Chemical & Drug Injuries

Chemical & Drug Injuries
Chemical & drug injuries

***All chemicals & drugs are capable of causing
injury or death.***
 accidental exposure
 self-administration
 accidental overdose
 non-medical use of street drugs
 unanticipated result of self-administered or
prescribed use of standard medicines.
 exaggeration of an intended pharmacologic effect
or an accompanying side effect
Adverse drug reactions (ADRs)
 any response to a drug that is noxious & unintended,
occuring at doses used in humans for prophylaxis,
diagnosis, or therapy, excluding failure to accomplish
the intended purpose; [mechanisms: direct toxicity to
cells; immunologic/idiosyncratic reactions; or due to
↓immunologic / hormonal host defenses]
Predictable ADRs: known side-effects; dose-related,
severity depends on route of administration
Unpredictable ADRs: unanticipated, usually
immunologic, idiosyncratic; dose & route of
administration do not affect the severity
Therapeutic agents
 ANALGESICS
 Aspirin
 Aspirin + Phenacetin
 NSAIDS (non-steroidal anti-inflammatory drugs): Ibuprofen,
Diclofenac,
 Acetaminophen/Paracetamol
 ANTIMICROBIALS
 ANTI-NEOPLASTIC AGENTS
 Anti-metabolites
 Immunosuppressives
Therapeutic agents: aspirin
 Therapeutic dose: 0.5-1.0 gm./day
 Lethal dose: 2-4 gm./day in children
10-30 gm./day in adults
 Acute toxicity: initial alkalosis--- fluid & electrolyte
imbalance--- metabolic acidosis--- death
 Chronic toxicity: (3 gm/day): dizziness, nausea,
vomiting, diarrhea, drowsiness, hallucinations,
convulsions, coma
 Known effects: analgesic; anti-platelet aggregation;
gastric irritant--- acute erosive gastritis
 Unpredictable ADRs: hypersensitivity: rashes,
urticaria, exfoliative dermatoses
Therapeutic agents: analgesics
 Aspirin + Phenacetin
 Toxicity: nephropathy : renal papillary necrosis
 NSAIDS:
 known side effect: gastric irritation;
 UADR: hypersensitivity
 Acetaminophen:
 therapeutic dose: 0.5 gm q 4 hrs.(up to 3gm/day)
 toxic dose: 15-25 gm;
 toxicity: nausea, vomiting, diarrhea; shock; hepatic injury
 pathology: hepatic necrosis; renal/myocardial damage
Therapeutic agents: anti-neoplastics
 Anti-metabolites
 Bone marrow suppression
 GI mucosal injury
 Hair follicle injury
 Immunosuppression
 Nonlethal mutations
 Initiation of some form of Cancer
 Immunosuppressives
 ↑ susceptibility to infections, esp. opportunistic
 ↑ risk of malignant lymphoma
Therapeutic agents:
antimicrobials/antibiotics
Hypersensitivity
 rashes, urticaria, exfoliative dermatoses
 anaphylaxis
Emergence of microbial resistance
 “super-infections”
Eradication of normal flora
 vitamin K deficiency--- bleeding diathesis
Common adverse drug reactions
& major offenders
 BLOOD (DYSCRACIAS)  BLOOD DYSCRACIAS
 Granulocytopenia  Anti-neoplastics
 Aplastic anemia  Immunosuppressants
 Pancytopenia  Chloramphenicol
 Hemolytic anemia  Quinidine
 thrombocytopenia  Methyldopa
 CNS  CNS
 Tinnitus, dizziness  Salicylates
 Acute dystonic reactions  Phenothiazine antipsychotics
 Parkinson’s syndrome  Sedatives
 CUTANEOUS  CUTANEOUS
 Urticaria  Sulfonamides
 Petechia  Hydantoin
 Exfoliative dermatitis  Anti-neoplastics
Common adverse drug reactions &
major offenders
 CARDIAC  CARDIAC
 Arrhythmias  Theophylline
 Cardiomyopathy  Hydantoin
 Doxorubicin, Daunorubicin
 HEPATIC  HEPATIC
 Fatty change  Tetracycline
 Cholestasis  Chlorpromazine, Estrogens
 Hepatocellular damage  Halothane, Acetaminophen,
INH
 PULMONARY  PULMONARY
 Acute Pneumonitis  Salicylates
 Interstitial fibrosis  Nitrofurantoin
 Asthma  Busulfan, Bleomycin
Common adverse drug reactions &
major offenders
 RENAL  RENAL
 Glomerulonephritis  Penicillamine
 Tubulointerstitial nephritis  Phenacetin, Salicylates
 Acute tubular nephritis  Aminoglycosides,
Cyclosporine, Amphotericin B
 SYSTEMIC  SYSTEMIC
 Anaphylaxis  Penicillin, Aspirin
 Lupus erythematosus  Hydralazine, Procainamide
syndrome
Common agents implicated in
fatal reactions
 Tricyclic anti-depressants  CNS depression
 Alprazolam
 Ipramine, Desipramine
 Nortriptyline
 Acetaminophen  Hepatic necrosis

 Halothane  Hepatic necrosis
 Aspirin  Metabolic acidosis; Fluid &
Electrolyte imbalance
non-medical use of street drugs
 Marijuana:  Euphoria; cognitive,

psychomotor, & sensory
delta-9-tetrahydrocannabinol alteration; but can reduce
in the resin of Cannabis sativa nausea in CA chemoTx, relieve
pain in tic doloreaux, can treat
glaucoma, convulsive seizures,
& asthma
 Shabu: metampethamine
 Sympathomimetic : Euphoria,
Tachycardia, Hyperytension
 Ecstasy:
MethyleneDioxyMetAmpethamine  Sympathomimetic: Euphoria,
Tachycardia, Hypertension
Non-medical use of street drugs
 Cocaine: alkaloid extract  potent CNS stimulant;

cardiorespiratory toxicity;
from the leaves of the Coca perinatal morbidity &
plant: pure- Crack; mortality; but effective
Cocaine hydrochloride local anesthetic
 Feelings of well-being,
 Heroin: opiate derived tranquility, sedation;
from the Poppy plant; the multisystem toxicity;
most hazardous street drug- infections, granulomas;
produces True Addiction sudden death from
(physical dependence) & overdose
intense fear of withdrawal
(“I’ll die without it”)
Non-therapeutic
chemicals
 Ethyl Alcohol: Acetaldehyde
 10 gm in 12 oz beer, 4 oz unfortified wine, or 1.5 oz 80-proof liquor
 rapidly absorbed in the stomach & small intestines
 Metabolized by the liver at the rate of 10gm/hr
 Acute intoxication: mainly affects the CNS & Stomach
• 20-30mg/dL= powerful depressant effect on cortical inhibitory
centers= loss of inhibitions= “party” syndrome; Euphoria;
disordered cognitive & motor functions
• 100mg/dL= legal level of intoxication= Ataxia
• 200-250mg/dL= narcosis= drowsiness
• 300-400mg/dL= coma; profound anesthesia; death
Non-therapeutic agents:
ethyl alcohol
 Chronic Alcoholism: induces injuries in all tissues
 Liver - most commonly & severely affected= fatty change, acute
hepatitis--- Cirrhosis
 CNS – Wernicke’s encephalopathy- ataxia, global confusion,
ophthalmoplegia, loss of neuropil & demyelination (vit B1 def) &
Korsakoff syndrome- profound memory deficit both recent & remote;
cerebellar degeneration; cerebral atrophy
 Fetal Alcohol Syndrome: microcephaly, cardiac defects, mental
deficiency, facial malformations
 Misc.: neuropathies; congestive cardiomyopathy; ↑frequency of
cancer in the larynx, oropharynx, esophagus, rectum, lung
Uncommon potentially fatal
nontherapeutic agents
 ARSENIC- in rat poison,  Nausea, vomiting, visceral
fruit sprays, weed killer; hemorrhages, liver & lung
binds sulfhydril CA
 CARBON MONOXIDE-  Systemic asphyxia: 1% fatal
odorless, tasteless, in in 10-20 min, 7% fatal in 5
cigarette smoke, fossil fuel min: cherry red
exhaust discoloration of mucosae
 CARBON  Centrilobular necrosis,
TETRACHLORIDE & Liver; renal ATN
CHLOROFORM
 CYANIDE- gas causes death  Histotoxic hypoxia; binds
within minutes; salts (100mg), cytochrome oxidase- cherry
within hours; antidote: Nitrite red discoloration, bitter
 INSECTICIDES almond odor
 Chlorinated hydrocarbons: chlordane,  Insecticides
Aldrin, DDT  Toxic neuronal injury
hyperexcitability,delirium,
 Organophosphates: Malathion, convulsions, coma
Pyrophosphates, Dimpylate  Muscle twitching, flaccid paralysis,
cardiac arrhythmias
 Chloracne, impotence, infertility
 Polychlorinated biphenyls: PCBs
 KEROSENE- accidental  Fulminant
ingestion or inhalation of bronchopneumonia; lipoid
fumes pneumonia; CNS depression
 Lead colic; lead line on gums;
 LEAD- paint, water (pipes), basophilic stippling of RBC;
newsprint, pottery glazes, gas anemia; encephalopathy;
exhaust, tin cans, moonshine demyelinating neuropathy
whiskey, occupational  Eosinophilic globules in renal
exposure tubules; neuronal toxicity;
 MERCURY- contaminated gingival deposits; “Minamata
fish, grain,fungicides, dse”- blindness, hearing loss,
dermatologic ointments, spasticity, paralysis
interior latex paints
 METHANOL- in solvents, paint Metabolic acidosis; CNS
removers, & anti-freeze; toxic depression; retinal ganglion
metabolite is Formalin necrosis= blindness
 POISONOUS MUSHROOMS  MUSHROOMS
 Amanita muscaria – rarely  Immediate
lethal; active metabolite is parasympathomimetic
muscarin effects: salivation, sweating,
miosis, bradycardia,
hypotension, GI Sx
 Amanita phalloides –death rate  Cardiovascular collapse;
is 30-50%; active metabolite is convulsions, coma, ATN,
amanitin centrilobular necrosis
Poisonous mushrooms
Amanita muscaria Amanita phalloides

Chemical & Drug Injuries

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Chemical & Drug Injuries

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Chemical & Drug Injuries

Chemical & drug injuries

 Acetaminophen  Hepatic necrosis

 Marijuana:  Euphoria; cognitive,

 Cocaine: alkaloid extract  potent CNS stimulant;

Amanita muscaria Amanita phalloides

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