertoxic myopathic syndrome – an

of lactrodectism? extreme manifestation of
envenomation with severe muscle
cramping and weakness accompanied
by acute chest or abdominal pain
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2. Facies latrodectismica – sweating,

facial grimace/contortion that may
accompany some envenomations
3. Pavor mortis – fear of death some
patients feel after envenomation
What are the life- Respiratory distress, severe HTN, CV

threatening complications of collapse
the black widow spider bite?
What are the treatments of Commonly, analgesics (i.e., opioids) and

the black widow spider bite? muscle relaxants (i.e., benzodiazepines)
are adequate to control pain. In severe
cases, Lactrodectus antivenom may be
utilized.
Which groups of individuals Young children, the elderly, and those

may particularly benefit with comorbidities
from antivenom therapy?
From what animal is the Horses. Consequently, there is a high in-

currently approved (in the cidence of anaphylaxis to the antivenom.
U.S.) antivenom derived? It should be used cautiously and in a set-
ting with rapid access to the medications
and supplies needed to treat anaphylaxis.
BROWN RECLUSE SPIDERS

Where are brown recluse In the Mississippi valley region of the
spiders (Loxosceles reclusa) U.S., primarily in the southern states, but
found? may extend up to parts of Illinois and
Iowa. Other Loxosceles species inhabit
the southwestern U.S.
What environment does the Dry, secluded, warm areas (e.g., wood-
brown recluse prefer? piles, basements, attics). They dislike areas
of activity (i.e., they are “reclusive”).
What are the distinguishing Brown to grey in color, medium size

features of the female (6–20 mm) with a dark brown violin-
brown recluse? shaped marking on the dorsal side of
cephalothorax, and legs 5⫻ the length of
the body. Similar to the black widow, the
female is larger and considered more
dangerous than the male.
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Describe a distinguishing Loxosceles species have three sets of eyes

feature of the brown recluse arranged in pairs (six total). Most other
eye structure. species of spiders have eight eyes.
When do brown recluse When the spider is threatened, mainly

bites most often occur? during April–October
What is the major toxic Sphingomyelinase D

component of brown recluse
venom?
What is the mechanism of Venom components, including sphin-

toxicity of sphingomyelinase gomyelinase D, have both hemolytic and
D? cytotoxic properties. This may result in
local tissue thrombosis, ischemia, and
necrosis.
What are the cutaneous Initially, the bite may be painful, but
effects of the brown recluse some do go unnoticed. Over a few hours,
bite? pain is followed by central blanching and
surrounding erythema. A vesicle or bulla
may develop in the central area followed
by progressive ulceration and necrosis.
Erythema and necrosis typically follow a
gravitational pattern as the venom
spreads throughout the tissue. Symptoms
vary with the amount of venom injected;
therefore, many bites have few sequelae.
Bites tend to be more severe over areas
of adipose tissue.
What is systemic loxoscelism? Syndrome of nausea, vomiting, fever,

weakness, rhabdomyolysis, and possibly
DIC that has been sporadically described
after brown recluse envenomation. Evi-
dence defining the etiology and mecha-
nism of this disease is limited.
What are the cutaneous 1. General wound care including cool

treatments of the brown compress application
recluse spider bite? 2. Tetanus prophylaxis
3. Extremity immobilization and serial
exams
4. Antimicrobial agents for secondary
infection
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What are the systemic Analgesics and supportive care

treatments of the brown
recluse spider bite?
Are there any antidotes for No. Historical use of wound excision,
brown recluse dapsone, and even electric shock therapy
envenomation? have not been definitively proven to
change outcomes.
SCORPIONS
There are multiple types of Stings from the Centruroides exilicauda
scorpions that are indigenous (the bark scorpion) are the most med-
to the U.S. Members of ically significant, as their venom contains
which genus are most a potentially lethal neurotoxin.
dangerous to humans?
What are the signs and Local pain and inflammation

symptoms of a sting from
other indigenous scorpions?
What states have the highest Arizona and parts of California, New
incidence of scorpion Mexico, Texas, and Nevada
envenomation?
How many cases of lethal Accurate data is sparse and unreliable;

scorpion envenomations however, in the U.S., only one death at-
have been reported? tributed to the Centruroides scorpion has
been reported since 1964.
What are the signs and Pain and swelling at the site of the sting
symptoms of a sting by the followed by local paresthesias are the
Centruroides exilicauda most commonly encountered. A number
scorpion? of sympathetic and parasympathetic nerv-
ous system manifestations can occur, in-
cluding vomiting, diarrhea, hypersaliva-
tion, sweating, tachydysrhythmias,
significant HTN, and wheezing. Muscular
weakness, via both peripheral and cranial
innervation, may be seen.
How are Centruroides Grade I – local pain/paresthesias

envenomations graded? Grade II – remote pain/paresthesias
Grade III – cranial/autonomic nerve dys-
function or skeletal muscle involvement
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Grade IV – combined cranial/autonomic

nerve dysfunction and skeletal muscle
involvement
Is there antivenom that can Yes. There are several antibody-derived

be used in Centruroides antivenoms, but their use is controversial,
exilicauda envenomations? as most envenomations may be ade-
quately managed with supportive care
alone. Antivenom may be indicated in
grade III or IV envenomations.
What are the physiologic Several individual toxins cause peripheral

effects of the venom from a neuronal sodium channel opening, caus-
Centruroides scorpion? ing repetitive neuron stimulation. Symp-
toms may involve both the autonomic
(e.g., HTN, tachycardia, salivation) and
the somatic nervous systems (e.g., fascic-
ulations, ataxia).
If a scorpion collector is Knowing the particular species of

stung, are there other scorpion is critical. Exotic scorpions
concerns? (especially from Africa) can be far more
dangerous and have greater health
consequences.
TICKS
What causes tick paralysis? A neurotoxin in the salivary glands of fe-
male ticks that is released during feeding
Name 2 tick species that 1. Dermacentor andersoni (western

cause tick paralysis in the United States)
U.S. 2. Dermacentor variabilis (southeastern
United States)
What symptoms characterize Acute, ascending paralysis, beginning

tick paralysis? with lower extremity weakness and pro-
gressing to respiratory failure and death.
It can also present with ataxia. Patients
can have sensory complaints. Exam will
reveal diminished or absent reflexes.
How is tick paralysis Removing the tick will cause resolution

treated? of symptoms within 24 hrs; therefore, a
thorough body search (i.e., hair, axillae,
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perineum, ear canals) is mandatory if this

disease is suspected.
What syndrome does tick Guillain-Barre syndrome (GBS). They

paralysis mimic, and how can be distinguished by the finding of
can the two be normal CSF analysis in tick paralysis
distinguished? (GBS will cause ↑ CSF protein).
How does a tick attach to its Using its chelicerae, the tick creates a
host? hole into the host’s epidermis into which
it inserts the hypostome. This structure
anchors the tick while it feeds. A salivary
anticoagulant promotes the free flow of
host blood.
For which disease agents do Bacteria, viruses, rickettsiae, protozoans

ticks serve as vectors?
What is the proper way to With forceps or tweezers, grasp the tick
remove a tick? near the head (close to the host skin) and
pull the tick straight off (do not twist).
Other methods of removal may cause the
tick to regurgitate into the wound → ↑
risk of disease transmission.
What is the disease agent Borrelia burgdorferi (spirochete)

that causes Lyme disease?
Which tick species are Ixodes scapularis (eastern U.S.), I. pacifi-

vectors for Lyme disease? cus (western U.S.), I. ricinus (Europe),
I. persulcatus (Europe, Asia), I. ovatus
(Asia), I. moschiferi (Asia)
How long must a tick ⱖ36 hrs

remain attached to transmit
Lyme disease?
What symptoms are 1. Early localized (stage 1) – 7 to 10 days

associated with early Lyme after bite, manifests as erythema
disease? migrans (“bull’s-eye” rash) in ⬃75% of
patients. This macular dermatitis starts
out as a small, painless, circular
macule or papule and expands slowly
over days to weeks, usually with some
central clearing and flu-like symptoms.
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2. Early disseminated (stage 2) – weeks

to months after the initial infection
with fatigue, fever, lymphadenopathy,
secondary annular lesions, transient
arthralgias, Lyme carditis (conduction
abnormalities including AV block),
meningitis, Bell’s palsy, and
radiculopathies
What signs and symptoms Rheumatologic – severe pain/swelling of

are associated with late the large joints, especially the knees
Lyme disease? CNS – encephalopathy
How is Lyme disease Clinical presentation is key; ⬍50% recall

diagnosed? a tick bite. It can be confirmed with
titers, but interpretation of the results is
complex.
What is the treatment for Antibiotics such as amoxicillin,

Lyme disease? azithromycin, cefuroxime, clar-
ithromycin, doxycycline, and tetracycline
are typically used to treat early Lyme
disease and are usually taken for 2 to 3
wks. Dose and duration of treatment
vary depending on severity. Late Lyme
disease with neurological symptoms is
treated with IV antibiotics, such as
ceftriaxone.
What is the disease agent Rickettsia rickettsii

that causes Rocky Mountain
Spotted Fever (RMSF)?
Which tick species are 1. Dermacentor variabilis (American dog

vectors for RMSF? tick) in the eastern U.S.
2. Dermacentor andersoni (Rocky
Mountain wood tick) in the western
U.S.
What is the classic triad of 1. High fever

symptoms associated with 2. Rash (2 to 4 days after fever; starts on
RMSF? palms, soles, wrists, and ankles, then
spreads centripetally to torso)
3. History of tick bite
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What are the other Severe headache, malaise, chills, myal-

symptoms associated with gias, abdominal pain, nausea, vomiting,
RMSF? diarrhea
Describe the progression of Initially a blanching macular rash that

the rash. develops into a petechial rash
How is RMSF treated? Tetracycline antibiotics, particularly

doxycycline. Chloramphenicol is an alter-
native for use in pregnant women.
What happens if RMSF goes Mortality up to 30%. With appropriate

untreated? treatment, the mortality rate drops to
⬃4%.
What is the agent that Francisella tularensis – a gram-negative

causes tularemia? coccobacillus
Which tick species are 1. Dermacentor andersoni (Rocky

vectors for tularemia? Mountain wood tick) in the western
U.S.
2. Amblyomma americanum (lone star
tick) in the eastern U.S.
3. Dermacentor variabilis (American dog
tick) in the eastern U.S.
4. Ixodes ricinus in Europe
Are ticks the only means of No. ⬎50% are transmitted by ticks, but it
transmitting tularemia? may also be carried in food and water and
by other arthropods (e.g., biting flies).
What signs and symptoms Multiple diverse syndromes are associ-

are seen with tularemia? ated with tularemia, but the typical
presentation includes abrupt onset of
fever, headache, fatigue, and vomiting. A
patient not demonstrating an ↑ HR in re-
sponse to fever is a characteristic finding.
How is tularemia treated? Antibiotics, such as streptomycin, gen-

tamicin, and tetracycline
What disease agent causes Protozoans – Babesia microti and Babesia

babesiosis? divergens
Which tick species are I. scapularis (U.S.) and I. ricinus (Europe)

vectors for babesiosis?
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What signs and symptoms Malaria-like symptoms for days to

are associated with months – fever, chills, fatigue, headache,
babesiosis? nausea, vomiting, AMS, DIC, hypotension,
respiratory distress, hemolytic anemia
How is babesiosis treated? Quinine sulfate plus clindamycin
What disease agent causes 1. Ehrlichia chaffeensis causes human

ehrlichiosis? monocytic ehrlichiosis (HME)
2. E. phagocytophila causes human
granulocytic ehrlichiosis (HGE)
These are small, gram-negative coc-
cobacilli belonging to the family
Rickettsiaceae.
What is the difference HME – affects mononuclear phagocytes,

between HME and HGE? found mostly in southern and south-
central U.S.
HGE – affects granulocytes, found in
upper midwestern and northeastern U.S.
Which tick species transmit Amblyomma americanum (HME) and

ehrlichiosis? Ixodes scapularis (HGE)
What signs and symptoms Similar presentations – fever, headache,

are associated with HME myalgias, pancytopenia, elevated hepatic
and HGE? transaminases. HME is typically less se-
vere and has a lower mortality rate.
How is ehrlichiosis treated? Tetracycline antibiotics, such as doxycy-

cline. Rifampin is an alternative for
tetracycline-allergic patients.
What disease agent causes Tick-borne encephalitis virus (TBEV), a

tick-borne encephalitis member of the family Flaviviridae
(TBE)?
What tick species transmit Ixodes ricinus (western and central

TBE? Europe) and Ixodes persulcatus (central
and eastern Europe)
What signs and symptoms 1. Incubation period – 7 to 14 days

are associated with TBE? 2. Viremic phase – 2 to 4 days, flu-like
symptoms
3. Remission – up to 8 days
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4. Neurogenic phase – only 20% to 30%

of patients, meningitis-like
presentation (i.e., fever, headache,
nuchal rigidity), encephalitis-like
presentation (i.e., confusion,
drowsiness, sensory disturbances,
partial paralysis), or a combination of
these
How is TBE treated? Supportive care. A TBE vaccine exists

and is routinely used in Europe.
Is TBE seen in the U.S.? Powassan encephalitis (POW) is a rare

form of TBE seen in the northeastern
U.S. and parts of Canada. It is transmit-
ted by Ixodes cookie and manifests as
severe fever, headache, nuchal rigidity,
nausea, vomiting, and fatigue, progress-
ing to confusion, seizures, respiratory dis-
tress, and paralysis.
What disease agent causes Colorado tick fever virus (CTFV), a

Colorado tick fever (CTF)? member of the family Reoviridae, genus
Coltivirus
What tick species transmits Dermacentor andersoni (western U.S.

CTF? and Canada)
What signs and symptoms After a 4-day incubation period, sudden

occur with CTF? fever, chills, headache, retroorbital
pain, photophobia, myalgias, malaise,
rash, abdominal pain, nausea, and
vomiting. The presentation may be
biphasic with a symptom-free period in
between.
How is CTF treated? Supportive care
What disease agent causes Borrelia recurrentis (spirochete)

tick-borne relapsing fever
(TBRF)?
What tick species transmit Soft ticks of the genus Ornithodoros

TBRF? (Asia, Africa, Middle East, and North and
South America)
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What signs and symptoms Recurrent episodes of high fever along

are associated with TBRF? with headache, myalgias, malaise,
photophobia, abdominal pain, nausea,
vomiting, rash, and confusion. Episodes
typically last ⬍1 wk and are separated
by 4 to 14 days between relapses.
How is TBRF treated? Doxycycline or erythromycin
What reaction can occur Jarisch-Herxheimer reaction. This in-

during treatment of TBRF? cludes fever, rigors, headache, diaphore-
sis, and hypotension.
OTHER
What are the significant Bees, wasps, and ants
species of stinging
hymenoptera?
What differentiates the sting The honeybee stinger characteristically

of the honeybee from other detaches in human flesh.
bees and wasps?
What is the greatest danger Allergic reaction to allergens (proteins) in

of the honeybee sting? the venom
Should the stinger of a Yes. This prevents additional venom

honeybee be removed injection.
immediately?
How does a bee sting result Respiratory dysfunction and/or anaphylaxis

in a fatality?
Why is an Africanized 1. Heightened defensive reaction (will

honeybee (AHB) attack attack a person within 10 m of the
more likely to result in a colony)
greater number of stings? 2. Respond in larger numbers
3. Are more persistent in following a
person (up to hundreds of meters
from the nest)
If a patient is allergic to the Not necessarily. The allergic reaction to

sting of a honeybee, are they bees is very species-specific.
also allergic to the stings of
other hymenoptera?
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What is the mechanism of Causes pain by directly affecting

toxicity of the Vespid wasp neurons or by releasing pain-inducing
venom? compounds
What is the protein in wasp Peptides called mastoparans

venom that causes the
release of histamine from
mast cells?
Which stinging ants are of Red fire ants and harvester ants
medical significance?
What is significant about the Red fire ants respond to disturbance with
red fire ant sting? vigorous mass stinging
What is the active chemical Alkaloids. These are cytotoxic, resulting

in fire ant venom? in skin necrosis, and they inhibit the
Na-K-ATPase of muscle cell membranes,
resulting in a postsynaptic neuromuscular
blockade.
How does a fire ant sting Initial burning sting, followed by a

progress? wheal (10 mm) with pruritus and
edema; 4 hrs later, sterile vesicles form,
and by 24 hrs, they turn into necrotic
pustules.
Can fire ant bites cause Yes. Systemic symptoms (and even
significant morbidity or fatalities) have been reported when
mortality? immobile victims (e.g., infants, frail
elderly) have suffered massive numbers
of stings.
Which spider’s bite mimics Hobo spider (Tegenaria agrestis)

the dermonecrotic lesion of
the Loxosceles reclusa
(brown recluse) and lives in
the Pacific Northwest?
Which spider’s body color Yellow sac spider (Family Clubionidae),

can change from yellow whose bites are usually self-limited
to greenish, pink, or
tan depending on its last
meal?
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The bite of which webless, The armed (or banana) spider (Phoneu-
aggressive, South American tria). Note that in North America there is
spider (often found around a large yellow spider, called the banana
banana plants) is neurotoxic spider, that is relatively harmless.
and can manifest with
immediate pain, salivation,
priapism, bradycardia,
hypotension, and occasional
death?
Which spider found in The six-eyed crab spider (Sicarius)

Africa and South America
possesses 6 eyes and is
considered very poisonous
(and there is no
antivenom)?
What is the result of the six- Severe tissue damage (more extensive
eyed crab spider bite? than that of the brown recluse) and possi-
bly death
Which large, aggressive Australian funnel-web spiders (Atrax and

spider found along the Hadronyche)
eastern coast of Australia
can cause a syndrome of
paresthesias,
hypersalivation, nausea,
vomiting, confusion,
dyspnea, profuse sweating,
hypotension, and death due
to pulmonary edema?
What is the mechanism of Slows closing of voltage-gated sodium

action of the venom? channels → repetitive action potentials
→ excessive release and eventual exhaus-
tion of neurotransmitters
Is there antivenom for the Yes

funnel-web spider?
Do tarantulas have a Yes. Reported problems are not typically

venomous bite? related to the bite, however. The spider’s
barbed hairs can get stuck in the eyes or
nose, causing irritation.
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What is Spanish fly? A purported aphrodisiac made from

dried blister beetles. Blister beetles con-
tain cantharidin, which can cause severe
oropharyngeal irritation, mucosal erosion,
hematemesis, flank pain, hematuria, and
renal dysfunction.
What is the blister beetle’s When a beetle is crushed, it releases

primary route of toxicity? cantharidin, which will cause vesicle
formation on contact with the skin;
these are not painful unless ruptured.
Ocular exposure will cause
conjunctivitis.
BOTULISM
What is botulism? A disease caused by systemic absorption

of botulinum toxin, which includes eight
serologically distinct, heat-labile proteins
(labeled A, B, C1, C2, D, E, F, G), of
which only A, B, E, and (rarely) F cause
illness in humans.
What produces botulinum? The anaerobic, spore-forming gram-

positive bacillus, Clostridium botulinum
What are the forms of 1. Infant

botulism? 2. Food-borne
3. Wound
4. Adult intestinal
5. Inhalational
6. Parenteral/injection
What conditions are An anaerobic, low-sodium, and non-

hospitable to C. botulinum? acidic medium. The toxin can be
inactivated by heating at 85°C (185°F)
for 5 min.
Where do C. botulinum 1. Under-processed canned/jarred foods

contaminations typically 2. Poorly preserved meat, sausage, fish,
occur? shellfish, jerky
3. Vegetables, fruit, olives (less
common)
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What is the mechanism of Toxin is endocytosed by the neuron →

toxicity of botulinum toxin? light chain of botulin proteolytically
cleaves various SNARE proteins → fail-
ure of synaptic vesicle fusion at presynap-
tic nerve terminus → no ACh release →
no neurotransmission
What is the onset time for Highly variable – symptoms may appear
an acute botulin poisoning? as early as 2 hrs post ingestion, with most
patients developing symptoms between
10 to 72 hrs; however, signs and symp-
toms may not be noticed for up to 8 days
What symptoms occur with The presenting symptoms follow a stereo-

acute botulin poisoning? typical pattern of descending weakness:
1. Cranial nerve dysfunction – dysphagia,
diplopia, dysarthria
2. Exam – ptosis, gaze paralysis, and
facial palsy are most often noted
3. Inhibition of muscarinic cholinergic
function – dry mouth, dilated pupils,
constipation
4. Descending motor paralysis affecting
the upper limbs, then the lower limbs
5. In severe cases, the intercostals and
diaphragm are affected, possibly
necessitating mechanical ventilation.
6. Food-borne botulism also may have
GI symptoms, including nausea,
vomiting, constipation, and diarrhea
(less common), that typically precede
neurological symptoms.
How does botulin poisoning Toxin cannot cross the blood-brain bar-
affect mental status? rier and, therefore, only affects the PNS.
Mental status should be normal unless
respiratory insufficiency has caused hy-
poxia or hypercarbia. Also, botulin will
not cause sensory deficits.
How is acute botulism 1. Supportive care, with attention to

treated? airway protection and ventilatory
support
2. Botulinum antitoxin. This therapy will
be empiric, based on clinical
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suspicion, as no confirmatory tests will

be readily available.
Why is it important to The paralysis caused by botulinum toxin

administer botulinum will persist until neural end plates are re-
antitoxin as early as generated. If a patient’s condition pro-
possible? gresses to the point of requiring mechan-
ical ventilation, that patient may become
ventilator-dependent for several months.
For this reason, it is important to recog-
nize botulism and initiate treatment with
antitoxin early.
Are antibiotics indicated for No. They have no effect on preformed

food-borne botulism? toxin; however, they may be needed to
treat secondary infections.
Which antibiotics should not Aminoglycosides and clindamycin may

be used when treating a exacerbate neuromuscular blockade.
patient with botulism?
What causes infant Infant botulism is the most common

botulism? form of botulism. It occurs when C. botu-
linum spores are ingested and germinate
in the GI tract. The bacteria then pro-
duce toxin, which are absorbed into the
body. Adult intestinal botulism is similar
to infant botulism. It occurs in adults who
have altered GI flora due to antibiotic
use, abdominal surgery, achlorhydria, or
inflammatory bowel disease.
What is the classic source of Honey. In actuality, infant botulism is

infant botulism? usually contracted by ingesting dust con-
taining C. botulinum spores. The soil in
southeastern Pennsylvania, Utah, and
California has the greatest chance of con-
taining these spores.
How does infant botulism May be subtle. Constipation is often the

present? initial symptom and may precede neuro-
logical symptoms by days. This can
progress to poor feeding, weak cry,
ptosis, weakness, and respiratory
insufficiency.
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What is wound botulism? Occurs when C. botulinum spores

contaminate wounds. They can germi-
nate and produce the toxin, which is
then systemically absorbed. Clinical
manifestations are similar to food-borne
botulism.
How is wound botulism Same as food-borne botulism; however,

treated? administration of antibiotics and drainage
and/or debridement of infected tissue
must also be performed
What is the LD50 of 1 ng/kg; therefore, 50–100 ng can be fatal

botulinum toxin?
Is there an antidote to Yes, a trivalent (A, B, E) antitoxin from

botulism? the CDC and a heptavalent antitoxin
from the US Army
Is the trivalent antidote No. This is, in part, due to the high rate
available from the CDC of adverse reactions and fear of
used to treat infant sensitizing infants against horses and
botulism? equine-derived products.
Is there an antidote for Yes. Recently, a human-derived immune

infant botulism? globulin (baby-BIG) has been
introduced and should be used to treat
infant botulism.
Can the presence of Yes. Diagnosis can be confirmed by de-

botulism be detected? tecting toxin in the patient’s serum, stool,
or wound drainage. The suspected food
should also be tested. The CDC or local
state health department should be con-
tacted to help with testing. They will also
provide the antitoxin.
What does an acute botulin First, this should only be done in a stabi-
poisoning electromyograph lized patient.
(EMG) look like? 1. Brief low-voltage compound motor
units
2. Low M wave amplitudes
3. Abundant action potentials
Note that up to 15% of affected individu-
als will have a normal EMG.
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What is the prognosis for Variable. With careful attention to

botulin poisoning? respiratory status, recovery is common,
although full recovery may take months.
How is botulin A used 1. Strabismus

therapeutically? 2. Blepharospasm
3. Spasmodic torticollis
4. Achalasia (investigational)
What adverse reactions can 1. Local dermatitis

occur following therapeutic 2. Ocular edema
botulin A administration? 3. Photophobia
4. Symptoms consistent with poisoning
ESSENTIAL OILS
What are essential oils? Polyaromatic hydrocarbons that have been

extracted from a single type of plant. The
oils are obtained through steam distillation
or cold pressing of the desired part (i.e.,
root, leaves, flowers) of the parent plant.
Why are essential oils so The chemicals in essential oils are highly
toxic? concentrated and, when ingested, are
quickly absorbed.
How are essential oils used? For their aromatic properties and as al-
ternative medicinal remedies
What is pennyroyal oil? Pennyroyal is derived from the plant

Mentha pulegium and has been used
since antiquity as an abortifacient and in-
sect repellant.
What is the mechanism of Pulegone (primary toxin) – binds to

pennyroyal toxicity? cellular proteins and depletes glutathione,
resulting in centrilobular hepatic necrosis
Menthofuran (P450 metabolite of pule-
gone) – inhibits glucose-6-phosphatase
→ prevents glycogen breakdown →
hypoglycemia
Describe the treatment of Primarily supportive with close monitor-

pennyroyal ingestion. ing for hypoglycemia. N-acetylcysteine
may be beneficial in repleting glutathione
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and decreasing the incidence of liver

failure.
How does oil of wintergreen Oil of wintergreen contains methyl salicy-

cause toxicity? late. Toxicity is identical to aspirin poi-
soning, although the oil is more quickly
absorbed, which results in a faster onset
of symptoms.
How many mL of pure oil of 5 mL (1 tsp) or ⬃21 regular strength

wintergreen is equal to 7 g (325 mg) aspirin tablets
of aspirin?
What is the treatment for oil Follows standard salicylate guidelines.

of wintergreen poisoning? Hydration and urine alkalinization are
indicated for mild toxicity. Hemodialysis
may be needed for severe toxicity.
What other essential oil is Clove oil. Ingestion of concentrated clove

known to cause oil may also result in CNS depression and
hepatotoxicity? seizures.
What are the manifestations Initially, nausea, vomiting, tachycardia,

of camphor toxicity? confusion, agitation, and CNS depression.
Seizures often develop within 30 min of
ingestion. Camphor odor may be evident
on the breath.
From what plant is camphor Cinnamomum camphora tree

derived?
Describe the toxic effects of Primary manifestation is CNS depres-

eucalyptus oil. sion/coma. Coma has been reported with
ingestion of as little as 5 mL.
What is melaleuca oil? Also known as tea tree oil, it is found in a

variety of cosmetic products. Contact
dermatitis and photosensitivity are
common after dermal exposure. CNS
depression and ataxia are reported after
ingestion of concentrated solutions.
FOOD POISONING, BACTERIAL
What is the most potent of Botulin

the bacterial food poisons?
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Which bacteria produce 1. Staphylococcus aureus

preformed toxins in food? 2. Clostridium perfringens
3. Bacillus cereus
4. Clostridium botulinum
What property of preformed Heat-resistance (i.e., not easily removed;

toxins makes them difficult or deactivated by cooking/boiling)
to eradicate?
What is the incubation Short – symptom onset within 6 to 12 hrs

period for bacteria with of consumption
preformed toxins?
What characterizes From 1 to 6 hrs post-ingestion, victims

staphylococcal food develop nausea with profuse vomiting
poisoning? and abdominal cramps. This is usually
followed by diarrhea. Fever is rare, and
symptoms typically last ⬍12 hrs.
What characterizes food From 8 to 16 hrs post-ingestion, patients

poisoning caused by develop watery diarrhea, abdominal
C. perfringens? cramping, and vomiting, though vomiting
is less frequently encountered. Symptoms
last 12 to 24 hrs.
What is unique about It causes two distinct clinical syndromes:

Bacillus cereus food 1. An “emetic” syndrome caused by a
poisoning? preformed toxin. This results in
vomiting and abdominal cramping
within 1 to 6 hrs and recovery within
12 hrs.
2. A “diarrhea” syndrome believed to be
caused by toxin produced in the gut.
This causes diarrhea and abdominal
cramping 8 to 16 hrs post-ingestion
with recovery by 24 hrs (usually).
What is the classic vehicle for Reheated fried rice

B. cereus food poisoning?
Will antibiotics be of benefit No

for gastroenteritis caused by
preformed toxins?
Which types of bacteria 1. Bacillus cereus

produce toxins in the gut? 2. Campylobacter jejuni
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3. Enterotoxigenic and
enterohemorrhagic Escherichia coli
4. Vibrio parahemolyticus
5. Clostridium perfringens
Consumption of which types 1. Clostridium botulinum

of bacteria may cause 2. Listeria monocytogenes
serious systemic poisoning? 3. Escherichia coli O157:H7
4. Shigella
Which types of bacteria, 1. Listeria monocytogenes

when ingested, may cause 2. Salmonella
an invasive gastroenteritis? 3. Vibrio parahemolyticus
4. Shigella
5. Yersinia enterolytica
6. Campylobacter jejuni
7. Enteroinvasive Escherichia coli
What is the etiology of Enterotoxigenic Escherichia coli (ETEC)

“traveler’s diarrhea”?
Found in milk, raw hot dogs, Listeria monocytogenes. This is why

deli meat, and pregnant women are advised to avoid
unpasteurized soft cheeses, cold cuts and soft cheeses.
which bacteria typically
causes a gastroenteritis
syndrome but can cause an
invasive infection in
immunocompromised
individuals?
Which bacteria produces a Clostridium perfringens

toxin in food and in the gut,
and may be found in meats
and gravy?
What finding on a stool Abundant WBCs

smear may differentiate a
bacterial etiology from other
causes of food poisoning?
Administration of antibiotics Hemolytic-uremic syndrome (HUS)

to patients with E. coli
O157:H7 increases the risk
of what condition?
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What is the most important Hand washing

preventative measure in
controlling food-borne
illness?
HERBAL PRODUCTS
What is the inherent risk in Quality control is relaxed and not regu-
taking herbal products? lated by the FDA, resulting in variability
in potency and purity.
For what is Ginkgo biloba 1. Dementia syndromes/memory aid

used? 2. Peripheral vascular disease
3. Tinnitus
4. Vertigo
What toxic effects may result Antiplatelet effects and GI distress

from Ginkgo biloba
ingestion?
What is the mechanism of 1. Agonism at alpha 1-, alpha 2-, beta 1-,
action of ephedra? and beta 2-adrenergic receptors
2. Release of stored catecholamines from
presynaptic nerve terminals and
inhibition of catecholamine reuptake
For what indications do 1. Weight loss

people take ephedra? 2. Enhance athletic performance (boost
energy)
What are the toxic effects of Tachycardia, HTN, cardiac dysrhythmias,

ephedra? psychosis, seizures, and possibly CVA.
Secondary to these effects, ephedra is
currently banned in the U.S.
Which herbal product St. John’s Wort. It is also associated with

classically causes early cataracts.
photosensitivity?
What are the reported uses 1. Antidepressant (for mild depression)

of St. John’s Wort? 2. Anti-inflammatory
3. Antimicrobial
How does St. John’s Wort It is a CYP3A4 and P-glycoprotein

induce drug interactions? inducer
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What drug levels have been Cyclosporin A, indinavir, nevirapine,

reported to be altered by midazolam, theophylline, amitriptyline,
St. John’s Wort? warfarin, digoxin, oral contraceptives
What hyperthermic, drug- Serotonin syndrome. This may result

induced syndrome can when St. John’s wort is combined with
(theoretically) result from other serotonergic agents.
St. John’s Wort?
What herbs have been Bajiaolian (Dysosma pleianthum), black

associated with cohosh (Cimicifuga racemosa), cascara
hepatotoxicity? (Rhamnus purshiana), celandine (Cheli-
donium majus), chaparral (Larrea triden-
tata), common comfrey (Symphytum
officinale), Russian comfrey (Symphytum
uplandicum), prickly comfrey (Symphy-
tum asperum), common germander (Teu-
crium chamaedrys), felty germander
(Teucrium polium), impila (Callilepsis
laureola), jin bu huan (Polygala
chinensis), kava (Piper methysticum), ma
huang (Ephedra sinica), American pen-
nyroyal (Hedeoma pulegoides), European
pennyroyal (Mentha pulegium), skullcap
(Scutellaria lateriflora), white chameleon
(Atractylis gummifera)
How does kava kava cause Mechanism is unknown, but it is thought

hepatotoxicity? to arise from contaminants in the manu-
facturing process. Natural kava, used
primarily by Pacific Islanders, has not
resulted in hepatotoxicity.
What is the hepatotoxic Pyrrolizidine alkaloids, which can cause

element in comfrey, and veno-occlusive disease of the liver
what are its specific effects
on the liver?
For what indications is 1. As an antimicrobial (especially for

goldenseal used? colds, in combination with echinacea)
2. Fever/inflammation
3. Drug abuse masking agent
4. Gallbladder disease
What are the toxic effects of Large doses have been associated with
goldenseal? nausea, vomiting, CNS depression,
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hyperreflexia, seizures, paralysis, and res-

piratory failure.
What electrolyte Chronic consumption of licorice root,

abnormalities are associated which contains glycyrrhizic acid, may
with licorice consumption? cause pseudohyperaldosteronism, result-
ing in hypokalemia and hypernatremia.
What herbal product used Lobelia, which contains lobeline

for smoking cessation
contains a substance similar
to nicotine?
What dietary supplement Manufactured L-tryptophan. This syn-

was associated with drome of myalgias, arthralgias, and
eosinophilia-myalgia eosinophilia was associated with
syndrome? L-tryptophan produced by a single
manufacturer in 1989 and 1990.
How is yohimbine used? Yohimbine is an alpha 2-adrenergic an-

tagonist derived from the yohimbe tree
and is often used as a stimulant and for
erectile dysfunction. Adverse effects in-
clude tachycardia, HTN, nausea, vomit-
ing, and diaphoresis.
Cantharidin, used as a Dermal irritation, GI hemorrhage,

topical wart remover, has delirium, ataxia, renal toxicity
what toxic side effects?
From where is cantharidin It is a vesicant produced by blister

obtained? beetles, most notably the Spanish fly.
What is the biggest danger Anaphylaxis in those allergic to the

of chamomile use? Asteraceae/Compositae families (ragweed
pollens)
Which herbals increase INR Devil’s claw, dong quai, garlic, ginseng,
and put patients who take papaya
warfarin at risk?
What are “Chinese patent “Herbal” medicines produced by poorly

medicines”? regulated Chinese pharmaceutical compa-
nies. Their popularity has expanded as the
worldwide use of alternative medicine has
grown. While touted to be herbal, these
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products have been found to contain a va-

riety of contaminants, including heavy
metals, pharmaceutical products (e.g.,
benzodiazepines, NSAIDs), and other
potentially harmful biologic products (e.g.,
centipede, toad secretions).
What are Ayurvedic Traditional Indian remedies that usually

medicines? contain heavy metals and herbal products.
Lead, arsenic, and mercury may be pres-
ent in large quantities in these products.
MARINE
INGESTED
Name some marine toxins Scombroid, ciguatera, tetrodotoxin
that cause their effects after (TTX), paralytic shellfish poisoning
ingestion. (PSP), neurotoxic shellfish poisoning
(NSP), amnesic shellfish poisoning (ASP),
diarrheal shellfish poisoning (DSP)
Scombroid poisoning Flushing of face and/or neck, sensation of

typically presents with what warmth without fever, metallic and/or
signs and symptoms? peppery taste in mouth, burning sensa-
tion of mouth and/or throat, nausea,
abdominal cramping, diarrhea. Bron-
chospasm and hypotension are possible.
How soon after ingestion of 5 to 90 min

scombrotoxic fish do
symptoms present?
How long do symptoms 12 to 24 hrs

typically last?
How do humans acquire Ingestion of poorly refrigerated or poorly

scombroid poisoning? preserved dark, or red-muscled, fish
(e.g., tuna, mackerel, mahi-mahi, herring,
sardine, anchovies)
What is the pathophysiology Effects are caused by large amounts of

of scombroid poisoning? histamine present in these fish, along
with other toxins that may potentiate his-
tamine’s effect.
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Does cooking these fish No. Histamine is heat-stable and unaf-

prevent scombroid fected by cooking.
poisoning?
What is the treatment for 1. Antihistamines – IV H1 and H2

scombroid poisoning? blockers (e.g., diphenhydramine and
cimetidine, respectively)
2. Bronchodilators (e.g., albuterol) can
be helpful for bronchospasm.
3. Severe cases with hypotension and
respiratory distress will require
aggressive treatment with IV fluids,
airway control, and possibly
epinephrine.
Ingestion of what types of Large predatory reef fish, including

fish have been implicated in snapper, grouper, sea bass, barracuda,
ciguatera poisoning? amberjack, mullet, tuna, and moray eel.
Sturgeon have also been implicated.
How is ciguatoxin (CTX) It is produced by the marine dinoflagel-

bioaccumulated? late Gambierdiscus toxicus, which grow
on algae and dead coral and are con-
sumed by herbivorous fish. The toxin is
concentrated up the food chain as larger
predatory fish consume multiple prey
containing CTX.
Onset of symptoms occurs Shows significant variability – as rapidly

how long after ingestion of as 15 min, but delays may occur out to
these contaminated fish? 24 hrs. Symptoms usually appear within
4 to 6 hrs following ingestion of contami-
nated fish.
What are the most common CNS – seizures, respiratory depression,

presenting symptoms of coma
ciguatera poisoning? CV – hypotension. Symptomatic brady-
cardia has occurred and has been hypoth-
esized to be due to CTX’s effects on the
muscarinic autonomic nervous system.
GI – nausea, vomiting, diarrhea, abdomi-
nal pain
PNS – paresthesias, hot/cold reversal,
headache, weakness, vertigo, ataxia,
myalgias, pruritus
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Hot and cold reversal is Often described as cold objects feeling

often cited as a classic hot. More accurately, though, contact
symptom of ciguatera with cold seems to cause painful tingling,
poisoning. What does this burning discomfort, or an electric shock
actually describe? sensation.
Co-ingestion of what other Ethanol. Ingestion of ethanol after recov-

toxin potentiates these ery can cause a recurrence of symptoms,
symptoms? and, therefore, should be avoided for up
to 6 months.
What is the mechanism of Binds to sodium channels → ↑ Na⫹ in-

action of CTX? flux → repetitive firing and constant acti-
vation. Also, sodium influx may lead to
axonal swelling and slowed conduction.
What characteristics make Stability in hot, cold, and acidic environ-

CTX a highly effective ments. It also does not alter the taste or
human poison? appearance of the fish.
What are the suggested 1. Administer supportive care with

treatments for CTX attention to the common presentation
poisoning? of dehydration with potential
electrolyte abnormalities secondary to
vomiting and diarrhea.
2. Symptomatic bradycardia should be
treated with atropine.
3. Pruritus can be treated with
antihistamines.
4. Mannitol 1 g/kg over 45 min has been
used to treat acute neurological
symptoms (although evidence for its
effectiveness is questioned)
5. Amitriptyline and gabapentin have
been used to lessen residual
neurologic symptoms.
Are there any long-term Yes. Patients may suffer from intermittent
sequelae from CTX paresthesias, pruritus, and myalgias for
poisoning? months to years after acute poisonings.
Is the ingestion of pufferfish No. TTX is found in many species,

the only cause of including blowfish, xanthid crabs, horse-
tetrodotoxin (TTX) shoe crabs, toadfish, California and Ore-
poisoning? gon newts, and the blue-ringed octopus.
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TTX poisoning presents with 1. Paresthesias are common and

what array of symptoms? typically the first symptom to be
reported, usually beginning within an
hour post-ingestion. Paresthesias
initially affect the tongue, lips, and
mouth and progress to involve the
extremities.
2. GI symptoms may be seen and
include nausea, vomiting, and diarrhea
(less often).
3. Headache, blurred vision, pleuritic
chest pain, dizziness, diaphoresis,
hypersalivation, and bronchorrhea
have been reported.
4. Dysphagia, aphonia, and other cranial
nerve abnormalities are possible.
5. Ascending paralysis progressing to
respiratory failure
6. Bradycardia, hypotension, and
refractory heart block
7. Death can occur within hours
secondary to respiratory muscle
paralysis or profound hypotension.
What is the mechanism of 1. Binds to voltage-gated sodium channel

action of TTX? site named toxin site 1 → inhibits Na⫹
influx → blockade of
neurotransmission at central,
peripheral, and autonomic sites →
poor nerve and muscle function
2. Direct relaxation of vascular smooth
muscle → hypotension
What is the treatment for 1. Aggressive supportive care, ensuring

TTX poisoning? adequate ventilation.
2. Hypotension should be treated with
IV fluids and vasopressors, if
necessary.
3. Temporary pacing for refractory heart
block may be needed.
4. Activated charcoal and gastric lavage
with alkaline solution can be
considered early following ingestion,
although these treatments are of
unproven benefit.
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5. Most patients require admission, with

care in an ICU setting if they
demonstrate significant clinical effects.
6. Long-term sequelae are rare if the
patient survives.
Can patients be exposed to Yes. The bite of the blue-ringed octopus

TTX by routes other than can cause TTX poisoning.
ingestion?
What are the neurological PSP, NSP, ASP (see above)

syndromes caused by
shellfish poisoning?
What is the major toxic Saxitoxin (STX)

component that causes
PSP?
What is the primary Similar to TTX, it binds to site 1 on the

mechanism of STX? voltage-gated sodium channel, causing in-
hibition of sodium influx.
What are the signs and Presents in a similar fashion to TTX and
symptoms of PSP, and how should be treated the same way
is it treated?
What agent is responsible Domoic acid

for amnestic shellfish
poisoning?
What is the mechanism of Domoic acid is a structural analogue of

action of domoic acid? glutamic acid and kainic acid and, there-
fore, will act as an excitatory neurotrans-
mitter. Overstimulation of the neurons →
excessive Ca2⫹ influx → cell death
What are the clinical Onset is from 15 min to 38 hrs post-

manifestations of domoic ingestion and can manifest with nausea,
acid poisoning? vomiting, abdominal cramps, diarrhea,
headache, confusion, ophthalmoplegia,
purposeless chewing, grimacing,
bronchorrhea, hypotension, dysrhyth-
mias, seizures, coma, and death.
What is the prognosis? Mortality is ⬃2%. Up to 10% can suffer

long-term antegrade memory deficits.
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Autopsy results implicate damage to both

the hippocampus and the amygdala.
What agent is responsible Brevetoxin

for NSP?
What is the mechanism of Opens sodium channels, producing simi-

action of brevetoxin? lar manifestations to ciguatera poisoning
How does DSP present? Severe GI symptoms (e.g., nausea, vomit-

ing, abdominal cramps, diarrhea) without
neurological symptoms. Onset is typically
30 to 120 min post-ingestion and should
be treated supportively.
What is clupeotoxism? Poisoning from the ingestion of plankton-

eating fish (i.e., sardines, herring, an-
chovies). Although rare, it is widespread
in the tropical and subtropical regions. It
can cause severe poisoning with a metal-
lic taste, GI distress, paresthesias, paraly-
sis, coma, and possibly death.
What is the treatment? Supportive care
What is palytoxin? A toxin originating in soft coral species

and occasionally found in the flesh of
some crabs and fish
What is the mechanism of Allows influx of cations into smooth,

action of palytoxin? skeletal, and cardiac myocytes, causing
muscle contraction
What are the symptoms of Severe myalgias, low back pain, chest
palytoxin poisoning? pain, respiratory distress (asthma-like),
hemolysis, and cardiac arrest
What do CTX, PSP, ASP, The toxins involved in all of these origi-
NSP, and DSP have in nate in dinoflagellates.
common?
Does there need to be a No. Not all outbreaks are associated with
“red tide” in order for there toxic algal blooms.
to be a risk of dinoflagellate-
associated shellfish
poisonings?
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INVERTEBRATES
Venomous marine 1. Porifera (sponges)
invertebrates come from 2. Annelida (bristleworms)
which phyla? 3. Cnidaria (jellyfish, corals)
4. Mollusca (octopus, cone snails)
5. Echinodermata (starfish, sea urchins)
What jellyfish are commonly 1. Box jellyfish (especially Chironex

implicated in human fleckeri and Carukia barnesi)
envenomations? 2. Portuguese man-of-war (Physalia spp.)
3. Sea nettles (Chrysaora spp.)
How do jellyfish With nematocysts – stinging cells that fire

envenomate humans? a venom-containing, harpoon-like appara-
tus into the victim
What are the common signs Immediate local pain/irritation and

and symptoms of jellyfish urticaria
envenomation?
Describe the general 1. Remove attached tentacles with hand

treatment of Cnidaria protection or a mechanical device.
envenomation. 2. Vinegar can be applied to inactivate
the venom.
3. Cover the affected area with paste of
baking soda, sand, or shaving cream,
and scrape with a flat-edged object to
remove remaining nematocysts.
4. Topical anesthetics may be used for
pain relief.
What treatments should be Avoid washing with fresh water or rub-

avoided after bing the site of envenomation, as either
envenomation? of these actions may result in discharge
of the nematocysts.
Chironex fleckeri Australia

envenomation has caused
multiple deaths along the
coast of what country?
Chironex fleckeri venom is Cardiotoxicity

believed to cause death by
what mechanism?
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To what jellyfish is there an Chironex fleckeri

antivenom?
What is Irukandji A painful hypertensive syndrome that has

syndrome? been described following stings from the
Irukandji jellyfish. The syndrome is char-
acterized by generalized and severe pain,
muscle spasm, HTN, tachydysrhythmias,
and rarely pulmonary edema.
The venom of which jellyfish Carukia barnesi, found in the Indo-

causes Irukandji syndrome, Pacific region. A similar syndrome has
and where is it found? been described following stings of other
jellyfish in U.S. waters. The latter is rare.
When should a baking soda When a sea nettle envenomation is sus-

slurry be used instead of pected (Chesapeake Bay)
vinegar to treat a jellyfish
envenomation?
What is sea bather’s A reaction to the venom of jellyfish larvae

eruption? that causes a pruritic, maculopapular rash
How can sea bather’s Remove swimwear and wash with salt
eruption be avoided? water (freshwater causes larvae to sting)
What echinoderms can 1. Sea urchins

envenomate humans? 2. Crown-of-thorns seastar
3. Sea cucumbers
What are the signs and Local pain and swelling, conjunctivitis
symptoms of echinoderm (from sea cucumber venom), rarely sys-
envenomation? temic features (i.e., nausea, vomiting,
hypotension)
What test can be useful in Plain x-ray to look for embedded spines
evaluating echinoderm
envenomation?
How do sponges generally They contain silica or calcium carbonate

cause injury? spicules that embed in the skin, result-
ing in mild dermatitis. These spicules
can usually be removed with adhesive
tape.
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How should “fire sponge” Copious irrigation and vinegar

envenomations be treated?
Bristleworm stings cause Local burning, urticaria, erythema

what signs and symptoms?
Cone snail venom can cause Respiratory failure due to paralysis. Cone
death by what mechanism? snail venom contains a variety of “cono-
toxins” that generally work by blocking
neuronal ion channels.
What octopus has been The Australian blue-ringed octopus

known to envenomate (Hapalochlaena spp.)
humans?
What is the mechanism of Neurotoxin that blocks voltage-sensitive

the Hapalochlaena spp. sodium channels
venom?
Hapalochlaena spp. venom Tetrodotoxin

is identical to what other
marine toxin?
VERTEBRATES
What are three ways marine 1. Venomous spines – sting rays,
vertebrates can poison venomous fish
people? 2. Venomous fangs – sea snakes
3. Ingestion – ciguatera, scombroid
What is the mechanism of Both traumatic and venomous. A whip-

stingray injury? ping tail movement results in puncture
wounds from the serrated spine, at which
time venom is introduced into the wound.
Where on the body do most Lower legs. After being stepped on, the
stingrays strike people? tail of the stingray reflexively curls like a
scorpion, usually striking the leg.
What is the treatment of a 1. Irrigation of the wound with removal

stingray envenomation? of any remaining spines
2. Immersion of the injured area in hot
(45°C/113°F) water for 30 to 90 min
3. Additional pain control with opioids
and local anesthesia may be necessary.
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4. Evaluate with radiography for retained

foreign body.
5. Prophylactic antibiotics
Why is hot water used to The toxin is heat-labile and degrades at

treat stingray higher temperatures.
envenomations?
Name some other fish that Scorpionfish, stonefish, weeverfish,

cause painful catfish
envenomations.
Describe the manifestations Extreme pain is the primary symptom.

of these envenomations. Blanching of the skin around the wound
may occur. Systemic symptoms are
generally mild but may include HTN,
tachycardia, nausea, vomiting, weakness,
and vertigo. Wounds should be
evaluated for the presence of foreign
bodies.
Stonefish are native to Tropical waters of the Central Pacific,

which waters? Indo-Pacific, and East African coastline
How is a stonefish Similar to stingray envenomation (i.e., re-

envenomation treated? move foreign material, irrigate, soak in
hot water, pain control). An antivenom to
stonefish is also available.
Where are venomous sea Tropical waters of the Indian and Pacific
snakes found? Oceans, including Hawaii. They are not
found in the Atlantic Ocean.
What are the clinical Generalized muscle aches and weakness

findings of a sea snake usually begin 30 min to 4 hrs after enven-
envenomation? omation. This may be followed by varying
degrees of ascending and bulbar paraly-
sis, depending on the extent of enveno-
mation. Nausea and vomiting will also
likely be present.
Describe the mechanism of Neurotoxins cause paralysis and

action of sea snake venom. respiratory failure. Hemotoxins and
myotoxins are also present, but to a lesser
extent.
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What is the treatment of 1. Light pressure immobilization of the

venomous sea snake bites? affected limb may be beneficial for
field transport.
2. Supportive care, including respiratory
support
3. Polyvalent sea snake antivenom is
available for multiple species.
MUSHROOMS
COPRINE GROUP
What is the name of the Coprinus atramentarius (aka “alcohol
most common coprine- inky” or “inky cap”)
containing mushroom?
What is the appearance Cap – 3 to 7 cm, smooth, ovular, grayish-

and the habitat of brown. The cap turns black and liquefies
C. atramentarius? after being picked.
Stalk – 4 to 5 cm
Spores – black
Habitat – along roadsides and in urban
areas during the fall months
Coprine toxins cause toxic Ethanol

symptoms when consumed
in combination with what
substance?
What physiologic enzyme is Aldehyde dehydrogenase

inhibited by coprine toxin?
What pharmacotherapy for Disulfiram

alcohol abuse yields
symptoms similar to coprine
toxin?
What mushroom produces Clitocybe clavipes (also known as “club-

symptoms identical to foot funnel cap”)
Coprinus species but has not
been shown to contain
coprine toxin?
Describe the appearance of Cap – 2–6 cm, flat, grayish-brown, with

C. clavipes. gills extending down to the stalk
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Stalk – 1–5 cm with a thickened base

Spores – white
What physical Symptoms are the same as those of a

manifestations are disulfiram reaction – nausea, vomiting,
associated with coprine flushing, distal paresthesias, tachycardia,
toxicity? possibly hypotension
What is the timing of 30 to 60 min after consumption of

symptom onset? ethanol. The toxin can remain systemi-
cally active up to 5 days; thus, symptoms
can occur with delayed ethanol
ingestion.
What is the treatment for 1. IV fluids and supportive care

coprine toxicity? 2. Antiemetics
3. Vasopressors for refractory
hypotension
CORTINARIUS GROUP
What is the principle toxin Orellanine
responsible for poisoning
from Cortinarius
mushrooms?
Describe the appearance Cap – small, bell-shaped, bright orange-

and habitat of the most brown
common orellanine- Stalk – yellow stalk
containing mushroom, Gills and spores – rust-colored
C. orellanus. Habitat – endemic to Europe and Japan,
increasingly found in the U.S., most often
grow beneath hardwood trees
What is the physiologic Mechanism is poorly defined, but it is

mechanism whereby thought to work by inhibition of alkaline
orellanine causes toxicity? phosphatase in the renal tubules →
↓ production of ADP and impaired
cellular metabolism
What are the initial clinical The symptoms are variable and dose-
manifestations of toxicity? dependent:
24 to 36 hrs post-ingestion – abdominal
pain, nausea, vomiting, thirst
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2 days to 2 wks post-ingestion – chills,

night sweats, flank pain, polyuria, or
oliguria
What is the ultimate Tubulointerstitial nephritis and acute

outcome for nearly 50% of renal failure, occurring 3 to 20 days post-
patients with orellanine ingestion
toxicity?
What 4 laboratory findings 1. Microscopic hematuria

may be helpful in detecting 2. Leukocyturia
early toxic renal failure? 3. Elevated BUN
4. Elevated creatinine
What measures are Supportive care with special attention to

recommended to treat renal function, which returns in ⬃50% to
orellanine toxicity? 65% of affected patients
CYCLOPEPTIDE GROUP
What are the 3 subgroups of 1. Amatoxin
cyclopeptides? 2. Phallotoxin
3. Virotoxin
Which subgroup is primarily Amatoxins. Phallotoxins may cause GI

associated with potentially upset if a large quantity is ingested,
lethal toxicity? while virotoxins are nontoxic to humans.
Can amatoxins be No. They resist heating, drying, and all

deactivated by proper forms of cooking and are insoluble in
preparation? water.
What is the name of the Amanita phalloides (aka the “death cap”)
most notorious and most
lethal of the cyclopeptide
mushrooms?
Describe the appearance of Cap – 4 to 15 cm, convex, white or

A. phalloides. greenish
Stalk – 5 to 17 cm, thick with a thin ring
and a large bulb at its base
Gills – white or green
Spores – white
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What is the natural habitat Throughout Europe and the coastal U.S.,
of A. phalloides? growing from late summer through fall,
often around hardwood trees (e.g., oak
chestnut, beech, birch, pine). It shares
both appearance and distribution with
many nontoxic mushrooms.
Through what physiologic Bind and inhibit RNA polymerase II,

mechanism do amatoxins preventing protein and DNA synthesis
cause toxicity? and causing cell death. This most pro-
foundly affects tissues of high cellular
turnover in the liver, renal tubules, and
GI tract.
What is the triad of clinical Phase 1 (6 to 24 hrs) – delayed-onset GI

phases encountered distress
following amatoxin Phase 2 (24 to 96 hrs) – apparent clinical
ingestion? recovery but declining hepatic and renal
function
Phase 3 (2 to 4 days up to 2 wks) – fulmi-
nant hepatic and renal failure
What physical manifestations Primarily GI – severe abdominal pain,

typify phase 1 of amatoxin cramping, watery diarrhea and emesis,
poisoning? potentially leading to dehydration and
circulatory collapse
What are the most ominous Hepatic encephalopathy, hypoglycemia,

clinical predictors of coagulopathy, metabolic acidosis
mortality in phase 3 of
amatoxin poisoning?
What is the Meixner test, Juice from a mushroom is dripped onto

and how can it detect the newspaper (must contain lignin) and
presence of amatoxin? allowed to dry. HCl is then added. A blue
color change within several minutes sug-
gests amatoxin is present.
What toxin can yield a false- Psilocybin

positive Meixner test?
Does activated charcoal Possibly. It can be repeated q2–4 hrs for

have a role in amatoxin 48 hrs following ingestion.
exposure?
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What are three specific 1. Silibinin (milk thistle)

pharmacologic therapies 2. N-acetylcysteine
that may provide 3. Penicillin (high-dose)
hepatoprotection from
amatoxin poisoning (though
supportive studies in
humans are still lacking)?
What other treatments may Extracorporeal albumin dialysis or liver

be effective in treating transplant for patients with hepatic fail-
amatoxin poisoning? ure. Treatment is otherwise supportive.
GASTROINTESTINAL IRRITANT GROUP

How many genera of 19 (including hundreds of species)
mushrooms are classified as
GI irritants?
What is the most commonly Chlorophyllum molybdites

ingested GI irritant
mushroom in North
America?
Describe the appearance of Cap – 10 to 40 cm, smooth, round, white,

C. molybdites. occasionally with brownish warts
Stalk – 5 to 25 cm, white, smooth
Gills – yellow, become green as the
mushroom ages
Spores – green
How can toxicity from the Adequate preparation – heating/boiling is

majority of GI irritant sufficient for many species
mushrooms be reduced or
prevented?
What is the clinical GI symptoms within 30 to 120 min of in-

presentation of acute gestion – abdominal cramping, watery di-
toxicity? arrhea, nausea, emesis. Chills, headaches,
and myalgias may also be present.
How long do symptoms Commonly 6 to 12 hrs, but the time-

typically last? course is dose- and species-dependent
What is the primary course Supportive care with consideration of

of treatment for toxicity? other, more toxic mushrooms that may
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have been co-ingested (especially if onset

of symptoms is ⬎2 hrs)
What is the general rule Patients with nausea and vomiting within
concerning the time-course 6 hrs of ingestion typically have a benign
of symptoms following course, whereas patients with nausea and
mushroom ingestion? vomiting beyond 6 hrs post-ingestion are
more likely to have ingested a cyclopetide
or other more toxic group of mushrooms;
however, one must always consider a
mixed-species ingestion.
What other poisonings must Pesticide, herbicide, bacterial food

be considered for nausea poisoning
and vomiting following
mushroom ingestion?
HALLUCINOGEN GROUP
What is the primary toxin Psilocybin
responsible for the
psychoactive effects of
hallucinogenic mushrooms?
What is the most common Psilocybe (also, some members of genera

genus of psilocybin- Gymnopilus, Panaeolus, and Stropharia)
containing mushrooms?
Describe the common Cap – 0.5 to 4 cm, brown, smooth, may

appearance of a Psilocybe become slippery or sticky when wet
mushroom. Stalk – 4 to 15 cm, thin
Spores – dark brown or black
With what drug of abuse LSD. Both augment serotonergic neu-

does psilocybin share a ronal activity.
similar structure and
function?
What is the common term for “Magic mushrooms”

hallucinogenic mushrooms?
What ancient civilization is The Aztecs

known to have used
hallucinogenic mushrooms
in religious ceremonies?
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What are the clinical 30 to 60 min post-ingestion – euphoria,

manifestations of psilocybin paresthesias, tachycardia, mydriasis,
intoxication? visual hallucinations, synesthesia, time
distortion. Seizures have been reported
with heavy intoxication.
How long do hallucinations 4 to 6 hrs

typically last?
What is the primary mode of Observation and supportive care. Placing

treatment for toxicity? patient in a dark room without sensory
stimuli may reduce hallucinations.
What pharmacologic Benzodiazepines for seizures or

therapies are recommended agitation
for intoxication?
IBOTENIC/MUSCIMOL GROUP
What two species of 1. Amanita muscaria
mushrooms are primarily 2. Amanita pantherina
known to contain ibotenic
acid and muscimol toxins?
What prominent children’s Alice in Wonderland

book depicts the Amanita
muscaria mushroom?
Describe the appearance Cap – 5 to 30 cm, bright orange or red,

and habitat of A. muscarina. covered in white warts
Stalk – hollow, white, upward-tapering
Habitat – often found under hardwood
and conifer trees throughout North
America, primarily in the western states
Describe the appearance Cap – 5 to 15 cm, reddish-brown that

and habitat of A. pantherina. darkens with age, may or may not have
warts
Stem – white with distinct rings
Habitat – found throughout North
America
What is the physiologic Ibotenic acid resembles the stimulatory

mechanism of ibotenic acid neurotransmitter glutamate and causes
toxicity? hallucinations, myoclonic activity, and
possibly seizures.
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To what substance is Muscimol

ibotenic acid metabolized?
What is the physiologic Muscimol agonizes GABA receptors,

mechanism of muscimol thereby causing CNS depression.
toxicity?
What are the clinical Variable and can resemble both the exci-
manifestations of toxicity? tatory or inhibitory nature of the toxin.
Symptoms include emesis, followed by
drowsiness, dizziness, ataxia, and confu-
sion. This may progress to myoclonic
jerking, hallucinations, delirium, seizures,
or coma.
What is the typical duration Typically 6 to 8 hrs, but may take up to

of symptoms? 48 hrs for full resolution
What pharmacologic Benzodiazepines for seizures or severe

therapies are recommended agitation
for toxicity?
What is the primary Supportive care, as the course is typically

treatment for toxicity? self-limiting
MONOMETHYLHYDRAZINES GROUP
What species of mushroom Gyromitra species, the most common
is responsible for being Gyromitra esculenta. These species
monomethylhydrazine contain the toxin gyromitrin
toxicity? (monomethylhydrazine).
What are three common 1. “Brain fungi”

names for G. esculenta? 2. “Beefsteak mushroom”
3. “False morel”
What is the appearance and Cap – dark, reddish-brown, irregular

the habitat of G. esculenta? shape (i.e., folded and resembles a
brain)
Stalk – 5 to 15 cm, long, thick, hollow
Habitat – endemic to Eastern Europe
and throughout N. America, grows in
sandy soil near pine trees during the
spring months
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For which highly sought- Morchella esculenta (common morel)

after, edible mushroom is
G. esculenta commonly
mistaken?
What is the physiologic Competitive inhibition of pyridoxine ki-

mechanism whereby nase → functional pyridoxine deficiency
monomethylhydrazine → ↓ GABA production/availability
causes toxicity?
What anti-tuberculosis Isoniazid (INH)

therapy has an adverse
reaction profile similar to
monomethylhydrazine?
In what industry is Aerospace industry. It is a primary com-

monomethylhydrazine ponent of rocket fuel.
found?
Can toxicity be reduced or Yes, with sufficient boiling; however, in-

prevented by adequate haling the hydrazine vapors can also be
preparation prior to toxic
ingestion?
Describe the initial clinical 5 to 12 hrs post-ingestion – emesis

presentation of toxicity. and diarrhea, followed by fatigue, dizzi-
ness, and headache, with potential
progression to delirium, seizure, and
coma
What late complication may Liver failure (3 to 4 days post-ingestion)

occur from toxicity?
What hematologic Methemoglobinemia or hemolysis

manifestation can result
from toxicity?
What are three specific 1. Pyridoxine (vitamin B6) for delirium

pharmacologic therapies and seizures
available for toxicity 2. Methylene blue for symptomatic
complications? methemoglobinemia or
methemoglobin level ⬎30%
3. Glucose for hypoglycemia
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MUSCARINE GROUP
What are the primary 1. Clitocybe
genera of mushrooms 2. Inocybe
containing sufficient levels Contrary to its name, Amanita muscaria
of muscarine to produce contains very little muscarine.
toxicity?
Describe the appearance Cap – 1.5 to 3 cm, flattened, grayish-

and habitat of Clitocybe brown
mushrooms. Stalk – 1 to 5 cm, tapered
Gills – run down along stalk
Habitat – found on lawns and in parks
during the summer and fall months
Describe the appearance Cap – 5 to 6 cm, conical, brown

and habitat of Inocybe Stalk – 2 to 10 cm, thin, covered in fine
mushrooms. white hairs
Gills – brown
Spores – brown
Habitat – found under conifer and hard-
wood trees during the summer and fall
months
What is the physiologic It is a pro-cholinergic agent, with the pri-

mechanism of toxicity from mary effect of stimulating acetylcholine-
muscarine? sensitive receptors of the parasympa-
thetic nervous system.
What acronym is helpful for DUMBELS

remembering the symptoms Defecation
associated with toxicity? Urination
Miosis
Bronchorrhea/Bronchospasm/
Bradycardia
Emesis
Lacrimation
Salivation
How long following toxin 15 to 45 min

ingestion do symptoms
typically present?
How long do symptoms 6 to 24 hrs, but this is dose-dependent

typically last?
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Is activated charcoal Yes, if initiated soon after ingestion

effective in toxicity?
List three pharmacologic 1. Atropine for severe cholinergic

therapies that may be symptoms. Respiratory symptoms,
beneficial in muscarine such as bronchospasm and
toxicity. bronchorrhea, should guide therapy.
2. Albuterol for bronchospasm
3. Benzodiazepines for agitation or
seizures
MYCOTOXINS
What are mycotoxins? Mycotoxins are chemicals produced by

filamentous fungi that may impart disease
to other organisms. Toxic substances in
mushrooms are not considered true
mycotoxins.
What is the purpose of Mycotoxins are produced by fungal me-

mycotoxins? tabolism and generally have little or no
use to the organism; however, some have
been speculated to provide an evolution-
ary advantage to the fungi.
How are humans typically Mycotoxins are found in small quantities

exposed to mycotoxins? in many grains, nuts, and seeds. Occa-
sionally, quantities are sufficient to cause
acute disease in humans. Examples in-
clude outbreaks of hepatitis in India re-
lated to aflatoxin, “red mold disease”
caused by trichothecene mycotoxins in
Japan and Korea, and even an outbreak
of possible ergotism that led to the Salem
Witch Trials. More recently, mycotoxins
have reportedly been used as biologic
weapons.
Which are potential Trichothecenes (T-2 toxin and vomi-

bioterrorism weapons? toxin), aflatoxins, ochratoxins, ergot
alkaloids, and fumonisin are capable of
inducing disease in humans and have
the most potential to be used as
bioweapons.
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What are trichothecenes? A family of ⬎60 compounds produced by

several fungi, including Fusarium,
Myrothecium, Phomopsis, Stachybotrys,
Trichoderma, and Trichothecium. All con-
tain a common 12, 13-epoxytrichothene
skeleton. T-2 toxin is regarded as the
most toxic of this class and has a reported
LD50 of ⬃1 mg/kg.
How was T-2 discovered? Multiple outbreaks of hemorrhagic GI

illness and leukopenia were reported in
the Ukraine and in Orenburg, Russia in
the 1930s and 1940s. In 1940, Soviet
scientists coined the term “stachybotry-
otoxicosis” to describe the acute syn-
drome of sore throat, bloody nasal
discharge, dyspnea, cough, and fever due
to Stachybotrys mycotoxins. These out-
breaks resulted in the isolation of T-2
toxin in 1968.
To what does the term The “yellow rain” attacks occurred in

“yellow rain” refer? Southeast Asia in the late 1970s. Report-
edly, a sticky yellow substance was
aerosolized by aircraft and bombs among
the Hmong tribes in Laos and Cambodia.
When falling on trees and dwellings, it
had the sound of rain. While speculated
to be T-2 toxin, debate exists as to the
true identity of yellow rain.
What are the routes of T-2 Inhalation, ingestion, dermal. This makes
exposure? the toxin a highly effective bioweapon
due to its multiple portals of entry.
How can T-2 be delivered as The toxins are extremely stable proteins
a biological warfare agent? resistant to heat, autoclaving, hypochlo-
rite, and ultraviolet light. They can be
delivered as dusts, droplets, or aerosols
from various dispersal systems and
exploding munitions.
What are the signs and Skin itching/irritation, vesicles, nausea,

symptoms of T-2 exposure? vomiting, diarrhea, upper airway irrita-
tion, and GI hemorrhage
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What is the management of 1. Supportive care, removal from the

T-2 toxicity? source of exposure, and
decontamination
2. Dexamethasone has improved survival
times in animal studies
3. Granulocyte colony-stimulating factor
(G-CSF) may be beneficial for bone
marrow suppression.
Are there any helpful None will be diagnostic:

laboratory studies? 1. CBC – useful in evaluating blood loss
due to GI hemorrhage and to monitor
for bone marrow suppression
2. Electrolytes and organ function tests
(i.e., LFTs, RFTs) should be
monitored as markers of the degree of
toxicity.
What are aflatoxins? Naturally occurring mycotoxins produced

by many species of Aspergillus. Aflatoxin
B1 is considered the most potent natural
carcinogen known.
Where are aflatoxins found? Crops frequently affected are cereals,

oilseeds, and tree nuts. They can also be
found in the milk of animals that have in-
gested contaminated feed.
Can aflatoxins be used as Yes. Iraq was known to have weaponized

bioweapons? alfatoxins before the first Gulf War.
What are the physical effects High-level exposure produces acute he-
of exposure? patic necrosis and cirrhosis. Chronic sub-
clinical exposure leads to an elevated risk
of liver cancer (IARC Group 1).
Is there any other associated Concurrent infection with hepatitis B

disease that increases the virus (HBV) during aflatoxin exposure
risks of chronic aflatoxin increases the risk of hepatocellular
exposure? carcinoma.
How does ochratoxin cause Nephrotoxicity. Its mechanism of action

disease? appears to be inhibition of protein syn-
thesis and induction of oxidation in the
renal tubules.
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Does ochratoxin cause acute No. Ochratoxin appears to cause disease

toxicity? only after chronic ingestion. Signs and
symptoms are those of progressive renal
failure.
How do ergot alkaloids Ergot alkaloids possess an indole ring

cause toxicity? structure and alpha-adrenergic agonist
properties. These features can result
in hallucinations and peripheral
vasoconstriction.
What is gangrenous Peripheral vascular insufficiency caused by

ergotism? the vasoconstrictive effects of ergots re-
sults in limb pain, numbness, and possibly
progression to dry gangrene and limb loss.
By what name was ergotism St. Anthony’s fire

known in the Middle Ages?
From which fungus is ergot Claviceps purpurea

derived?
What is convulsive ergotism? Seizures, muscle spasms, paresthesias,

mania, and psychosis that occur as a re-
sult of the toxin. GI effects (i.e., nausea,
vomiting, diarrhea) precede CNS effects.
Hallucinations may occur and are similar
to those produced by LSD.
What is the treatment for 1. Remove the source of exposure.

ergot poisoning? 2. Benzodiazepines for seizures
3. Sodium nitroprusside or phentolamine
may be used for treatment of
vasoconstriction.
PLANTS
ANTICHOLINERGIC
Name the prototypical Atropa belladonna (aka “deadly

anticholinergic plant. nightshade”)
List other plants known to 1. Datura stramonium (jimsonweed)

contain anticholinergic 2. Mandragora officinarum (European
alkaloids. mandrake)
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3. Hyosyamus niger (henbane)

4. Brugmansia arborea (angel’s trumpet)
5. Atropa belladonna (deadly nightshade)
What is the primary toxin in Atropine, may contain hyoscyamine and

anticholinergic plants? scopolamine
Describe the Competitive inhibition of postsynaptic

pathophysiology of atropine muscarinic receptors
poisoning.
How many milligrams of ⬃0.1 mg

atropine are contained in
each jimsonweed seed?
Which plant was responsible Datura stramonium, aka “Jamestown

for poisoning British troops weed” or jimsonweed
at Jamestown during the
American Revolutionary
War?
Recite the mnemonic used “Dry as a bone, red as a beet, mad as a

to remember anticholinergic hatter, blind as a bat, hot as a hare, full as
signs and symptoms. a flask”
List signs and symptoms Dry mucous membranes, dry and flushed
characteristic of the skin, psychosis/delirium, mydriasis,
anticholinergic toxidrome. hyperthermia, loss of bowel sounds,
urinary retention, tachycardia
Why are anticholinergic They have the ability to produce

plants often abused? hallucinations.
How long may symptoms May last for days, depending on species
last following ingestion of an and part of the plant ingested
anticholinergic plant?
List basic treatment 1. Supportive care with consideration of

principles. activated charcoal
3. Consider physostigmine for
therapeutic or diagnostic purposes.
What is the half-life of ⬃1 hr; therefore, anticholinergic symp-

physostigmine? toms are likely to recur
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CARDIAC GLYCOSIDES
What plants are known to 1. Oleander (Nerium oleander)

contain cardiac glycosides? 2. Yellow oleander (Thevetia peruviana)
3. Foxglove (Digitalis purpurea)
4. Lily of the valley (Convallaria majalis)
5. Red squill (Urginea maritime)
How do cardiac glycosides Natural cardiac glycosides (e.g., ouabain,

exert their toxic effects on a oleandrin, scilliroside, thevetin) resem-
cellular level? ble the medication digoxin. Inhibition of
Na-K-ATPase → ↑ intracellular Ca2⫹
(via sodium-calcium exchange) and ↑ ex-
tracellular K⫹.
What effects do cardiac 1. Positive inotropy

glycosides have on 2. Negative AV nodal dromotropy
myocardial tissues? 3. Generation of myocardial irritability
How might an acute Nausea, vomiting, bradycardia (or tachy-

overdose of cardiac cardia), AMS, blurred/discolored vision
glycosides present? (yellow-green halos around objects),
headache, fatigue
What is the most common PVCs

ECG manifestation of
cardiac glycoside toxicity?
What are the other possible Tachydysrhythmias with AV block are

ECG manifestations? typical, but almost any dysrhythmia may
occur; exceptions to this are atrial fibrilla-
tion or flutter with rapid ventricular re-
sponse. Pathognomonic rhythms include
biventricular tachycardia and paroxysmal
atrial tachycardia with AV block.
What doses of cardiac As little as a few seeds or a few leaves

glycosides are considered may be enough to cause severe toxicity.
toxic? Patients may also become symptomatic
after inhalation of smoke from these
plants.
What laboratory tests are Potassium level and ECG

particularly useful for
evaluation?
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What electrolyte abnormality Hyperkalemia

is a marker of toxicity?
Are digoxin levels useful for Cardiac glycosides often cross-react with
evaluation? serum digoxin levels; therefore, they are
useful as a marker of exposure but are
not predictive of toxicity or outcome.
List the basic principles of 1. Supportive care with consideration of

treatment. activated charcoal
2. Treatment of hyperkalemia
3. Digoxin immune Fab for select cases
List the indications for 1. Hyperkalemia (K⫹ ⬎5.0 mEq/L)

digoxin immune Fab. 2. New AV block
3. Dysrhythmias
Should standard digoxin No. These formulas will underestimate

immune Fab formulas apply the total dose necessary.
for treatment of plant-
induced cardiac glycoside
toxicity?
Which cardiac glycoside- Yellow oleander (Thevetia peruviana)

containing plant is a major
cause of intentional self-
poisoning in underdeveloped
countries, such as Sri Lanka?
CYANOGENIC GLYCOSIDES
What are some common Cassava root (Manihot esculenta), hy-

plant sources of cyanide drangea (Hydrangea spp.), bitter almonds
toxicity? (Prunus spp.), peach pits (Prunus spp.),
apricot pits (Prunus spp.), apple seeds
(Malus spp.)
What are the 2 most 1. Amygdalin

prevalent cyanogenic 2. Linamarin
glycosides?
Name the amygdalin- Laetrile

containing product that was
historically promoted for
cancer treatment.
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What is the pathophysiology Hydrolysis of cyanogenic glycosides →

of poisoning from release of hydrogen cyanide → cy-
cyanogenic glycosides? tochrome oxidase a3 inhibition → block-
ade of electron transport and oxygen
utilization
What are the symptoms of Headache, dizziness, nausea, vomiting,

acute cyanide toxicity? abdominal pain, and anxiety minutes to
hours post-ingestion. In severe cases, this
may be followed by confusion, hypoten-
sion, seizures, coma, and death.
What are the signs of acute High anion-gap metabolic acidosis, ↑

cyanide toxicity? lactic acid, ↑ venous oxygen saturation
What is the reported “Bitter almond” odor on breath or vomitus

characteristic odor
associated with cyanide
toxicity?
Describe the manifestations Signs of upper motor neuron toxicity,

of chronic cyanogenic (e.g., spasticity, hyperreflexia), visual dis-
glycoside exposure. turbances, and hypothyroidism
By what names is this Konzo or tropical spastic paraparesis

disease known?
How is acute cyanide 1. Supportive care with consideration of

toxicity treated? activated charcoal
2. Patients with symptom progression
and those with acidosis should receive
a cyanide antidote.
What cyanide antidotes are 1. Traditional cyanide antidote kit –

available for treatment? amyl and sodium nitrite (induce
methemoglobinemia to bind
cyanide), thiosulfate (provides sulfur
for conversion of cyanide to
thiocyanate)
2. Hydroxocobalamin (preferred) –
alternative treatment used in Europe
and recently approved by the FDA for
use in the United States. It binds
cyanide to form cyanocobalamin
(vitamin B12).
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DERMATITIS-PRODUCING
What plants most commonly Poison ivy, poison oak, and poison sumac
cause allergic contact (in that order). These members of the
dermatitis? genus Toxicodendron exceed all other
causes combined.
Where are poison ivy, In the U.S. Poison ivy is found primarily
poison oak, and poison east of the Rockies, poison oak to the
sumac found? west of the Rockies, and poison sumac in
marshy areas of the southeast.
What are other plants Ginkgo tree, mango tree and fruit, and
associated with allergic cashew tree and nuts. Mango and cashew
contact dermatitis? are in the same plant family as poison ivy
(Anacardiaceae).
What is the toxic compound An oleoresin called urushiol causes a type

released by these plants, IV hypersensitivity response. In severe
and what type of response cases, a type I response with anaphylaxis
do they elicit? may be seen.
How long after exposure is Usually within 1 to 2 days in a previously

the dermatitis seen? sensitized person and within 10 days in
an individual without prior exposure.
Symptom onset in ⬍5 min may occur in
the rare case of anaphylaxis.
What are the physical Mild – linear, erythematous and pruritic

findings? lesions with small papules and vesicles
Severe – diffuse erythema and edema,
severe pruritus/pain, bullae
Respiratory symptoms (i.e., cough, dysp-
nea, oropharyngeal swelling) may occur
following aerosol exposure from burning
plants.
What percentage of people 50% to 70% react to exposure, though

are susceptible? this is dose-dependent. 10% to 15% are
extremely sensitive.
How is allergic contact 1. Immediate washing with soap and

dermatitis treated? water
2. Topical preparations (e.g., domeboro,
calamine, oatmeal baths, Burrow
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solution) may help alleviate mild to

moderate symptoms.
3. PO antihistamines for pruritus
4. Topical steroids are acceptable for
mild symptoms; severe symptoms
warrant oral steroids tapered over a
2-wk period.
What type of response is Rapid response to direct toxin injection

elicited by exposure to (i.e., histamine, ACh, serotonin) from the
stinging nettle (Urtica plant when disturbed. The histamine is
dioica)? responsible for skin irritation, while the
ACh causes a burning sensation.
Where is stinging nettle Northern Europe, Asia, and North

found? America
Do plants cause other forms Yes. Plants can cause irritant dermatitis
of dermatitis? by both immune and nonimmune-
mediated mechanisms.
What are some plants that Wolfsbane (Aconitum napellus), Christ-

cause nonimmune-mediated mas rose (Helleborus niger), buttercup
irritant dermatitis? (Ranunculus spp.), meadow rue (Thalic-
trum foliosum)
What is the mechanism of These plants contain toxins that pass

toxicity of these plants? through the dermis and cause direct re-
lease of histamine from mast cells.
Name some plants that Tulips (Tulipa spp.), mustard (Brassica

cause immune-mediated and Sinapis spp.), rapeseed (Brassica
irritant dermatitis. spp.), garlic (Allium sativum)
What is the mechanism of Transdermally absorbed toxins from

this type of dermatitis? these plants produce a type I hypersensi-
tivity reaction.
What is the most common Furocoumarins

toxin involved in
phytophototoxic reactions?
What is a phytophototoxic Certain ingested or dermally absorbed

reaction? plant toxins may cause sensitivity to
UV rays, resulting in severe sunburn
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symptoms in sun-exposed areas. Chronic

hyperpigmentation of the involved skin
may occur after the exposure.
Name some common plants Celery (Apium graveolens dulce), carrot

that may cause (Daucus carota), parsley (Petroselinum
phytophototoxic reactions. crispum), parsnip (Pastinaca sativa),
Queen Anne’s lace (Ammi majus), grape-
fruit (Citrus paradissi), lemon (Citrus
limon), lime (Citrus aurantifolia)
GASTROINTESTINAL IRRITANTS
What are some plants that 1. Pokeweed (Phytolacca americana)

are commonly reported to 2. Hollybush (Ilex aquifolium)
cause GI irritation as their 3. English ivy (Hedera helix)
sole toxic effect? 4. Wisteria (Wisteria spp.)
5. Poinsettia (Euphorbia spp.)
Are these the only plants No. Many poisonous plants are irritating
that cause GI upset? to the GI tract, but these plants solely
produce GI symptoms.
What is the general Many of these plants contain saponin gly-

mechanism of GI irritants? cosides, which cause direct GI irritation.
What specific laboratory Mitogens in pokeweed stimulate leuko-

abnormality may be found cyte proliferation and may cause signifi-
after pokeweed exposure? cant leukocytosis. This finding may be
present 2 to 4 days following ingestion or
exposure through compromised skin and
may last for weeks.
What are the general Nausea, vomiting, abdominal pain,

symptoms of GI irritant diarrhea
toxicity?
When do symptoms of GI Generally within 2 to 4 hrs of ingestion,

irritant poisoning typically but onset is dose-dependent
arise?
Can pokeweed be eaten Yes, but only after the toxin (phytolac-
without harmful effects? cotoxin) is properly boiled out
(parboiled)
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How much mistletoe can be As few as 3 mistletoe berries can cause

consumed without toxic significant GI upset.
effect?
What symptoms accompany Nausea, vomiting, diarrhea. Death has

holly toxicity? been reported from aspiration of
berries.
How should GI irritant Supportive care with consideration of

toxicity be managed? activated charcoal if within 2 hrs of in-
gestion. Fluid and electrolyte abnormali-
ties may be sufficient to warrant hospital
admission.
NICOTINICS
What are some common All plants in the genus Nicotiana (to-
plant sources of nicotine bacco), including Nicotiana rustica (Indian
toxicity? or Aztec tobacco), Nicotiana tabacum
(common tobacco) and Nicotiana glauca
(tree tobacco)
What other alkaloids are Coniine, lobeline, sparteine, arecoline,

similar to nicotine? cytosine, N-methylcytisine
What plants contain Broom (sparteine), blue cohosh (N-

nicotine-like alkaloids? methylcytisine), golden chain (cytisine),
hemlock (coniine)
What herbal substance is Lobeline, a nicotine receptor agonist

often used to treat nicotine from the species Lobelia inflata
addiction?
What famous philosopher Socrates, from the poison hemlock plant

was put to death by coniine (Conium maculatum)
poisoning?
What are the signs and GI symptoms (i.e., nausea, vomiting,

symptoms of nicotine diarrhea), followed by headache,
poisoning? diaphoresis, tachycardia, muscle fascicu-
lations, hyperthermia, progressing to
seizures, respiratory depression, brady-
cardia, paralysis, and death.
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Describe the symptomatic Stimulatory symptoms (sympathetic)

progression of nicotine appear to dominate initially and are then
poisoning. followed by muscarinic effects.
Describe the Nicotine results in stimulation of the

pathophysiology of nicotine sympathetic and parasympathetic post-
poisoning. ganglionic neurons along with stimulation
of the motor end plate.
What is green tobacco Nicotinic symptoms due to transdermal

illness? nicotine absorption into the systemic cir-
culation in tobacco workers following
repetitive exposure to moist, green
tobacco leaves
How is nicotine poisoning 1. Supportive care

treated? 2. Atropine may be given for
bronchorrhea, bronchoconstriction, or
bradycardia.
3. Benzodiazepines should be given for
seizures.
What is the LD50 of Adult – 40 to 60 mg (⬃1 mg/kg body

nicotine? weight)
Child – amount in one cigarette (or three
cigarette butts), when ingested, is enough
to make a child severely ill
OXALATES
What are the two Soluble and insoluble

types of oxalates found in
plants?
What plants most commonly Philodendron spp., Caladium spp.,

cause toxicity due to Dieffenbachia spp. (dumb cane),
insoluble calcium oxalate? Spathiphyllum spp. (peace lily),
Arisaema spp. (jack-in-the-pulpit)
What is the pathophysiology Calcium oxalate crystals are contained in

of insoluble oxalate toxicity? needle-like bundles called raphides.
When the leaves are broken or chewed,
mechanical stimulation of these raphides
causes discharge of the oxalate needles.
These needles cause irritation of the oral
mucosa, lips, and tongue, as well as the
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skin and conjunctivae, resulting in local

pain and edema.
What population is most Children ⬍5 yrs who inquisitively ingest

susceptible to insoluble houseplants; however, others also have
oxalate exposure? been exposed (e.g., foragers)
What treatment modalities 1. As most cases are self-limited,

are available for oxalate analgesics are often sufficient.
exposure? 2. Remove plant material from the
mouth, and assess the airway in oral
exposures.
3. Irrigate eyes and skin for these
exposures.
4. Monitor for airway compromise due to
edema.
What are soluble oxalates? Oxalic acid is found in rhubarb leaves

(Rheum officinale), sorrel (Rumex spp.),
and starfruit (Averrhoa carambola),
among others.
How do soluble oxalates Chelation of calcium and other divalent

cause toxicity? cations. Hypocalcemia may result in
weakness, hyperreflexia, tetany, dysrhyth-
mias, and seizures. Formation of calcium
oxalate crystals in the renal tubules may
result in renal failure. Rarely, calcium ox-
alate crystals may form in other organs
(e.g., brain, spinal cord), resulting in
AMS, paralysis, or other systemic toxicity.
What ECG findings may be QTc prolongation (due to hypocalcemia)

present with soluble oxalate
toxicity?
What is the treatment of IV calcium should be given for dysrhyth-

soluble oxalate toxicity? mias, tetany, and seizures. Adequate
urine output should be maintained with
IV fluids.
SODIUM CHANNEL OPENERS
What role do sodium Control Na⫹ influx through the cell’s

channels play in cells? plasma membrane in response to action
potentials
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What plants contain 1. Veratrum viride (false

substances that cause hellebore), Veratrum album
toxicity by opening (white hellebore), Veratrum
(activating) sodium californicum (skunk cabbage), and
channels? some plants from genus Zigadenus
(e.g., death camus) contain veratrum
alkaloids.
2. Rhododendron spp., Kalmia
angustifolia (sheep laurel), and Kalmia
latifolia (mountain laurel) contain
grayanotoxins.
3. Aconitum spp. (e.g., wolfsbane,
monkshood) contain aconitine.
How do they enter the Primarily by ingestion, although there

body? can be absorption through mucous mem-
branes (e.g., sneezing powder made from
white hellebore)
By what mechanism do Bind to and open voltage-gated sodium

these toxins affect the channels → ↑ Na⫹ influx
sodium channels?
What clinical effects occur Vomiting, diarrhea, abdominal pain,

with poisoning by these paresthesias, diaphoresis, blurred vision,
plants? hypotension, syncope, convulsions.
Cardiotoxic effects may develop and
include sinus bradycardia, nodal
rhythms, and complete AV block with
hypotension. Other conduction
abnormalities, such as a transient Wolff-
Parkinson-White pattern, have been
observed.
Are any antidotes available No. Treatment is primarily supportive.

for the sodium channel Hypotension and bradycardia can be
openers? treated with IV fluids and atropine.
Activated charcoal can be considered
if the patient presents soon after
ingestion.
Sodium channel Cardiac glycosides. Both ↑ intracellular

opener toxicity mimics Na⫹ → ↑ automaticity and ↑ vagal tone.
the effects of what other
toxin?
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What laboratory value will Potassium. Sodium channel openers do

help distinguish poisoning not affect the Na-K-ATPase and,
with a sodium channel therefore, will not cause hyperkalemia.
opener from poisoning with
a cardiac glycoside?
What is mad honey Toxicity resulting from the ingestion of

poisoning? honey produced by bees primarily using
nectar from grayanotoxin-containing
Rhododendron spp.
What genus of poisonous Veratrum

plants is mistaken for edible
leeks (Allium tricoccum)?
Why might someone ingest Its bulb resembles that of an onion.

death camases (Zigadenus
spp.)?
SOLANINE
What plants are common Most members of the genus

sources of solanine toxicity? Solanum contain solanine to varying
degrees. The toxin is most concentrated
in unripe fruits, sprouts, stalks, and
stems.
Name some common 1. Solanum nigrum (black nightshade)

solanine-containing plants. 2. S. tuberosum (common potato)
3. S. melongena (eggplant)
4. S. pseudocapsicum (Jerusalem cherry)
5. Lycopersicon esculentum (tomato)
Does cooking these plants Baking, boiling, and microwaving appear

alter their toxicity? to only minimally lower the levels of
solanine. Deep frying at 170°C (338°F) is
known to degrade solanine and substan-
tially lower levels.
What are the signs and Nausea, vomiting, diarrhea, abdominal

symptoms of solanine cramps, and hyperthermia are the
toxicity? predominant symptoms. In severe cases,
hallucinations, delirium, cardiac
dysrhythmias, seizures, and coma have
been reported.
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What is the typical time- Onset is 2 to 24 hrs post-ingestion, and du-

course of symptoms? ration is up to several days but depends on
the amount and parts of the plant ingested.
Describe the mechanism of Solanine inhibits cholinesterase in vitro,

solanine toxicity. which is speculated to cause the majority
of toxic effects. In addition, the solanine
structure resembles that of cardiac glyco-
sides, and it appears to alter cell mem-
brane sodium transport, both of which
may be mechanisms of cardiotoxicity.
What is the treatment for Supportive care

solanine poisoning?
What novel depicts an Into the Wild by Jon Krakauer

Alaskan adventurer whose
demise may have been
hastened by the effects of
solanine poisoning?
TOXALBUMINS
What plants contain Ricinus communis, Abrus precatorius,

toxalbumins? Jatropha curcas
What toxalbumin is listed as Ricin

Schedule 1 under the
Chemical Weapons
Convention?
What toxalbumin was found Ricin

enclosed in letters sent
through the U.S. mail on
multiple occasions?
What are the plant sources Castor beans (ricin) and jequirity beans
of ricin and abrin? (abrin)
Where are the castor bean Castor bean plant – native to east Africa,
plant (Ricinus communis) although now grows in many tropical and
and the jequirity bean plant warm regions, including the southern U.S.
(Abrus precatorius) found? Jequirity bean plant – primarily in South-
east Asia, has spread to some subtropical
regions, including Florida
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What is the most common Ornamental purposes (e.g., rosary beads,

use of jequirity beans? maracas). They are known as “rosary
peas.”
Describe the structure and They consist of an A and a B subunit.

toxic mechanism of the The B subunit allows for cellular
toxalbumins. entry by binding to galactose-
containing receptors on the cell
membrane, while the A subunit
causes toxicity. The A subunit
depurinates an adenine base of the 60S
ribosomal subunit. This prevents
binding of elongation factor 2 (EF2)
and subsequently stops protein
translation by RNA polymerase.
What are the signs and The clinical effects depend on the route
symptoms of toxalbumin and amount of exposure, with parenteral
exposure? and inhalational exposure being most
potent. The most frequent presentation
after oral exposure is oropharyngeal irri-
tation and GI distress, with abdominal
pain, nausea, vomiting, and diarrhea.
With more severe poisonings, symptoms
can progress to dehydration, shock, GI
hemorrhage, hemolysis, and renal or he-
patic injury. If symptoms are severe,
delirium, seizures, coma, and death may
ensue.
What is the time course for After ingestion of ricin, symptoms will
symptom development? usually be evident within 4 to 6 hrs,
although this may be delayed for up to
10 hrs. The symptom progression can
take 4 to 36 hrs to fully manifest.
How is toxalbumin exposure Supportive care focusing on adequate

treated? hydration. If a patient presents early after
ingestion, activated charcoal should be
given.
Is swallowing a whole castor No. The toxin is found primarily within

or jequirity bean the seed coat, and the bean must be
dangerous? chewed to break the hard outer shell and
release the toxalbumin.
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OTHER
Betel nut (Areca catechu) is Hallucinations and cholinergic

a commonly chewed plant in symptoms – sweating, salivation,
the Indian, Asian, and hyperthermia
Pacific cultures. What are
the symptoms of
intoxication?
What is the primary toxin in Arecoline, a cholinergic agent that also

betel nuts? has weak nicotinic effects
What is the potential long- Oral cancers

term health effect of betel
nut chewing?
Tea made from which Comfrey

“medicinal” plant may
contain pyrrolizidine
alkaloids?
Pyrrolizidine alkaloid Chronic exposures cause veno-occlusive

poisonings affect what organ hepatic disease, and acute poisoning re-
in the body? sults in hepatic necrosis.
What is the mechanism of These agents are metabolized to

pyrrolizidine alkaloid reactive pyrrole species by the P450
toxicity? system. Chronic exposure results in
intimal proliferation in the hepatic
vasculature, sinusoidal congestion, and
veno-occlusive disease. Acute toxicity
appears to be mediated through oxidative
stress.
Plants of the Strychnos Strychnine (seeds – Strychnos nux-

genus contain what two vomica) and curare (bark – Strychnos spp.)
potent toxins?
Acute poisoning by the Muscle spasms and rigidity with pre-

strychnine toxin causes what served mental status
symptoms?
By what mechanism does Antagonizes glycine receptors in the

strychnine act? spinal cord and brainstem
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Toxic ingestion of the curare Competitive acetylcholine antagonism at

toxin causes paralysis by the nicotinic receptors in the neuromus-
what mechanism? cular junction. It has been used to de-
rive nondepolarizing neuromuscular
blockers.
Glycyrrhizin found in Pseudohyperaldosteronism, resulting in

licorice root causes what hypokalemia and hypertension, along
disorder in humans? with sodium and water retention
By what mechanism does Inhibits 11-beta-hydroxysteroid dehydro-

glycyrrhizin act? genase, which is the enzyme necessary
for conversion of cortisol to cortisone, re-
sulting in elevated cortisol levels
Morning glory and peyote Hallucinogenic properties secondary to

cactus are consumed by direct serotonin effects
humans because they have
what properties?
Name two common plants 1. Colchicum autumnale (Autumn

that contain colchicine. crocus)
2. Gloriosa superba (Meadow saffron)
What other plant toxins acts Podophyllin and vinca alkaloids

similarly to colchicine?
What species of plants Podophyllum spp. (the American man-

contain podophyllin? drake, or mayapple, and the wild
mandrake)
What is the mechanism of They inhibit cellular division by blocking

colchicine, podophyllin, and microtubule formation
vinca alkaloid toxicity?
What are the symptoms of Nausea, vomiting, diarrhea, bradycardia,

colchicine, podophylline, hypotension, alopecia, bone marrow sup-
and vinca alkaloid pression, and progression to multisystem
poisoning? organ failure. Vinca alkaloid and
podophyllin ingestions may also result in
peripheral neuropathy.
Name the toxin that is the Cicutoxin, from the water hemlock
most common cause of plant- (Cicuta maculata)
related deaths in the U.S.
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Cicutoxin poisoning Nausea, vomiting, diaphoresis, bradycar-

produces what signs and dia, hypotension, ↑ bronchial secretions,
symptoms? seizures that may progress to status
epilepticus
What should be the 1. Aggressive supportive care and

approach for treatment of immediate gastric lavage
the cicutoxic patient? 2. Benzodiazepines for seizures
3. Atropine for ↑ secretions
4. Consider hemodialysis
Karwinskia toxin, found in Ascending symmetric motor neuropathy,

buckthorn, wild cherry, and similar to Guillain-Barre Syndrome
coyotillo, causes what (GBS)
symptomatology?
How does the Karwinskia Cerebral spinal fluid is normal in

toxic neuropathy differ from Karwinskia toxicity, as opposed to GBS,
GBS? which has ↑ proteins in the CSF.
What is the treatment for Supportive therapy. Recovery is generally

Karwinskia toxic slow.
neuropathy?
Esculoside is the toxin Vomiting, diarrhea, muscle twitching,

found in horse chestnut weakness, incoordination, mydriasis,
and may cause which paralysis, stupor
symptoms?
What is capsaicin? The active ingredient in peppers and

pepper spray
How does capsaicin work? It induces release of substance P from

sensory nerve terminals
REPTILES
SNAKES
Elapidae
What are the major species The family Elapidae consists of coral
of Elapidae and where are snakes found in the U.S., as well as cobras,
they found? mambas, and kraits found in Africa, Asia,
Australia, and the Pacific Ocean regions.
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What are the three genera Micrurus fulvius fulvius (Eastern coral
of the Elapidae family found snake), Micruroides euryxanthus (Sonoran
in the U.S.? coral snake), Micrurus fulvius tenere
(Texas coral snake)
What physical characteristics 1. Small, round head with no pits and a

do coral snakes display? black snout
2. Round pupils
3. Short fangs (1–3 mm) attached to
maxillae
4. Bright bands of black and red
separated by yellow rings
5. Often confused with Scarlet King
Snake, which has yellow and red
bands separated by black rings
What is the old folk rhyme “Red on yellow, kill a fellow, red on
that is used to identify coral black, venom lack.”
snakes?
What are the local 1. Snake exhibits “chewing” mechanism

characteristics of a coral on extremity or digit, but absence of
snake bite? cytotoxins leaves little localized
injury.
2. Minimal edema
3. Minor pain immediately following bite
How do Elapid venoms exert Through neurotoxins that interfere with

their effect? neuronal transmission at the
neuromuscular junction to provoke an
often delayed onset of neurologic
symptoms
What are the signs and General malaise, weakness, paresthesias,

symptoms of systemic slurred speech, diplopia, dysphagia,
toxicity resulting from stridor, respiratory arrest, total body
Elapid envenomation? paralysis (up to 3 to 5 days)
What is the life-threatening Respiratory arrest

complication from Elapid
envenomation?
What are the treatments for 1. Limb immobilization with loose

Elapid envenomation? compression dressing may be
beneficial for field transport.
13486_CH08.qxd 10/31/08 12:21 PM Page 434
2. Aggressive airway management at first

indication of paralysis
3. Following coral snake bite,
Micrurus fulvius antivenom is
indicated if patient reports
any indication of a legitimate
bite, despite presence of signs or
symptoms
4. All symptomatic patients should
receive antivenom
5. Antivenom for exotic species may be
available from zoos. Local poison
centers may be helpful in obtaining
antivenom.
6. Supportive care, monitor for
hypersensitivity to antivenom
Viperidae
What 2 subfamilies of snakes 1. Crotalinae – pit vipers

does the Viperidae family 2. Viperinae – vipers without pits
contain?
Which is most Crotalinae

commonly found in the
United States?
What are the three genera Crotalus (large rattlesnakes), Sistrurus

that comprise the Crotalinae (massasauguas and pigmy rattlesnakes),
subfamily? Agkistrodon (copperheads and
cottonmouths)
Where are Crotalinae Approximately 25 species reside in

found? the U.S. and are mostly confined to the
southeast, southwest, and the
Appalachian mountain regions.
What physical characteristics 1. Triangular heads

do Crotalinae display? 2. Elliptical pupils
3. Paired, hollow fangs that can contract
into roof of mouth and can grow up to
2–4 cm in length
4. “Pits” (heat sensing organs) located
between the eye and the nostril
5. A single row of sub-caudal scales
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6. Copperheads have distinct reddish-

brown heads with hourglass patterns
on body
7. Cottonmouths have a unique white-
colored buccal mucosa
When do the Crotalinae Usually when startled or provoked, with a

most often strike? striking range of half the body length.
Most bites occur between May and
October, as the snakes hibernate during
the colder months.
What are the primary As these venoms are primarily digestive

features of crotaline enzymes, local tissue necrosis and
envenomation? coagulopathy are the predominant
findings.
What are the local 1. Puncture wounds, which can be single

characteristics of a crotaline or multiple and involve localized pain.
bite? Serosanguinous drainage may occur
from the wounds.
2. Localized edema and ecchymosis
typically beginning 15 to 30 min
after the bite and may progress
throughout entire limb in 6 to 8 hrs,
dependent upon amount of venom
injected
3. Hemorrhagic blistering may occur
within 24 to 36 hrs after bite
4. Localized tissue necrosis may occur
several days after bite
Do all bites result in No. Up to 20% of bites do not result in

envenomation? envenomation; these are referred to as
“dry bites.”
What are the major toxic Collagenase, hyaluronidase, lecithin, and

components of crotalind divalent metal ions such as zinc, copper,
venom? and magnesium, ribonuclease and
deoxyribonuclease, acetylcholinesterase,
phospholipase, protease
What are the 3 distinct 1. Benign defibrination

hematologic effects of 2. Isolated thrombocytopenia
crotalid venom? 3. DIC = like syndrome
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Which U.S. rattlesnake Crotalus scutulatus (Mojave rattlesnake) –

carries a neurotoxic venom? Mojave toxin A
What are the neurotoxic Blockade of ACh at the neuromuscular

effects of rattlesnake junction, causing paresthesias, fascicula-
venom? tions, cranial nerve paresis, respiratory
arrest
What are the signs and Pain at site of puncture, metallic taste in
symptoms of systemic mouth, generalized weakness, confusion,
toxicity as caused by progressive edema, abdominal pain,
crotaline envenomation? nausea and vomiting, dyspnea,
tachycardia, hypotension
What are the life- Anaphylaxis, cardiac/pulmonary/cerebral

threatening complications edema, ARDS, shock, DIC, multi-organ
arising from a severe system failure
envenomation?
What laboratory tests may CBC, electrolytes, PT/PTT, INR,

be helpful? fibrinogen, BUN, blood glucose, UA,
electrolytes
What treatments should Suction, ice, warmth, constriction bands,

be avoided in the incision, excision, charcoal poultices
prehospital care of an
envenomation?
What are the treatments for 1. Immobilize the limb

envenomation? 2. In moderate to severe envenomation,
crotaline polyvalent immune Fab
antivenom (CroFab) is indicated and
should be administered as early as
possible. Monitor for hypersensitivity
reaction to antivenom.
3. Antivenom for exotic species may be
available from zoos. Local poison
centers may be helpful in obtaining
antivenom.
4. Provide supportive care.
5. FFP and platelets as indicated by
significant bleeding
6. Local wound care
7. Observation for at least 4 hrs in
suspected “dry bites”
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OTHER
What are the two species of 1. Gila monster (Heloderma suspectum)

venomous lizards? 2. Mexican beaded lizard (Heloderma
horridum)
Where is the Gila monster The U.S. southwest and northern

found? Mexico
Where is the Mexican Mexico

beaded lizard found?
Of what is the venom Similar to the venom produced by

composed? rattlesnakes, including serotonin,
phospholipase A2, kallikrein-like
bradykinin-releasing substances,
and gilatoxin
Describe venom production Venom is produced in glands in the

and release. lower jaw and is secreted into the
saliva when the animal is agitated. En-
venomation occurs when the animal
bites the victim, attaching itself and
performing a chewing motion. Venom
is introduced into the wound through
grooves in the loosely attached teeth.
Accidental envenomations are
extremely rare.
What systemic signs and Common signs include nausea, vomiting,

symptoms may occur? diaphoresis, and dizziness. Rarely,
hypotension, tachycardia, respiratory
distress, nonspecific T-wave changes or
conduction delays on ECG, and hemor-
rhage (due to abnormal hemostasis) may
occur.
What local signs and Severe pain, edema, lymphangitis,

symptoms may occur? vasospasm, hemorrhage, cyanosis,
necrosis (rare)
What complication of a These lizards are notorious for being

lizard bite may lead to a difficult to remove once attached.
more severe envenomation?
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What are the risk factors for Long bite time (most important),
systemic involvement? extremes of age, comorbid illness. Prior
exposures may result in anaphylaxis.
What initial wound care is 1. Irrigate/clean thoroughly

advised? 2. Direct pressure to control bleeding
3. Dress and splint affected extremities
to limit movement.
4. Elevate affected extremity to
minimize edema and pain.
5. DO NOT USE suction devices,
tourniquets, pressure immobilization
devices, or ice, as they may result in
additional tissue damage.
What treatments are advised 1. Supportive care

in the systemically 2. Opiate analgesia (often for days to
symptomatic patient? weeks)
3. Wound exploration with plain x-ray to
help identify retained teeth
4. Update tetanus. Prophylactic
antibiotics are not typically necessary.
What laboratory studies CBC, BMP, coags, UA. May see leuko-
should be ordered? cytosis and thrombocytopenia (rare). If
infection is suspected (rare), wound cul-
tures should be obtained.
What wound care 1. Clean wound with soap and water daily.
instructions should the 2. Flush wound with hydrogen
patient receive at discharge? peroxide.
3. Apply topical antiseptic.
4. Redress wound in clean dressings.
Which lizard’s saliva Gila monster – it contains an incretin

stimulates insulin secretion analog, promoting insulin secretion.
in hyperglycemia and is
used in some diabetic
medications?
What other species of lizard The komodo dragon (Varanus komodoen-

might be considered sis) does not have a true venom, but con-
“toxic”? tains over 50 types of bacteria in its saliva
that cause infection and sepsis following a
bite.
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TETANUS
Which toxin-producing Clostridium tetani

anaerobe is responsible for
causing the neurologic
disorder tetanus?
What are the four clinical 1. Local

patterns associated with 2. Cephalic
tetanus? 3. General
4. Neonatal
How many cases of tetanus There were an average of 43 cases per

occur in the U.S. annually? year from 1998–2000. The prevalence is
much higher in developing nations due to
poor vaccination rates, poor sanitation,
and improper wound care.
How does Clostridium tetani Spores from C. tetani are ubiquitous in

cause tetanus? the environment. They can enter the
body through any break in the integu-
ment. Once in the body they transform
into a vegetative bacterium that pro-
duces tetanospasmin (aka “tetanus
toxin”), which travels to alpha motor
neuron synapses in the spinal cord and
brainstem via retrograde axonal trans-
port. Once there, it blocks muscle relax-
ation by blocking the release of the
presynaptic inhibitory neurotransmitters
GABA and glycine, resulting in tonic
muscular contractions and intense mus-
cle spasms due to disinhibition of spinal
cord reflex arcs.
What conditions must be The spores germinate under anaerobic

present to allow C. tetani to conditions. Trauma usually introduces
cause disease? C. tetani spores, with chronic skin ulcers,
gangrene, and parenteral drug abuse also
being causes. Co-infection with other
bacteria, presence of a foreign body,
necrotizing tissue, crushed tissue, and
localized ischemia may all contribute to
infection.
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What is the incubation 1 day to 2 months, but averages 7 days.

period for C. tetani? This is partially dependent on wound
location in relation to the CNS
(tetanospasmin must travel
centripetally).
What is the relationship The longer the incubation period, the

between incubation period milder the clinical symptoms
length and disease severity?
What is the most common Generalized tetanus, with trismus

form of tetanus, and what is (“lockjaw”) and risus sardonicus (from
the most common ↑ tone in the orbicularis oris) often ap-
presenting symptom? pearing first. Initial complaints are often
neck stiffness, sore throat, or difficulty
opening the mouth.
How does generalized 1. Other muscle groups, beginning with

tetanus progress? the neck muscles and progressing to
involve the trunk and extremities,
develop rigidity and spasms. This can
result in opisthotonus (extreme
arching of the back and neck).
2. Uncontrolled spasms in response to
even minor external stimuli which can
resemble convulsions. These can be
severe enough to cause fractures or
tendon avulsions.
3. Laryngospasm can cause asphyxiation,
and chest wall rigidity can also cause
respiratory compromise.
4. Autonomic hyperactivity, manifesting
as irritability, tachycardia,
dysrhythmias, HTN, hyperthermia,
and bronchorrhea
5. Mentation is typically preserved.
Why does tetanus cause Tetanoplasmin also disinhibits

these autonomic symptoms? sympathetic reflexes at the spinal
level, which may result in autonomic
dysfunction.
How long do symptoms last? Symptoms can progress for up to 2 wks,

after which autonomic disturbances and
spasm resolve in ⬃2 wks. Rigidity may
last an additional 6 wks.
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What toxicologic causes 1. Strychnine

should be considered when 2. Dystonia
evaluating a patient for
tetanus?
What is localized tetanus? Occurs when the rigidity and pain stay
localized to the site of the inoculation.
This has a better prognosis if it remains
localized.
What is cephalic tetanus? A pattern of tetanus that results from a

head wound or from chronic otitis media.
It presents with cranial nerve palsies and
may progress to generalized tetanus.
What is the most common Failure to use aseptic technique while

cause of neonatal tetanus? cleaning the necrotic umbilical stump of
neonates born to poorly immunized
mothers
When does neonatal tetanus First 14 days of life. It usually begins

usually manifest itself? with weakness, poor feeding, and irri-
tability and progresses to rigidity and
spasms. Prognosis is extremely poor, with
a mortality rate of up to 90%.
What serum test may Serum antibody level ⬎0.01 IU/mL, as

indicate a reduced this suggests immunity
likelihood of tetanus?
What are the major goals in 1. Supportive care – ensure an intact

the treatment of tetanus? airway and adequate ventilation. Be
prepared to intubate.
2. Stop toxin production – wound care
and antibiotics
3. Neutralize unbound toxin – IM
human tetanus immune globulin
4. Control muscle spasms – initially
administer benzodiazepines, NMB
may be necessary to control
spasms/allow adequate ventilation
5. IV MgSO4 can inhibit neurotransmitter
release, helping to control muscle
spasms and autonomic hyperactivity.
6. Labetalol may be considered for
refractory HTN.
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What is the traditional drug Penicillin G

of choice against C. tetani?
Why is penicillin not an It can function as a GABA antagonist and

ideal choice to treat worsen symptoms. Metronidazole is the
tetanus? antibiotic of choice.
How frequently should Immunization series in childhood with

tetanus toxoid boosters q10 yrs
immunizations be
administered?
What are the two general 1. Active – administration of an antigen

types of immunization? to stimulate immunologic defenses
against a repeat exposure
2. Passive – administration of preformed
antibodies to neutralize circulating
antigen
Which types of Tetanus toxoid is a form of active

immunization are tetanus immunization, while tetanus immune
toxoid and tetanus immune globulin is a form of passive
globulin? immunization.
Does tetanus immune No. The immune globulin only neutral-

globulin neutralize bound izes unbound toxin.
tetanospasmin?
Is the tetanus immune No. It does not penetrate the blood-brain

globulin effective in barrier.
neutralizing unbound toxin
in the brain?
What should be Human tetanus immune globulin

administered if a patient
needs tetanus immune
globulin but has had a
previous serum sickness
reaction to equine-derived
products?
In what types of wounds It should be considered in all wounds in

should one consider tetanus which the dermal barrier has been
prophylaxis? breached.
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How does the management Tetanus immune globulin may need to

of tetanus in the elderly be administered more frequently to
differ from that in younger elderly patients with tetanus due to
patients? declining antibody titers with age.
What should one do if a Give tetanus toxoid. Administration of

patient presents with a tetanus toxoid is indicated in all wounds
clean, minor wound and without a known record of a primary
does not know if he has series of three doses of toxoid.
received a primary series of
three doses of tetanus
toxoid?
A patient presents with a Give tetanus toxoid. Administration of

high-risk (i.e., puncture, tetanus toxoid is indicated for all serious
contaminated, or with crush wounds if it has been ⬎5 yrs since the
injury) wound and states last booster and for all minor wounds if it
that she last received a has been ⬎10 yrs.
tetanus booster 7 years ago.
What should be done?
A patient presents with a Administer tetanus immune globulin pro-

high-risk wound and states phylactically to provide passive immunity,
that he has not received the and initiate the series of tetanus toxoid
primary series of tetanus administration.
toxoid. What do you do?
Can tetanus toxoid be given Yes. Tetanus toxoid is FDA category C

during pregnancy? (indeterminate) and may be used in
pregnancy.
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Chapter 9 Therapies
ACETYLCYSTEINE (N-ACETYLCYSTEINE, NAC)
What is N-acetylcysteine An amino acid derivative with known

(NAC)? efficacy in cases of APAP overdose
What is the mechanism of 1. It is a precursor to glutathione and

action of NAC in APAP binds to the APAP P450 metabolite
overdose? NAPQI, preventing its hepatotoxic
effects and facilitating its renal
excretion.
2. May also bind NAPQI directly and
reduce it back to APAP
3. Binds to NO to form S-nitrosothiol,
whose vasodilatory effects can improve
brain, cardiac and renal perfusion
4. Acts as a free radical scavenger
When should NAC be Within 8 hrs of ingestion to prevent

started after a toxic hepatic damage. If the patient presents
ingestion? soon after ingestion, it is acceptable to
wait for a 4-hr APAP level. If close to or
beyond 8 hrs post-ingestion, NAC should
be started upon arrival while APAP and
transaminase levels are pending.
How may NAC be PO, IV

administered?
What are the benefits of the 1. Better patient tolerability and

IV preparation? compliance
2. Can easily be given to
lethargic/intubated patients
3. Requires less overall nursing time
4. May decrease length of hospital stay
What is the standard PO – loading dose of 140 mg/kg (diluted

NAC dosing for acute, to 5% in flavored beverage to make more
uncomplicated APAP palatable), then 70 mg/kg q4 hrs for total
toxicity? of 18 doses
444
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Chapter 9 / Therapies 445
IV – three steps:
1. Loading dose of 150 mg/kg, diluted in
200 mL D5W, given over 15 min
2. Second dose of 50 mg/kg, diluted in
500 mL D5W, given over 4 hrs
3. Third dose of 100 mg/kg, diluted in
1 L D5W, given over 16 hrs
In uncomplicated cases of Generally, APAP levels must be

APAP overdose, for how undetectable, the patient should have
long should NAC therapy be minimal to no symptoms of APAP
given? poisoning (i.e., nausea, vomiting, abdo-
minal pain), and the parameters of liver
damage (i.e., transaminases, INR) should
be normal or significantly improved from
peak levels.
What complications are PO – unpleasant taste, nausea, vomiting,

associated with NAC urticaria (rare)
therapy? IV – anaphylactoid reaction (i.e., flushing,
rash, hypotension), which is rate-
dependent
Are there contraindications 1. Pregnancy category B. The risk of

to using NAC therapy in APAP toxicity is far more dangerous to
pregnancy or in children? mother and fetus than the risk of an
anaphylactoid reaction.
2. Young children may have difficulty
with excess free water when giving
the standard adult IV solution; in
this instance, a final NAC
concentration of 40 mg/mL should
be used.
3. Neonates (preterm and full-term) have
been safely treated with the IV
preparations; however, necrotizing
enterocolitis has been seen with oral
solutions.
For what other toxic 1. Amanita mushroom

ingestions may NAC be of 2. Pennyroyal
theoretical benefit? 3. Clove oil, chloroform, carbon
tetrachloride, and valproic acid-
induced hepatotoxicity
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ANTIVENOM
BLACK WIDOW
What is the effect of black Significantly shortens course and

widow (Latrodectus mactans) decreases severity of symptoms, speeds
antivenom? recovery
From what animal is the Horses (equine)

current U.S. antivenom
derived?
How is the antivenom Horses are hyperimmunized with

produced? Latrodectus mactans venom. Serum is
then removed, and antibodies (along with
residual proteins) are extracted.
What is the biggest concern Anaphylaxis and serum sickness.

when giving black widow Caregivers should always be prepared
antivenom? for anaphylaxis and have IV fluids, epi-
nephrine, diphenhydramine, and intuba-
tion equipment at the bedside prior to
administering the antivenom.
What are indications for 1. Systemic symptoms, including pain

antivenom administration? and HTN, refractory to muscle
relaxants and analgesics
2. Pregnant patients with concern for
uterine contractions
3. Vulnerable patients, including
children and the elderly, should
lower one’s threshold for giving
antivenom.
Are there any Known hypersensitivity to horse serum or

contraindications to black widow antivenom
antivenom therapy?
How should the antivenom 1. In a setting with full resuscitation

be administered? capabilities, by slow IV drip over 15 to
30 min
2. Reconstitute lyophilized vial, and swirl
for up to 30 min (do not shake), then
dilute in saline to total volume of
50 mL.
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How many vials are used? Typically 1, but more may be used based
on symptoms, not weight.
Are other black widow Antivenoms are made in South Africa,

antivenoms available? Australia, and Mexico but are not cur-
rently available in the U.S.
SCORPION
How many species of 1, the bark scorpion (Centruroides

scorpion found in the U.S. exilicauda)
are systemically poisonous?
Where is the bark scorpion Southwestern U.S. and northern Mexico

found?
Is there an antidote? Yes. In the U.S., an antivenom was devel-

oped by the Arizona State University
Antivenom Production Laboratory for use
only in Arizona but was never approved
by the FDA and is no longer in produc-
tion, so supplies are limited. Scorpion
antivenom is also manufactured in Mexico
for various Centruroides species but is
currently unavailable in the U.S.
From what animal is the The antivenom is made from the serum
U.S. antivenom produced? of goats who have been hyperimmunized
with bark scorpion venom.
What is the mechanism of Immunoglobulins in the antivenom bind

action of the antivenom? directly to the scorpion venom.
What are the indications for Scorpion antivenom may be used for
giving scorpion antivenom? severe symptoms, including grade 3 and
4 envenomations. Vulnerable populations,
including children and the elderly, are
more likely to benefit from antivenom.
What is the concern with Anaphylaxis and serum sickness. Care-

using the antivenom? givers should always be prepared for ana-
phylaxis and have IV fluids, epinephrine,
diphenhydramine, and intubation equip-
ment at the bedside prior to administer-
ing the antivenom.
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Are there any Known hypersensitivity to goat serum or

contraindications to scorpion antivenom
scorpion antivenom
therapy?
What should be done before Skin test for hypersensitivity, although a

administering the negative skin test does not exclude an
antivenom? anaphylactic reaction.
SNAKE
What antivenoms are 1. Crotalidae polyvalent antivenom

available for crotaline (Wyeth-Ayerst)
envenomation in the U.S.? 2. Crotalidae polyvalent immune Fab
(CroFab)
From what animals are 1. Wyeth-Ayerst – horses (equine)

these antivenoms derived? 2. CroFab – sheep (ovine)
What is the benefit of a Fab It lacks the immunogenic Fc fragment

fragment? and is, therefore, much less likely to
result in anaphylaxis or serum sickness.
How are Fab fragments After sheep are immunized to 4 North

made? American snake species (Crotalus
adamanteus, Crotalus atrox, Crotalus scu-
tulatus, and Agkistrodon piscivorus), the
IgG is cleaved with papain to isolate the
Fab portion from the immunoglobulin.
What are the indications for Persistent proximal progression of

crotalidae polyvalent swelling or significant systemic symptoms
immune Fab therapy? (e.g., tachycardia, hypotension, coagu-
lopathy, thrombocytopenia)
What is the standard dosing 1. Initial dose is 4 to 6 vials (based on

of crotalidae polyvalent symptom severity)
immune Fab? 2. If systemic symptoms and
proximal progression are not
controlled after initial treatment, an
additional 2 vials may be given up to
three times.
3. After achieving control, 2 vials should
be given q6 hrs 3 doses.
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What are the potential Anaphylactoid reactions, febrile

adverse effects of crotalidae reactions, serum sickness. True anaphy-
polyvalent immune Fab laxis is rare.
administration?
Are there any Relative contraindications include hyper-

contraindications to giving sensitivity to sheep serum, papayas, or
crotalidae polyvalent papain.
immune Fab?
What are the adverse effects High incidence of allergic reaction/ana-

of crotalidae polyvalent phylaxis (25%) and even higher rate of
antivenom (Wyeth)? serum sickness (50%)
Are there any Known hypersensitivity to horse serum or

contraindications to crotalidae polyvalent antivenom
crotalidae polyvalent
antivenom therapy?
What is the standard dosing Typically, 3 to 5 vials initially. An addi-

of crotalidae polyvalent tional 3 to 5 vials can be given, based on
antivenom? severity.
What antivenom is available The only elapid native to the U.S. is

for Elapidae envenomation? the coral snake. An equine-derived
antivenom is available for this species;
however, this antivenom is no longer in
production, and supplies are expected to
become limited.
What are the indications for Any neurologic symptoms related to

coral snake antivenom Eastern or Texas coral snake
therapy? envenomation
What are common side Similar to those of crotalidae polyvalent

effects of coral snake antivenom, including high rates of
antivenom? allergic/anaphylactic reactions and serum
sickness
What additional treatment Be prepared for anaphylactic reactions by

measures should be having fluids, epinephrine, diphenhy-
considered when dramine, and intubation equipment at
administering antivenom? the bedside.
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Are antivenoms available for Yes. In the U.S., many are available
exotic snakes? through zoos, depending on the species
involved. Dosing instructions vary greatly.
Indications for antivenom administration
are similar to those of U.S. snakes and
depend on the type of toxin involved (i.e.,
neurotoxin vs. tissue toxin). Caregivers
should always anticipate anaphylactic
reactions.
What is not taken into The patient’s weight

account when dosing any
snake antivenom?
ATROPINE AND GLYCOPYRROLATE
What is the physiologic Competitive inhibition of ACh binding at

mechanism of action of both muscarinic receptors
atropine and glycopyrrolate?
How do the effects of Atropine has central and peripheral

atropine and glycopyrrolate effects, while glycopyrrolate does not
differ? cross the blood-brain barrier and, there-
fore, acts only peripherally.
What are the toxicologic 1. Treatment of respiratory and GI

indications for atropine symptoms due to poisoning with
therapy? AChE inhibitors (e.g., organo-
phosphates, carbamates)
2. Treatment of respiratory and GI
symptoms due to poisoning with
muscarinic agents (e.g., pilocarpine,
methacholine, muscarinic mushroom
poisoning)
3. Treatment of drug-induced
bradycardia secondary to increased
parasympathetic tone or AV nodal
conduction abnormalities
What is the dosing of Adults – 1 to 2 mg IV initially

atropine in Children – 0.02 mg/kg IV (minimum
organophosphorus 0.1 mg)
compound and carbamate Both – double dose if no improvement
poisonings? after 3 to 5 min. OP and carbamate poi-
sonings may require very large doses
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(10–100 mg over a few hours) to achieve

appropriate atropinization.
What is the typical dose of Adults – 0.5 to 1 mg IV

atropine for drug-induced Children – 0.02 mg/kg (maintain dose
bradycardia? within 0.1 to 1 mg)
What are the primary dosing Respiratory symptoms (i.e., bronchorrhea

endpoints when treating and bronchoconstriction) should guide
organophosphorus treatment, with the endpoint of therapy
compound and carbamate being drying of secretions, ease of venti-
poisonings? lation, and clear lung fields on exam.
In organophosphorus and No. Tachycardia may be a response to

carbamate poisonings, does hypoxia and may improve once respira-
tachycardia preclude tory symptoms improve.
atropine therapy?
What are the potential side Anticholinergic toxidrome

effects of atropine therapy?
Are there any Pre-existing anticholinergic toxidrome,

contraindications to treating urinary retention, acute angle closure glau-
with atropine or coma. History of cardiac disease is a rela-
glycopyrrolate? tive contraindication as these patients may
not tolerate a faster heart rate; however, if
a marked cholinergic syndrome exists,
atropine can be administered even if the
patient has a history of urinary retention,
heart disease, or angle closure glaucoma.
What is the dose of atropine 2 mg atropine IM

delivered by the military
auto-injector (Mark I kit)?
What other component is Pralidoxime 600 mg

included in the Mark I kit?
BARBITURATES
What is the mechanism of Enhance GABA effects by ↑ duration of

action of barbiturates? GABAA-mediated chloride channel open-
ing → ↑ intracellular Cl → membrane
hyperpolarization and ↓ neuronal electri-
cal activity
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Barbiturates are useful in Generally used as second/third line

treating what toxicologic agents for treating toxin-induced seizures
problems? and ethanol withdrawal refractory to
benzodiazepines
Which barbiturate is Phenobarbital

most commonly used
when treating seizures
and other toxicologic
conditions?
Barbiturates are more Theophylline

effective than
benzodiazepines in animal
models for treating or
preventing seizures due to
what class of agents?
Why might phenobarbital be At high concentrations, barbiturates

useful in treating isoniazid- can directly open the GABAA
induced seizures? chloride channel. For this reason,
phenobarbital may be useful in condi-
tions of GABA depletion, where
benzodiazepines are ineffective. Rapid
administration of pyridoxine is impera-
tive, regardless of the adjunctive
therapy used.
Barbiturates may be Flumazenil. Phenobarbital is the treat-

necessary if seizures ment of choice for seizures precipitated
develop following by administration of flumazenil.
administration of what
antidote?
What are possible adverse Hypotension and respiratory depression

effects of barbiturate
administration?
Patients with what condition Porphyria

should not receive
barbiturates?
The metabolism of which None. Induction of hepatic enzymes is

drug is enhanced by acute seen only with chronic use.
phenobarbital use?
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BENZODIAZEPINES
What are some examples of 1. Short-acting – triazolam, alprazolam,

benzodiazepines? midazolam
2. Long-acting – lorazepam, clonazepam,
diazepam, flurazepam
How are benzodiazepines 1. Seizures

commonly used for 2. Agitation
treatment of the toxicologic 3. Ethanol/sedative-hypnotic withdrawal
patient? 4. Toxin-induced sympathomimetic
syndrome
5. Serotonin syndrome
6. Muscle relaxation
How are benzodiazepines PO, IM, IV

administered?
What is the mechanism of Bind GABA receptors and increase

action of benzodiazepines? their frequency of opening in response
to endogenous GABA, thereby
increasing the inhibitory effect of
GABA. Benzodiazepines do not open
GABA receptors independently of
GABA binding, whereas high-dose
barbiturates can.
Why are benzodiazepines They target the route of the seizure,

considered first-line which is generally a lack of neuro-
treatment for toxin-induced inhibitory transmission (GABA).
seizures?
How do benzodiazepines They blunt the cocaine-induced

treat cocaine-induced chest catecholamine surge and the corresponding
pain? HTN, tachycardia, and vasoconstriction.
What is the typical dosing of Adults – 1 to 2 mg IV/PO/IM initially,

lorazepam? then titrate to effect
Children – 0.05 to 0.1 mg/kg initially
Are there any contraindi- Known hypersensitivity to benzodi-

cations to benzodiazepines? azepines. Monitor for CNS and respira-
tory depression.
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BENZTROPINE
For what condition is Dystonic reactions

benztropine utilized in
toxicology?
What is the mechanism of Antagonizes ACh (muscarinic) and

action of benztropine? histamine receptors
How does benztropine work While the mechanism is not fully known, it
to treat dystonia? appears to help restore the balance between
dopaminergic and cholinergic transmission.
What is the dosing for In adults, 1 to 2 mg IV/IM (0.02 mg/kg

benztropine? for children) for dystonic reactions. The
PO form is generally given as prophylaxis
for recurrence of dystonia (1 to 2 mg
q12 hrs). Following a dystonic reaction,
PO benztropine should be continued for
the following 48 to 72 hrs.
What are the adverse effects Anticholinergic toxidrome

of benztropine?
Are there any Pre-existing anticholinergic toxidrome,

contraindications to giving urinary retention, acute angle closure
benztropine? glaucoma. History of cardiac disease is a
relative contraindication, as these
patients may not tolerate a fast heart rate.
BICARBONATE
When bicarbonate is given Sodium, as sodium bicarbonate

IV, with what cation is it (NaHCO3)
usually combined?
Toxicity from what OTC ASA

medication is treated with
sodium bicarbonate to
enhance elimination?
What electrocardiogram QRS prolongation and subsequent dys-

finding(s) associated with rhythmias (drug-induced cardiac sodium
drug toxicity is treated with channel inhibition)
sodium bicarbonate?
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How does sodium Generally, the excess sodium load is

bicarbonate treat sodium thought to competitively overcome
channel blockade? sodium channel blockade. Some
medications (i.e., CAs) have been
shown to bind sodium channels less
tightly in an alkalotic environment. This
may pertain to other sodium channel
blockers as well.
What are the criteria for QRS widening 100 msec, dysrhythmias,
giving sodium bicarbonate hypotension
for sodium channel blocker
toxicity?
What ECG findings are QRS widening with RAD in the

further suggestive of sodium terminal 40 msec of the QRS, best
channel blockade? seen as positive forces (“terminal
R wave”) at the end of the QRS in lead
aVR
How do you administer 1 to 2 mEq/kg IV bolus initially.

sodium bicarbonate in Repeated treatment should be based on
sodium channel blocker clinical condition and ECG findings (i.e.,
overdose? widened QRS), with a goal serum pH of
7.45 to 7.55.
How does sodium Salicylate is a weak acid. In the

bicarbonate treat salicylate presence of an alkalotic environment,
toxicity? a greater fraction of salicylate becomes
ionized. This helps to prevent distri-
bution of salicylate into the tissues, as
well as salicylate resorption in the
kidneys.
Above what toxic salicylate 40 mg/dL

level is sodium bicarbonate
therapy considered?
How is sodium bicarbonate Combine 150 mEq sodium bicarbonate

dosed for treatment of with 1 L of D5W. 40 mEq of potassium
salicylate toxicity? chloride should be added per liter
once urine is produced, in order to
prevent hypokalemia. The rate should
be started at twice the maintenance
fluid rate.
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What potentially lethal Hypokalemia secondary to intracellular

complication of sodium shifts and renal elimination of K in
bicarbonate therapy must be exchange for H. In the setting of
considered in patients hypokalemia, the kidney preferentially
treated for either salicylate reabsorbs K in exchange for H. This
or sodium channel blocker prevents effective urinary alkalinization.
toxicity? Serum K levels should be checked
frequently during therapy.
For which irritant gas Chlorine gas. Bicarbonate helps to

exposure may nebulized neutralize the formed hydrochloric acid.
sodium bicarbonate be an The large surface area of the lungs is
effective therapy? thought to dissipate heat and prevent
thermal injury.
How should sodium For symptomatic patients, 1 mL of

bicarbonate be dosed in sodium bicarbonate (7.5% or 8.4%
chlorine gas exposure? solution) can be added to 3 mL of
sterile water and nebulized.
Are there any Care should be taken in patients with

contraindications to renal failure, CHF, volume overload,
bicarbonate therapy? hypernatremia, or preexisting alkalemia.
BOTULINUM ANTITOXIN
What is contained in Antibodies to botulin types A, B, and E

botulinum antitoxin?
In what animal is the Horse; therefore, patients receive

antitoxin made? equine-derived serum
What is the action of Binds circulating toxin, halting disease

botulinum antitoxin? progression. It has no action on toxin
bound to nerve terminals; therefore, it
does not reverse the disease. As a result,
early administration is important to limit
disability.
Where can physicians obtain 1. Local/state health departments

antitoxin? 2. The Centers for Disease Control and
Prevention
What is the dose and route 1 vial diluted in saline (10 mL), infused
of administration? IV over 30 to 60 min
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What is the indication for High clinical suspicion of botulism poi-

antitoxin administration? soning. Do not delay treatment waiting
for confirmatory lab results.
What is the incidence of Historically reported as 9%, so be well-

allergic reaction to prepared to address anaphylactic reactions.
antitoxin? Skin testing has previously been recom-
mended prior to administration of the
antitoxin; however, this may not predict
an allergic reaction, as one study showed
50% of those with an acute reaction had
a negative skin test. The rate of serious
adverse reactions has been only ⬃1%
since the recommended dose was re-
duced to 1 vial. As a result of these points,
treatment of severe exposures should not
be delayed to perform skin testing.
Which patients should not The equine-derived antitoxin is not rec-

routinely receive antitoxin? ommended to treat infant botulism. This
is not only because of the high rate of
adverse reactions, but also due to the fear
of lifelong sensitization of infants to
horses and equine-derived products.
Is there an antitoxin A human-derived immune globulin

available for children? (baby-BIG) is available and should be
used to treat infant botulism. Currently,
this antidote is only available from the
California State Health Department.
Is there an antitoxin effec- Yes. The US army possesses an antitoxin

tive against type F botulism? against all 7 (A–G) serotypes of botulism
BROMOCRIPTINE
For what indications has 1. Neuroleptic malignant syndrome

bromocriptine been (NMS)
advocated in the toxicologic 2. Cocaine withdrawal (controversial)
patient?
What is the mechanism of 1. Dopamine receptor agonism

action of bromocriptine? (hypothalamus and neostriatum)
2. Mild alpha-adrenergic receptor
antagonism
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How is bromocriptine PO, with poor bioavailability (6%). This

administered? may limit its use in an intubated patient.
What are the adverse effects Common side effects include GI upset
of bromocriptine? (e.g., nausea, vomiting, diarrhea) and
transient hypotension with initiation
of therapy, with a potential for the
development of HTN. Cardiac dys-
rhythmias, exacerbation of angina,
thrombosis (e.g., myocardial infarction),
peripheral vasoconstriction, and uterine
contractions have also been reported but
are rare.
What is the typical dosing of 2.5 to 10 mg PO q6 to 8 hrs for adults

bromocriptine?
CALCIUM
What are the clinical 1. Hypotension due to CCB poisoning

indications for use of 2. To reduce pain and extent of injury
calcium? due to hydrofluoric acid burns
3. Symptomatic hypocalcemia from
fluoride, ethylene glycol, oxalate, or
IV citrate toxicity
4. Hyperkalemia with ECG changes or
cardiac symptoms
5. Hypermagnesemia
When is calcium gluconate 1. When administering through a

indicated over calcium peripheral IV, as calcium chloride
chloride? can cause significant extravasation
injury
2. For topical application and intra-
arterial or local injection following
exposure to hydrofluoric acid
How is calcium dosed when Recommendations vary. A reasonable

treating a CCB overdose? strategy would be an initial bolus of
0.6 mL/kg of 10% calcium gluconate or
0.2 mL/kg of 10% calcium chloride
infused over 5 to 10 min. Additional
calcium can be given based on the
clinical response. Repeated boluses or
an infusion are both acceptable.
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Is calcium useful in Yes. Although more commonly used in

beta-blocker overdose? CCB overdoses, calcium has been shown
to increase inotropy in animal studies and
case reports of beta-blocker overdose.
What is the mechanism of A rise in intracellular Ca2 is necessary

action of calcium? for appropriate excitation-contraction
coupling. Both CCBs and beta blockers
blunt the rise in intracellular Ca2 in
response to depolarization. In theory,
increasing the amount of extracellular
Ca2 can overcome competitive block-
ade, and/or increase Ca2 entry through
unaffected channels and, thus, improve
inotropy.
What are some adverse Rapid administration can cause bradycar-

effects of IV calcium dia and hypotension. Large doses can
administration? cause weakness, nausea, somnolence, and
syncope. Extravasation can cause signifi-
cant local tissue necrosis.
What has been theorized as Calcium administration was theorized to

an important interaction of exacerbate the increase in intracellular
calcium and digoxin toxicity? Ca2 caused by digoxin, thereby poten-
tially increasing the risk of dysrhythmias
or cardiac arrest caused by impaired
relaxation of the myocytes. Animal
studies, however, have not demonstrated
this effect.
How could a patient with a Administer digoxin immune Fab followed

mixed CCB and digoxin by calcium.
overdose be treated?
How is calcium utilized in 1. First-line treatment involves making a

treating hydrofluoric acid 2.5% calcium gluconate gel for topical
exposure? application. Mix 3.5 g of powdered
calcium gluconate in 150 mL of water-
soluble lubricant.
2. If pain is not relieved, calcium
gluconate may be administered intra-
arterially or IM.
3. Ocular exposures may be treated with
1% calcium gluconate eye drops.
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4. Systemic hypocalcemia, manifested by

cardiac dysrhythmias or tetany, must
be treated with IV calcium.
Is calcium advocated for IV calcium has been advocated in the

treating black widow spider past to alleviate pain and muscle spasm
bites? associated with black widow envenoma-
tions; however, evidence for its effective-
ness is lacking, and its use is currently not
recommended.
CALCIUM DISODIUM ETHYLENEDIAMINE-

TETRAACETIC ACID (CaNa2EDTA)
What is CaNa2EDTA? A water-soluble chelating agent for

enhanced elimination of toxic metals
How does CaNa2EDTA Divalent metals displace calcium,

eliminate toxic metals? forming a water-soluble complex that
is excreted renally.
With which metals does Lead (primary target of therapy), zinc,

CaNa2EDTA interact? iron, manganese, copper
What is the primary toxi- Chelation of lead in patients with marked

cologic use of CaNa2EDTA? toxicity
Can CaNa2EDTA alone be No. CaNa2EDTA does not cross the

used as a treatment for lead blood-brain barrier. It may mobilize body
encephalopathy? lead stores that then redistribute to the
brain, worsening encephalopathy. When
used for lead encephalopathy,
CaNa2EDTA must be preceded by BAL.
How is CaNa2EDTA IV, IM

administered?
How is CaNa2EDTA Adults – 2 to 4 g IV over 24 hrs

typically dosed for lead Children – 1000 to 1500 mg/m2 IV over
encephalopathy? 24 hrs
Both – infusion should not start until
4 hrs following dose of BAL
How is CaNa2EDTA Excreted unchanged

metabolized?
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What are contraindications to 1. Renal insufficiency, especially anuria

CaNa2EDTA administration? 2. Hepatitis
What are the effects of Chelation of other essential metals

CaNa2EDTA? (especially zinc), nephrotoxicity,
dehydration, muscle weakness, and
cramps
Can disodium EDTA be No! Disodium EDTA primarily chelates

used to chelate lead? Ca, which may result in QT prolonga-
tion, dysrhythmias, seizures, and death.
L-CARNITINE
What is L-carnitine, and 1. Amino acid derivative

what does it do? 2. Assists in bringing long-chain fatty
acids into mitochondria
3. Assists in bringing short-/medium-
chain fatty acids out of mitochondria
How does valproic acid Carnitine is necessary for valproic acid

induce carnitine deficiency? metabolism. While the mechanism of
carnitine depletion is not fully known,
one mechanism appears to be the combi-
nation of valproic acid with carnitine to
form valproylcarnitine, which is excreted
in the urine.
How is L-carnitine used for 1. Treatment of valproic acid-induced

valproic acid toxicity? hyperammonemia, especially in
patients with AMS/encephalopathy
2. Treatment of valproic acid-induced
hepatitis
3. Prophylactic therapy for prevention of
valproic acid-induced
hyperammonemia (theoretical)
4. Acute valproic acid overdose with high
(450 mg/L) valproic acid levels
(theoretical)
How does L-carnitine work 1. Supplies the carnitine necessary for

as an effective therapy? metabolism of valproic acid
2. Allows for metabolism of long-chain
fatty acids
3. ↓ endogenous ammonia concentrations
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What is the recommended 100 mg/kg IV q8 hrs

dose of L-carnitine to treat
valproic acid-induced
encephalopathy or
hepatotoxicity?
What is the route of intake IV, PO (commercial PO preparation is

of L-carnitine? acetyl-L-carnitine)
What are the side effects of Primarily GI – nausea, vomiting, diar-

L-carnitine use? rhea, abdominal cramps. Patients may
also develop a “fishy” body odor.
CHARCOAL (ACTIVATED)
How do you “activate” Heating charcoal in the presence of

charcoal? steam puts holes in the charcoal,
increasing its surface area.
Activated charcoal (AC) Adsorption of toxins onto the surface of

works by using what the charcoal
chemical property?
One gram of AC has how 400 m2 (a tennis court covers 260 m2)
much surface area?
What is the standard initial 1 g/kg, optimally in a 10:1 ratio of AC to

dose of AC for the treatment xenobiotic
of toxic ingestions?
Why should you not give Risk of aspiration. Aspirated charcoal

charcoal to a patient who is causes severe lung injury. Numerous
confused or somnolent? deaths have been reported. Intubated
patients may receive charcoal via NG tube.
What medication is often co- Sorbitol, in order to promote passage of

administered with AC, and the charcoal through the GI tract
why?
Following what type of Caustics

poisoning is charcoal
absolutely contraindicated?
What is the position of the The AACT’s 2005 position paper states,
American Academy of “activated charcoal should not be admin-
Clinical Toxicology on AC? istered routinely in the management of
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poisoned patients. There is no evidence

that the administration of activated
charcoal improves clinical outcome.”
Guidelines from other societies vary,
with most recommending charcoal in
the first hour in patients at low risk for
aspiration.
Can activated charcoal be Yes. Although prehospital protocols vary,

given by prehospital care most prehospital providers may give
providers without physician activated charcoal without physician
contact? contact to patients with suspected recent
ingestions; however, definitive proof does
not exist to demonstrate that this changes
outcome.
For how long after an Generally, within the first hour

ingestion is it helpful to give
AC?
For which toxic ingestions Theophylline, caffeine, salicylate,

may multidose activated phenobarbital, carbamazepine,
charcoal be beneficial? phenytoin, and sustained-release
products
Multidose activated Amanita phalloides (“death cap”). This

charcoal is recommended for may be helpful in clearing the toxin
the treatment of what highly because enterohepatic circulation occurs.
toxic mushroom for which
there is no known antidote?
If you give multidose No. Sorbitol is not given multiple times

activated charcoal, do you because of the risk of electrolyte
give sorbitol with each dose? abnormalities.
What are the risks of As with a single dose, aspiration is a risk.

multidose AC? Additionally, multidose charcoal
increases the risk of bowel obstruction
and electrolyte abnormalities (e.g.,
hypernatremia, hypermagnesemia).
CYPROHEPTADINE
What was the first use of As an antihistamine to treat allergy

cyproheptadine? symptoms and urticaria
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For what toxicologic Serotonin syndrome

syndrome can treatment
with cyproheptadine be
considered?
Why might cyproheptadine It is an antagonist at 5HT1a and 5HT2a

be effective in treating receptors. Overstimulation of these
serotonin syndrome? receptors causes serotonin syndrome, and
cyproheptadine has proven beneficial in
animal models and human case reports.
What is the classic triad of 1. AMS

serotonin syndrome? 2. Autonomic instability (e.g., hyperther-
mia, tachycardia)
3. Neuromuscular dysfunction
What are the limitations of 1. Only available PO – limits usefulness

using cyproheptadine to in patients with profound symptoms
treat serotonin syndrome? 2. Can cause sedation – may be benefi-
cial but clouds the clinical picture
3. Anticholinergic properties preclude its
use if there is any suspicion of anti-
cholinergic toxicity.
4. Effectiveness has not been proven in
rigorous clinical experiments; there-
fore, supportive care, benzodi-
azepines, and active cooling are the
cornerstones of treatment for sero-
tonin syndrome.
What dose of Dosing has been inconsistent among

cyproheptadine should be case reports. A reasonable regimen is 4 to
given to treat serotonin 8 mg q6 hrs with/without a loading dose
syndrome? of 12 mg. Avoid administering 32 mg
over 24 hrs.
Cyproheptadine can be con- Ergot-induced vasospasm

sidered in the treatment of
what other toxicologic issue?
What other agents have Chlorpromazine and olanzapine

5HT2 blocking effects and
have been considered for
the treatment of serotonin
syndrome?
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CYANIDE ANTIDOTE PACKAGE
What three medications are 1. Amyl nitrite

contained in the cyanide 2. Sodium nitrite
antidote kit? 3. Sodium thiosulfate
How are the medications Sodium thiosulfate and sodium nitrite

packaged? are IV preparations. Amyl nitrite is in
the form of pearls for inhalation. Each
kit contains enough medication to treat
two adults.
What is the adult dose for Amyl nitrite – pearls are crushed and
each medication? inhaled or administered through bag-
valve-mask. They are administered
intermittently, and a new pearl should be
used q 3 min.
Sodium nitrite – 300 mg IV (packaged in
10 mL)
Sodium thiosulfate – 12.5 g IV (packaged
in 50 mL)
How are these medications Sodium nitrite – use caution due to risk
dosed in children? of excessive methemoglobinemia.
Ideally, doses are calculated using weight
and Hgb level. When Hgb is normal,
10 mg/kg is recommended. If Hgb is
unknown, 6 mg/kg is reasonable, as this
will be safe even with significant anemia.
Sodium thiosulfate – 1.65 mL/kg of
25% solution IV over 10 min
Do all three medications No. Amyl nitrite is included for those

need to be administered? patients without IV access. If sodium
nitrite can be administered IV, there is no
need to give amyl nitrite via inhalation.
What is the mechanism of Nitrites induce methemoglobinemia;

action of the amyl and methemoglobin has a higher affinity
sodium nitrite? for cyanide than does normal Hgb.
Methemoglobin will draw both bound
and unbound cyanide away from
cytochrome a3, allowing it to return
to its primary role in the production
of ATP.
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What is the mechanism of Thiosulfate donates a sulfur moiety to

action of sodium thiosulfate? hepatic rhodanese, which catalyzes the
metabolism of cyanide. The availability of
sulfur is typically the rate-limiting step in
the conversion of cyanide to its less toxic
metabolite, thiocyanate.
What are the potential side Hypotension is the most significant side
effects of nitrite effect (secondary to the vasodilatory
administration? effects of nitrites). Also, methemoglobine-
mia lowers the oxygen-carrying capacity.
This is especially concerning when treat-
ing cyanide-poisoned patients with pre-
sumed carbon monoxide exposure, as
occurs in smoke inhalation victims.
What patient population can Renal failure. Thiocyanate can accumulate

have adverse effects after and have toxic effects, including abdominal
sodium thiosulfate pain, vomiting, rash, hypertertension, and
administration? CNS dysfunction. If symptoms are severe
enough, thiocyanate may be dialyzed.
What additional therapy Although antidotal therapy is extremely

should always be admin- important, supportive care, including
istered to patients with a 100% oxygen, hemodynamic support, and
potential cyanide exposure? correction of acidosis, is vital.
What are the indications for Any patient clinically suspected of having
treatment with the cyanide cyanide toxicity. This should be consid-
antidote kit? ered in any patient with sudden loss of
consciousness and any combination of
seizures or hemodynamic instability with-
out a definitive cause. There are several
laboratory clues for cyanide poisoning,
including metabolic acidosis (lactic acido-
sis) and a narrowing of the oxygen satura-
tion between an arterial and a mixed ve-
nous blood sample; however, therapeutic
action may be needed before the results
of these diagnostic tests are available.
How is the use of the It is often recommended that one forgo

cyanide antidote kit administration of the nitrite component
different for a victim of in smoke inhalation victims, at least until
smoke inhalation? a carboxyhemoglobin level is determined.
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DANTROLENE
Name two conditions or 1. Malignant hyperthermia (MH)

diagnoses for which 2. NMS
dantrolene is most
commonly used as a
therapeutic agent.
For what other conditions 1. Serotonin syndrome refractory to

has dantrolene been used traditional therapy
(with some anecdotal 2. Severe hyperthermia/heatstroke with
evidence)? associated muscular rigidity
What is the rationale for Dantrolene “uncouples” skeletal muscle

using dantrolene? contraction from nerve impulses. It can,
therefore, be used to relieve muscular
rigidity and subsequent hypermetabolic/
hyperthermic states.
What is the mechanism of Binds ryanodine receptor (RYR-1)

action of dantrolene? → ↓ Ca2 release from sarcoplasmic
reticulum → limits actin-myosin
interaction → ↓ skeletal muscle tone
What is the dose of 2 to 3 mg/kg IV q15 min, titrated to

dantrolene? effect (max 10 mg/kg). Generally, a
maintenance dose of 1 to 2 mg/kg IV/PO
q6 hrs is needed for 2 to 3 days to pre-
vent recurrence.
What are the most common Nausea and vomiting following PO

side effects? administration. Weakness is expected to
occur, which may lead to respiratory
depression. Sedation, confusion, and
photosensitivity have also been reported.
Does dantrolene cause No. These muscle types contain the

myocardial suppression or RYR-2 ryanodine receptor, which is not
affect smooth muscles? affected by dantrolene.
DEFEROXAMINE
For what clinical indication Iron poisoning

is deferoxamine primarily
used?
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From what is deferoxamine Culture of Streptomyces pilosus

derived?
At what iron level should There is no absolute level. The

you initiate treatment with decision to treat with deferoxamine
deferoxamine? must be made on clinical grounds
and should not be delayed to wait for
a serum level; however, a level
500 mg/dL is generally accepted
as a critical threshold to warrant
treatment.
What are the clinical Persistent emesis and/or diarrhea, meta-

indications for deferoxamine bolic acidosis, shock, AMS (i.e., lethargy,
treatment? coma), and/or an x-ray positive for multi-
ple pills
What is the mechanism of Forms octahedral complexes with loosely

action of deferoxamine? bound/unbound Fe3 to form a water-
soluble complex, ferrioxamine, which is
eliminated in the urine
How should it be Start at 15 mg/kg/hr IV over 6 hrs (max

administered? 1 g/hr), then reevaluate need for further
therapy
What is the most common Deferoxamine-induced hypotension

adverse effect? may occur, especially with rapid
infusion. Adequate hydration must
be assured before infusion is
initiated.
What is the risk of Infusions administered 24 hrs may

prolonged infusion? cause acute lung injury, according to
case reports.
What are the 1. Primary hemochromatosis

contraindications to 2. Documented hypersensitivity to
deferoxamine? deferoxamine
3. Severe renal disease (unless the
patient is undergoing dialysis)
For which infections are 1. Yersinia enterocolitica

iron-overloaded patients at 2. Zygomycetes
higher risk after 3. Aeromonas hydrophila
deferoxamine treatment?
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What are the major drug 1. Prochlorperazine – may cause coma

interactions with or AMS
deferoxamine? 2. Vitamin C – may lead to cardiac
dysfunction
What color does the urine May turn pink (“vin rosé”) due to
turn following deferoxamine ferrioxamine
administration in iron-toxic
patients?
For what other metal toxicity Aluminum

is deferoxamine used?
DIALYSIS
What are the characteristics 1. Low protein-binding

of a toxin that is amenable 2. Low volume of distribution (1 L/kg)
to removal from blood by 3. Water-solubility
dialysis? 4. Low molecular weight (500 Daltons)
What toxins are readily SMEL IT

removed from blood by Salicylates
dialysis? Methanol/metformin
Ethylene glycol
Lithium
Isopropanol (usually indicated only in
severe cases)
Theophylline
What factors are considered 1. Is the toxin readily removed by dialysis?

when deciding whether to 2. Does the toxin, in the amount
initiate dialysis for ingested, have significant toxicity?
treatment of overdose? 3. Serum toxin level (varies by toxin)
4. Clinical status
5. Acid-base status
6. Availability of resources and appropri-
ate vascular access
7. Can other methods be used to treat
the poisoning (antidotes)?
8. Is the normal means of elimination
impaired (renal failure)?
Is dialysis effective in No. At low (therapeutic) blood levels,

removing salicylate from salicylates are highly protein-bound. The
blood with a low serum percentage of unbound salicylate increases
salicylate level? as blood levels rise to the point of toxicity.
13486_CH09.qxd 10/30/08 7:26 AM Page 470
What additional treatment 1. Correction of acid-base status

benefits does hemodialysis 2. Control of fluid status
provide? 3. Metabolite removal
What are the possible 1. Hypotension

adverse reactions to 2. Hypo- or hyperthermia
dialysis? 3. Removal of other therapeutic drugs
DIMERCAPTOPROPANESULFONIC ACID (DMPS)
What is DMPS? 1. Water-soluble chelating agent used in

heavy metal poisoning
2. Analog of dimercaprol (British anti-
Lewisite or BAL)
For which heavy metal Mercury, arsenic, lead

toxicities is DMPS typically
used?
Is DMPS approved for use Not currently FDA-approved but is avail-

in the U.S.? able for use as an investigational drug
What are the possible PO, IV, IM

routes of administration for
DMPS?
Why is DMPS potentially DMPS does not cross the blood-brain

more neuroprotective barrier and, therefore, does not allow
than the common chelator, mercury redistribution to the CNS.
BAL?
How is DMPS excreted? Primarily renally, but also through the bile
How is DMPS dosed for a IV bolus (sterile water solution) – 3 to

severe mercury or arsenic 5 mg/kg q4 hrs over 20 min
exposure? PO (once clinically stable) – 4 to 8 mg/kg
q6 hrs
What are the potential 1. Urticaria

adverse effects of DMPS? 2. Local irritation
3. Hypotension (rate-related in IV
infusions)
4. Erythema multiforme/Stevens-
Johnson syndrome (rare)
5. Chelation of other essential metals
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What, if any, are the contra- Known hypersensitivity or severe renal

indications to DMPS use? insufficiency
DIETHYLDITHIOCARBAMATE
What are the indications for Treatment of choice for nickel carbonyl
diethyldithiocarbamate poisoning, although still considered an
(DDC)? investigational drug. It is not indicated
for elemental or inorganic nickel.
How is DDC administered? PO
What is the mechanism of Chelation of organic nickel compounds to

action of DDC? excretable forms
What intoxicating substance Ethanol. DDC may produce a disulfiram

must be avoided with DDC reaction, yielding flushing, nausea,
therapy? vomiting, vertigo, tachycardia, and
hypotension.
How is DDC similar to Disulfiram is metabolized to DDC

disulfiram? and produces the same aldehyde dehy-
drogenase and dopamine hydroxylase
inhibition.
DIGOXIN IMMUNE FAB
What are the two Digifab (Protherics) and Digibind

preparations of digoxin (GlaxoSmithKline)
immune fragments?
What are the parts of an Fc fragment – the fragment

immunoglobulin (antibody)? “crystallizable” region that binds to
receptors on immune cells and comple-
ment proteins
Fab fragment – the fragment “antigen
binding” that binds the specific antigen
How are the digoxin immune After sheep are injected with digoxindi-
fragments prepared? carboxymethoxylamine (DDMA), they
develop a cross-reactive antibody to
digoxin. This is isolated from the serum,
and the Fc portion is proteolytically
cleaved with papain, leaving the Fab
fragments as the primarily component of
the preparation.
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What patients may have an Those with known allergies to:

allergy to digoxin immune 1. Sheep proteins
fragments? 2. Papaya
3. Papain (derived from papaya)
What are the indications for 1. Potassium 5.0 mEq/L following

digoxin immune fragments? acute cardiac glycoside ingestion
2. Hemodynamic instability
3. Life-threatening dysrhythmias
4. History of large ingestion (i.e., 10 mg
in an adult) or serum level 10 ng/mL
4 to 6 hrs post-ingestion may warrant
treatment, regardless of symptoms.
What are the benefits of Reversal of digitalis-induced dysrhyth-

treatment with digoxin Fab mias, conduction disturbances, myocar-
fragments? dial depression, and hyperkalemia in
severely poisoned patients.
What are the sources of 1. Digoxin

cardiac glycoside poisoning? 2. Venom of toads from the Bufo genus
3. Ingestion of plants containing cardiac
glycosides (e.g., oleander, lily of the
valley, foxglove)
How does use change in a The digoxin-Fab complex is excreted in

patient with renal failure? the urine; therefore, elimination of the
digoxin-Fab complex is delayed in renal
failure, and free digoxin levels gradually
increase after Fab administration.
Rebound cardiac glycoside toxicity is
rare but has been reported.
Can dialysis be used to No. Hemodialysis does not enhance elim-

eliminate the digoxin-Fab ination of digoxin-Fab complex.
complexes?
If the digoxin concentration If severely poisoned acutely, 5 to 10 vials

is unknown, how much should be given at a time, with subse-
Digifab should be quent observation of clinical response.
administered? An empiric dose of 2 vials is often suffi-
cient for chronic digoxin poisoning.
How much digoxin will 40 mg 0.5 mg digoxin

(1 vial) of Digifab bind?
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How do you calculate how 1. Known amount ingested:

much Digifab to administer?
the number Total digitalis
of vials to ingested (mg)
administer 0.5 mg
2. Known serum level in chronic steady
state:
the number Serum digoxin con- patient’s body
[
of vials to centration (ng/mL) weight (kg)
administer 100
]
How do the doses differ in Higher doses may be required due to
poisoning with non-digoxin lower affinity for the non-digoxin cardiac
cardiac glycosides? glycosides.
How should it be If cardiac arrest is imminent or has

administered? occurred, the dose can be given as a
bolus; however, it should be infused
over 30 min in stable patients.
How quickly does it work? Patients can have reversal of ventricular

dysrhythmias within 2 min, and most
patients have settling of toxic dysrhyth-
mias within 30 min of Fab administra-
tion. Within 6 hrs, 90% of patients will
have completely or partially responded to
the medication.
What laboratory test is Serum digoxin concentration. Measured

unreliable after digoxin digoxin levels may increase soon after
immune fragment administration of digoxin immune frag-
administration? ments, although the digoxin will not be
pharmacologically active because it is
largely bound to the immune fragments.
DIMERCAPROL
For what purpose was Developed by the British as an antidote

dimercaprol developed? for Lewisite, an organic arsenical com-
pound used as a vesicating chemical
weapon. It is also known as British anti-
Lewisite, or BAL.
How is dimercaprol Deep IM

administered for heavy
metal chelation?
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In what substance is Peanut oil

dimercaprol dissolved?
What are its indications? 1. Treatment of lead encephalopathy as

adjunctive therapy with CaNa2EDTA
2. Severe inorganic arsenic toxicity
3. Inorganic mercury toxicity
4. Gold toxicity
What is the mechanism of Dimercaprol’s sulfhydryl groups chelate

action of dimercaprol? heavy metals to form a stable complex
capable of renal excretion
What are the 1. Iron, cadmium, selenium, or uranium

contraindications for poisoning, as these metal-dimercaprol
dimercaprol? complexes are toxic
2. Peanut allergy
3. G6PD deficiency (may cause
methemoglobinemia)
4. Use with caution in thrombocy-
topenic/coagulopathic patients and in
those who are hypertensive
What are the adverse effects 1. HTN

of BAL? 2. Injection-related – sterile abscess,
painful administration
3. Febrile reaction
4. Cholinergic symptoms – nausea,
vomiting, salivation, lacrimation,
rhinorrhea
5. Hemolysis in G6PD-deficient patients
6. Chelation of essential metals, resulting
in deficiency
What are the typical dosing 1. Lead encephalopathy – 75 mg/m2 IM

regimens for BAL? q4 hrs for 5 days (must be followed by
CaNa2EDTA 4 hrs after injection)
2. Inorganic arsenic/inorganic mercury
poisoning – 3 mg/kg IM q4 hrs for 48
hrs, then q12 hrs for 7 to 10 days
DIMETHYL-P-AMINOPHENOL (DMAP)
What are some alternative 4-DMAP, 4-dimethylaminophenolate

names for this chemical?
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DMAP is used as an antidote Cyanide

for toxicity from which
substance?
What is the clinical effect of Induces methemoglobinemia, which is

DMAP? often the first step in treating cyanide
poisoning. In Germany, it is used
instead of sodium nitrite for treating
cyanide poisoning.
How does DMAP induce Catalyzes the transfer of electrons

methemoglobinemia? from Fe2 (ferrous) iron to O2. In the
process, oxidized Fe3 (ferric) iron is
produced.
How does Cyanide has higher affinity for ferric iron

methemoglobinemia aid in than it does for cytochrome oxidase a3 in
the treatment of cyanide the respiratory chain of mitochondria.
poisoning? This will free cytochrome a3 and allow
normal cellular respiration.
What is the dose of DMAP 3.25 mg/kg is the recommended

used for cyanide poisoning? dose; therefore, 250 mg or 5 mL of
5% solution IV is a reasonable dose for
an adult of unknown weight. It can be
given IM, if necessary. It should only be
administered to comatose patients in
whom cyanide poisoning is a reasonable
certainty.
What medication must be Sodium thiosulfate. It acts as a sulfhydryl

administered along with donor to the rhodanese enzyme, which
DMAP? converts cyanide into thiocyanate (elimi-
nated in the urine).
What advantage does DMAP It works faster and can induce a greater
have over the nitrites? degree of methemoglobinemia than
sodium nitrite.
What are the adverse effects Excessive methemoglobinemia and

of DMAP? hemolysis
What are the possible Cyanosis, nausea, headache, dizziness,

clinical effects of dyspnea, confusion, seizures
methemoglobinemia?
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How is DMAP reversed, if Methylene blue; however, this could

necessary? theoretically release cyanide bound to
methemoglobin, causing reexposure.
When should DMAP be When there is a question of

avoided? combined cyanide and CO exposure
(as in smoke inhalation from a
structure fire). DMAP-induced
methemoglobinemia, in combination
with significant carboxyhemoglobin,
could markedly impair O2 transport.
DIPHENHYDRAMINE
What are the clinical uses 1. Treatment of symptoms of histamine

for diphenhydramine in the excess (e.g., urticaria)
realm of toxicology? 2. Prophylaxis against hypersensitivity to
antivenoms or antitoxins
3. Treatment of EPS due to neuroleptic
drugs (e.g., dystonia)
4. Antipruritic agent (due to insect bites
or plant exposures)
How is diphenhydramine PO, IV, IM, topically

administered?
What is the mechanism of 1. Histamine (H1) receptor blockade

action of diphenhydramine? 2. Anticholinergic activity
3. Sodium channel blockade
What are the 1. Angle-closure glaucoma

contraindications for 2. Obstructive uropathy (e.g., from
diphenhydramine prostatic hypertrophy)
administration? 3. Preexisting anticholinergic symptoms
What is the typical dosing of Depending on symptom severity,

diphenhydramine? 25–50 mg in adults (1.25 mg/kg in
children) IV/IM/PO q6 hrs
What are the acute side CNS depression (may cause

effects of diphenhydramine paradoxical agitation in children),
use? AMS, hyperthermia, urinary
retention, skin flushing, tachycardia,
blurred vision
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ETHANOL
For what toxins is ethanol Methanol and ethylene glycol

used as an antidote?
By what mechanism does Competitive inhibition of alcohol

ethanol work as an antidote? dehydrogenase blocks the conversion
of toxic alcohols (i.e., methanol and
ethylene glycol) to toxic metabolites.
What difficulties should be 1. IV solution is not FDA approved

considered regarding the 2. IV solution is hyperosmolar
use of ethanol as an 3. Frequent serum ethanol determi-
antidote? nations are required to maintain
therapeutic levels
4. Hypoglycemia may develop in children
If used as an antidote, what 100 mg/dL. At this level, the metabolism of

is the target serum ethanol both methanol and ethylene glycol by alco-
level? hol dehydrogenase is completely blocked.
Following toxic alcohol No. Ethanol, at appropriate doses, will

ingestion, does ethanol block the formation of toxic metabolites;
remove the acidic however, once these metabolites are
metabolites? formed, only further metabolism or
hemodialysis will remove them.
Describe the dosing of an Generally, 10 mL/kg loading dose of

ethanol infusion. 10% ethanol solution, then 1 to
2 mL/kg/hr maintenance dose, will
keep serum ethanol concentrations at
100 mg/dL; however, rates of metabolism
vary greatly.
Is ethanol dialyzable? Yes; therefore, the infusion rate must

be doubled for patients receiving
hemodialysis.
The maintenance infusion 1. Chronic alcoholics

rate must be adjusted for 2. Other patients with induced
which patient populations? cytochrome enzymes
3. Patients receiving hemodialysis
What are some common Hypoglycemia (especially in children),

complications of ethanol phlebitis, inebriation
infusion?
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Are any laboratory tests Serum ethanol level and blood glucose
important during ethanol checks should be done every hour.
infusion?
For what other poisoning SMFA. While data on human efficacy is

may ethanol be an antidote? limited, ethanol may supply the necessary
acetate to overcome SMFA’s inhibition of
the TCA cycle.
FLUMAZENIL
What type of medication is Benzodiazepine antagonist (1,4-

flumazenil? imidazobenzodiazepine)
What is the mechanism of Competitive inhibition of the benzodi-

action of flumazenil? azepine receptor with subsequent
prevention of GABA potentiation in
the CNS
Is flumazenil routinely No. It should not be administered as

indicated for a nonspecific coma-reversal drug and
benzodiazepine overdose? should be used with extreme caution
after intentional overdose.
Why should one avoid It has the potential to precipitate

flumazenil in these withdrawal in benzodiazepine-
circumstances? dependent individuals and/or induce
seizures in those at risk. Also,
overdoses of benzodiazepines alone are
rarely fatal. Fatalities can occur in
mixed overdoses with other CNS
depressants (e.g., ethanol, opioids,
other sedatives) due to synergistic
activity.
How is flumazenil most To treat iatrogenic benzodiazepine over-

commonly used? medication during procedural sedation or
monitored anesthesia care
What is the adult dose of 0.5 to 5 mg (adults). Typically, begin

flumazenil? with 0.2 mg IV over 30 sec, then titrate
in 0.5 mg doses at 1 min intervals.
What is the time of onset of 1 to 2 min, peak effect in 6 to 10 min

flumazenil?
13486_CH09.qxd 10/30/08 7:26 AM Page 479
What is the duration of 45 to 90 min. Patients will always need

action of flumazenil? to be monitored for re-sedation, and
additional doses may be necessary.
What are the risks Primarily seizures and benzodiazepine

associated with withdrawal, although cardiac
administering flumazenil? dysrhythmias are possible
What groups of patients are 1. Chronic benzodiazepine use

more likely to develop (habituated user)
seizures? 2. Co-ingestant that lowers the
seizure threshold (e.g., CAs,
cocaine, methylxanthines,
diphenhydramine)
3. Preexisting seizure disorder
What medication should be Barbiturates are the first-line agents.

used to treat seizures
induced by flumazenil?
What is the preferred Airway management and supportive care

treatment of benzodiazepine with observation until symptoms resolve
overdose?
In what type of overdose Young children with no history of seizure

patient could flumazenil be disorder and who are on no chronic
considered? benzodiazepine therapy who present
with respiratory depression after isolated
benzodiazepine ingestion
FOLIC ACID
What is folic acid? An essential B-complex vitamin

(vitamin B9)
Are folic acid and folinic No. Folinic acid is the activated form
acid the same compound? of folic acid and does not need to be
activated by dihydrofolate reductase
(DHFR) in order to be used in cellular
processes. Folic acid requires further
activation (by DHFR) before use.
How is folic acid used as a As adjunctive therapy for the treatment

therapy for toxic ingestions? of methanol ingestions
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What is the mechanism of Enhances conversion of formic acid (toxic

action of folate? metabolite of methanol) to CO2 and water
How should folate be IV

administered to treat
methanol ingestion?
What dose of folate should Though no specific dose is widely

be used to treat methanol accepted, the following are suggested:
ingestions? Adults – 50 mg IV q4 hrs 6 doses
Children – 1 mg/kg IV q4 hrs 6 doses
Are there any Known hypersensitivity

contraindications to folate
administration?
FOMEPIZOLE (4-METHYLPYRAZOLE, 4-MP)
What are other commonly 1. Antizol is the U.S. trade name.

encountered names for this 2. 4-methylpyrazole (4-MP) is the
antidote? chemical name.
What is the mechanism of Competitive inhibition of alcohol

action of 4-MP? dehydrogenase, which prevents certain
alcohols from being converted to their
more toxic metabolites
4-MP is indicated in Methanol and ethylene glycol

preventing the toxic effects
of which toxic alcohols?
What are the indications for 1. Ethylene glycol or methanol level

treatment with 4-MP? 20 mg/dL
2. Known ingestion of ethylene glycol or
methanol (if a serum level cannot be
obtained quickly)
3. Clinical suspicion of ethylene glycol or
methanol ingestion and 2 of the follow-
ing: pH 7.3, serum bicarbonate
20 mg/dL, or osmol gap 10
4. 4-MP can also be considered for
patients with an unexplained acidosis
(especially if there is an osmol gap)
and for those who are clinically
intoxicated with a negative serum
ethanol.
13486_CH09.qxd 10/30/08 7:26 AM Page 481
What other antidote should Ethanol

be considered if 4-MP is not
readily available for
methanol or ethylene glycol
poisonings?
How could 4-MP decrease By blocking the formation of acetal-

the severity of disulfiram or dehyde by alcohol dehydrogenase.
disulfiram-like reactions to Acetaldehyde is responsible for many of
ethanol? the toxic effects of the disulfiram-ethanol
reaction (i.e., flushing, diaphoresis, nau-
sea, vomiting, tachycardia, hypotension).
Should 4-MP be used for No. This would prolong the metabolism
isopropyl alcohol ingestions? of isopropanol to its less toxic metabolite,
acetone.
How is 4-MP dosed? Loading dose of 15 mg/kg IV, then

10 mg/kg IV q12 hrs 4 doses.
Subsequent doses are given at 15 mg/dL
if therapy extends beyond 48 hrs.
Should 4-MP dosing be Yes. Dosing should be increased to

altered if the patient is q4 hrs during hemodialysis.
undergoing hemodialysis? At start of dialysis – if most recent dose
was 6 hrs ago, give another dose
At end of dialysis – if most recent dose
was 3 hrs earlier, give full dose; if most
recent dose was 1 to 3 hrs earlier, give
half dose
GLUCAGON
What is glucagon? A polypeptide hormone that is naturally

produced in the pancreas and is currently
synthesized by pharmaceutical companies
Why must glucagon be given It is destroyed in the GI tract and would

parenterally? have no effect if given PO.
What is the mechanism of 1. Binds to specific glucagon receptors

action of glucagon? → activates adenylyl cyclase → ↑
cAMP production → ↑ cardiac in-
otropy and chronotropy, ↑ hepatic
glycogenolysis and gluconeogenesis,
GI smooth muscle relaxation
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2. A metabolite of glucagon
(miniglucagon) increases arachidonic
acid in cardiac cells, which improves
myocardial contractility, partly by
increasing Ca2 stores in the
sarcoplasmic reticulum.
What was the original Treatment of hypoglycemia when a

indication for glucagon? patient cannot tolerate PO glucose and/or
when IV glucose is unavailable
For what other indications is 1. Principally to ↑ BP as a primary treat-

glucagon utilized? ment for beta-blocker poisoning and as
adjunctive therapy for CCB poisoning
2. To correct myocardial depression after
overdose with TCAs, quinidine, or
procainamide
3. To facilitate passage of an esophageal
foreign body
How does glucagon improve Beta-blocker – bypasses blocked cardiac

cardiac function in patients beta-adrenergic receptors to ↑ intracellu-
with beta-blocker or CCB lar cAMP → activates protein kinase A →
poisoning? ↑ Ca2 influx through voltage-sensitive
calcium channels → ↑ sarcoplasmic retic-
ulum Ca2 stores
CCB – facilitates Ca2 entry → may ↑
inotropy. It may also be used in conjunc-
tion with IV calcium and high-dose in-
sulin therapy.
How soon are the effects of 1 to 2 min

glucagon seen after
administration?
How long do glucagon’s 10 to 15 min

cardiac effects persist?
How should glucagon be 1. For hypoglycemia or facilitating pas-

administered? sage of an esophageal foreign body,
1 mg IV is recommended.
2. For hypotension following an over-
dose, 50 to 150 g/kg (5–10 mg) IV is
recommended. If there is a positive
13486_CH09.qxd 10/30/08 7:26 AM Page 483
response, an infusion should be started

due to glucagon’s short duration of
action. The infusion rate should be the
amount of the effective bolus per hour
(usually 5–10 mg/hr in adults), which
can then be titrated to effect.
What must be remembered Use saline or D5W to dissolve the

when reconstituting glucagon. Previous packages in the
glucagon for injection? U.S. contained phenol as a diluent.
With the large doses used in treating
an overdose, a toxic dose of phenol could
be administered.
What are the adverse effects Nausea and vomiting are common, espe-
of glucagon use? cially with larger doses; therefore, it should
only be administered to patients with a
protected airway. Glucagon may also cause
hyperglycemia and hypokalemia.
GLUCOSE
What is glucose? A 6-carbon carbohydrate used for

energy by the body. The biologically
active isomer (d-glucose) is also known
as dextrose.
How is glucose administered? PO, IV
When is glucose Hypoglycemia, hyperkalemia, CCB

administration indicated? toxicity, beta-blocker toxicity, undiffer-
entiated AMS
Why is glucose used to treat It is used as an adjunct to insulin therapy,

hyperkalemia? which results in the shifting of potassium
into cells.
Why is glucose administered Hypoglycemia is a common cause of

in patients with AMS.
undifferentiated AMS?
How should glucose be used May be administered as intermittent

in a sulfonylurea overdose? boluses; however, continuous infusion of
5% to 10% dextrose may be more effec-
tive in maintaining euglycemia.
13486_CH09.qxd 10/30/08 7:26 AM Page 484
What is one potential IV glucose infusion may induce further

problem when using insulin release, resulting in paradoxical
glucose for a sulfonylurea hypoglycemia.
overdose?
How is glucose used for Glucose and insulin are used together in
CCB and beta-blocker a treatment called hyperinsulinemia-
overdose? euglycemia therapy.
What is the mechanism CCBs cause insulin resistance in over-

behind hyperinsulinemia- dose. Glucose provides the carbohy-
euglycemia therapy? drates necessary for cardiac metabolism,
while high doses of insulin help to over-
come the insulin resistance and allow
glucose to enter the myocardial cells
→ ↑ cardiac inotropy.
What is the typical dose of Adults – 1 to 2 mL/kg of D50 solution

glucose used for treating Children – 2 to 4 mL/kg of D25 solution
hypoglycemia?
When is oral glucose 1. No secure airway

contraindicated? 2. Inability to swallow
3. Hyperglycemia
What are toxic effects of 1. Hyperglycemia

glucose administration? 2. Irritation/phlebitis at administration
site when given IV (especially with
rapid push)
3. Tissue necrosis if IV catheter
infiltrates
4. Wernicke-Korsakoff syndrome in
thiamine-deficient patients
HALOPERIDOL AND DROPERIDOL
What type of medications Butyrophenone class neuroleptics

are droperidol and (antipsychotics). Droperidol is
haloperidol? considered “medium potency,”
while haloperidol is considered “high
potency.”
How do these drugs help Dopamine receptor blockade (D2

mediate psychotic receptors in the mesolimbic system of
symptoms (mechanism of the brain)
action)?
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For what are these Rapid tranquilization and treatment of

medications most typically acute psychosis
used in the emergency
department?
How is this accomplished? The sedative properties are mediated

through alpha 2-adrenergic receptor
agonism, droperidol more so than
haloperidol.
What side effects might be Akathisia, dystonia, parkinsonian symp-

expected with dopamine toms, and tardive dyskinesia. These are
receptor blockade? likely due to blockade of dopamine re-
ceptors in the nigrostriatal pathway.
Above what dose are these With 10 mg haloperidol (cumulative),

side effects more likely? the risk of EPS increases.
What cardiac side effects QT prolongation and torsade de pointes

have been described for this
class of medications?
Which one received a “black Droperidol

box” warning from the FDA
in 2001 because of the
concern over QT
prolongation?
Are these agents used as No. Benzodiazepines are effective in

first-line agents for the managing agitation and have an excellent
sedation of patients with safety profile; however, occasionally small
toxin-induced agitation? doses of haloperidol or droperidol may
be helpful in managing severe agitation
refractory to benzodiazepines.
What are some conditions 1. Overdose that causes excessive

for which haloperidol or dopaminergic stimulation (e.g.,
droperidol may be useful? methylphenidate, pemoline)
2. Conditions in which hallucinations are
potentially contributing to the agita-
tion (e.g., delirium tremens)
What are some 1. May exacerbate hyperthermia by in-

disadvantages to using hibiting diaphoresis due to an anti-
haloperidol or droperidol to cholinergic effect
treat toxin-induced agitation?
13486_CH09.qxd 10/30/08 7:26 AM Page 486
2. Could worsen the condition if agita-

tion was secondary to NMS
3. Could further prolong the QT interval
if given for an overdose of a QT-
prolonging agent
What other medication can Benzodiazepines (e.g., midazolam,

be given in conjunction with lorazepam)
haloperidol or droperidol to
augment the sedative effects
and provide rapid control?
HISTAMINE-2 RECEPTOR ANTAGONISTS (H2 BLOCKERS)
What are the toxicologic 1. Toxin-induced gastritis (e.g., isopropyl

uses of H2 blockers? alcohol)
2. Adjunctive therapy for the treatment
of scombroid toxicity
3. Adjunctive therapy and/or pretreatment
for allergic/anaphylactoid reactions
Why are H2 antagonists Large amounts of histamine released

useful for allergic during an allergic response may cause
symptoms? nausea and GI distress through stimula-
tion of acid production. There are also a
small number of H2 receptors in the skin,
smooth muscle, and heart.
Name the 4 H2 receptor 1. Cimetidine

antagonists available in the 2. Ranitidine
U.S. 3. Famotidine
4. Nizatidine
What are the dosages for Cimetidine – 300 mg IV/PO/IM q8 hrs

common H2 blockers? Ranitidine – 50 mg IV/IM q8 hrs or
150 mg PO q12 hrs
For what other treatment Cimetidine is an inhibitor of the P450

can cimetidine potentially system. Theoretically, it may be used to
be used? block the production of toxic metabolites
following the ingestion of substances
whose metabolism through the P450 sys-
tem generates toxins (e.g., APAP, carbon
tetrachloride, Amanita mushrooms);
however, studies have not demonstrated
clinical efficacy in humans.
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HYDROXOCOBALAMIN
What is hydroxocobalamin? Synthetic precursor of vitamin B12
For what is Given its safety profile, hydroxocobalamin

hydroxocobalamin should be administered to any patient
indicated? suspected of having cyanide toxicity. It
can be given empirically to victims of
smoke inhalation with profound metabolic
(lactic) acidosis, hemodynamic instability,
or other signs of cyanide poisoning.
What is the mechanism of Acts as a chelating agent for cyanide.

action of hydroxocobalamin? Hydroxocobalamin combines with
cyanide in an equimolar ratio to form
cyanocobalamin. Cyanocobalamin is also
known as vitamin B12; it is nontoxic and
renally eliminated.
How is hydroxocobalamin 5 g IV for adults, 70 mg/kg for children.

administered when treating This should be given over 15 min. It is
cyanide poisoning? supplied in 250 mL vials, each contain-
ing 2.5 mg of hydroxocobalamin, which
are to be diluted in 100 mL of normal
saline.
Which medicine should also Sodium thiosulfate. Together, these

be administered when agents have synergistic effects, increasing
treating a patient with their antidotal efficacy; however, they
hydroxocobalamin? should not be administered at the same
time or through the same line, as thiosul-
fate will bind to hydroxocobalamin and
render it inactive.
What are the adverse effects Good safety profile, overall. Allergic
of hydroxocobalamin reactions have been reported but only in
administration? patients receiving long-term treatment
for pernicious anemia. Virtually every pa-
tient receiving a 5 g dose will develop or-
ange-red discoloration of the skin,
mucous membranes, and urine, which
typically resolves in 24 to 48 hrs. The dis-
coloration of the serum may interfere
with several laboratory tests. Also, a
pustular rash has developed in some
individuals receiving hydroxocobalamin.
13486_CH09.qxd 10/30/08 7:26 AM Page 488
Its appearance was delayed until 1 wk

following infusion, and it resolved in 6 to
38 days.
What are the advantages of As it does not induce methemoglobine-

hydroxocobalamin over the mia, hydroxocobalamin is safe to adminis-
traditional cyanide antidote ter to victims of smoke inhalation who
kit? are at risk for significant carboxyhemo-
globinemia. This is important because
smoke inhalation is the most commonly
reported cause of cyanide poisoning, and
the nitrite portion of the cyanide antidote
kit is not typically administered in these
cases. Also, hydroxocobalamin adminis-
tration can cause transient HTN, which
may be advantageous in the hemodynam-
ically unstable patient.
HYPERBARIC OXYGEN
What is hyperbaric oxygen A treatment modality in which a patient

(HBO)? is placed in a sealed pressure chamber
and breathes oxygen at a pressure 760
mmHg, or 1 atmosphere.
What are the physiologic 1. ↑ partial pressure of O2 in the blood

effects of HBO? (Henry’s law)
2. ↓ size of undissolved gas bubbles
(Boyle’s law)
Name some other postulated 1. Stimulates fibroblast proliferation and

effects of HBO therapy. angiogenesis (promotes wound heal-
ing)
2. WBC cytotoxicity is enhanced, and
WBC vessel wall adherence is de-
creased.
3. Directly bactericidal to anaerobic
bacteria and bacteriostatic to aerobic
bacteria
For which toxicologic 1. CO – may reduce cognitive sequelae

exposures has HBO therapy in severe poisoning, but patient
been advocated? selection criteria are not well-defined.
Indications that have been advocated
(but not proven) include AMS,
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pregnancy, age 36 yrs, exposure

24 hrs, cerebellar dysfunction, and
carboxy-Hgb level 25%.
2. Cyanide – no proven role, may help if
concomitant CO exposure (smoke
inhalation)
3. Concentrated hydrogen peroxide
ingestion with arterial gas embolism
(AGE) – gastric mucosal perforation
may allow gas bubbles to enter venous
circulation and embolize to the brain,
resulting in stroke symptoms
4. Loxosceles spider envenomation
(brown recluse) – for wound healing
of necrotic ulcers
5. Methemoglobinemia – if refractory to
methylene blue, can support tissue
oxygen demands independent of Hgb
6. Methylene chloride – indications
similar to CO poisoning due to the
development of CO as methylene
chloride is metabolized
Why is HBO only a Very little data exists to support HBO

consideration in the above use, except in decompression illness
exposures? (DCI) and AGE.
What are adverse effects of 1. O2 toxicity–reactive oxygen species

HBO? produce oxidant damage to mem-
branes and cellular components
2. Pulmonary toxicity–type II alveolar
cells have ↓ surfactant production,
acute reversible exudative process.
Continued hyperbaric exposure can
result in permanent damage via
fibrosis, fibroblast proliferation, and
hyperplasia.
3. Lowers seizure threshold
4. Visual toxicity–reversible myopia,
scotomata
5. Barotrauma–direct mechanical
damage to tissue
How are oxygen toxicity 1. ↑ air breaks between breathing 100%

symptoms managed? O2
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2. ↓ pressure/depth – the only variable to

change in a monoplace (single patient)
chamber, as it is filled with 100% O2
What is an absolute Untreated pneumothorax (PTX) – will

contraindication to HBO? expand on ascent, potentially causing a
tension PTX
What are relative 1. Prior chest surgery, resulting in air

contraindications to HBO trapping and barotrauma
therapy? 2. Lung disease – same as above
3. Viral infections – prevent middle
ear/sinus pressure equalization
4. Recent middle ear surgery – same as
above
5. Optic neuritis – possible ↑ optic
nerve pathology
6. Seizure disorders – ↑ risk of seizures
7. High fever – ↓ seizure threshold
8. Congenital spherocytosis
9. Claustrophobia
10. Unstable patients (if using a mono-
place chamber) – they are inaccessi-
ble if rapid interventions are needed
11. Disulfiram use – inhibits superoxide
dismutase
12. Premature infants – risk of retrolen-
tal fibroplasia, causing blindness
13. Concurrent use of antineoplastic
agents (e.g., doxorubicin, cisplatin,
bleomycin)
Are all recompression No. Monoplace chambers accommodate

chambers the same? one supine patient and are filled entirely
with 100% O2, which the patient breathes
during the entire treatment. Multiplace
chambers accommodate two or more pa-
tients sitting upright or supine, along with
an attendant, and are filled with ambient
air consisting of 21% O2. Tight-fitting avia-
tion masks are utilized to administer 100%
O2 intermittently during the treatment,
reducing the risk of oxygen toxicity.
Portable recompression chambers may be
used in remote or austere environments.
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INAMRINONE (PREVIOUSLY AMRINONE)
What are the primary Inotropy and vasodilation

actions of inamrinone?
What is the mechanism of 1. Inhibition of myocardial cell phospho-

action of inamrinone? diesterase activity → ↑ intracellular
cAMP → ↑ inotropy
2. Vascular smooth muscle relaxation →
↓ preload and afterload
What are the primary Treatment of CCB, beta-blocker, or

toxicologic indications for mixed beta- and alpha-blocker overdose
inamrinone? refractory to conventional management
techniques
By what route, and in what Loading dose – 0.75 mg/kg IV over 2

dosage, is inamrinone to 3 min (may be repeated once in
administered? 30 min)
Infusion – 5 to 10 g/kg/min IV
What is the approximate 2 to 5 min

onset of action?
How long is the duration of 0.5 to 2 hrs following IV administration

action?
What is the 5 to 8 hrs (can be prolonged in patients

approximate half-life of with CHF)
inamrinone?
In which organ is Liver

inamrinone
metabolized?
What are the potential Thrombocytopenia, dysrhythmias,

adverse effects of hypotension, nausea, vomiting,
inamrinone? injection site irritation, exacerbation
of outflow tract obstruction in
patients with hypertrophic subaortic
stenosis
What, if any, are the Known hypersensitivity to inamrinone or

contraindications to to sulfites (metabisulfite is used as a drug
inamrinone usage? preservative)
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INSULIN
Insulin can be used for 1. CCB toxicity with hypotension (possi-

treating which toxicologic bly with dextrose)
emergencies? 2. Beta-blocker toxicity with hypotension
(possibly with dextrose)
3. Vacor toxicity
What are contraindications 1. Hypoglycemia

for insulin use? 2. Known hypersensitivity to insulin
components
What cells increase glucose Skeletal muscle cells, cardiac myocytes,

uptake when stimulated by adipose tissue
insulin?
What are the adverse effects 1. Hypoglycemia

of insulin? 2. Hypokalemia
3. Local pain/irritation at the site of
injection
4. Lipodystrophy at injection site
(uncommon)
What is the serum half-life ⬃4 to 5 min

of regular human insulin?
What substances may 1. Epinephrine

antagonize the effects of 2. Corticosteroids
insulin? 3. Glucose (PO or IV)
4. Glucagon
What are the effects of 1. CCB overdose causes insulin

CCBs on insulin secretion? resistance.
2. CCBs block voltage-dependent
(L-type) calcium channels within beta
islet cells of the pancreas → ↓ Ca2
influx → ↓ exocytosis of insulin stored
in secretory granules → insulin
deficiency
What is the effect of CCB The combination of insulin resistance

overdose on myocardial with decreased systemic insulin
metabolism? production impairs myocardial
glucose uptake, further depressing
contractility.
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What name is given to Hyperinsulinemic-euglycemic therapy

insulin therapy for CCB
toxicity?
Why is insulin useful in The blockade of insulin’s effect by CCBs

treating the hemodynamic is competitive. Administration of high-
effects of CCB toxicity? dose insulin → ↑ glucose uptake by car-
diac myocytes → ↑ myocardial function.
What is the mechanism of While hyperinsulinemic-euglycemic ther-

action of insulin in a beta- apy has been shown to be efficacious in
blocker overdose? beta-blocker poisoning, the exact mecha-
nism has not been well-defined.
What dosing of insulin There is no universal dose. Supra-physio-

should be provided to treat logical doses of insulin, much higher than
hypotension due to CCB or those used for the treatment of DKA, are
beta-blocker toxicity? required to overcome CCB-induced
insulin resistance.
How should insulin be Recommended regimens vary. An

administered? infusion of regular insulin may be
started and rapidly titrated up to 1 to 2
U/kg/hr as needed to support blood
pressure. Blood sugar should be
measured frequently, with IV dextrose
administered to maintain euglycemia.
With significant CCB toxicity, supple-
mental glucose is often not necessary.
Patients may remain hyperglycemic
despite massive insulin infusions. K
should also be monitored.
How long may it take before Up to 30 min. Additional supportive care

a therapeutic benefit is should be employed until effects are
observed? seen.
What is the dose of insulin 0.1 U/kg regular insulin IV (with 25 g IV

used for treating adults with D50)
hyperkalemia?
Is there a simpler dosing Begin with 5 to 10 U regular insulin IV

recommendation that does (with D50 as above), then infuse 1 L of
not require calculations? D20 with 40 to 80 U regular insulin over
2 to 4 hrs.
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How often should glucose q30 min

levels be monitored while
treating hyperkalemia with
insulin?
Is there a way to use insulin Yes. By giving an IV dextrose load (25 g

to treat hyperkalemia if you D50), the non-diabetic patient will re-
have no insulin readily spond by releasing endogenous insulin;
available? this method is not as effective as adminis-
tering exogenous insulin.
What is the mechanism for Insulin → ↑ activity of skeletal muscle

insulin’s role in Na-K-ATPase → ↑ K influx (thereby ↓
hyperkalemia? serum K)
After providing exogenous ⬃15 min

insulin, how long does it
take for the serum
potassium to fall?
How long does the drop in Several hours

potassium last?
Is insulin safe to use during Yes (category B). It does not cross the
pregnancy? placenta.
IODIDE
What is iodide? The anion (I) of iodine, which exists as

7 different species in aqueous solution –
iodide, triiodide, hypoiodite ion, iodate
ion, iodine cation, hypoiodic acid, and
elemental iodine
What is the toxicologic Potassium iodide (KI) is indicated for pre-

indication for iodides? venting the development of thyroid cancer
in those exposed to radioactive iodine.
Where is radioiodine found? Commonly used in medical applications

and in nuclear reactors
What is the time frame for Optimally, it is given 1 hr prior to the ex-
administration of iodides in posure (as prophylaxis), but it may still be
the setting of radioiodine beneficial up to 4 hrs post-exposure.
exposure?
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What is the recommended The doses recommended by the FDA

dose and duration of are:
therapy after exposure? Adults – 130 mg
Children (3 to 18 yrs) – 65 mg
Infants and children (1 month to 3 yrs) –
32 mg
Newborns (0 to 1 month) – 16 mg
Daily dosing should continue until the
risk of exposure is eliminated.
How do iodides work in the They are readily absorbed by the thyroid
setting of a radiological gland, saturating the gland with iodide
exposure? and preventing uptake of any radioactive
iodide.
Who benefits the most from Children have a far greater risk of
treatment with KI? developing cancer secondary to radioac-
tive iodine exposure; therefore, adults
over 40 yrs are generally not advised to
take KI unless there is a projected
thyroid dose of 5 Gray (500 rads).
Children and pregnant, or lactating,
women should receive prophylaxis for
projected exposure of 5 rads.
How are iodides PO in salt form, most commonly as

administered? potassium iodide (KI)
Can iodide be given in Yes; however, it is recommended that

pregnancy? pregnant and lactating women take only
1 dose, as iodide readily crosses the pla-
centa and is found in breast milk.
How else is iodide used? Iodide salts were the mainstay of treat-
ment for hyperthyroidism prior to the ad-
vent of thioamides. Historically, they
were also used as antimicrobials.
IPECAC SYRUP
What is ipecac syrup? An alkaloid oral suspension that induces

vomiting
Where is this found in In plants belonging to the family

nature? Rubiacea
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Name the two key Emetine and cephaeline

components.
How is ipecac used? Historically, ipecac was used as an emetic

in the case of a potentially poisonous
ingestion or intentional overdose. Ipecac
is no longer recommended for GI
decontamination.
What is the mechanism of Emetine produces irritation of the gastric

action of ipecac? mucosa, while cephaeline causes stimula-
tion of the medullary CTZ.
What is the time to onset of 15 to 30 min

action of ipecac?
What are symptoms of acute Nausea, vomiting, diarrhea

ingestion of ipecac?
What are the cellular effects Emetine-mediated inhibition of protein

of chronic use? synthesis in skeletal muscle
ISOPROTERENOL
What is isoproterenol? Sympathomimetic drug that targets beta-

adrenergic receptors
What is the mechanism of Stimulates beta 1- and beta 2-adrenergic

action of isoproterenol? receptors → ↑ chronotropy and inotropy,
as well as bronchodilation, vasodilation,
and hepatic glycogenolysis
What are toxicologic Refractory drug-induced torsade de

indications for isoproterenol pointes (TdP)
use?
Where is isoproterenol Primarily by COMT in the liver

metabolized?
What is the half-life of IV 2.5 to 5 min

isoproterenol?
What contraindications VF, VT (except TdP), and history of

prevent administration of congenital long QT syndrome. History
isoproterenol? of ischemic heart disease is a relative
13486_CH09.qxd 10/30/08 7:26 AM Page 497
contraindication, as these patients may

not tolerate an ↑ HR.
What is the recommended Adults – 2 g/min initially, then titrate to

dose of isoproterenol used patient response (2 to 10 g/min)
for treating TdP? Children – 0.1 g/kg/min initially (effec-
tive dose is typically 0.2 to 2 g/kg/min)
What is the goal of Suppression of TdP. This is generally

isoproterenol therapy in achieved when the patient’s HR is 90 to
TdP? 140 beats/min.
What is the mechanism by Not fully understood. Isoproterenol ap-

which isoproterenol treats pears to suppress TdP by ↑ HR, which
TdP? helps to homogenize repolarization
among myocardial cells.
LEUCOVORIN
What is the common name Leucovorin

for folinic acid?
What is leucovorin? The metabolically active form of folic acid
How is folic acid activated? Folic acid is converted, by dihydrofoliate

acid reductase (DHFR), to tetrahydrofolic
acid, which is a precursor of folinic acid.
What is the mechanism of Acts as a cofactor for production of

action of folinic acid? purine nucleotides and thymidylate in the
formation of DNA
What are the uses of 1. Treatment of methanol poisoning

leucovorin? 2. Rescue therapy for high-dose
methotrexate therapy
3. Treatment of methotrexate overdose
4. Treatment of trimethoprim- and
pyrimethamine-induced bone marrow
suppression
How does leucovorin Methotrexate inhibits the formation of

overcome methotrexate tetrahydrofolate, which halts DNA syn-
toxicity? thesis. Leucovorin overcomes this block-
ade by supplying the necessary folinic
acid for purine synthesis.
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What is the dosing of Initial dose of leucovorin should be

leucovorin after the amount of methotrexate ingested.
methotrexate overdose? Generally, an initial dose of 100 mg/m2 of
leucovorin will be sufficient for all but
the most severe poisonings. This dose
should optimally be given within 1 hr of
ingestion. Subsequent doses of leucov-
orin may be adjusted based on
methotrexate levels.
At what point can leucovorin When methotrexate blood levels are

therapy be stopped after 0.01 mol/L and there are no signs of
methotrexate overdose? bone marrow suppression
What are some adverse 1. Hypercalcemia may result from the

effects of leucovorin? calcium salt.
2. Intrathecal administration can result
in neurotoxicity and death.
3. Seizures have been reported.
LIDOCAINE
What are the toxicologic Suppression of refractory ventricular dys-

indications for lidocaine? rhythmias induced by cardiac toxins, par-
ticularly cardiac glycosides and possibly
CAs (controversial)
What is the mechanism of Inhibits fast sodium channels without pro-

action of lidocaine? longing the QRS (type Ib antidysrhyth-
mic) → slows phase 0 of action potential
How does lidocaine abolish By depressing conduction in aberrant

ventricular dysrhythmias? tissue and, thus, stopping re-entrant
circuits
What is the effect of Minimally suppresses conduction

lidocaine on the SA and AV
nodes?
When is lidocaine Adams-Stokes syndrome, Wolff-

contraindicated? Parkinson-White syndrome, AV block,
bradycardia, hypotension, hypersensitivity
to lidocaine or amide anesthetics
What are some toxic CNS Dizziness, confusion, agitation, seizures,

side effects of lidocaine? coma
13486_CH09.qxd 10/30/08 7:26 AM Page 499
What are some toxic cardiac Worsened dysrhythmias, AV block,

side effects of lidocaine? bradycardia, cardiac arrest
Where is lidocaine Liver

metabolized?
What is the typical dose of 1 mg/kg IV

lidocaine used for treating
dysrhythmias?
What is the maximum safe Without epinephrine – 3 to 5 mg/kg

dose of lidocaine for local (⬃30 mL of 1% solution)
anesthesia? With epinephrine – 7 mg/kg (⬃50 mL of
1% solution)
What is the maximum safe 3 mg/kg total

dose of systemic lidocaine
for dysrhythmias?
What increases risk factors 1. Liver dysfunction (lidocaine is metab-

for lidocaine toxicity? olized in the liver)
2. Low protein states (lidocaine is
protein-bound)
3. Certain medications – cimetidine,
ciprofloxacin, clonidine, phenytoin,
beta-blockers
MAGNESIUM
For what toxin-induced 1. Torsade de pointes induced by agents

conditions is magnesium that prolong the QT interval
indicated? 2. Hypercalcemia
3. Treatment of soluble barium (i.e., bar-
ium carbonate) ingestions
4. Digoxin toxicity (functions at the Na-
K-ATPase to indirectly antagonize the
drug)
5. Hypomagnesemia caused by ingestion
of fluorides (e.g., hydrofluoric acid,
ammonium bifluoride)
What is the mechanism of Competitive antagonism of cellular Ca2

action of magnesium? influx, which may decrease the likelihood
of delayed after-depolarizations and in-
hibit presynaptic ACh and catecholamine
release. Too large a dose of magnesium
13486_CH09.qxd 10/30/08 7:26 AM Page 500
will, therefore, impair muscle contrac-

tion, leading to paralysis and ileus, and
interfere with cardiac conduction.
Why is magnesium Magnesium can theoretically ↑ Na-K AT-

administration potentially Pase activity, directly interfering with
helpful after a digoxin digoxin. Also, by ↓ Ca2 influx, it may sup-
overdose? press delayed after-depolarizations and,
therefore, lessen the risk of dysrhythmias.
This is only a temporizing measure until
digoxin immune Fab can be administered.
What dose of magnesium is Magnesium can be given PO to convert

given for barium ingestions, soluble barium to insoluble barium
and how does it work? sulfate. Recommended doses include:
Adults – 30 g PO (or by NG tube)
Children – 250 mg/kg PO (or by NG tube)
Magnesium can be used to IV magnesium has been used to treat

treat what aquatic Irukandji syndrome caused be envenoma-
envenomation? tion by the jellyfish Carukia barnesi. It is
theorized that magnesium will ↓ cate-
cholamine release, reducing the HTN, ag-
itation, and pain caused by this syndrome.
What initial dose of 2 g magnesium sulfate over 10 to 20 min

magnesium is typically (to avoid hypotension)
administered?
What are some of the side 1. GI irritation if given PO

effects of magnesium 2. Blunted deep tendon reflexes
administration? 3. Impairment of cardiac function, lead-
ing to bradycardia and hypotension
4. Diaphoresis and flushing
In which patient populations Patients with renal disease, hypotension,

should magnesium be used and/or AV block
with caution?
METHYLENE BLUE
What is methylene blue? An alkaline thiazine dye
What is the toxicologic indi- Symptomatic methemoglobinemia, which

cation for methylene blue? typically occurs at levels 20%
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How is methylene blue IV administration is irritating and painful.

administered, and what are Local tissue damage is possible, even
the potential adverse without extravasation.
effects?
How is it dosed? Adults/Children – 1–2 mg/kg IV over 5

min, followed by a fluid bolus to
minimize local irritation
Neonates – 0.3–1 mg/kg
Repeat dosing may be required in cases
of continued absorption of the etiologic
agent.
What is the time to onset of Within 30 min

action?
What is the mechanism of Methylene blue is reduced to

action of methylene blue? leukomethylene blue in the presence
of NADPH and NADPH methemoglo-
bin reductase. Leukomethylene blue
then reduces methemoglobin to
hemoglobin.
What enzyme must be G6PD. It is a component of the hexose

present for methylene blue monophosphate pathway that generates
to work properly as an the NADPH necessary for reduction of
antidote? methylene blue to leukomethylene blue.
Name an undesired Paradoxical production of methemoglo-

potential effect of binemia by oxidation of Hgb (at high
methylene blue. doses or with dysfunctional NADPH
methemoglobin reductase)
Does methylene blue cause Yes, blue-green discoloration of the urine

any urinary symptoms? with possible dysuria
Is methylene blue effective It is impossible to know before a trial

in patients with G6PD dose is given. Those with an African
deficiency? subtype generally have enough G6PD
activity to respond to methylene blue,
whereas those with a Mediterranean
subtype are unlikely to respond. In the
latter case, other options, such as
exchange transfusion and HBO, should
be considered.
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NALOXONE, NALTREXONE, AND NALMEFENE
What do these medications They are all opioid antagonists.

have in common?
What are the differences Route of administration and duration of

among these medicines action
(generally)?
Which medication is Naloxone

typically used in the
setting of acute opioid
toxicity?
In the patient with AMS, 1. Miosis

what two signs should raise 2. Respiratory depression
your suspicion for opioid
toxicity?
Name five different routes IV, IM, SQ, ET, intranasal

of administration for
naloxone.
What is the dose of 0.4–2 mg titrated slowly as the initial

naloxone? starting dose
How is naloxone 0.4 mg of naloxone is mixed with 10 mL

administered? of normal saline and given slowly (i.e.,
1 mL/min) IV until clinical effects are
seen.
What are the effects of 1. Acute opioid withdrawal

administering a larger than 2. Unmasking effects of co-intoxicants
necessary dose to a patient (e.g., cocaine)
with acute opioid
intoxication?
What is the clinical goal in Improved respiratory effort without signs

the administration of or symptoms of withdrawal
naloxone?
How long should overdose The half-life of naloxone is ⬃30–60 min.

patients be monitored Patients should be monitored for ⬃5 half-
after reversal of CNS lives (4 hrs) to make certain that re-
depression with sedation does not occur.
naloxone?
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What condition can signi- Renal failure

ficantly prolong the half-life
of naloxone and subsequently
delay the clinical appearance
of re-sedation?
How can symptoms of Continuous naloxone infusion. Generally,

re-sedation be treated? two-thirds of the initial reversal dose per
hour will maintain adequate arousal.
What opiates may require Methadone, fentanyl, diphenoxylate,

larger than usual doses to propoxyphene, pentazocine
reverse?
How is nalmefene Parenterally

administered?
How is nalmefene different It is a long-acting antagonist, with a dura-

from naloxone? tion of action of ~4 hrs.
Why might this be an 1. Fewer changes in the patient’s level of

advantage? consciousness
2. Limited need to re-dose the medication
Why might this be a Precipitation of prolonged withdrawal

disadvantage? symptoms
What is different about While it is also a long-acting antagonist, it

naltrexone? is administered PO instead of parenterally.
What is its primary Long-term opioid detoxification (outpa-

indication? tient addiction management)
NEUROMUSCULAR BLOCKERS
How are neuromuscular Broadly classified as depolarizing (DNMB)

blockers classified? and non-depolarizing (NDNMB) based on
their activity at the postsynaptic ACh re-
ceptor of the neuromuscular junction
What are some common 1. DNMB – succinylcholine

neuromuscular blockers? 2. NDNMB (aminosteroids) –
mivacurium, tubocurarine,
pancuronium, vecuronium
3. NDNMB (benzylisoquinolinium
diesters) – atracurium, cisatracurium
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What are the toxicologic 1. To facilitate paralysis and orotracheal

indications for intubation in patients with hypoxia
neuromuscular blockers? or lack of airway protection and in
those requiring other life-saving
procedures
2. To ↓ muscular hyperactivity, along
with associated hyperthermia and
rhabdomyolysis, in refractory strych-
nine poisoning and tetanus
3. To ↓ muscular hyperactivity, along
with associated hyperthermia and
rhabdomyolysis, in refractory NMS,
serotonin syndrome, and uncoupling
syndromes
What is the mechanism of 1. Binds postsynaptic ACh receptor →

action of succinylcholine? membrane depolarization → muscle
fasciculations
2. As depolarization continues, the
muscle is temporarily insensitive to
ACh → phase I block.
What is the mechanism of Competitive inhibition of postsynaptic

action of NDNMBs? ACh receptors
What are some adverse 1. Histamine release

effects from neuromuscular 2. Anaphylactic shock (most commonly
blockers? with rocuronium)
Why should long-acting They may hide the physical manifesta-

NMBs be avoided in the tions of seizures.
toxicologic patient?
What testing modality EEG monitoring

should be available for
chemically paralyzed
patients with toxin-induced
seizures?
How is succinylcholine Plasma cholinesterase (primary) and

metabolized? alkaline hydrolysis (minimal)
What are some 1. Hyperkalemia

contraindications for the use 2. Known plasma cholinesterase
of succinylcholine? deficiency
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3. ↑ ICP or IOP
4. History of malignant hyperthermia
5. History of recent severe burn or crush
injury
6. History of progressive neuromuscular
disease
7. OP or carbamate poisoning
What is the dosing of Succinylcholine – 1 to 1.5 mg/kg IV

common NMBs? Vecuronium – 0.1 mg/kg IV
Rocuronium – 0.6 mg/kg IV
How are NDNMBs Aminosteroids (e.g., pancuronium,

metabolized? vecuronium, pipecuronium) – hepatic
metabolism
Synthetic benzylisoquinolinium drugs
(e.g., tubocurarine, metocurine) – elimi-
nated renally or metabolized by plasma
cholinesterase
How can neuromuscular AChE inhibitors can be given to ↑ junc-

blockade by NDNMBs be tional ACh levels.
reversed?
What drugs can be used to 1. Neostigmine, pyridostigmine, and

reverse NDNMBs? edrophonium ↑ ACh levels.
2. Atropine can be given to limit
bradycardia.
Why are AChE They inhibit plasma cholinesterase, pro-

inhibitors contraindicated longing the effects of succinylcholine.
for succinylcholine
reversal?
What are some adverse 1. Prolonged weakness due to

effects of neuromuscular accumulated metabolites or
blockers? lengthened drug activity
2. Post-op respiratory problems due to
paralysis/weakness of diaphragm
3. Malignant hyperthermia
OCTREOTIDE
What is octreotide? Somatostatin peptide analog that inhibits

endogenous insulin secretion
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What are the toxicologic Treatment of hypoglycemia caused by

indications for its use? sulfonylurea or quinine toxicity
What is the mechanism of 1. ↓ cellular Ca2 influx by a G-protein-

action of octreotide? mediated process → inhibits insulin
release
2. Stimulates Gi-coupled receptor → ↓
adenylate cyclase activity → ↓ cAMP
production → inhibits insulin release
When should octreotide be When hypoglycemia is refractory to IV

used to treat drug-induced dextrose
hypoglycemia?
What is the dosage of Adults – 50 g SQ/IV q6 hrs

octreotide used for treating Children – 4 to 5 g/kg/day SQ/IV
drug-induced hypoglycemia? divided q6 hrs (max 50 g per dose)
How is octreotide packaged, As an injectable liquid and as a depot for-

and which formulation mulation. Do not use the depot formula-
should be used? tion for toxicologic indications.
What adverse effects can 1. Potential for hypoglycemia (octreotide

octreotide cause? also inhibits glucagon secretion, which
may outlast the inhibition of insulin
secretion)
2. Local irritation at injection site
3. GI distress
4. Anaphylactoid reactions (rare)
PENICILLAMINE
What is D-penicillamine? A penicillin metabolite initially identified

in the urine of patients taking penicillin.
It was later found to be an effective
chelating agent.
What are the primary Chronic exogenous copper toxicity and

indications for D- Wilson’s disease. D-penicillamine may be
penicillamine therapy? beneficial in acute copper poisoning, but
its efficacy has not been validated.
Are there other indications Treatment of lead, arsenic, and mercury

for D-penicillamine toxicity, although it is considered a sec-
therapy? ond-line therapy. Due to adverse effects
seen with its use for lead chelation, it has
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been supplanted by succimer. It should

be used only when succimer or BAL
CaNa2EDTA cannot be tolerated.
How is D-penicillamine 1 to 1.5 g/day PO divided q6 hrs

dosed?
How is D-penicillamine Renally

excreted?
What are some potential 1. Aplastic anemia or agranulocytosis

adverse effects of D- 2. Renal disease
penicillamine? 3. Pulmonary disease
4. Hepatitis and pancreatitis
5. Chelation of other essential metals
6. Hypersensitivity reaction, especially in
those with penicillin allergy (25% in
this population)
7. Chronic use – cutaneous lesions,
immune dysfunction
How does D-penicillamine Through chelation of zinc

alter the sensation of taste?
What other uses exist for 1. Treatment of Wilson’s disease –

D-penicillamine? chelates copper for renal excretion
2. Rheumatological disorders –
immunosuppressant action
3. Cystinuria – binds cystine, increasing
its solubility
PHENTOLAMINE
What is phentolamine? An IV vasodilator
How does phentolamine Competitive antagonism at peripheral

work? alpha 1-adrenergic receptors
What are the general Hypertensive crisis that results from

toxicologic indications for alpha-adrenergic receptor stimulation
phentolamine?
For what specific toxins is 1. Sympathomimetic toxicity (e.g.,

phentolamine typically used? cocaine, amphetamines, ergot alkaloids)
2. MAOI drug interactions/tyramine
crisis
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3. Limb-threatening ischemia secondary

to vasoconstrictor extravasation
4. Alpha-2 agonist withdrawal syndrome
Why is phentolamine useful Has been shown to ↓ cocaine-induced

for cocaine-induced chest coronary artery vasoconstriction
pain?
How is it dosed and 1 to 5 mg IV bolus repeated until

administered? resolution of symptoms or induction of
hypotension. Exact dosing is toxin-
dependent. It may also be administered
as an IV infusion. In areas of ischemia
induced by infiltrated vasoppressors,
infiltration of 0.5 mg of phentolamine can
speed recovery.
What is the typical onset of Within 2 min when given IV

action?
What are the adverse effects Hypotension and reflex tachycardia

of phentolamine therapy?
PHENYTOIN AND FOSPHENYTOIN
What is phenytoin? An anticonvulsant of the hydantoin

structural class (related to the
barbiturates)
What is fosphenytoin? Phenytoin with a phosphate group

attached to the hydantoin anhydride
nitrogen (promotes water solubility)
What is the mechanism of Voltage-gated sodium channel blockade

action underlying
phenytoin’s therapeutic
effect?
In what cardiac drug toxicity Cardiac glycoside-induced dysrhythmias

has phenytoin use been
reported to be of benefit?
How does phenytoin exert Phenytoin is a type 1b antidysrhythmic

its antidysrhythmic effect? (sodium channel blocker that does not
prolong QRS duration). It suppresses
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ventricular irritability without slowing AV

nodal conduction.
In what types of drug Cocaine, lidocaine, theophylline

toxicities has phenytoin use
been found to increase
toxicity?
What is the typical IV dose 15 to 20 mg/kg

of phenytoin?
What is the maximum rate 50 mg/min. Rates greater than this are
of phenytoin infusion? associated with hypotension and CV
collapse. This is likely related to the
propylene glycol diluent.
What side effects are Stevens-Johnson syndrome, anticonvul-

associated with phenytoin sant hypersensitivity syndrome, systemic
use? lupus erythematosus-like syndrome,
blood dyscrasias, hepatitis drug-drug
interactions, gingival hyperplasia, “purple
glove syndrome” (not associated with
fosphenytoin)
What is “purple glove Limb (usually hand) ischemia, swelling,

syndrome”? and discoloration related to the IV
infusion of phenytoin. Compartment
syndrome and necrosis are possible
sequelae.
PHYSOSTIGMINE AND NEOSTIGMINE
What enzymes are AChE and butylcholinesterase

antagonized by
physostigmine and
neostigmine?
What physiological effect 1. Reverses anticholinergic effects

does this have? 2. Can lead to cholinergic toxidrome
How do physostigmine and Physostigmine is a tertiary amine, while

neostigmine differ? neostigmine is a quaternary amine.
What does this mean Physostigmine crosses the blood-brain

physiologically? barrier, and neostigmine does not.
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What does this mean Physostigmine affects the CNS, while

clinically? neostigmine has strictly peripheral effects.
What are the toxicologic 1. Treatment of anticholinergic

uses of physostigmine? toxidrome
2. Differentiation of anticholinergic
delirium from other disease entities
(e.g., meningitis, encephalitis,
psychosis)
3. Reversal of anticholinergic effects
during surgery
How can neostigmine be To reverse effects of NDNMBs

used therapeutically?
What dose of physostigmine 0.5 to 2.0 mg slow IV push (2 mg in

is recommended in the 10 mL normal saline given at 1 mL/min)
treatment of an
anticholinergic toxidrome?
What are the possible Seizures, bradycardia, asystole (particu-

adverse effects of treating larly in CA overdose), cholinergic excess
anticholinergic patients with
physostigmine?
What would you expect to The effect of succinylcholine would last

happen if you gave much longer than normal
succinylcholine to a patient
who had received
physostigmine?
What would be the antidote Atropine

for a physostigmine or
neostigmine overdose?
PRALIDOXIME (2-PAM) AND OTHER OXIMES
What is pralidoxime Pralidoxime chloride, or Protopam

(2-PAM)? (2-PAM), is a member of the oxime
group used to reactivate AChE after
inhibition by OPs. 2-PAM is the only
oxime approved in the U.S.
To whom is 2-PAM To patients who have suspected

administered? OP/nerve agent (NA) poisoning and are
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demonstrating moderate (i.e., fascicula-

tions, vomiting, respiratory difficulty) to
severe toxicity. Atropine is also adminis-
tered for its antimuscarinic properties (↓
bronchorrhea and wheezing), while 2-
PAM can treat both nicotinic and mus-
carinic effects.
How should 2-PAM be IV/IM. The preferred route is IV,

administered? although IM administration with a Mark I
auto-injector is acceptable in the field
prior to establishing an IV line. The initial
dose should be given as quickly as
possible to prevent aging (permanent
inactivation of the AChE molecule).
What is the dose for 2-PAM? Initially, 1 to 2 g (20 to 50 mg/kg in

children, max 2 g) diluted in 100 mL NS
given over 15 to 30 min. It is important
to note that 2-PAM is rapidly excreted
by the kidney with a half-life of 90 min;
therefore, a continuous infusion is often
recommended after the loading dose to
maintain therapeutic levels. The current
WHO recommendation is a 30 mg/kg
bolus followed by an 8 mg/kg/hr
infusion. A reasonable treatment
regimen for severely poisoned adult
patients would be 2 g IM or slow IV
infusion over 15 to 30 min, followed by
a 500 mg/hr infusion.
How is 2-PAM delivered Each Mark I auto-injector delivers

when using Mark I kits? 600 mg 2-PAM 2 mg atropine.
Three Mark I auto-injectors are
recommended to treat severely
poisoned patients. This delivers 1.8 g of
2-PAM, which is nearly the max
recommended initial dose of 2 g; there-
fore, if after administration of 3 Mark I
kits a patient is still exhibiting respira-
tory distress, further treatment should
include only the atropine portion of
subsequent Mark I kits to avoid exces-
sive 2-PAM administration.
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Is there a therapeutic Early administration is advocated to

window of administration prevent the OP-AChE complex from
time for 2-PAM? undergoing hydrolysis, losing one of the
OP alkyl groups and forming an irre-
versible covalent bond between toxin and
enzyme. This “aging” process is variable,
depending on the specific agent. For
example, NA aging ranges from 2 to
6 min for soman (GD) to 48 hrs for VX.
For the insecticide malathion, it is
⬃3.5 hrs, and for parathion, it is 33 hrs.
What is the mechanism of OPs form a covalent bond with the active
2-PAM? site of AChE, preventing it from inacti-
vating ACh. 2-PAM is attracted to the
active site of AChE, and its nucleophilic
oxime moiety will attack the phosphate
atom of the OP, displacing it from the
active site and reactivating the enzyme.
Are there side effects of 1. Rapid administration may cause HTN,

2-PAM? tachycardia, laryngospasm, muscle
rigidity, and transient neuromuscular
blockade.
2. Use in myasthenic patients may
precipitate a crisis.
Is 2-PAM indicated for No. AChE poisoned by carbamates does

carbamate poisoning? not undergo aging; however, it is reason-
able to consider administration of prali-
doxime to a patient presenting with
cholinergic crisis of unknown etiology.
PROPOFOL
What is propofol? A sedative-hypnotic agent
What are the effects of Amnesia and sedation, but not analgesia
propofol?
How is it administered? As an emulsion, due to the fact that it is

an oil at room temperature
Where does propofol act? Activates the chloride channel at the

GABAA receptor and antagonizes the
NMDA receptor
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Where is propofol In the liver by cytochrome P450

metabolized?
How is propofol used in the As a sedative agent to induce/maintain

toxicologic patient? anesthesia, as an anticonvulsant, and
secondary to its activity at the GABA
receptor, it may be beneficial in ethanol
withdrawal
In what patient populations 1. Patients 3 yrs old

is propofol use 2. Hyperlipidemic states
contraindicated? 3. Patients with hypersensitivity to
soybeans or eggs
What is the main risk of Over-sedation

propofol excess?
What signals over- Hypoventilation, hypoxia, hypotension

sedation with propofol in
the conscious sedation
patient?
When should a lower With concomitant use of

dose of propofol be used benzodiazepines, opiates, or other CNS
to prevent over-sedation? depressants
How long does it take for 2 min

propofol to wear off?
What is propofol infusion Mostly seen in children after long-term

syndrome? propofol infusion (48 hrs at 5 mg/kg/h),
it consists of heart failure, rhabdomyolysis,
severe metabolic acidosis, and renal
failure.
What do you want to avoid Rapid bolus doses (higher risk of adverse
when giving propofol to the reactions)
elderly?
What are other adverse Pancreatitis, discolored (green)

effects of propofol use? urine, metabolic acidosis,
hyperlipidemia, seizures, burning at
IV site, cardiac conduction
disturbances, bronchospasm, acute
renal failure
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PROPRANOLOL
What is the mechanism of Competitive blockade of beta 1- and

action of propranolol? beta 2-adrenergic receptors (i.e., non-
selective beta-blocker)
How is propranolol typically To control the effects of excessive beta-

used in toxicology? adrenergic stimulation
\
What are some specific 1. Methylxanthine-induced dysrhythmias
indications for propranolol (theoretical)
in toxicology? 2. Thyroid hormone-induced
tachycardia and dysrhythmias
– ↓ HR and prevents dysrhythmias,
also blocks peripheral conversion of
T4 → T3
3. Halogenated hydrocarbon-induced
myocardial sensitization and subse-
quent dysrhythmias
How does propranolol treat Methylxanthines activate beta 1- and

methylxanthine-induced beta 2-adrenergic receptors, resulting in
hypotension? tachycardia and peripheral vasodilation.
Beta 1-adrenergic blockade ↓ HR →
improved ventricular filling during
diastole. Beta 2-adrenergic blockade
prevents peripheral vasodilation. This is
theoretical, as definitive evidence is
lacking.
In what situations should 1. Comorbid asthma/other respiratory

propranolol be used with diseases – beta 2-adrenergic blockade
extreme caution? can cause bronchoconstriction
2. CHF – cardiodepressant effects can
worsen heart failure
3. Ethanol intoxication – can disguise
tremors and tachycardia resulting
from alcoholic hypoglycemia
What are the adverse effects 1. Bradycardia, hypotension, CHF

of propranolol therapy? 2. Precipitation of bronchospasm in
susceptible individuals
3. Induction of unopposed alpha-
adrenergic stimulation with subse-
quent HTN in patients poisoned with
sympathomimetics
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Should propranolol be No. Propranolol blocks only beta-

given to patients with adrenergic receptors. Unopposed alpha-
sympathomimetic-induced adrenergic effects may result in
hypertension? worsening HTN.
What is the typical IV dose Adults – 0.5 to 3 mg

of propranolol? Children – 0.01 to 0.1 mg/kg (max 1 mg)
PROTAMINE
What is the primary Heparin reversal

indication for protamine?
From what is protamine Salmon sperm/testes

derived?
How is protamine IV
administered?
What is the mechanism of Once hydrolyzed, basic (cationic) amino

action of protamine? acids of the protamine peptide form ionic
bonds with heparin, thereby neutralizing
it and causing dissociation of heparin and
antithrombin III.
Does protamine work on Partially, reduces ⬃60% of the anti-factor

LMWHs? Xa effect
What is the “rebound Heparin anticoagulation within 8 hrs after

effect”? receiving an apparently adequate dose of
protamine
What are the three types of 1. Systemic hypotension

adverse reactions possible 2. Anaphylactoid reactions
after protamine 3. Rare, but potentially fatal, pulmonary
administration? HTN
Why is protamine To prevent rate-related hypotension and

administered slowly? hypersensitivity reactions. Whenever ad-
ministering protamine, have all equip-
ment and medications to treat an acute
allergic reaction readily available.
Pretreatment with what Indomethacin

drug can limit the adverse
hemodynamic affects?
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What are the risk factors for 1. Prior exposure to protamine

an adverse reaction to 2. Vasectomy/infertile male
protamine? 3. Allergy to fish
4. Use of NPH insulin
5. Any prior medication allergy
6. Rapid infusion rate
Upon what parameter is the Amount of heparin remaining in the

dose of protamine based? body, based on dose received and time
since administration. One mg of
protamine will bind 100 U of
unfractionated heparin. For overdoses
involving an unknown amount of
heparin, 25 to 50 mg may be given
slowly over 15 min. PTT should be
monitored for up to 8 hrs to determine
the need for additional dosing.
What doses should be given 1. 0 to 30 min – 1 to 1.5 mg/100 U

0 to 30 min after heparin heparin
administration? 30 to 60 min 2. 30 to 60 min – 0.5 to 0.75 mg/100 U
after? 2 hrs after? heparin
3. 2 hrs – 0.25 to 0.375 mg/100 U
heparin
PRUSSIAN BLUE
How is Prussian blue PO

administered?
What is Prussian blue? A crystal lattice of iron and cyanide, ini-

tially synthesized as a pigment in 1704
What are its indications? 1. Thallium toxicity

2. Radiocesium exposure (i.e., “dirty
bombs”)
What is the mechanism of Potassium ions are typically bound in

action of Prussian blue? the lattice upon administration.
Large univalent cations (e.g., thallium,
cesium) are preferentially bound,
becoming trapped within the crystal
lattice. This interrupts enterohepatic
and entero-enteric recirculation of
these toxins and enhances their
elimination.
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What physiologic state may Ileus. Consider promotility agents.

hinder Prussian blue’s
effectiveness?
What are the common side Hypokalemia and constipation. It is

effects of Prussian blue recommended that Prussian blue be dis-
administration? solved in 50 mL of 15% mannitol to act
as a cathartic.
How is Prussian blue dosed? 1. Adult – 3 g q8 hrs

2. Children (ages 2 to 12) – 1 g q8 hrs
What will turn blue Feces, sweat, tears

following administration?
Is cyanide poisoning a No. Cyanide release is minimal.

concern after Prussian blue
administration?
PYRIDOXINE (VITAMIN B6)
What is pyridoxine? 1 of 8 water-soluble B vitamins
What are the toxicologic 1. Seizures induced by hydrazine toxicity

indications for pyridoxine? (i.e., hydrazine, monomethylhy-
drazine, gyromitrin, INH), cycloserine
toxicity and theophylline toxicity
2. Ethylene glycol toxicity – drives
glyoxylic acid (toxic) → glycine
(nontoxic)
3. May help dyskinesias caused by
dopamine agonists (e.g., L-dopa)
How does pyridoxine help to Administration of pyridoxine overcomes

treat hydrazine-induced the competitive inhibition of pyridoxine
seizures? phosphokinase by hydrazine, allowing for
the production of GABA.
What are the doses of 1. INH toxicity – 1 g IV per g INH (give

pyridoxine for the above 5 g initially if INH amount unknown),
clinical indications? rate 1 g/min
2. Monomethylhydrazine toxicity –
25 mg/kg IV
3. Ethylene glycol toxicity – 50 mg
IV/IM q6 hrs until resolution
4. Cycloserine poisoning – 300 mg/day
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Which type of mushroom Gyromitra esculenta mushrooms

contains the toxin contain the toxin gyromitrin
monomethylhydrazine? (monomethylhydrazine).
What is the one possible Peripheral neuropathy (inhibits myelin

side effect of chronic production at the dorsal root ganglion).
pyridoxine This has been reported in patients taking
supplementation? as little as 200 mg daily 1 month.
How does this neuropathy Poor coordination and ↓ light touch/

present? temperature/vibratory sensation
SILIBININ OR MILK THISTLE (SILYBUM MARIANUM)
What is milk thistle? A plant with active flavonoids
What is the functional Silymarin

extract of milk thistle?
What is the active Silibinin

component of silymarin?
For what natural toxic Mushroom poisoning with Amanita

ingestion is milk thistle phalloides. Although no studies defini-
advocated as a treatment? tively document its efficacy following
Amanita mushroom poisoning, silymarin
has few side effects and is considered a
beneficial therapy.
Why is milk thistle sold in Considered to provide liver protection

herbal stores?
What is the mechanism of Appears to block uptake of amatoxin into

silibinin? the hepatocyte. It also may increase ribo-
somal protein synthesis and works as an
antioxidant.
How is silymarin typically 20 to 50 mg/kg day IV, optimally started

dosed? within 48 hrs of mushroom exposure
Are there any adverse Nausea/GI upset. Allergic reactions may

effects of silymarin? occur in ragweed-sensitive patients.
Has milk thistle been FDA- No

approved for these
treatments?
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SUCCIMER (DMSA)
What is DMSA? Dimercaptosuccinic acid, a water-soluble

analog of BAL
How is DMSA administered? PO
What is the dosing 350 mg/m2 or 10 mg/kg PO q8 hrs

schedule? 5 days, then q12 hrs 2 wks
What are the advantages of 1. PO route available

succimer over CaNa2EDTA 2. Better tolerated, particularly by
or BAL? children
3. Fewer contraindications
For what indications is 1. Primary use is for lead poisoning

DMSA currently used? without encephalopathy
2. Investigational for arsenic/mercury
toxicity
At what serum lead levels 45 g/dL. Below this level there is no
should chelation be initiated evidence of efficacy, and it may be
in children? harmful.
What is the mechanism of As an analogue of BAL, it chelates heavy

action of DMSA? metal ions to form an excretable complex.
What are the adverse effects Rare reports of nausea, vomiting,

of DMSA? diarrhea, transient transaminitis, and
dermatitis. Also, there is minimal chela-
tion of essential metals, such as zinc and
copper.
How is DMSA eliminated? 1. Primarily excreted in urine as an

unchanged drug or as disulfides
2. Bile
Should DMSA be used in No. DMSA is only indicated for PO use.

severe lead intoxication? BAL is the preferred chelator in the
encephalopathic patient.
THIAMINE (VITAMIN B1)
What is thiamine? 1 of 8 water-soluble B vitamins that

serves as an essential cofactor for carbo-
hydrate metabolism, often as thiamine
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pyrophosphate (TPP) during oxidative

decarboxylation reactions
What are the complications 1. Beriberi (dry or wet)

of thiamine deficiency? 2. Infantile beriberi (if breastfeeding
mother is thiamine-deficient)
3. Wernicke-Korsakoff syndrome
What are some risk factors Alcoholism, anorexia nervosa, hyperemesis

for thiamine deficiency? gravidarum, loop diuretics, gastric bypass
For what indications is 1. Beriberi (dry and wet)

thiamine used? 2. Treatment and prevention of
Wernicke’s encephalopathy
3. Ethylene glycol poisoning
When is thiamine used When administering glucose in any

empirically? alcoholic patient with AMS. This
ostensibly prevents worsening of
Wernicke-Korsakoff syndrome by
bolstering thiamine levels before glucose
metabolism depletes them. Thiamine
administration should also be considered
in any patient presenting with AMS or
with coma, especially if at risk for
malnutrition.
When treating a patient with No. Do not withhold dextrose while

AMS, should dextrose be awaiting delivery of thiamine. Thiamine
withheld until thiamine is should be administered with glucose or
administered? soon after glucose administration if
thiamine deficiency is suspected.
What is the classic clinical 1. AMS

triad for Wernicke’s 2. Ophthalmoplegia
encephalopathy? 3. Ataxia
How often is this triad seen? 10% to 15% of cases
What diagnostic criteria Consider the diagnosis in a patient with

should be used? two of the following four conditions:
1. Nutritional deficiency
2. Ocular findings (often nystagmus)
3. Ataxia
4. AMS
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What is the dose of 100 mg IV

thiamine?
How soon after Symptoms may begin to improve within

administration of thiamine hours to days; however, many patients
do symptoms begin to have persistent deficits.
improve?
What is Korsakoff’s A syndrome characterized by

syndrome? anterograde amnesia and confabulation,
it usually becomes evident after
treatment of Wernicke’s encepholapa-
thy. It can be prevented by early
treatment of Wernicke’s, but once it
develops, thiamine administration may
have little to no effect.
What is the main Acute pulmonary edema due to rapid

complication of giving increase in afterload
thiamine to a patient with
wet beriberi?
By what mechanism does Thiamine functions as a cofactor in the

thiamine reduce toxicity conversion of glyoxylic acid to alpha-
after an ethylene glycol hydroxy-beta-ketoadipate (a nontoxic
ingestion? metabolite).
VASOPRESSORS
What is the mechanism of Direct stimulation of alpha 1-adrenergic

action of phenylephrine? receptors → vasoconstriction, ↑ PVR and
↑ BP
What are the toxicologic Hypotension secondary to an overdose of

indications for vasodilatory agents (e.g., alpha-1 antago-
phenylephrine? nists, dihydropyridine CCBs)
What is the typical dose of 0.5 g/kg/min IV infusion, titrate up to 5

phenylephrine? to 8 g/kg/min IV, as needed to improve
BP
What are the positive Stimulation of peripheral alpha-adrenergic

hemodynamic effects of receptors → vasoconstriction and
phenylephrine? corresponding ↑ SBP and DBP
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What are the negative As there is no effect on beta-1 receptors,

hemodynamic effects of phenylephrine does not ↑ chronotropy or
phenylephrine? inotropy; therefore, the vasoconstriction
may ↓ cardiac output and/or cause reflex
bradycardia.
Why would administration CAs are alpha-1 antagonists, adding to

of phenylephrine be their ability to induce hypotension. In
favored for increasing BP addition, CAs are anticholinergic agents,
in a CA-toxic patient who is causing tachycardia. Phenylephrine will
hypotensive despite counteract the alpha-1 blockade without
adequate fluid worsening the tachycardia.
resuscitation and sodium
bicarbonate?
What is the mechanism of Direct alpha- and beta 1-adrenergic

action of norepinephrine? receptor agonism, with a relatively
stronger effect on the alpha receptor
How is norepinephrine IV (large bore)

administered?
Why should norepinephrine Extravasation may lead to tissue necrosis

be infused into large veins?
What is the effect of Peripheral vasoconstriction and ↑ venous

norepinephrine on the heart return (preload). Weak beta-1 receptor
and vasculature? effects → ↑ chronotropy and inotropy
with coronary artery dilation.
What are the indications for Hypotension refractory to other

norepinephrine? conventional modalities (i.e., glucagon,
calcium, hyperinsulinemia-euglycemia
therapy) secondary to toxicity from
cardio-depressant or vasodilatory drugs
(e.g., alpha-blockers, beta-blockers,
CCBs)
How much norepinephrine Begin with 1 g/min, then titrate to

should be administered effect. Typical dose is 8 to 20 g/min.
when treating a patient
experiencing severe
hypotension secondary to
drug intoxication?
13486_CH09.qxd 10/30/08 7:26 AM Page 523
What is the pediatric dosing Begin with 0.05 to 0.1 g/kg/min, then
for hypotension and shock? titrate to hemodynamic improvement
(max 1 to 2 g/kg/min).
What are some reported 1. HTN

side effects of 2. Tachydysrhythmias
norepinephrine? 3. Nausea and vomiting
4. Headache, anxiety, tremor
5. End-organ ischemia
6. Extravasational ischemia/necrosis
7. Possible allergic/anaphylactic reactions
in patients sensitive to sulfite
preservatives
How is epinephrine IV, IM, SQ, ET, inhaled

administered?
What are the toxicologic 1. Hypotension refractory to other

indications for epinephrine? conventional modalities (i.e., glucagon,
calcium, hyperinsulinemia-euglycemia
therapy) secondary to toxicity from
cardio-depressant drugs (e.g., CCBs,
beta-blockers)
2. Treatment of anaphylactic/severe ana-
phylactoid reactions
3. Cardiac arrest
How is epinephrine Largely by COMT and MAO in the liver,

metabolized? then excreted renally
What is the half-life of ⬃2 min

epinephrine?
What is the mechanism of 1. Direct stimulation of alpha 1-, beta 1-

action of epinephrine? and beta 2-adrenergic receptors → ↑
cAMP
2. Stabilizes mast cells and prevents
histamine release
What is the typical dose of 1. Allergic reaction/anaphylaxis – typical

epinephrine? adult dose is 0.3 to 0.5 mg IM/SQ
(0.01 mg/kg in children, max 0.5 mg)
2. Hypotension – initially 1 g/min
(0.01 g/kg/min in children), then
titrate to effect
13486_CH09.qxd 10/30/08 7:26 AM Page 524
What are the positive 1. Beta 1-adrenergic agonism → ↑

hemodynamic effects of myocardial inotropy and chronotropy
epinephrine? → ↑ cardiac output.
2. Peripheral alpha-adrenergic receptor
agonism → vasoconstriction with cor-
responding ↑ SBP and DBP.
What are the negative 1. Induces irritability of the autonomic

hemodynamic effects of conduction system and increases the
epinephrine? incidence of dysrhythmias
2. HTN with subsequent ICH, acute
pulmonary edema, and ACS
What laboratory abnor- Hyperglycemia, hypokalemia, hypophos-

malities are expected during phatemia, and leukocytosis
treatment with epinephrine?
How does a patient’s pH Acidemia ↓ CV effects

affect the hemodynamic
impact of epinephrine?
What adverse reactions can Anxiety, headache, tachycardia,

occur with epinephrine palpitations, tremor
administration?
What is dopamine? An endogenous catecholamine that func-

tions as an adrenergic receptor agonist
and neurotransmitter. It is produced syn-
thetically and may be given IV for its
vasoconstrictive and inotropic properties.
How can dopamine be used 1. Hypotension that is refractory to fluid

in the toxicologic patient? resuscitation and is due to ↓ cardiac
output or peripheral vasodilation
2. Bradycardia refractory to
atropine/pacing
Where is dopamine Liver, kidneys, and plasma by MAO and

metabolized? COMT
What is the half-life of ⬃2 min

dopamine?
What is the mechanism of Dose-dependent. It specifically stimu-

action of dopamine? lates alpha-adrenergic, beta 1-adrenergic,
13486_CH09.qxd 10/30/08 7:26 AM Page 525
and dopaminergic receptors. Beta 1-

adrenergic receptors are favored at low
doses, while alpha-adrenergic effects pre-
dominate at higher doses.
What is one drawback to the Dopamine exerts much of its vasoconstric-

use of dopamine? tive effects indirectly (by inducing norep-
inephrine release); therefore, outcome
may be variable in the toxicologic patient.
Direct-acting agents (i.e., norepineph-
rine, phenylephrine, epinephrine) are
generally preferred.
What dose can achieve Low (0.5 to 2 g/kg/min) – dopaminergic

therapeutic effects? effects (i.e., renal and mesenteric
vasodilation)
Moderate (2 to 10 g/kg/min) – beta
effects (i.e., ↑ inotropy and chronotropy)
High (10 to 20 g/kg/min) – alpha effects
(i.e., vasoconstriction)
When does dopamine reach Onset in 5 min, duration up to 10 min

therapeutic effect?
How is dopamine IV infusion

administered?
VITAMIN K1 (PHYTONADIONE)
What is vitamin K? A fat-soluble vitamin found in certain

types of plants and produced in the intes-
tine by bacteria. Vitamin K is essential to
life.
How many forms of vitamin 3 (2 natural, 1 synthetic)

K are there?
What are the forms? 1. K1 (phylloquinone) – plants, cow’s

milk, soy oil
2. K2 (menaquinone) – synthesized by
intestinal bacteria
3. K3 (menadione) – synthetic
In what food sources is Leafy vegetables (e.g., spinach, celery),

vitamin K most abundant? cheese, cow’s milk, liver
13486_CH09.qxd 10/30/08 7:26 AM Page 526
For synthesis of what specific II, VII, IX, X

coagulation factors does the
liver require vitamin K?
Can vitamin K be used as an 1. Warfarin toxicity

antidote for any toxic 2. Ingestion of anticoagulant
ingestion? (superwarfarin) rodenticides (i.e.,
hydroxycoumarins and indandiones)
Why is vitamin K effective as Both warfarin and the superfarwarins

an antidote? cause coagulopathy by inhibiting the
enzyme vitamin K1 reductase, which
reduces vitamin K1 2,3-epoxide to
vitamin K1 hydroxyquinone. The latter is
used in coagulation factors (II, VII, IX,
X). Vitamin K supplementation supplies
the active cofactor for the generation of
coagulation factor synthesis.
Which form of vitamin K Vitamin K3

will not work as an antidote?
Should vitamin K be No. Following an acute overdose, do not

administered to suspected give vitamin K prophylactically, as this
warfarin or superwarfarin may mask a clinically significant inges-
rodenticide overdoses? tion. Follow PT/INR in 48 hrs to evaluate
for developing toxicity. Initiate treatment
only when PT is prolonged or the patient
is actively bleeding.
By what routes can vitamin PO, IV, IM (not recommended due to

K be administered? potential for hematoma)
What is the potential IV vitamin K may cause anaphylactoid

complication of IV vitamin K reactions
therapy?
What is the goal of vitamin Restore the PT to normal in the case of

K therapy? rodenticides and to therapeutic range in
the case of patients receiving anticoagu-
lant therapy
How long will it take for 8 to 24 hrs. For control of acute hemor-
vitamin K to exert its full rhage, FFP 10 to 15 mL/kg may be given
effect? to restore coagulation factors.
13486_CH09.qxd 10/30/08 7:26 AM Page 527
OTHER
What is metoclopramide? A promotility and antiemetic agent used

to treat toxin-induced nausea and prevent
ileus
What is the mechanism of 1. Antagonism at dopamine (D2) recep-

action of metoclopramide? tors in the CTZ (responsible for
nausea/vomiting)
2. ↑ GI motility (including contractions
of the small intestine) by stimulating
5HT4 receptors
What are the typical side Sedation and EPS

effects of metoclopramide?
How is metoclopramide Adults – 10 to 20 mg IM/IV

typically dosed? Children – 0.01 mg/kg/dose in children
(max 20 mg)
What is mannitol? An osmotic diuretic that has been used to

prevent renal dysfunction in patients with
rhabdomyolysis
What are the potential 1. Treatment of neurologic dysfunction

toxicologic uses of mannitol? in ciguatera poisoning
2. Diluent for the delivery of Prussian
blue (to act as a cathartic)
3. Prevention of renal dysfunction in
patients with toxin-induced
rhabdomyolysis
4. Treatment of ↑ ICP in patients with
drug-induced or idiopathic intracranial
HTN (pseudotumor cerebri)
What are the adverse effects 1. Fluid overload (due to rapid expansion
of mannitol? of intravascular volume)
2. Electrolyte abnormalities (e.g.,
hyponatremia) due to movement of
water into the extracellular space, as
well as the creation of a hyperosmolar
state
3. Renal failure with high doses (thought
to be caused by renal vasoconstriction
and ↓ renal perfusion)
13486_CH09.qxd 10/30/08 7:26 AM Page 528
What is apomorphine? A morphine derivative that was

previously used as an emetic agent but is
no longer used for this purpose in humans
Why was apomorphine use The CNS depression caused by this agent
abandoned by toxicologists? significantly increased the risk of
aspiration following its desired effect of
inducing emesis.
In what toxicologic GI decontamination following toxic

situations was apomorphine ingestions. It was preferred over syrup of
previously indicated? ipecac in agitated patients, as apomor-
phine can be given SQ.
What are contraindications 1. Concurrent use of serotonin (5HT3)

to apomorphine receptor antagonists (e.g.,
administration? ondansetron)
2. Known hypersensitivity reaction to
apomorphine or the metabisulfite
preservative
What is the mechanism of Dopamine (D2) receptor agonism in the

action of apomorphine? CTZ
What are the adverse effects CNS depression, injection site irritation,
seen with apomorphine headache, priapism, orthostatic
administration? hypotension, QT prolongation, nausea,
and vomiting
What is methocarbamol? Carbamate derivative of guaifenesin
What formulations are IM, IV, PO

available for
methocarbamol?
What is the action of Skeletal muscle relaxation through CNS

methocarbamol? depression
What are the toxicologic Adjunctive therapy for muscle spasms

uses of methocarbamol? induced by black widow spider
envenomation, tetanus, and strychnine
poisoning
What is the half-life of 1 to 2 hrs

methocarbamol?
13486_CH09.qxd 10/30/08 7:26 AM Page 529
Where is methocarbamol Liver

metabolized?
What is the IV dosage for Typical adult dosing is 1 to 2 g (15 mg/kg

adults? in children) IV over 5 min, followed by
continuous infusion of 0.5 g (10 mg/kg in
children) over 4 hrs. This infusion may be
repeated q6 hrs. Recommended daily
doses should not exceed 3 g.
In what patient population Those with hepatic or renal impairment,

should methocarbamol be seizure disorder, or history of myasthenia
used with caution? gravis
What are the side effects of Sedation, hypotension, nausea, vomiting,

methocarbamol possibly allergic reaction
administration?
What is sodium polystyrene A cation-exchange resin typically used in

sulfonate (SPS)? the treatment of hyperkalemia
How can SPS be used as an SPS has been shown to bind lithium
antidote? and enhance its elimination in animal
studies. It may be useful in lithium
poisoning, especially if given PO soon
after exposure.
What electrolyte must be Potassium, as SPS may induce

monitored after SPS hypokalemia
administration?
What are IV fat emulsions Also known as intralipid, it is a mixture of

(IFE)? triglycerides, phospholipids, and choline
that has been studied as an antidote for
certain drug intoxications.
How is IFE used in While still under investigation, studies

toxicology? have shown efficacy for treating bupiva-
caine, verapamil, and clomipramine
toxicity in animal models.
What is the proposed Proposed mechanisms include acting as a

mechanism of action of IFE? lipid sink for fat-soluble drugs, providing
a substrate for myocardial energy, and
modulating ion channels.
13486_CH09.qxd 10/30/08 7:26 AM Page 530
What are the potential Fat emboli syndrome, increased absorp-

limitations of IFE therapy? tion of the toxin from the GI tract,
interaction with other antidotes, egg/soy
allergies, liver disease, disorders of lipid
metabolism
What is diazoxide? A thiazide which has no diuretic activity

but acts as a vasodilator
Diazoxide has been used as Sulfonylureas

an antidote for poisoning
with which type of
medication?
What is the mechanism of Opens ATP-sensitive potassium channels

action of diazoxide? on pancreatic beta cells → hyperpolari-
zation → ↓ insulin release. This directly
interferes with the sulfonylurea mecha-
nism of action, which is to close these
potassium channels.
What are the adverse Hypotension, tachycardia, and sodium

reactions to diazoxide and water retention. For this reason,
administration? diazoxide is only used if the patient’s
hypoglycemia is refractory to IV glucose
and if octreotide is unavailable.
For what poisoning is Nicotinamide (vitamin B3) has been used

nicotinamide indicated? to prevent toxicity due to Vacor (PNU)
ingestion; however, a parenteral form of
nicotinamide is no longer available in the
U.S. and now must be substituted with
niacin. Niacin is less effective and may
cause vasodilation and impaired glucose
tolerance. As both of these can exacer-
bate the effects of Vacor poisoning,
substitution with niacin is controversial.
13486_CH10.qxd 10/31/08 12:25 PM Page 531
Chapter 10 Visual Diagnosis in

Medical Toxicology
A 4-year-old boy is found Ricin

chewing on the seed
pictured. What toxin is he at
risk of absorbing?
The snake pictured bit a Copperhead (Agkistrodon contortrix)

15-year-old girl on the foot. induced tissue necrosis
What complication of snake
envenomation is the patient
most at risk for contracting?
531
13486_CH10.qxd 10/31/08 12:25 PM Page 532
A 22-year-old man is on a Scopolamine

cruise and touches his eye
after placing a patch on his
skin for motion sickness.
What agent was contained
within the patch?
A 35-year-old Columbian As a “body packer.” These packets are

female is caught in the double-wrapped condoms filled with co-
airline restroom with this caine that are then swallowed by the
bag in her possession. How “body packer.”
would drug traffickers refer
to her?
13486_CH10.qxd 10/31/08 12:25 PM Page 533
Chapter 10 / Visual Diagnosis in Medical Toxicology 533
The plant pictured contains Podophylline, found within the mayapple

what toxin? plant (Podophyllum peltatum)
A young boy is found Lead

chewing on paint chips in his
100-year-old home. What
toxin, evident on this x-ray, is
he at risk of absorbing?
13486_CH10.qxd 10/31/08 12:25 PM Page 534
After eating the berries from Leukocytosis, from the pokeberry plant
the plant pictured, what (Phytolacca americana)
abnormality may be seen on
a CBC?
Following ingestion of this Liver dysfunction from Amanita

mushroom, what organ phalloides
dysfunction may occur?
The woman pictured noted Angiotensin-converting enzyme inhibitors

that her lower lip was (ACE inhibitors), causing angioedema
swollen. What group of
antihypertensive agents is
responsible?
13486_CH10.qxd 10/31/08 12:25 PM Page 535
What is the name for this Mees’ lines

nail finding induced by
arsenic poisoning?
For what purpose is the tent Decontamination

visualized in the picture
utilized?
13486_CH10.qxd 10/31/08 12:25 PM Page 536
What is the name of this False hellebore (Veratrum viride)

poisonous plant?
A teenager was found Lysergic acid amide (a relative of LSD),

chewing and ingesting the from Hawaiian baby woodrose seeds
seeds pictured. What (Argyreia nervosa)
substance was he attempting
to derive from these seeds?
This creature uses what Nematocyst from jellyfish (class Scypho-

envenomation apparatus to zoa of the phylum Cnidaria)
deliver its marine toxin?
13486_CH10.qxd 10/31/08 12:25 PM Page 537
What is the name given to Bezoar

the radiopacity visualized in
the stomach?
A mechanic’s high-pressure Emergent surgical debridement due to

grease gun discharges and the deep penetration of grease through
strikes his skin in the area his tissues
noted. What is the correct
management of this injury?
What is the name of the Brown recluse (Loxosceles reclusa)

spider pictured?
13486_CH10.qxd 10/31/08 12:25 PM Page 538
After ingestion of the lead Endoscopic removal

foreign body pictured here,
what is the next appropriate
step in management?
A 53-year-old male is found Carbon monoxide with bilateral lesions of

comatose in an unventilated the globus pallidus
home with a running
gasoline-powered generator.
A head CT is performed, and
the results are pictured.
What toxin is most likely
responsible?
13486_CH10.qxd 10/31/08 12:25 PM Page 539
The spider in the picture Muscle spasms due to envenomation

bites a college student. What by this black widow spider
muscle complaint may he (Latrodectus spp.)
develop?
A 23-year-old male overdoses Rhabdomyolysis, with this case manifest-

on phenobarbital. He is ing pressure necrosis of the skin
found comatose with the
findings pictured. What
complication is he at risk for
developing?
What is the name of the Fly agaric mushroom (Amanita muscaria)

mushroom pictured?
13486_CH10.qxd 10/31/08 12:25 PM Page 540
A young child who has been Acute allergic reaction

taking amoxicillin for the
past 5 days is noted to
develop the findings
pictured. What is this
reaction?
A child begins to scream Buck moth caterpillar (Hemileuca maia)

after picking up the insect
noted. He develops pustules
at the sites of contact with
his skin. What is the name of
this caterpillar?
A young child swallows lamp Aspiration pneumonia

oil and presents with
dyspnea and cough. What is
the etiology of his findings?
13486_CH10.qxd 10/31/08 12:25 PM Page 541
A pet store owner is stung by Warm water immersion

his pet lionfish. He has
excruciating pain in his hand.
What initial therapy should
be performed?
The fish pictured is eaten by Tetrodotoxin, from the pufferfish (family

a local fisherman. He Tetradontidae)
develops rapid-onset
ascending paralysis. What
toxin is responsible?
13486_CH10.qxd 10/31/08 12:25 PM Page 542
The child pictured recently Stevens-Johnson syndrome

had their phenytoin dose
increased and subsequently
developed a progressive
rash. What is the name of the
condition pictured?
What class of Cyclic antidepressants with the ECG

antidepressants may be manifesting tachycardia secondary to an-
responsible for the ECG ticholinergic effects and QRS prolonga-
findings noted in the tion secondary to cardiac sodium channel
picture? blockade
13486_CH10.qxd 10/31/08 12:25 PM Page 543
The marine animal pictured In the tail of the stingray (family

has an envenomation Dasyatidae)
apparatus located where?
What illicit drug is pictured? Ecstasy (methylenedioxymetham-

phetamine)
A 34-year-old is found with Endocarditis

this paraphernalia in his
pocket and presents with
altered mental status, a new
murmur, and fever. What
condition must be ruled out
in this patient?
13486_CH10.qxd 10/31/08 12:25 PM Page 544
Chronic use of what laxative Senna, causing finger clubbing

causes the condition
pictured?
What are the findings noted “Track marks” from IV drug use
in the picture?
The markedly radiopaque Lead

metaphyseal lines seen in
this radiograph are caused
by exposure to which heavy
metal?
13486_CH10.qxd 10/31/08 12:25 PM Page 545
A patient’s arm is bitten by a Dry bite (occurs in 10% to 20% of snake

poisonous snake. Besides the bites), meaning that no venom is
two puncture wounds noted, introduced
no pain or edema develops
at the site. This is known as
what type of bite?
The poisonous plant pictured Poison hemlock (Conium maculatum)

smells like a carrot. What is
the name of this plant?
A young female presents Nicotine toxicity due to “green tobacco

with nausea, vomiting, sickness”
tachycardia, and
hypertension after picking
this plant without gloves.
What toxicity is she
manifesting?
13486_CH10.qxd 10/31/08 12:25 PM Page 546
A poisonous snake bites a Ice, tourniquet, suction, excision, incision

child’s finger. What first aid
procedures should be
avoided?
An herbalist ingests the plant Digoxin immune Fab, for toxic ingestion
pictured and presents with of foxglove (Digitalis purpurea)
hypotension, bradycardia,
and hyperkalemia. What is
the appropriate antidote?
13486_CH10.qxd 10/31/08 12:25 PM Page 547
What syndrome would Anticholinergic toxidrome, from jimson-

develop from ingestion of weed (Datura stramonium) toxicity
the seeds of the plant
pictured?
Would hypoglycemia or Hyperglycemia, due to CCB’s ability to

hyperglycemia be expected block peripheral insulin receptors
in a calcium channel blocker
(CCB) poisoned patient
presenting with the ECG
pictured?
13486_CH10.qxd 10/31/08 12:25 PM Page 548
The plant pictured causes Type 4 allergic reaction, by poison ivy

what type of allergic (Toxicodendron radicans)
reaction?
Following a propoxyphene Sodium bicarbonate

overdose, this QRS complex
is noted on the ECG. What is
the treatment of choice for
this finding?
13486_CH10.qxd 10/31/08 12:25 PM Page 549
A cocaine overdose victim Hyperkalemia with characteristic changes

presents to the ED. His consisting of peaked T waves, QRS pro-
initial rhythm strip is shown. longation, and loss of P waves
What electrolyte abnormality
may be accounting for the
finding(s) noted?
A child bites the seeds of the Calcium oxalate crystals, from the Jack-
plant pictured and develops in-the-pulpit plant (Arisaema triphyllum)
immediate pain and swelling
of his lips. What is the cause
of these clinical findings?
A 22-year-old female Opioid toxicity, causing miosis and

presents with the findings dysconjugate gaze (note the asymmetric
pictured, along with CNS pupillary light reflex)
and respiratory depression,
after injecting illicit drugs.
What is the most likely
etiology?
13486_CH10.qxd 10/31/08 12:25 PM Page 550
What is the name of the “Skin popping,” the subcutaneous injec-

findings noted in this picture tion of a drug, causing abscesses
of a drug abuser?
What is the most likely Cardiac sodium channel, which leads to

electrolyte channel inhibited QRS prolongation
in an overdose patient
presenting with the rhythm
strip pictured?
13486_ABBREV.qxd 10/31/08 12:17 PM Page 551
= Abbreviations
5-HT 5-Hydroxytryptamine (serotonin)
ABG Arterial blood gas
ACh Acetylcholine
AChE Acetylcholinesterase
ACS Acute coronary syndrome
ALT Alanine aminotransferase
AMI Acute myocardial infarction
AMS Altered mental status
APAP N-acetyl-p-aminophenol (acetaminophen)
aPTT Activated partial thromboplastin time
ARDS Acute (adult) respiratory distress syndrome
ASA Acetylsalicylic acid (aspirin)
AST Aspartate aminotransferase
ATP Adenosine triphosphate
AV Atrioventricular
BAL British anti-Lewisite
BP Blood pressure
BUN Blood urea nitrogen
CA Cyclic antidepressant
cAMP Cyclic adenosine monophosphate
CBC Complete blood count
CDC Centers for Disease Control and Prevention
cGMP Cyclic guanosine monophosphate
CHF Congestive heart failure
CNS Central nervous system
CO Carbon monoxide
COMT Catechol-O-methyltransferase
COPD Chronic obstructive pulmonary disease
CPK Creatine phosphokinase
CSF Cerebrospinal fluid
CTZ Chemoreceptor trigger zone
CV Cardiovascular
CVA Cerebrovascular accident
CXR Chest x-ray
DBP Diastolic blood pressure
DIC Disseminated intravascular coagulation
DKA Diabetic ketoacidosis
DM Diabetes mellitus
ECG Electrocardiogram
551
552 Abbreviations
EEG Electroencephalogram
EPS Extrapyramidal symptoms
ET Endotracheal
FDA Food and Drug Administration
FFP Fresh frozen plasma
G6PD Glucose-6-phosphate dehydrogenase
GABA Gamma-aminobutyric acid
GI Gastrointestinal
GU Genitourinary
HDL High-density lipoprotein
Hgb Hemoglobin
HIV Human immunodeficiency virus
HMG-CoA 3-Hydroxy-3-methylglutaryl-coenzyme A
HTN Hypertension
IARC International Agency for Research on Cancer
ICH Intracranial hemorrhage
ICP Intracranial pressure
IM Intramuscular
INR International normalized ratio
IOP Intraocular pressure
IV Intravenous
LD50 Dose of a particular toxin which is lethal in 50% of the
tested population exposed
LFT Liver function test
LMWH Low-molecular-weight heparin
LSD Lysergic acid diethylamide
MAO Monoamine oxidase
MAOI Monoamine oxidase inhibitor
MRI Magnetic resonance imaging
NADH Nicotinamide adenine dinucleotide (reduced)
NADPH Nicotinamide adenine dinucleotide phosphate
(reduced)
NAPQI N-acetyl-p-benzoquinoneimine
NATO North Atlantic Treaty Organization
NG Nasogastric
NMDA N-methyl-D-aspartate
NMS Neuroleptic malignant syndrome
NSAID Nonsteroidal anti-inflammatory drug
OP Organophosphate
OTC Over-the-counter
PCP Phencyclidine
PNS Peripheral nervous system
PO Oral (Latin per os)
PPE Personal protective equipment
Abbreviations 553
PPV Positive pressure ventilation

PR Rectally (Latin per rectum)
PT Prothrombin time
PTT Partial thromboplastin time
PVC Polyvinyl chloride, premature ventricular contraction
RAD Right axis deviation
RBC Red blood cell
RFT Renal function test
RSI Rapid sequence induction
SA Sinoatrial
SBP Systolic blood pressure
SMFA Sodium monofluoroacetate
SQ Subcutaneous
SSRI Selective serotonin reuptake inhibitor
SVT Supraventricular tachycardia
TCA Tricarboxylic acid cycle (Krebs cycle, citric acid cycle)
UA Urine analysis
US United States
UV Ultraviolet
VF Ventricular fibrillation
VT Ventricular tachycardia
WBC White blood cell
WHO World Health Organization
WWI World War I
WWII World War II
13486_INDEX.qxd 10/31/08 3:31 PM Page 554
Index
A. phalloides, 404 ibotenic, 408–409

Abdominal pain, 51, 148, 286 ingestion, 155
Absolute lymphocyte count, 246 injuries from, 154
Acarbose, 87 lysergic, 345, 536
Acetaldehyde, 140 ocular, 155
Acetaminophen, 15t, 17–19 selenious, 301
acidosis and, 19 soluble oxalic, 229
definition of, 17–19 tissue damage caused by, 154
four hour treatment level, 19 valproic, 124–125
half-life of, 17 Acneiform eruptions, 168
labeling of, 17 Acrodynia, 294
liver and, 18 Actinomycin-D, 66
metabolite, 17 Activated charcoal, 13, 305, 463
plasma, 18 Acute allergic reaction, 541
poisoning, 18 Acute amphetamine intoxication, 133
toxicity, 17 Acute arsenic intoxication, 263–264
high risk for, 18 Acute arsenic poisoning, 264
Acetate, 140 Acute benzene poisoning, 164
Acetone, 214 Acute botulism, 382
Acetylcysteine, 444–446 Acute inhalation, 253
Acidic agents, 176 Acute lung injury, 249
Acidosis Acute nerve poisoning, 353
acetaminophen and, 19 Acute oral ricin poisoning, 357
elevated anion gap metabolic, 184 Acute pyrethrin, 329
high anion gap metabolic, 193, 232 Acute Radiation Syndrome (ARS), 245
lactic, 55, 84, 210 Acute renal failure, 179
metabolic, 112, 202, 207, 283 Acute toxicity, 159
non-anion gap, 253 Acute vesicant exposure, 362
Acids, 154–156. See also Hydrofluoric acid Adams-Stokes syndrome, 498
boric, 165–166 Adenosine blockade, 115
calcium disodium ethylenediaminete- ADHD. See Attention deficit
traacetic, 460–461 hyperactivity disorder
commons uses of, 154 Adipose tissue, 188
dichlorophenoxyacetic, 313 Adrenergic neuron terminals, 109
dimercaptosuccinic, 519 Aeromonas hydrophila, 468
DMPS, 470–471 Aerosol propellants, 181
domoic, 396 Aerosolized benzodiazepines, 345
environmental/industrial toxins, Aerosolized carbonaceous particulate
154–156 matter, 248
exposure, 176 Aflatoxins, 364, 414
folic, 479–480 Africanized honeybee (AHB), 378
folinic, 218 Agent 15, 356
glycolic, 193 Agent orange, 189, 314
glyoxylic, 193 Aging, 326, 351
554
13486_INDEX.qxd 10/31/08 3:31 PM Page 555
Index 555
AHB. See Africanized honeybee Ammonia, 156–158, 176

Airway management, 26 aqueous, 157
AKA. See Alcoholic ketoacidosis inhalation of, 157
Akathisia, 53, 485 Ammonium bifluoride, 197
Albuterol, 58 Amotivational syndrome, 147
Alcohol. See also Drugs Amoxapine, 33, 36
dehydrogenase, 139, 140, 195, 217 Amoxicillin, 29, 374
intoxication, 4, 140 Amphetamines, 132–133
rubbing, 214 Amphibians, 366–367
toxic, 5 Amphibole, 161
Alcoholic ketoacidosis (AKA), 140 Ampicillin, 29
Aldehyde dehydrogenase, 402 Amygdalin, 418
Alkali acid injuries, 154 Amyl nitrate pearls, 184, 465
Alkaline, 156 Anaerobic metabolism, 210
sodium, 190 Anaphylaxis, 436
thiazine dye, 500 Anemia, 256
Alkaloids, 379 aplastic, 507
anticholinergic, 415 functional, 225
pyrrolizidine, 430 hemolytic, 128
rauwolfia, 109–110 hypochromic, 256
vinea, poisoning, 431 megaloblastic, 103
Allergic reaction Anesthetics, 21–23
acute, 541 effect, 8
type 4, 549 local, 23–25
Alpha 1-adrenergic blockade, 54 Angina pectoris, 100
Alpha-adrenergic receptors, 72 Angioedema, 25, 26
Alpha-glucosidase, 3, 87 Angiotensin receptor blockers, 26–27
Alpha-latrotoxin, 368 Angiotensin-coverting enzyme inhibitors,
Alpha-naphthylthiourea (ANTU), 331 25–26, 534
Aluminum related angioedema, 26
emanation of, 256 Anhydrosis, 48
exposure, 256 Anion gap, 3–4
hydroxide, 186 metabolic acidosis, 105, 163, 184, 202
phosphide, 258 elevated, 184
toxicity, 256 high, 193, 232
Amanita negative, 158
mushroom, 445 poisoning testing, 3–4
phalloides, 534 Annual radiation dose limits, 247
Amantadine, 20–21 Antacids, 97
Amatoxin, 405 Anthracyclines, 66
Amblyomma americanum, 376 Anthrax spores, 364
Amblyopia, 50 Antibacterial agents, 27–30
American Academy of Clinical symptoms from, 27
Toxicology, 462 Antibiotics, 209, 374
American Revolutionary War, 416 Anticholinergics, 30–32
Aminoglycosides, 28, 383 alkaloids, 415
Aminophylline, 115 delirium, 510
Aminosteroids, 505 plants, 415–416
Amitriptyline, 33 toxidrome, 31, 139, 548
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556 Index
Anticoagulants, 331–333 Argyria, 303

effects, 51 Aromatic odor, 234
poisoning, 332 Arrhythmias, 8
Anticonvulsants, 32–33 ARS. See Acute Radiation Syndrome
Antidepressants, 33–43 Arsenic, 262–265
atypical, 41 Arsine, 262–265
cyclic, 543 Arthropods, 367–371. See also Spiders
tricyclic, 64 Aryl hydrocarbon receptor, 189
Antidiarrheal agents, 43–44 Asbestos, 161–162
Antidotes, 14–15 Asphyxia, 227
Antidysrhythmic agents Aspiration pneumonia, 541
type I, 118–121 Aspirin tablets, 111
type II, 121–122 Ataxia, 32, 57, 77, 129
type III, 122–123 Atrazine, 318
type IV, 123–124 Atropa belladonna, 415
Antiemetics, 53 Atropine, 30, 149, 353, 450–451
therapy, 166 Attention deficit hyperactivity disorder
Antifungal agents, 45–47 (ADHD), 33
Antihistamines, 30, 47–49 Atypical antidepressants, 41
Antihyperintensives, 77 Australian funnel-web spiders, 380
Antihyperlipidemia agents, 49–51 Autonomic instability, 38
Antimalarial agents, 51–52 Autumn crocus, 69
Antimony, 258–261 Avermectins, 330
fumes, 259 Ayurvedic medicines, 392
ingestion, 259 Azide, 162–163
poisoning, 259 Azole antifungals, 47
spots, 260 Azoxystrobin, 313
Antimotility agents, 43
Antiperspirants, 256
Antipsychotic agents, 52–54 Babesiosis, 375
Antiretroviral agents, 54–55 Baby woodrose seeds, 536
Antisecretory agents, 43 Bacillus cereus, 387
Antiseptics, 158–161 Baclofen, 114
Antispasmodics, 30 Bacterial food poisoning, 407
Antitoxins, 457 Bad trip, 143
administration, 457 Bagging, 144
botulinum, 383, 456–457 BAL. See Dimercaprol
Antivenom Barbiturates, 55–56, 113, 451–452, 479
administration, 446, 449 administration, 452
crotalidae polyvalent, 449 burns, 56
for scorpions, 447 in drug tests, 56
therapy, 369 mechanism of action of, 56
Antiviral agents, 54–55 Baritosis, 267
Ants, 378 Barium, 265–267
ANTU. See Alpha-naphthylthiourea containing radiologic contrast, 266
Aplastic anemia, 507 ingestion, 266, 500
Apomorphine, 528 Bark scorpion, 447
Aquatic envenomation, 500 Batrachotoxins, 367
Aqueous ammonia, 157 Bazett’s formula, 7
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Index 557
Bees, 378 Botulin, 59–60

Benzene, 163–165 in biological warfare, 343
chronic exposure, 164 Botulinum, 381
Benzocaine, 23 antitoxin, 383, 456–457
Benzodiazepines, 2, 15t, 49, 56–58, 113, clostridium, 342, 381
135, 169 poisoning, 343
aerosolized, 345 toxicity mechanism of, 342
chronic, 479 toxin, 342–344
iatrogenic, 478 Botulism, 59
mechanism of, 57 acute, 382
therapies, 453 food-borne, 383
Benztropine, 454 infant, 383
Bertholite, 180 natural toxins, 381–385
Berylliosis, 268 wound, 384
Beryllium, 267–269 Bradycardia, 69, 97, 150, 510
Beta 2-adrenergic agonists, 58–59 Bradykinin, 26
Beta-adrenergic stimulation, 58 Bretylium, 123
Beta-blockers, 15t, 39 Bristleworm stings, 400
toxicity, 493 Bromates, 166–167
Betadine, 212 Bromides, 167–169
Betel nuts, 430 poisoning, 221
Bezoar, 537 preparations, 220
Bicarbonate therapy, 456 Bromism, 168
Biguanides, 84 Bromoderma, 168
Biliary elimination, 291 Brompheniramine, 167
Biogenic amines, 37 Bronchiolitis obliterans, 226
Biological warfare, 343 Bronchorrhea, 321
Bioterrorism weapons, 412 Bronchospasm, 171
Bismuth, 269–270 Brown recluse spiders, 369–371,
toxicity, 270 538
Bitter almond, 419 eye structure of, 370
Biventricular tachycardia, 75 females, 369
Black box warning, 33 Buck moth caterpillar, 541
Black henbane, 30 Bufo toad venom, 366
Black phosphorus, 237 Bufotenine, 143
Black widows, 367–369 Bulbar palsy, 3
antivenom, 446 Buspirone, 107, 113
spider bite, 369, 446 Butyrophenones, 52
venom, 368
Bleach, 176, 180
Body packers, 151, 532 C. perfingens, 387
Body stuffers, 151 C. tetani, 439
Bone marrow suppression, 46, 125, Cadmium, 270–272
227 Caffeine, 60–62
Bong, 146 as stimulant, 61
Borane exposure, 166 toxicity of, 62
Borates, 165–166 Calcium, 4, 458–460
Boric acid, 165–166 disodium, 276
Boron, 165–166 gluconate, 200, 458
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558 Index
mechanism of, 459 CBD. See Chronic beryllium disease

oxalate crystals, 193, 194, 424, 550 CCB poisoning, 482
Calcium channel blocker (CCB), 548 Central Nervous System (CNS), 57, 107,
Calcium disodium ethylenediaminete- 170, 175, 247
traacetic acid (CaNa2EDTA), Centruroides, 371
460–461 Cephaeline, 89, 496
Camphor, 62–64, 169–170, 223 Cephalic tetanus, 441
ingestion, 63 Cephalosporins, 140
toxicity, 169, 386 Cerebral ischemia, 134
uses of, 62, 169 CFC. See Chlorofluorocarbons
Campylobacter, 387 Chalcosis, 277
CaNa2EDTA. See Calcium disodium Charcoal, 462–464
ethylenediaminete-traacetic acid activated, 13, 305, 463
Capsaicin, 432 hemoperfusion, 316
Carbamates, 321–322 therapies, 462–464
exposure, 322 Chelation, 276, 292
poisoning, 450 Chemical agents of terrorism, 342–365
Carbamazepine, 33, 64–65 botulinum toxin, 342–344
Carbidopa, 292 incapacitating agents, 344–345
Carbon disulfide, 76, 170–172 incendiary agents, 345–346
Carbon monoxide (CO), 172, 173, 222, 539 nerve agents, 347–353
poisoning, 249 phosgene, 353–355
Carbon tetrachloride, 174–175 ricin, 356–359
detection of, 175 3-Quinuclidinyl benzilate, 355–356
metabolization of, 174 vesicants, 360–363
uses of, 174 vomiting agents, 363–364
Carbonic anhydrase, 32 Chemical asphyxiants, 249
Carboplatin, 298 Chemical pneumonitis, 301
Carboxyhemoglobin, 223, 466 Chemotherapeutic agents, 65–67
Carcinogen, 274 Chewing tobacco, 149
copper as, 278 Chironex fleckeri, 398
Carcinogenecity, 189 Chloracne, 189
Cardiac dysrhythmias, 137, 196 Chloral hydrate, 113, 233
Cardiac glycosides, 15t, 73, 417–418 Chloramine fumes, 176
Cardiac sodium channel blockade, 124 Chloramine gas, 156
Cardiac tissue, 118 Chlorates, 178–179
Cardiotoxicity, 36, 68 Chlordiazepoxide, 57
Carisoprodol, 114 Chlorhexidine, 158
Carnitine, 461 Chlorine, 179–180, 205
Carson, Rachel, 323 mechanism of, 180
Carukia barnesi, 500 Chlorine gas, 456
Cassava root, 418 Chlorofluorocarbons (CFC), 202
Catecholamines, 175 Chloroform, 174, 181–182
excess, 109 exposure to, 182
Catechol-O-methyl transferase uses for, 181
(COMT), 37 Chlorophenoxy, 313–316
Cathartics, 97 Chlorophyllum molybdites, 406
Cationic surfactants, 185 Chloropicrin, 221
Caustics, 176–178 Chloroquine, 52
ingestion, 177 Chlorpromazine, 52
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Chlorpropamide, 84 Cocaine, 133–135, 250

Cholecalciferol, 333–334 effects, 134
Cholelithiasis, 51 freebasing, 133
Cholestyramine, 50 induced chest pain, 453, 508
Cholinergic excess, 510 metabolization of, 134
Cholinesterase, 100 withdrawal, 457
Chrome cleaning agents, 197 Cock walk, 292
Chrome holes, 273 Cocoa, 60
Chromium, 272–274 Coffee, 60
Chronic benzodiazepine, 479 Colchicine, 69–70, 431
Chronic beryllium disease (CBD), 268 Colesevelam, 50
Chronic dysphoria, 137 Colestipol, 50
Chronic germanium exposure, 281 Colloidal silver, 302
Chronic glycol toxicity, 206 Colorado tick fever (CTF), 377
Chronic lithium toxicity, 290 Comfrey, 430
Chronic nickel exposure, 297 Common neuromuscular blockers, 503
Chronic phenol toxicity, 235 Common rodenticide, 308
Chronic phthalate poisoning, 239 COMT. See Catechol-O-methyl transferase
Chronic selenium exposure, 301 Confusion, 77, 82
Chronic thallium toxicity, 304 Conjunctivitis, 156
Chronic toluene abuse, 253 Contrast dye, 212
Chrysiasis, 282 Co-oximeter, 219
Cicutoxin poisoning, 432 Copper, 276–279
Cigarettes, 149 as carcinogen, 278
Ciguatera poisoning, 393 Copperhead, 531
Ciguatoxin (CTX), 393 Coprine group, 402–403
Cimetidine, 486 Coral snake antivenom, 449
Cinchonism, 52 Corneal injury, 182
Citrate, 201 Cortinarius group, 403–404
Claviceps purpurea, 78 Coumarin-derived rodenticides, 333
Clitocybe mushrooms, 411 COX. See Cyclooxygenase enzymes
Clomipramine, 33 C-peptide, 83
Clonidine, 68–69, 107 Crotalid envenomation, 15t
related agents and, 68–69 Crotalidae polyvalent antivenom, 449
Clonus, 38 Crotalinae, 434
Clostridium botulinum, 342, 381 Crotalus scutulatus, 436
Clostridium perfringens, 388 Crush injuries, 99
Clostridium tetani, 439 Cryptorchidism, 312
Clove oil, 63, 445 CTF. See Colorado tick fever
Clupeotoxism, 397 CTX. See Ciguatoxin
CN. See Cyanide Cutaneous flushing, 128
CNS. See Central Nervous System Cyanide (CN), 15t, 102, 183–185, 210, 475
CNS depression, 57, 175 antidote kit, 184
CNS excitation, 107, 170 antidote package, 465–466
CNS/CV syndrome, 247 mechanism of, 183
CO. See Carbon monoxide poisoning, 249
Cobalt, 274–276 Prussian blue and, 517
medicinal uses of, 275 Cyanogenic glycosides, 418–419, 419
skin exposure, 275 Cyanosis, 225
Cocaethylene, 134 Cyclic antidepressants, 543
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Cyclobenzaprine, 114 Dextromethorphan, 38, 138–139, 167

Cyclooxygenase enzymes (COX), 104 bromide, 139
Cyclopeptide group, 404–406 toxicity of, 139
Cyclophosphamide, 66 DHFR. See Dihydrofolate reductase;
Cyproheptadine, 38, 43, 463–464, 464 Dihydrofolic acid reductase
Cystic acneiform lesions, 189 Diabetes, Type 2, 87
Cystinuria, 507 Dialysis, 291, 469–470
Cystosolic transformation, 222 encephalopathy, 257
Cytochrome oxidase, 172 Diarrhea
Cytotoxic metabolites, 191 syndrome, 387
traveler’s, 388
Diazoxide, 85, 126, 530
Dantrolene, 22, 467 DIC. See Disseminated intravascular
Dapsone, 70–72 coagulation
Date rape drug, 57 Dichlorodiphenyltrichloroethane
DCI. See Decompression illness (DDT), 322
DDC. See Diethyldithiocarbamate Dichlorophenoxyacetic acid, 313
DDMA. See Digoxindicarboxymethoxy- Dietary supplements, 295
lamine Diethyldithiocarbamate (DDC), 297,
DDT. See Dichlorodiphenyl- 471
trichloroethane Diethylene glycol, 206
Deadly nightshade, 30, 415 Difenoxin, 44
Death camases, 427 Digifab, 473
Decompression illness (DCI), 489 Digitalis purpurea, 73
Decongestants, 72–73 Digoxin, 73–76, 547
Decontamination, 155 elimination of, 74
dermal, 11 immune, 418
external, 244 fab, 471–473
gastrointestinal, 12–15 fragments, 472
of isocyanates, 214 indications for, 74
ocular, 11–12 levels, 75
DEET. See N,N-diethyltoluamide mechanism action of, 74
Deferoxamine, 467–469 Digoxindicarboxymethoxylamine
Delayed-onset pulmonary toxicity, 225 (DDMA), 471
Delta-9-tetrahydrocannabinol (THC), Dihydrofolate reductase (DHFR),
146 479
Demeclocycline, 28 Dihydrofolic acid reductase (DHFR),
Depigmentation, 235 497
Depression, severe, 37 Diltiazem, 123
Dermacentor andersoni, 372 Dimercaprol (BAL), 260, 282
Dermacentor variabilis, 372 Dimercaptopropanesulfonic acid
Dermal decontamination, 11 (DMPS), 470–471
Dermal inhalation, 183 Dimercaptosuccinic acid, 519
Dermatitis, 281, 313 Dimethyl sulfoxide (DMSO), 187
nickel, 296, 297 Dimethyl-p-aminophenol (DMAP),
plants producing, 420–422 474–476
reversible, 313 Dinitrophenol (DNP), 231–232
Detergents, 185–187 toxicity of, 232
Dexfenfluramine, 132 Dioxins, 188–190
Dextroamphetamine, 132 disasters with, 188
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poisoning, 190 marijuana, 146–147

toxicity, 189 mescaline, 147–148
Dipeptidyl peptidase-4, 87 nicotine, 149, 424
Diphenhydramine use, 476 opioids, 150–152
Diphenoxylate, 44 phencyclidine, 152–153
Diphenylhydramine, 53, 476 date rape, 57
poisoning, 31 induced bradycardia, 451
Diquat, 314–316 induced hypoglycemia, 506
Direct-acting vasopressors, 25 metabolites, 6
Disease(s) NSAIDs, 104–105
chronic beryllium, 268 potassium efflux channel blocking, 9t
lyme, 373, 374 sodium channel blocking, 10t
Parkinson’s, 37, 106, 110, 292 urine, screening, 6–7
progressive pulmonary, 268 weight-loss, 77
renal, 271, 281 Dry bite, 546
Shaver’s, 257 Dry mouth, 3
Wilson’s, 278 Dry mucous membranes, 48
wool-sorter’s, 364 Dysconjugate gaze, 550
Disinfectants, 158–161 Dysphagia, 395
Disk batteries, 190–191 Dysrhythmias
Disopyramide, 119 cardiac, 46, 137, 196
Disseminated intravascular coagulation freon-induced, 203
(DIC), 137 Dystonic reactions, 44
Disulfiram, 76–77, 402
Dithiocarbamates, 170, 311
Diuretics, 77–78, 289 Echinoderm envenomation, 399
Dizziness, 27, 139, 148, 253 Ecstasy, 544
DMPS. See Dimercaptopropanesulfonic EEG monitoring, 350
acid Elapidae envenomation, 433, 449
DMSO. See Dimethyl sulfoxide Electrocardiogram, 7–10
DNA synthesis, 67 Electromagnetic radiation (EMR), 240
DNP. See Dinitrophenol Electromyograph (EMG), 384
Domoic acid, 396 Elemental iron, 282
Dopamine, 37, 44, 524 Elevated anion gap metabolic acidosis,
receptor antagonism, 53 184
Doxepin, 33 Elevated manganese levels, 292
Doxycycline, 378 Elevated osmolar gap, 214
D-penicillamine, 506 Emergence reaction, 94
Droperidol, 484–486 Emergent EEG monitoring, 350
Drowsiness, 150 Emergent endoscopic battery removal,
Drugs 190
of abuse, 132–153 Emetine, 89, 496
amphetamines EMG. See Electromyograph
cocaine, 133–135 EMR. See Electromagnetic radiation
designer, 135–138 Encainide, 121
dextromethorphan, 138–139 Endocarditis, 544
ethanol, 139–141 Endoscopy, 155
gamma-hydroxybutyrate, 141–142 Endrotracheal intubation, 1
hallucinogens, 142–144, 407–408 Engine coolant, 192
inhalants, 144–145 Enterohepatic circulation, 13
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562 Index
Envenomations Exacerbation, 41
aquatic, 500 Excessive methemoglobinemia, 475
crotalid, 15t Exocrine glands, 30
echinoderm, 399 Exothermic neutralization, 177
elapidae, 433, 449 Exotic scorpions, 372
human, 398 External contamination, 244
sea snake, 401 Extrapyramidal reactions, 44
severe, 437 Extrapyramidal symptoms (EPS), 171
stingray, 401 Ezetimibe, 50, 51
Environmental air pollution, 225
Environmental Protection Agency
(EPA), 231 False hellebore, 536
Environmental/industrial toxins, Fast-acting sodium channels, 118
154–255. See also acids; Cyanide; Fat solubility, 6
Ethylene glycol Fat-soluble vitamins, 126
Eosinophilia-myalgia syndrome, 391 Fenamic acids, 104
EPA. See Environmental Protection Fenfluramine, 132
Agency Fetal hemoglobin, 173
Epinephrine, 24, 492 Fibrates, 51
EPS. See Extrapyramidal symptoms Fipronil, 330
Erethism, 294 Fire sponge, 400
Ergot derivatives, 78–80 Flecainide, 121
Erythema multiforme, 470 Fluconazole, 47
Erythromycin, 378 Flumazenil, 57, 114, 479
Escherichia coli, 388 Flunitrazepam, 57
Esculoside, 432 Fluorides, 197–200
Esophageal burns, 177 Fluoroacetate, 200–201
Essential oils, 63 Fluorouracil, 46
ingestion, 64 Flushed skin, 48
Ester-linked aminoesters, 23 Flushing, 150, 225
Ethanol, 50, 136, 139–141, 477–478, 481 Fly agaric mushroom, 30, 540
absorption of, 139 Folic acid, 479–480
Ethanol administration, 217 Folinic acid, 218
Ethanol dialyzable, 477 Fomepizole (4-methylpyrazole, 4-MP),
Ethanol intoxication, 140 217, 480–481
Ethyl, 224 Food poisoning, 386–389
Ethylene dibromide, 191–192 Food-borne botulism, 383
Ethylene glycol, 15t, 192–195, 477, 480 Foreign bodies, 245
ingestion of, 192 Formaldehyde, 201–202, 216
monobutyl ether, 206 Foscarnet, 55
monomethyl, 206 Fosphenytoin, 108, 508–509
poisonings, 139, 193 Freons, 202–204
Ethylene oxide, 195–197 Fungicides, 311–313
exposure to, 196, 199
Etomidate, 22
Eucalyptus oil, 64, 386 G. esculenta, 409
Euglycemia therapy, 122 G6PD Deficiency, 51
Euphoria, 137 Gadolinium, 300
Europium, 300 Gallium, 279–280
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Index 563
Gamma-hydroxybutyrate (GHB), 135, Glyoxylic acid, 193

141–142. See also Date rape drug; Gold, 281–282
Rohypnol Gold sodium thiomalate, 281
mechanism of, 142 Golden poison dart frog, 367
other chemicals converted to, 141 Gout, 69
Gangrenous ergotism, 415 Granulocyte colony-stimulating factor
Garlic, 301 (G-CSF), 70
Gases Gray baby syndrome, 29
chloramine, 156 Green tobacco illness, 424, 546
chlorine, 456 Gymnopilus, 407
environmental/industrial toxins, 204–205 Gyromitra species, 409
germane, 280 Gyromitra esculenta, 518
high solubility of, 205
highly soluble irritant, 347
irritants, 204, 347 Hallucinogens, 142–144
Gastric aspiration, 159 abuse of, 143
Gastric lavage, 12–13, 260 group, 407–408
Gastrointestinal decontamination, 12–15 Halogenated hydrocarbon, 202, 204
Gastrointestinal irritant group, 406–407, Halons, 202–204
422–423 Haloperidol, 484–486
Gastrointestinal syndrome, 246 Halothane, 167
G-CSF. See Granulocyte colony- Hand washing, 389
stimulating factor Hapalochlaena, 400
Gelled hydrocarbons, 345 HBO. See Hyperbaric oxygen
Germane gas, 280 Hearing loss, 78
Germanium, 280–281 Heavy metals, 256–310
GI distress, 75, 167, 271 Hehnestritt, 292
Gila Monster, 437 Hellebore, 536
Gingivostomatitis, 294 Hematopoietic syndrome, 246
Gingko biloba, 389 Hemodialysis, 46, 84, 96, 195, 217, 261, 316
Glipizide, 84 Hemoglobin
Globus pallidus, 539 fetal, 173
Glucagon, 122 level, 224
cardiac effects, 482 Hemolysis, 179
Glucocorticoids, 89, 269 Hemolytic anemia, 128
Glufosinate toxicity, 320 Hemoperfusion, 164
Glutaraldehyde, 159 Hemorrhagic cystitis, 66
Glyburide, 84 Heparin, 80–81, 515
Glycerol monoacetate, 201 Heparin-induced thrombocytopenia
Glycine receptor antagonism, 336 (HIT), 81
Glycoaldehyde, 193 Hepatic metabolism, 84, 106, 132
Glycol. See also Ethylene glycol Hepatitis, 91
diethylene, 206 Hepatosplenomegaly, 312
ethers, 206–207 Herbal products, 389–392
Glycol toxicity, 194 hepatotoxicity associations, 390
Glycolic acid, 193 Herbalist, 547
Glycophosphate, 318 Herbicides, 178, 313–316, 407
Glycopyrrolate, 450 Heroin, 250
Glycyrrhizin, 431 Hexachlorobenzene, 312
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564 Index
HF. See Hydrofluoric acid Hyperchloremia, 212

High anion gap metabolic acidosis, Hyperglycemia, 58, 116, 124, 143, 548
193, 232 Hyperinsulinemia, 122
High osmol gap, 218 Hyperinsulinemic-euglycemic therapy,
High solubility, 204 484, 493
gases, 205 Hyperkalemia, 25, 27, 49, 75, 81, 121,
water, 304 122, 418, 550
High-dose barium ingestions, 266 Hypermagnesemia, 97
High-dose IV penicillin, 28 Hypernatremia states, 97
Highly soluble irritant gas, 347 Hyperreflexia, 38, 116
Highly volatile aromatic hydrocarbon, Hypersalivation, 294
252 Hypersensitivity syndrome, 33
Histamine-2 receptor antagonists, 486 Hypersensitivity, type IV, 296
HIT. See Heparin-induced Hypertension, 27, 40, 68, 109, 123
thrombocytopenia Hyperthermia, 38, 137, 143
Hobo spiders, 379 Hyperthyroidism, 212
Hoigne syndrome, 29 Hypnotic toxidrome, 113
Hormone, polypeptide, 481 Hypocalcemia, 8, 186, 230, 238
Hormones, thyroid, 117–118 Hypochlorite, 156
Household bleach, 159 Hypochromic anemia, 256
Huffing, 144 Hypoglycemia, 122, 482, 484, 492, 505
Human tetanus immune globulin, 442 contribution of, 85
Human-derived immune globulin, 384 Hypoglycemic agents, 81–88
Hydralazine, 126 insulin, 81–83
Hydrocarbons, 207–210 sulfonylureas, 84–86
aryl, receptor, 189 Hypokalemia, 8, 58, 68–69, 112, 116,
aspiration, 208, 209 267, 456, 493–494
environmental/industrial toxins, Hypomagnesemia, 8, 186, 266
207–210 Hyponatremia, 290
gelled, 345 Hypophosphatemia, 116
halogenated, 202, 204 Hypopituitarism, 82
highly volatile aromatic, 252 Hyporeflexia, 129
ingestion, 209 Hypospadias, 312
mechanisms of, 208 Hypotension, 25, 54, 58, 69, 103, 150,
Hydrofluoric acid (HF), 155, 197 162, 466, 470, 508, 513, 521
burns, 458 methylxanthine-induced, 514
exposure, 459 systemic, 515
Hydrogen peroxide, 159 Hypothermia, 8
Hydrogen sulfide, 210–211 Hypotonic lavage fluids, 13
Hydrogen sulfide concentrations, 211 Hypoventilation, 513
Hydromorphone, 106 Hypoxia, 225, 321, 513
Hydrophobicity, 239
Hydroxocobalamin, 184, 487–488
Hydroxychloroquine, 52 Iatrogenic benzodiazepine over-
Hydroxycoumarins, 526 medication, 478
Hyperammonemia, 125 Ibotenic acid, 408–409
Hyperbaric oxygen (HBO), 172, 488–490 Ibuprofen, 104
Hyperbilirubinemia, 128 Iliac crest bone biopsy, 258
Hypercalcemia, 127, 333, 498 Illnesses
Hypercapnia, 99 decompression, 489
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Index 565
green tobacco, 424, 546 carbamates, exposure, 322

manifest, 247 DDT, 322
Imidacloprid toxicity, 330 DEET, 329
Imidazoline, 72 organochlorines, 322–323
Imipramine, 33 organophosphates, 324–327
Immediate pain, 156 pyrethrins, 327–329
Immune-mediated effects, 248 Insulin, 81–83, 492–494
Inactivated sodium channels, 119 enteral administration of, 83
Inamrinone, 491 history of, 82
Incendiary agents, 345–346 Intermediate syndrome, 327
Indomethacin, 515 Internal contamination, 244
Infant botulism, 383 Intestinal absorption, 313
INH. See Isoniazid Intimacy, 137
Inhalants, 144–145 Into the Wild (Krakauer), 428
general classes of, 144 Intoxication
long-term effects of, 145 acute amphetamine, 133
Inhalation, 191 acute arsenic, 263–264
acute, 253 amphetamine, 133
of ammonia, 157 arsine, 265
anthrax, 365 barbiturates, 56
of asbestos, 161 chronic arsenic, 264
dermal, 183 concomitant ethanol, 194
gallium exposure, 279 ethanol, 140
of iodine, 212 ketamine, 93
large inhalation exposures, 230 toxic alcohol, 4
phosgene, 355 Intracranial hemorrhage, 1
smoke, 248–249 Intraluminal agents, 43
tin, 305 Intrathecal administration, 498
Inhibitors Intravascular hemolysis, 179
angiotensin-coverting enzyme, 25–26, Invasive gastroenteritis, 388
534 Iodide, 494–495
monoamine oxidase, 37–39 Iodine, 211–213
nonnucleoside reverse transcriptase, 54 ingestion of, 212
nucleoside reverse transcriptase, 54 inhalation of, 212
phosphodiesterase, 101 toxicity, 212
selective serotonin reuptake, 39–41 Ion flux, 32
serotonin and norepinephrine Ionizing radiation, 241, 243
reuptake, 41 sources, 241
Injuries Ipecac syrup, 89–90, 285, 495–496
from acids, 154 Iron, 15t, 282–285
acute lung, 249 absorption, 283
alkali acid, 154 poisoning, 467
corneal, 182 Irritants, 346–347
crush, 99 gas, 204, 347
lung, 98 gastrointestinal, 406–407, 422–423
multi-system trauma/crush, 99 mucosal, 311, 363
ocular acid, 155 poorly water-soluble, 354
stingray, 400 toxic, 204
Inocybe mushrooms, 411 Isocarboxazid, 37
Insecticides, 321–331 Isocyanates, 213–214
13486_INDEX.qxd 10/31/08 3:31 PM Page 566
566 Index
Isoniazid, 15t Leukocyte adherence, 173

mechanism action of, 91 Leukocytosis, 534
metabolism of, 91 Leukopenia, 103
Isoniazid (INH), 91, 410 Lewisite, 262, 361
induced seizures, 452 Licorice consumption, 391
Isopropanol, 214–215 Lidocaine, 25, 120, 498–499
Isoproterenol, 496–497 Linamarin, 418
Ixodes scapularis, 373, 376 Lindane, 323
Linezolid, 30, 39
Lionfish, 542
Jack-in-the-pulpit plant, 550 Lipid solubility, 254
Jamestown, 416 Lipodystrophy, 492
Jarisch-Herxheimer reaction, 29 Liquid caustics, 177
Jaundice, 128 Lithium, 95–96, 288–291
Jellyfish, 537 carbonate, 288
Jequirity beans, 429 mechanism of action of, 289
Jimson weed, 30, 416 metabolism of, 95
Joint, 146 observing, 96
toxicity, 95, 96
Liver, 77
Karwinskia toxin, 432 Lobelia, 391
KCN. See Potassium cyanide Lobelia inflata, 423
Ketamine, 92–95 Local anesthetics, 23–25
antidote for, 94 Local irritation, 470
definition of, 92 Local pain, 371
effects of, 93 Lophophora williamsi, 147
emergence reaction, 94 Lorazepam, 453
recreational doses of, 92 Low acute toxicity, 147
street names for, 92 Lung injury, 98
Knock down phenomenon, 210 Lupus erythematosus, 67
Komodo dragon, 438 Lyme disease, 373, 374
Korsakoff’s syndrome, 521 Lymphocyte count, 246
Krakauer, Jon, 428 Lysergic acid, 345, 536
Krebs cycle, 200, 303
Macrophages, 161
Lacrimating agents, 347 Macrolides, 28
Lactate dehydrogenase, 224 Magic mushrooms, 407
Lactic acidosis, 55, 84, 210 Magnesium, 4, 96–98, 499–500
Laetrile, 418 burns, 345
Lamotrigine, 32, 33 dust, 98
Large bowel mucosa, 96 filtering of, 97
Large inhalation exposures, 230 medical preparation for, 96
Large tablet masses, 111 Malaria, 51
Latrodectus species, 367 Malignant hyperthermia (MH), 21, 467
Laudanosine, 100 Manganese madness, 292
Lavender, 64 Manganese toxicity, 159, 291–292
Lead, 285–288, 534, 545 Manifest illness, 247
Leucovorin, 30, 66, 89 Mannitol, 527
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Index 567
Maprotiline, 33, 36 3,4-methylenedioxy-N-

Marijuana, 146–147 methylamphetamine (MDMA),
Mark I kit, 352 132. See also Ecstasy
Mastoparans, 379 Methyl bromide, 220–221
MDMA. See 3,4-methylenedioxy-N- Methyl salicylate, 63
methylamphetamine Methylene blue, 71, 219
Medium-acting agents, 83 Methylene chloride, 145, 222–223
Mees lines, 535 Methylphenidate, 132
Mefloquine, 52, 67 Methylxanthine-induced dysrhythmias,
Megaloblastic anemia, 103 514
Meixner test, 405 Methylxanthine-induced hypotension, 514
Melaleuca oil, 386 Metoclopramide, 45, 527
Mentha pulegium, 385 Metronidazole, 28
Meperidine, 44, 106, 107 Mexican beaded lizard, 437
Mercury, 292–295 Mexiletine, 120
absorption, 293 Miglitol, 87
elimination, 295 Minimally toxic household products,
Mescaline, 143, 147–148 228–229
Metabolic acidosis, 112, 202, 207, 283 Mining, 271
Metabolism Minoxidil, 126
anaerobic, 210 Miosis, 54, 135
hepatic, 84, 106, 132 Mitral valve prolapse, 8
urea, 200 Molybdenum, 295–296
Metabolites Monday morning fever, 310
acetaminophen, 17 Monoamine oxidase inhibitors, 37–39
cytotoxic, 191 Monomethylhydrazines group,
drug, 6 409–410
Metal fume fever, 271, 308, 310–311 Monoplace chambers, 490
Metaldehyde, 215–216 Morchella esculenta, 410
poisoning, 216 Morphine, 106
Metalloid, 258 Moscow Theater, 344
Metformin, 84 Mothballs, 223–224
Methadone, 107 MPTP. See 1-methyl-4-phenyl-1,2,3,6-
Methanol, 15t, 480 tetrahydropyridine
ingestions, 480 Mucosal irritation, 203, 302, 311,
intoxication, 216 363
Methcathinone, 138 mucous membrane irritation, 165,
Methemoglobin, 101 176
Methemoglobinemia, 24, 30, 52, 145, Mucous membranes, 174
167, 218, 220, 223, 225, 410, MUDILES mnemonic, 4
475, 533 Munchausen’s syndrome, 90
inducers, 218–220 Muscarine group, 411–412
symptomatic, 500 Muscimol group, 408–409
Methocarbamol, 528 Muscle rigidity, 137
Methotrexate poisoning Muscle spasms, 540
and methotrexate toxicity, Mushrooms
89, 497 Amanita, 445
1-methyl-4-phenyl-1,2,3,6- Clitocybe, 411
tetrahydropyridine (MPTP), 136 coprine group, 402–403
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568 Index
cortinarius group, 403–404 Neuromuscular hyperactivity, 40

cyclopeptide group, 404–406 Neuronal sodium channels, 107
fly agaric, 30, 540 Neuropsychiatric symptoms, 52
gastrointestinal irritant group, 406–407 Niacin, 128
hallucinogen group, 407–408 Nickel, 296–298
Inocybe, 411 carbonyl, 296
magic, 407 dermatitis, 296, 297
monomethylhydrazines group, 409–410 Nicotine, 149. See also Chewing tobacco
muscarine group, 411–412 poisoning, 424
muscimol group, 408–409 replacement, 149
Mustard agent, 361 tobacco and, 423
Mustard toxicity, 361 Nicotinics, 423–424
Myasthenia gravis, 28 NIH. See Isoniazid
Mycotoxins, 412–415 Nitrates, 100–101, 218
Mydriasis, 3, 48 Nitric oxides (NO), 102
Myeloneuropathy, 22 Nitrites, 101–102, 224–225
Myelosuppression, 298 administration, 466
Myocardial ischemia, 8 Nitrofurantoin, 28
Myocardial repolarization, 7 Nitrogen
Myocardium, 182 mustards, 66
Myoglobin, 172 oxides, 225–228
Myopathy, 49, 70 Nitroprusside, 102
Myristicin, 64, 148 Nitrous oxides, 103–104
NMDA. See N-methyl-D-aspartate
receptor
NAC. See N-acetylcysteine N-methyl-D-aspartate receptor
N-acetylcysteine (NAC), 444 (NMDA), 93
Nalmefene, 502–503 NMS. See Neuroleptic malignant
Naloxone, 44, 69, 106, 139 syndrome
Naltrexone, 502–503 N,N-diethyltoluamide (DEET), 329
Napalm, 346 NNRTI. See Nonnucleoside reverse
Naphthalene, 223 transcriptase inhibitors
Nateglinide, 86 NO. See Nitric oxide
Nausea, 32, 148, 483 Non-anion gap acidosis, 253
NDNMB. See Nondepolarizing Noncardiogenic pulmonary edema,
neuromuscular blockers 107, 214
Negative anion gap, 158 Nondepolarizing neuromuscular blockers
Nematocyst, 537 (NDNMB), 99, 326
Neonatal tetanus, 441 Non-digoxin cardiac glycosides, 473
Neonates, 445 Nonnucleoside reverse transcriptase
Neostigmine, 505, 509–510 inhibitors (NNRTI), 54
Nephrogenic diabetes insipidus, 96 Nonsteroidal anti-inflammatory drugs
Nephrogenic systemic fibrosis, 300 (NSAIDs), 104–105
Nerium oleander, 73 Nontoxic household products, 228–229
Nerve agent exposure, 349, 351 Norepinephrine, 37, 522
Nerve agent poisoning, 349, 351 Novichok nerve agents, 348
Neuroleptic malignant syndrome (NMS), NRTI. See Nucleoside reverse
20, 457 transcriptase inhibitors
Neuromuscular blockers, 98–100, NSAIDs. See Nonsteroidal anti-
503–505 inflammatory drugs
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Index 569
Nucleoside reverse transcriptase immediate, 156

inhibitors (NRTI), 54 local, 371
Nutmeg, 64, 143 oropharyngeal, 294
Palytoxin, 397
Panaeolus, 407
Ochratoxins, 414 Pancreatitis, 91, 513
Ochronosis, 235 Pancuronium, 167
Octreotide, 505–506 Paradichlorobenzene, 223
Ocular acid injuries, 155 Paraquat, 316–318
Ocular decontamination, 11–12 Parkinsonian symptoms, 106
Olestra, 240 Parkinson’s disease, 37, 110, 292
Oliguric renal insufficiency, 269 PCBS. See Polychlorinated biphenyls
OP. See Organophosphates PCP. See Pentachlorophenol;
OP exposure, 325 Phencyclidine
Opioids, 43, 105–107, 150–152 Peanut oil, 474
opiates and, 106 PEG-ES. See Polyethylene glycol-
toxicity, 550 electrolyte solution
ultra-potent, 344 Penicillamine, 506–507
Opisthotonus, 250 Penicillin G, 442
Opium poppy, 106 Pennyroyal oil, 63, 64, 385, 445
OP/nerve agent exposure, 350 Pentachlorophenol (PCP), 231–232, 311
Optic neuritis, 91 Perchloroethylene, 232–234
Oral calcium salts, 230 Peripheral alpha-1 receptors, 126
Oral glucose therapy, 83 Peripheral neuritis, 91
Oral ricin poisoning, 357 Peripheral neuropathy, 103, 171
Organic arsenic, 265 Peripheral vasoconstriction, 522
Organochlorine fungicides, 311 Peripheral vasodilation, 100
Organochlorines, 322–323, 323 Personal protective equipment
Organophosphates (OP), 324–327, 347 (PPE), 11
Organophosphorus, 450 Pesticides, 165, 311–341, 407
Organotins, 306 fungicides, 311–313
Oropharyngeal burning, 314 Peyote, 147
Oropharyngeal pain, 294 Phencyclidine (PCP), 152–153
Osmolality, 5 Phenelzine, 37
Osmolar gap, 4–6, 194 Phenformin, 84
toxins elevating, 6t Phenobarbital, 33, 452
Osmotic diuresis, 279, 298 Phenol, 234–236
Osteomalacic dialysis osteodystrophy, 257 marasmus, 235
Oxalates, 424–427 pharmacokinetics of, 235
crystals, 194 as preservative, 234
Oxalic acid, 229–230 toxicity mechanism of, 234
Oxygen Phenothiazines, 52
delivery, 218 Phentolamine, 507–508, 508
therapy, 269 Phenylephrine, 72, 521
Oxymetazoline, 68 Phenylethylamine, 148
Phenytoin, 2, 33, 107–108, 120,
508–509, 543
Pain Phosgene, 204, 353–355
abdominal, 51, 148, 286 Phosphides, 236–237
cocaine-induced, 453, 508 Phosphine, 236–237
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570 Index
Phosphodiesterase inhibitors, 101 diquat, 315

Phosphorus, 237–238 ergot, 80
black, 237 ethylene glycol, 139, 193
burns, 346 fluorides, 199
red, 237 food, 386–389
white, 237, 345 glycol ether, 207
Phossy jaw, 238 metaldehyde, 216
Photosensitivity, 51 methotrexate, 89
Phthalates, 238–239 nerve, 349, 351, 353
Physostigmine, 32, 37, 48, 509–510 nicotine, 424
Phytophototoxic reactions, 422 oral ricin, 357
Piperazine-based substances, 135 palytoxin, 397
Plague, 364 phosgene, 355
Plants, 415–432 potential, 1
anticholinergic, 415–416 scombroid, 392–393
dermatitis-producing, 420–422 serious systemic, 388
gastrointestinal irritants, 422–423 SMFA, 335
nicotinics, 423–424 strychnine, 337
oxalates, 424–427 testing, 3–6
sodium channel openers, 425–427 anion gap, 3–4
solanine, 427–428 management, 10–15
toxalbumins, 428–429 osmol gap, 4–6
viperidae, 434–436 tetramine, 341
Plasma acetaminophen, 18 vinea alkaloid, 431
Platinum, 298–299 volatilized nerve agent, 349
Pneumonitis, 176, 209 wintergreen, 386
PNU. See Vacor Polar bear liver, 127
Podophyllin, 70, 431, 533 Polychlorinated biphenyls (PCBs),
POEA. See Polyoxyethyleneamine 239–240
Poison dart frogs, 366 Polyclonal antibodies, 88
Poison hemlock, 546 Polyethylene glycol-electrolyte solution
Poison ivy, 549 (PEG-ES), 14
Poisoning Polymorphic ventricular tachycardia, 7
acetaminophen, 18 Polyneuropathy, 70
acute arsenic, 264 Polyoxyethyleneamine (POEA), 318
acute benzene, 164 Polypeptide hormone, 481
anticoagulants, 332 Polyvalent immune Fab therapy, 448
antimony, 259 Poorly water-soluble irritants, 354
arsenic, 264, 535 Portable recompression chambers, 490
bacterial food, 407 Postsynaptic action, 32
barium, 267 Potassium, 4, 288
bromides, 221 bromate, 166
carbon monoxide, 249 chlorate, 178
chronic phthalate, 239 efflux channel blocking drugs, 9t
cicutoxin, 432 influx, 58
ciguatera, 393 info cells, 483
dioxins, 190 Potassium cyanide (KCN), 183
diphenylhydramine, 31 Potential poisoning, 1
diphydramine, 31 POW. See Powassan encephalitis
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Index 571
Powassan encephalitis (POW), 377 Quinidine, 119

PPE. See Personal protective equipment like effect, 8
PR interval prolongation, 123 Quinine, 52
Pralidoxime, 326, 510–512 toxicity, 506
Pralidoxime chloride (2-PAM), 351 3-Quinuclidinyl benzilate, 355–356
Priapism, 380
Primidone, 33
Procainamide, 119, 120 Radiation, 240–248
Procaine, 23 damage, 243
Procarbazine, 39 dose, 242
Progressive interstitial pulmonary electromagnetic, 240
fibrosis, 161 equal absorbed doses of, 242
Propafenone, 121 measurement of, 242
Prophylactic antibiotics, 209 Radioactivity, 242
Prophylactic vitamin K therapy, 130 Radioiodine, 494
Prophylaxis, 51 Radiosensitive mammalian tissues, 243
Propofol, 22, 512–513 Ragweed allergy, 328
Propofol infusion, syndrome, 23, 513 Rare earths, 299–300
Propoxyphene, 150 Rauwolfia alkaloids, 109–110
Propranolol, 514–515 Recompression chambers, 490
Proserotonergic agents, 138 Red man syndrome, 29
Prostaglandin D2, 128 Red phosphorus, 237
Protamine, 515–516, 516 Red pigmentation, 301
Prototypical chlorophenoxy herbicide, 313 Red Squill, 338–339
Pruritus, 128, 150 Red tide, 397
Prussian blue, 3–5, 516–517 Reflex tachycardia, 58, 126, 508
Pseudoephedrine, 72 Renal cell carcinoma, 167
Pseudohyperchloremia, 168 Renal disease, 271, 281
Psilocybin, 407 Renal dysfunction, 46
Psychedelic agent, 147 Renal elimination, 217
Pufferfish, 394 Renal failure, 151, 315
Pulegone, 385 acute, 179
Pulmonary edema, 162, 354 Renal heparin, 80
freon and, 203 Renal insufficiency, 83, 84, 102
Pulmonary fibrosis, 123 Repaglinide, 86
progressive interstitial, 161 Reptiles, 432–436
Puncture wounds, 245 Respiratory depression, 135
Puppy glove syndrome, 509 Respiratory tract irritation, 171, 210
Pyraclostrobin, 313 Reversible dermatitis, 313
Pyrazolones, 104 Rhabdomyolysis, 49, 137, 153, 251, 540
Pyrethrins, 327–329 Rheumatoid arthritis, 52
Pyrethroids, 327–329 Ricin, 356–359, 531
Pyridostigmine, 167 antidote, 358
Pyridoxine, 30, 195 biological warfare, 358
Pyrrolizidine alkaloid, 430 Rifampin, 29
Right axis deviation, 35
Right bundle branch block, 354
QRS prolongation, 34, 52 Risus sardonicus, 336
QTc prolongation, 52 RNA synthesis, 67
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572 Index
Rocky Mountain Spotted Fever Self-contained breathing apparatus

(RMSF), 374 (SCBA), 196
Rocuronium, 505 Sensory neuropathies, 129
Rodenticides, 129, 308, 331–341, 526 Serine hydroxyl residue, 347
anticoagulants, 331–333 Serious systemic poisoning, 388
ANTU, 331 Serotonergic neurons, 137
cholecalciferol, 333–334 Serotonin, 37, 44, 109
pyrethrins, 327–329 reuptake inhibition, 138
red squill, 338–339 syndrome, 38, 39, 42, 138, 289, 464
sodium monofluoroacetate, 334–335 Serotonin and norepinephrine reuptake
strychnine, 335–337 inhibitors (SNRIs), 41
Vacor, 337–338 Serum antimony levels, 260
Roentgen, 242 Serum management, 97
Rohypnol, 113 Several hepatotoxicity, 50
Rosiglitazone, 86 Severe depression, 37
Roundup brand weed killer, 318 Severe envenomation, 437
Rubbing alcohol, 214 Sewage treatment, 180
Rubiacea, 495 SIADH. See Syndrome of inappropriate
Rumack-Matthew nomogram, 18 anti-diuretic hormone
Silibinin/milk thistle, 518
Silver, 302–303
Salem witch trials, 79 Simple asphyxiants, 248
Salicylates, 110–113, 455 Sinus tachycardia, 41
clinical presentation of, 111 Sirolimus, 89
methyl, 63 Sitagliptin, 87
Salmon sperm, 515 Six-eyed crab spider, 380
Salvinorin A, 143 Skeletal muscle relaxants, 30, 114–115
Saxagliptin, 87 Skeletal muscle spasms, 250
Saxitoxin (STX), 396 Skin popping, 551
SCBA. See Self-contained breathing Slow infusion rate, 46
apparatus Smelting, 271
Schizophrenia, 52, 153 SMFA poisoning, 335
Scombroid poisoning, 392–393 SMFA toxicity, 335
Scopolamine, 167, 532 Smoke
Scorpions, 371–372, 447–448 composition of, 248
bark, 447 inhalation, 248–249, 249
exotic, 372 Smoking, 162
natural toxins, 371–372 Snakes, 432–436, 448–450
Sea bather’s eruption, 399 Elapidae, 432–434
Sea snake envenomation, 401 Viperidae, 434–436
Sea snake venom, 402 SNARE proteins, 382
Second-generation antihistamines, 47 Snowfield vision, 216
Sedation, 109 SNRIs. See Serotonin and norepinephrine
Sedative-hypnotic agents, 113–114, 114 reuptake inhibitors
Seizures, 510 Sodium, 288
Selective serotonin reuptake inhibitors bicarbonate, 120, 454, 549
(SSRIs), 39–41 channel blockade, 31, 455
Selenious acid ingestion, 301 channel blocker toxicity, 455
Selenium, 300–302 channel blocking drugs, 10t
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Index 573
channels, 426 Sulfonamides, 29

chlorate, 178, 319 Sulfonylureas, 84–86, 506
ingestion, 320 Sulfur dioxide, 251–252
hydroxide, 229 Sunscreen, 314
hypochlorite, 186 Superwarfarins, 332
monofluoroacetate, 334–335 Supportive care, 271, 279, 428
nitroprusside, 183 Symmetric ascending paralysis, 207
opener toxicity, 426 Sympathetic adrenergic overstimulation,
thiosulfate, 466, 475 117
Sodium polystyrene sulfonate (SPS), 529 Sympathomimetic toxidrome, 31, 133
Solanine, 427–428 Sympathomimetics, 72
containing plants, 427 Symptomatic methemoglobinemia, 500
Soluble oxalates, 425 Syndrome of inappropriate anti-diuretic
Soluble oxalic acid, 229 hormone (SIADH), 65
Somatostatin peptide, 505 Syndromes
Spanish fly, 381 acute radiation, 245
Speedball, 133 Adams-Stokes, 498
Sphingomyelinase D, 370 amotivational, 147
Spiders CNS/CV, 247
Australian funnel-web, 380 diarrhea, 387
hobo, 379 eosinophilia-myalgia, 391
six-eyed crab, 380 febrile, 308
yellow sac, 379 gastrointestinal, 246
SPS. See Sodium polystyrene sulfonate gray baby, 29
SSDS. See Sudden sniffing death hematopoietic, 246
syndrome Hoigne, 29
SSRIs. See Selective serotonin reuptake hypersensitivity, 33
inhibitors hypertoxic myopathic, 368
St. Anthony’s Fire, 79 intermediate, 327
Stannosis, 306 Irukandji, 399
Stevens-Johnson syndrome, 543 Korsakoff’s, 521
Stibine, 261 Munchausen’s, 90
Stinging nettle, 421 neuroleptic malignant, 20, 457
Stingray, 544 NMS, 20, 457
Stingray envenomations, 401 propofol infusion, 23, 513
Stingray injury, 400 puppy glove, 509
Stonefish, 401 red man, 29
Strength aspirin tablets, 111 serotonin, 38, 39, 42, 138, 289, 464
Strobilurins, 313 Stevens-Johnson, 543
Stropharia, 407 sudden sniffing death, 145
Strychnine, 249–251, 335–337 withdrawal, 114
lethal doses of, 250 Wolff-Parkinson-White, 498–499
Strychnos, 430 Synergistic vasodilation, 101
STX. See Saxitoxin Synthetic chlorinated organic
Succimer, 519 compounds, 239
Succinylcholine, 99, 504, 505 Systemic involvement, 438
Sudden sniffing death syndrome Systemic loxoscelism, 370
(SSDS), 145 Systemic oxalic acid toxicity, 230
Sulfhydryl groups, 293, 303 Systemic oxygen utilization, 249
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574 Index
T-2 exposure, 413, 414 digoxin immune fab, 471–473

Tachycardia, 58, 73, 143, 352 dimercaprol, 473–474
biventricular, 75 dimercaptopropanesulfonic acid,
polymorphic ventricular, 7 470–471
QRS-complex, 119 diphenyhydramine, 476
reflex, 58, 126, 508 ethanol, 477–478
sinus, 41 euglycemia, 122
Tachydysrhythmias, 120, 417, 523 flumazenil, 478–479
TBE. See Tick-borne encephalitis folic acid, 479–480
TBRF. See Tick-borne relapsing fever fomepizole (4-methylpyrazole, 4-MP),
Tea, 60 480–481
Terminal R wave, 35 glucagon, 481–483
Terrorism. See Chemical agents of haloperidol/droperidol, 484–486
terrorism histamine-2 receptor antagonists, 486
Tertiary amines, 31 hydroxocobalamin, 487–488
Tetanus, 336, 439–442 hyperbaric oxygen, 488–490
cephalic, 441 hyperinsulinemic-euglycemic, 484,
immune globulin, 442, 443 493
localized, 441 inamrinone, 491
natural toxins, 439–442 insulin, 492–494
neonatal, 441 iodide, 494–495
prophylaxis, 442 isoproterenol, 496–497
toxoid, 443 leucovorin, 497–498
Tetracaine, 23 magnesium, 499
Tetraethylthiuram disulfide, 76 methylene blue, 500–501
Tetramine, 340, 341 NAC, 445
Tetrodotoxin (TTX), 367, 392, 542 naloxone, 502–503
Thallium, 303–305 oral glucose, 83
THC. See Delta-9-tetrahydrocannabinol oxygen, 269
Theophylline, 115–116, 452 phentolamine, 508
Therapies, 444–530 polyvalent immune Fab, 448
acetylcysteine, 444–446 pralidoxime, 510–512
antiemetics, 166 prophylactic vitamin K, 130
antivenom, 446–447 propofol, 512–513
barbiturates, 451–452 propranolol, 514–515
benzodiazepines, 453 protamine, 515–516
benztropine, 454 Prussian blue, 516–517
bicarbonate, 454–456 pyridoxine, 517–518
bromocriptine, 457–458 silibinin/milk thistle, 518
calcium, 458–460 succimer, 519
calcium disodium ethylenediaminete- thiamine (Vitamin B1), 519–521
traacetic acid, 460–461 vasopressors, 521–525
charcoal, 462–464 vitamin K1, 525–526
cyanide antidote package, 465–466 Thermite, 345
cyproheptadine, 463–464 Thermometers, 293
dantrolene, 467 Thiamine, 195, 520
deferoxamine, 467–469 Thiocyanate, 102
dialysis, 469–470 Thrombocytopenia, 103, 299, 448
diethyldithiocarbamate, 471 Thyroid hormones, 117–118
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Index 575
Tiagabine, 33 glufosinate, 320

TIBC. See Total iron-binding capacity glycol, 194
Tick-borne encephalitis (TBE), 376 gold, 281
Tick-borne relapsing fever (TBRF), imidacloprid, 330
377 lithium, 95, 96
Ticks, 372–378 low acute, 147
Tin, 305–306 magnesium, 97
inhalation, 305 manganese, 159, 291–292
toxicity, 306 manifestations, 403
Tissue preservatives, 158 methotrexate, 497
Tissue toxicity, 199 mustard, 361
Tocainamide, 120 opioids, 550
Tocainide, 121 pentachlorophenol, 232
Toluene, 252–254 perchloroethylene, 233
intoxication levels of, 253 phthalates, 238, 239
Topical analgesics, 63 prolonged, 31
Topical antifungal agents, 158 SMFA, 335
Topiramate, 33 sodium, 426
Total iron-binding capacity (TIBC), solanine, 428
285 strychnine, 250
Toxalbumin exposure, 429 systemic, 345, 368
Toxalbumin-producing bean, 359 systemic oxalic acid, 230
Toxic alcohol intoxication, 4, 140 thallium, 304
Toxic alcohols, 5 tissue, 199
Toxic effects, 73, 115 vitamin A, 127
Toxic ingestion, 547 vitamin E, 127
Toxic irritant gases, 204 wintergreen cause, 386
Toxic psychosis, 152 Toxicologic emergencies, 1
Toxicities Toxicology screen, 3
acetaminophen, 17 Toxicodenderon, 420
acute, 159 Toxidromes, 2–3, 2t
of arsine, 263 Toxin-induced agitation, 485
of botulinum, 342 Track marks, 545
of caffeine, 62 Traditional cyanide antidote kit, 488
camphor, 169, 386 Tramadol, 150
chronic, 116 Transferrin, 283
chronic glycol, 206 Traveler’s diarrhea, 388
chronic lithium, 290 Trialkyltin, 312
chronic phenol, 235 Tributyltin, 312
copper, 277 Trichloroethane, 254–255
delayed-onset pulmonary, 225 Trichloroethanol, 233
dermal, 169, 306 Trichloroethylene, 254–255
of detergents, 185 Trichothecenes, 413
of dextromethorphan, 139 mycotoxins, 359–360, 412
digoxin, 459 Tricyclic antidepressants, 64
of dinitrophenol, 232 Trifloxystrobin, 313
dioxins, 189 Tripping, 143
formaldehyde, 202 Trivalent, 259
of freons, 203 Troglitazone, 86
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576 Index
TTX. See Tetrodotoxin Veratrum, 427

TTX poisoning, 395 Vertebrates, 400–402
Tularemia, 375 Vesicants, 360–363
Type 2 diabetes, 87 Vespid wasp venom, 379
Type I antidysrhythmic agents, 118–121 Vibrio parahemolyticus, 388
Type II antidysrhythmic agents, Vietnam War, 314
121–122 Vildagliptin, 87
Type III antidysrhythmic agents, Vinclozolin, 312
122–123 Vinca alkaloid poisoning, 431
Type IV antidysrhythmic agents, Vineyard sprayer’s lung, 278
123–124 Viperidae, 434–436
Type IV hypersensitivity, 296 Vitamin A toxicity, 127
Typical antipsychotics, 52 Vitamin E toxicity, 127
Tyramine, 37 Vitamin K1, 130, 525–526
Vitamins, 126–130, 519–521, 525–526
Volatilized nerve agent poisoning,
Ultra-potent opioids, 344 349
Unbound toxin, 442 Vomiting, 32, 77, 148, 483
Union Carbide Plant, 214 agents, 363–364
Urea metabolism, 200
Urinary alkalinization, 456
Urine drug screening, 6–7
Warfarins, 51, 129–131
Urticaria, 470
metabolism of, 130
skin necrosis, 130
super, 332
Vacor (PNU), 337–338
toxicity, 526
Valproic acid, 124–125
Warm water immersion, 542
Vanadium
Warning property, 205
excretion of, 307
Wasps, 378, 379
pentoxide, 306
WBI. See Whole bowel irrigation
Vancomycin, 28
Weakness, 32
Vasoconstriction, 73
Weight-loss drugs, 77
Vasodilation, 225
Wernicke’s encephalopathy, 520
peripheral, 100
Whippets, 227
synergistic, 101
White phosphorus, 237, 345
Vasodilators, 125–126
Whole bowel irrigation (WBI), 14
Vasopressors, 26, 521–525
Wilson’s disease, 278
Vecuronium, 505
Wintergreen poisoning, 386
Venlafaxine, 42
Withdrawal syndrome, 114
Venom
Wolff-Parkinson-White syndrome,
black widows, 368
498–499
Bufo toad, 366
Wool-sorter’s disease, 364
components, 370
Wound botulism, 384
crotalid, 435
sea snake, 402
vespid wasp, 379
Venomous lizards, 437 Xanthine dehydrogenase, 295
Ventricular tachydysrhythmias, 120 Xanthine oxidase, 295
Verapamil, 123 Xerostomia, 40
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Index 577
Yellow oleander, 418 Zinc, 307–309

Yellow rain, 413 chloride, 307
Yellow sac spider, 379 oxide, 307
Yersinia enterocolitica, 468 phosphide, 308
Yohimbine, 391 Zolpidem, 113
Ytterbium, 300 Zygomycetes, 468

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13486_FM.

qxd 11/1/08 1:16 AM Page i

RECALL SERIES EDITOR

JOHN P. BENNER, NREMT-P

Acquisitions Editor: Charles W. Mitchell

Copyright © 2010 Lippincott Williams & Wilkins, a Wolters Kluwer business.

351 West Camden Street 530 Walnut Street

Library of Congress Cataloging-in-Publication Data

We wish to acknowledge our spectacular Administrative Assistants, Heather

Seth Althoff, MD Jeffrey D. Ferguson, MD,

Brian T. Fengler, MD Nicholas D. Hartman

Joshua Hilton, MD Todd Larson

Brian B. Hughley Richard M. Law

Jason A. Inofuentes Benjamin J. Lehman, MD

James Platts-Mills Stephen Stacey

1 Evaluation of the Poisoned Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Valproic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

Ethylene Oxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195

7 Chemical Agents of Terrorism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342

Gastrointestinal Irritants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422

Folic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479

Chapter 1 Evaluation of the

Toxicologic emergencies are commonly encountered in the practice of

When evaluating a patient who has presented with a potential poisoning, it is

monitor urinary output, as this is one of the best indicators of adequate

Table 1-1. Toxidromes

Anticholinergic Mydriasis, dry skin, dry mucous membranes, decreased

Cholinergic Miosis, lacrimation, diaphoresis, bronchospasm,

Opioid Sedation, miosis, decreased bowel sounds, decreased

Sedative-hypnotic Sedation, decreased respirations, normal pupil size,

Serotonin syndrome Altered mental status, tachycardia, hypertension,

Sympathomimetic Agitation, mydriasis, tachycardia, hypertension,

Chapter 1 / Evaluation of the Poisoned Patient 3

toxidromes and their characteristics. It is important to note that patients may

When evaluating the intoxicated patient, there is no substitute for a thorough

Anion gap [Na] [Cl HCO3]

This equation allows one to determine if serum electroneutrality is being

bicarbonate) are represented in the equation. There are other contributors to

It is imperative that clinicians who admit poisoned patients initially

Chapter 1 / Evaluation of the Poisoned Patient 5

solution (mOsm/L)]. This concentration can be measured by use of an

[BUN] [glucose] [ethanol] [methanol]

[ethylene glycol] [isopropanol]

If a significant osmol gap is discovered, the difference in the two values

Table 1-2. Toxins Causing Elevated Osmol Gap

Osmotic contrast dyes

ingestion. If the osmol gap obtained is particularly large, it suggests that an

URINE DRUG SCREENING

Chapter 1 / Evaluation of the Poisoned Patient 7

co-ingestions. Conversely, many drugs of abuse (e.g., ketamine, fentanyl) are

QT prolongation is considered to occur when the corrected QT interval (QTC)

Chapter 1 / Evaluation of the Poisoned Patient 9

Table 1-3. Potassium Efflux Channel Blocking Drugs

Table 1-4. Sodium Channel Blocking Drugs

Class IA antidysrhythmics Orphenadrine

treat empirically with 1-2 mEq/kg of sodium bicarbonate. A post-treatment

After initial evaluation and stabilization of the poisoned patient, it is time to

Chapter 1 / Evaluation of the Poisoned Patient 11

DECONTAMINATING THE POISONED PATIENT

Chapter 1 / Evaluation of the Poisoned Patient 13