Pharmacology o uses genetic engineering to alter bacteria to

• from Greek φάρμακον, pharmakon, "drug"; and produce chemicals that are therapeutic and
-λογία, -logia, “study” effective
• how drugs interact within biological systems to  Inorganic Compounds
affect function o salts of various elements (have therapeutic
• study of the interactions that occur: effects in the human body)
– between a living organism o used to treat various conditions
– exogenous chemicals that alter normal o aluminum (antacid for hyperacidity)
biochemical function. o fluoride (prevention of dental carries and
Drug osteoporosis)
 substance (or mixture of substances) used in the:
o diagnosis Drug Classifications
o cure  Prescription
o treatment o an order (often in written form) by a qualified
o prevention of disease  health care professional to a pharmacist or
 Pharmacodynamics other therapist for a specific treatment to be
o study of the biochemical and physiological provided to their patient
o COMPONENTS
effects of drugs
o drug’s mechanism of action  Date & time the drug is written
 Drug name
 Pharmacokinetics
 Drug dosage
o study of the absorption, distribution,
 Route of administration
biotransformation (metabolism) and excretion
 Frequency & duration of administration
of drugs
 Signature of the physician
o LADME (liberation, absorption, distribution,
 Non-Prescription
metabolism, and Excretion)
o Over-the-counter medications
 Other Terms
 Investigational
o PHARMACOTHERAPEUTICS
o subjected to clinical studies in order to evaluate
 study of how drugs may best be used in the
the usefulness of the drug in treating the
treatment of illnesses
disease it claims to affect
 which drug would be most or least
 Illicit Drugs or Street Drugs
appropriate to use for a specific disease
o Distributed illegally; are used for non-medical
 what dose would be required.
o PHARMACOGNOSY purposes, generally to alter mood or feeling
o E.g. Heroin, Nubain, Cytotec
 study of drugs derived from herbal and
other natural sources   Orphan
o TOXICOLOGY o For a rare disease (affecting fewer than 200,000
 study of poisons and poisonings; deals with in the US)
the toxic effects of substances on the living o Study of these drugs often neglected because
organism. profits from sales may not be enough to cover
costs of development
Sources of drugs
 Plants Pregnancy Categories
o digitalis (purple foxglove)  Category A - Adequate and well-controlled studies
o vincristine (periwinkle) have not shown a risk to the fetus in the first
o morphine (opium) trimester of pregnancy (and there is no evidence of
 Animals risk in later trimesters).
o Insulin (from pigs and cows)  Category B - Animal reproduction studies have
o Vaccine - killed/attenuated microorganisms failed to demonstrate a risk to the fetus and there
from horses are no adequate and well-controlled studies in
 Synthetics pregnant women.
 Category C - Animal reproduction studies have
shown an adverse effect on the fetus and there are
 no adequate and well-controlled studies in humans,  American Journal of Nursing
but potential benefits may warrant use of the drug  Internet
in pregnant women despite potential risks.
 Category D - There is positive evidence of human
fetal risk based on adverse reaction data from The Nursing Process in Pharmacology
investigational or marketing experience or studies  Assessment
in humans, but potential benefits may warrant use o Forms basis on which the care is:
of the drug in pregnant women despite potential  Planned
risks.  Implemented
 Category X - Studies in animals or humans have  Evaluated
demonstrated fetal abnormalities and/or there is o Assess for:
positive evidence of human fetal risk based on  Findings/Cues
adverse reaction data from investigational or  Subjective cues
marketing experience, and the risks involved in use  Objective cues
of the drug in pregnant women clearly outweigh  Drug history
potential benefits. o Drug History
NOTE: A= Absolutely use it. B=Better to use it or  to evaluate the patient’s need for
benefits outweigh the risks. C=Cutting too medication
close. Could use it. D= Don’t use it. X= Cross it out. It’s  to obtain current and past use of medicines
contraindicated. (OTC medicines, prescribed medicines,
herbal products, illicit drugs)
Drug Names  to identify problems related to drug therapy
 Chemical  to identify risk factors in drug therapy
o systematically derived name which identifies  Diagnosis
the chemical structure of the drug; shows the o Based on analysis of the assessment data
exact chemical constitution of the drug and o May be actual or potential
exact placing of atoms o Examples:
o e.g. N- Acetyl-para-aminophenol  KNOWLEDGE DEFICIT r/t LACK OF
 Generic EXPERIENCE WITH MEDICATION REGIMEN
o given before drug becomes official; reflects AND SECOND GRADE READING LEVEL AS AN
some important pharmacological or chemical ADULT AS EVIDENCED BY INABILITY TO
characteristic of the drug PERFORM A RETURN DEMONSTRATION
o e.g. acetaminophen AND INABILITY TO STATE ADVERESE
 Brand EFFECTS TO REPORT TO THE PRESCRIBER
o followed by the symbol ®  RISK for INJURY R/T forgetfulness
o indicates the name is registered, that its use is  INEFFECTIVE THERAPEUTIC REGIMEN
restricted to the owner of the drug (usually the MANAGEMENT R/T lack of finances
manufacturer of the product)  Planning
o Tylenol o characterized by goal setting (or expected
outcomes) which represent effectiveness of
Sources of drug information nursing care:
 Sources of Drug Information  patient goals
o Pharmacopoeia  state of desired patient behaviors or
o Formulary responses
o Nursing textbook o Include:
o Package insert  identification of the therapeutic intent for
o Reference books every medication
o PDR  side effects to be expected and reported
o Drug facts & comparisons  identification of the recommended dosage
o Nursing drug guide/ handbook and route of administration
o Journals  scheduling of the administration of
 Medical letter medication
  teaching the patient to keep written records o Short gut syndrome (has decreased absorption
of his responses capacity compared to a normal person)
 additional teaching as needed:  Psychological
 techniques of administration, proper o Attitudes and expectations
storage of medication o Willingness to take the medications as
o Implementation prescribed (compliance)
 Nursing actions necessary to achieve  Dependence
outcomes: o also known as addiction or habituation
 Independent o withdrawal symptoms (physical)
 Dependent o emotionally attached to the drug (emotional)
 Interdependent  Tolerance
 Include: o when higher doses are required to produce the
 Client teaching and education same effect that lower doses once provided
 ADMINISTRATION OF DRUG o May be caused by psychological dependence
 ASSESSMENT of DRUG EFFECTIVENESS  Cumulative Effects
 SELF-ADMINISTRATION o if the next doses are administered before
 DIET previously dose was fully metabolized
 SIDE EFFECTS o may result in drug toxicity
 CULTURAL CONSIDERATIONS o rate of consumption exceeds rate of
o Evaluation metabolism
 On-going process that assesses for:
 effectiveness of the medication (as Drug interactions
prescribed)  Additive
 observation of signs and symptoms of o 2 drugs with similar effects lead to a double
recurring illness effect (1+1=2)
 development of the side/ adverse  Synergistic
effects o the combined effect of 2 drugs is ≥ the sum of
 effectiveness of the health teaching or the effect of each drug given alone
client education o Ex: ampicillin + sulbactam= prolonged action of
the antibiotic
Factors influencing drug action  Antagonistic
 Age o 1 drug interferes with the action of another
o extremes of age are most sensitive to dosage o Ex: tetracycline + antacid = DECREASE
and response: absorption of the tetracycline
 newborns  Interference
 infants o 1 drug inhibits the met. / excretion of a 2 nd drug,
 elderly causing INCREASE activity of the 2nd drug
 Body Weight o Ex: probenecid + spectinomycin = PROLONGED
o Dosage depends on the weight antibacterial activity from spectinomycin due to
 overweight (increase) blocking renal excretion by probenecid
 underweight (decrease)  Incompatibility
Note: Pediatrics always uses mg/kg o should not be mixed together or administered at
 Metabolism/Genetics the same site;
o Individual genetic susceptibilities metabolize o signs are haziness, a precipitate, or a change in
medications differently color of solution when mixed
o Lack of enzymes may prolong plasma level (and  ampicillin + gentamicin = amp. inactivates
increase risk of toxicity) gentamicin
o Field of pharmacogenomics
 Illnesses Other Terminologies
o pathologic conditions alter rate of absorption,  Desired action
distribution, metabolism and excretion o Expected response
 Side effect
 o Effect other than what is intended (due to o Agonist (produces a response)
pharmacological effects of the drug); occurs o Antagonist (counters/depresses the response
when the medication is administered regardless  Used in antidote therapies
of the dose.

 Adverse effect
o Range of undesirable responses (unintended Phases of Clinical trials
and at normal doses) which can cause mild to Phase Subjects Description
severe reactions
o An adverse event is an undesired occurrence • Determines dose-
that results from taking a medication correctly. response relationship and
o Toxicity pharmacokinetics of the
o Severe adverse effect (with the quality of being Normal new drug (exception is a
poisonous) I human cancer drug)
 Carcinogenicity volunteers • Effects of dosages
o Ability to induce cells to mutate and become are observed (to
malignant determine significant
o Teratogenicity - Induces birth defects response or toxic effect)
Small
Reactions to drugs • Effect is compared
number of
 Photosensitivity - Sensitivity to light with a placebo
sick patients
o Skin II drug/agent (to determine
with target
o Eyes if agent truly has desired
disease
 Hypersensitivity (volunteers)
effect)
o Exaggerated immunologic response to a drug
(considered a foreign substance) Many human • Same above except
 Idiosyncratic volunteers with double-blind studies
o Occurs in first intake of drug (due to differences sick with • Effect is compared
in metabolism between individuals) target to standard or previous
III
disease up to treatment
Principles of Drug Actions 6000 cases in strategies/protocols/
 Drugs do not create new cellular functions (but only some agents
alter them) centers)
o antibiotic slows the growth and/or reproduction All patients • Post-marketing
of microbial organisms sick with surveillance
o drug action is relative to the physiological state IV target • Detects toxicities
which existed when the drug was administered. disease (as early to prevent major
 Drugs may interact with the body in several prescribed) therapeutic disasters
different ways
o alter the chemical composition of a body fluid
o accumulate in certain tissues because of their Guiding Principles (CHECK)
 Check why the medication is given & know the
affinity for a tissue component (forming a
classification of the drug
chemical bond with specific receptors with in
the body)  How will you know if the medication is effective?
What are your assessment parameters in
 Drug response (or strength of the effect) depends
monitoring the effects of the drug?
on the drug molecule’s fit in the receptor site
o Precise fit  strong effect  Exactly what time should the medication be given?
 Client teaching tips. What are the therapeutic and
o Loose fit  weak effect
side effects of the medication?
 Agonist-Antagonist drugs exert both agonist and
antagonist responses
 Keys to giving it safely. You should be able to o pH
identify interventions to counteract the adverse o Drug concentration
effects of the drug. o Dosage form
o Hepatic first-pass effect
o Enterohepatic recycling
o Route of administration
 Nature of absorbing surface
o Absorption through a single layer of
cells is faster compared to the multi-
layered skin
Phases of drug therapy  Respiratory epithelium (steroids)
Pharmaceutic  Intestinal epithelium (carbohydrates)
o Disintegration - Breakdown of a tablet into smaller  Hepatic First-Pass effect:Inactivation of
particle drugs by hepatic enzymes before the drug
o Dissolution - Dissolving process of the smaller reaches systemic circulation for distribution
particles in the GIT fluid prior to absorption o Bioavailability  percentage of
o Depends on: administered drug dose that reaches
 Rate limiting systemic circulation
 Time it takes for the drug to disintegrate,  Enterohepatic recycling:Absorption of drug
dissolve, and be available for the body to from bile into small bowel and then into
absorb circulating system
 Excipients  Route of Administration - Linked to the
 Fillers (inert substances/additives) to allow blood supply (vascularity)
a drug to take on a particular size and shape
Route of Factors Affecting
 Enhances drug dissolution
Administration Absorption
 Increases absorbability of a drug
 Examples: Intravenous (IV) Blood volume (vascularity)
o Potassium  Penicillin potassium
o Sodium  Penicillin G sodium Intramuscular (IM) and Perfusion, fat content, and
Subcutaneous (SQ) temperature
Pharmacokinetics Acidity of the stomach,
o Process of drug movement to achieve drug action length of time in stomach,
o Four (4) processes: (ADME) Oral blood flow to GIT,
 Absorption - Movement of drug particles from presence of interacting
GI tract to body fluids through passive or active food or drug
absorption, or pinocytosis
 Passive - Drug molecule moves from a Perfusion, integrity,
region of relatively higher to lover presence of food,
Mucus Membrane
concentration without requiring energy smoking, length of time in
 Active - Process that uses energy to actively the area
move a molecule across a cell membrane
o Pinocytosis (Cell Drinking) - Process by  Distribution-Process by which drug becomes
which cells carry the drug across the available to body fluids and body tissues
membranes through engulfing the drug  Factors influencing distribution:
particles o Blood flow
 Factors affecting absorption: o Affinity to body tissues
o Blood flow o Protein-binding effect
o Pain  Manner of Distribution
o Stress and food o Protein-binding - Drugs that bind with
o Exercise specific protein components such as:
o Nature of the absorbing surface  Bound portion is inactive (does not
o Drug solubility exert pharmacologic response)
  Unbound portion is active (free
1 2 hours 10 mg 50%
drug)
 Toxicity may occur: 2 4 hours 5 mg 25%
 Too much of free-circulating
drugWhen 2 highly-protein 3 6 hours 2.5 mg 12.5%
bound drugs are given to a 4 8 hours 1.25 mg 6.25%
patient with liver disease or low
albumin
o Blood-brain barrier - Protective system  Excretion
of cellular activity (keeps foreign  Process of eliminating substances by body
invaders/poisons away from CNS) organs or tissues (as part of natural
 Highly lipid-soluble drugs most metabolic activity)
likely to pass through blood-brain  Kidneys (main route of elimination [free,
barrier water-soluble, and unbound drugs])
 Antibiotics cannot pass through  Urine pH  influences drug excretion
 CNS effects by medications result o Acidic  elimination of weak base
from indirect processes and not by drugs
the actual response of the CNS to o Alkaline  elimination of weak acid
the drug drugs
o Placenta (and breastmilk)  Others (bile, feces, lungs, saliva, sweat,
 Drugs readily pass through (can breastmilk)
affect the developing fetus)
 Secreted into breastmilk Summary of Pharmacokinetics
Categor
Description
y

A NO RISK evident
NO RISK evident in human or animal
B
studies
C RISK cannot be ruled out
D (+) evidence of risk exists
X CONTRAINDICATED in pregnancy

 Metabolism-Chemical changes a substance

undergoes in the body (such as through
enzymatic action)
 Drugs are metabolized in both GI tract and
liver
 Most drugs inactivated by liver enzymes
and converted into water-soluble
substances (for renal excretion)
 Half-life (t ½) -Time it takes for ½ of the
drug concentration to be eliminated
Pharmacodynamics
o First order - Proportional rate of
o Study of drug concentration and its effects on the
elimination to concentration
body
o Zero order - Constant rate of
o Drug response can cause a primary and secondary
elimination regardless of concentration
physiologic effect
T1/ Time Dosage (at  Primary  desirable
Percentage left
2 Elapsed 20mg start)  Secondary  may or may not be desirable
  Example:
 Diphenhydramine HCL (1st generation
antihistamine)
o Treats allergies (primary)
o CNS depression (secondary)
o Receptor Theory:
 Drugs act through receptors by binding through
a receptor to produce (initiate) a response or to
block (prevent) a response
o Drug Actions:
 Replace or act as substitutes for missing
chemicals
 Increase or stimulate certain cellular activities
 Depress or slow cellular activities
 Interfere with the functioning of foreign cells
(such as invading microorganisms)
o Onset of Action:Time it takes to reach the minimum
effective concentration (MEC) after a drug is
administered
o Peak of Action:Condition that occurs when the drug
reaches its highest blood or plasma concentration
o Duration of Action:Length of time the drug exerts a
pharmacological effect
o Agonists:Drugs that produce a response
o Antagonists:Drugs that block a response
o Therapeutic Index:Measures margin of safety of a
drug
 Narrow margin of safety (low therapeutic index)
 Wide margin of safety (high therapeutic index)
 The closer the ratio is to “1”, the greater the
danger of toxicity
o Therapeutic Range (therapeutic window):Between
minimum effective concentration in the plasma and
minimum toxic concentration
 e.g. Paracetamol (10 mg to 15 mg /kg)
o Peak Drug Level:Highest plasma concentration of a
drug at a specific time
o Trough Level:Lowest plasma concentration of a
drug and measures rate at which drug is eliminated
 Indicates rate of elimination of a drug
 o Binds to cholinergic receptors (causes
stimulation)
B. Indirect-acting
o Inhibits the enzyme, “cholinesterase”
 Result: more acetylcholine is
available at the receptors

Indirect-Acting Cholinergic Agents

- Reversible
o Binds cholinesterase for only minutes to
hours
- Irreversible
o Forms a permanent covalent bond
o Body needs to synthesize new
cholinesterase to use it
Drug Effects
- As seen when the PSNS is stimulated
- Rest and digest
SLUDGE:
o Salivation
o Lacrimation
o Urinary Incontinence
o Diarrhea
o Gastrointestinal cramps
o Emesis
- Stimulation:
o Intestines and bladder (gastric secretions,
CHOLINERGICS AND BLOCKERS motility, and urinary frequency)
o Pupils (constriction, and reduced
CHOLINERGIC AGENTS intraocular pressure)
- Drugs that stimulate the parasympathetic nervous o Salivary and sweat glands
system (opposes the SNS) - Cardiovascular
- Also known as: cholinergic agonists o Decreased heart rate
Parasympathomimetics o Vasodilation
- Mimics the effects of Acetylcholine (Ach) - Respiratory
- Two (2) types, determined by: o Bronchial constriction
o Location o Narrowed airways
o Action (once stimulated) - Dose-dependent:
o Nicotinic and Muscarinic receptors o Recommended (muscarinic receptors)
 Desired effects
Nicotinic Receptors o High doses (nicotinic receptors)
- Found in the ganglia of both PSNS and SNS  Undesirable effects
- Named because it can be stimulated by the alkaloid Clinical Uses
“nicotine” - Direct-acting agents:
o Reduce intraocular pressure (topical
Muscarinic Receptors application)
- Named because it can be stimulated by the alkaloid o Useful for glaucoma and intraocular surgery
“muscarine” o Drugs: acetylcholine
- Located postsynaptically: carbachol
o Smooth muscle pilocarpine
o Cardiac muscle
o Glands of parasympathetic fibers o Direct-acting agents: Bethanechol
o Effector organs of cholinergic sympathetic  Bladder and GI tract:
fibers  increases tone and
motility
Mechanism of Action  relaxes their sphincters
A. Direct-acting (agonist) (allows to empty)
  useful for postsurgical scopolamine ipratropium Isopropamide
atony
- Indirect-acting Agents: oxybutynin Propantheline
o Cause skeletal muscle contractions
o Useful for diagnosis and treatment of tolterodine trihexethyl
myasthenia gravis
o Used to reverse neuromuscular blocking Effects
agents and anticholinergic poisoning - Cardiovascular:
(antidote) o Small doses: decrease heart rate
o Drugs: physostigmine o Large doses: increase heart rate
Pyridostigmine - CNS
o Small doses: decrease muscle rigidity &
o Indirect-acting Agents: Donepezil Tremors
(Aricept) o Large doses: drowsiness,
 Treatment of mild to moderate disorientation, and
Alzheimer’s disease hallucinations
 Helps increase or maintain
memory and learning - Genitourinary
abilities o Relaxed detrusor muscle
Toxicity o Increased constriction of internal sphincter
Muscarinic Toxicity o Result: urinary retention
- CNS stimulation - Glandular
- Miosis (and spasm of accommodation) o Decreased bronchial secretions, salivation,
- Bronchoconstriction sweating
- Excessive GI and GU smooth muscle activity - Respiratory
- Increased secretory activity (sweat glands, lacrimal o Decreased bronchial secretions
glands, GI tract) o Dilated bronchial airways
- Vasodilation

Nicotinic Toxicity
- Ganglionic stimulation
- Fasciculations (and eventual paralysis) Clinical Uses
- Stimulation (convulsions) followed by depression CNS:
- Strongly addictive (even in small doses) - Decreases muscle rigidity and tremors (Parkinson’s
disease, and extrapyramidal reactions)
__________________________________________________ Respiratory:
- Asthma and bronchospasms (exercise-induced)
CHOLINERGIC BLOCKING AGENTS - Chronic bronchitis
- Drugs that block or inhibit the actions of - COPD
acetylcholine (ACh) in the PSNS Cardiovascular disorders:
- Sinus node dysfunction
Mechanism of Action - Symptomatic 2nd degree heart block
- Competitive antagonists - Sinus bradycardia with hemodynamic compromise
o Competes with ACh (for the same receptor (advanced life support)
site) Gastrointestinal:
- Block Ach at the muscarinic receptors in the PSNS - Peptic ulcer disease
o Once bound to these receptors, nerve - Irritable bowel disease
transmission is inhibited - GI hypersecretory states
o Result: ACh is unable to bind to receptor Poisoning:
site (and unable to cause - Parathion (can be given atropine as antidote)
its cholinergic effects)
Natural Synthetic Semisynthetic Toxicity
“Dry as a bone, hot as a pistol, red as a beet, mad as a hatter.”
atropine anisotropine clidinium
Treatment is symptomatic:
belladona dicyclomine glycopyrrolate o Hyperthermia (cooling blankets or
hyoscyamine hexocyclium homatropine evaporative cooling)
 o Severe tachycardia (low doses of  BZ2 mediates anti-anxiety and impairment of
physostigmine) cognitive functions

Barbiturates:
Central Nervous System Depressants - Prolong GABA activity
- Increase duration of Cl channel opening
Must Know Terms - Have GABA-mimetic activity at high doses
 Addiction - Do not act through BZ receptors
- State of response to a drug whereby drug taker - Have own binding sites on GABAA complex
feels compelled to use the drug, and suffers - Also inhibit complex I of electron transport chain
anxiety when separated from it (NADH coenzyme Q reductase)
 Anesthesia Sedatives
- Loss of consciousness associated with an - Drugs that have an inhibitory effect on the CNS
absence of response to pain - They reduce:
 Anxiolytic o Nervousness
- Drug that reduces anxiety; a sedative o Excitability
 Dependence o Irritability
- State of response to a drug whereby removal of o Without causing sleep
the drug evokes unpleasant, and possibly life- Hypnotics
threatening symptoms; often the opposite of the - Calm or soothe the CNS to the point that they
drug’s effects cause sleep
 Hypnosis
- Induction of sleep Sedative-Hypnotics
 REM sleep - Effects are dose-dependent:
- Phase of sleep associated with rapid eye o Low doses  Calm or soothe the CNS
movements; most dreaming takes place during o High doses  sleep
this stage
 Sedation Barbiturates
- Reduction of anxiety - First introduced in 1903
 Tolerance - Standard agents for insomnia and sedation
- Reduction in drug effect requiring an increase in  Habit-forming
dosage to maintain the same response - Only a handful are used today due to safety and
efficacy of Benzodiazepines
Principles regarding Sedatives and hypnotics  Have four (4) categories according to duration of
action:
Sedative-hypnotics a. Ultrashort:
- chemically heterogenous class of drugs which  Thiamylal
produce dose-dependent CNS depressant effects  Thiopental
- Ranges from sedation, to anesthesia, to b. Short:
respiratory depression, and death  Pentobarbital
- Major subgroup is the benzodiazepines  Secobarbital
- Other subgroups are still in use c. Intermediate:
o Barbiturates  Aprobarbital
o Miscellaneous agents (carbamates,  Butabarbital
alcohols, and cyclic ethers) d. Long:
Mechanisms:  Phenobarbital
 Activation of:  Narrow therapeutic index
o GABAA  inc. Cl influx o Range of the dosage is very limited/small
o GABAB  inc. K influx o Even a small increment above the dosage is
 Both result in hyperpolarization rapidly toxic
 Mechanism of Action:
Benzodiazepines: o Potentiate GABA (gamma-aminobutyric
- Potentiate GABA acid)
- Increase frequency of Cl channel opening  Site of Action:
- Act through BZ receptors (part of GABAA o Brainstem (reticular formation)
complex) o Cerebral cortex
 BZ1 mediates sedation  Drug Effects:
 o Low doses? Sedative Note: Zolpidem (Ambien) and Zaleplon (Sonata)
o High doses? Hypnotic (also lowers RR) are non-BZ agents which share the same
Notorious enzyme characteristics as hypnotic agents
inducers  Mechanism of Action:
 Therapeutic Uses: - Depress CNS activity
o Hypnotics - Affect hypothalamic, thalamic, and limbic
o Sedatives systems of the brain
o Anticonvulsants - Benzodiazepine receptors
o Surgical Procedures
 Side Effects:  Drug Effects:
o CNS? Drowsiness, vertigo, lethargy, - Calming effect on the CNS
mental depression, coma - Useful in controlling agitation and anxiety
o Respiratory? Respiratory depression,  Therapeutic Uses:
apnea, - Sedation, sleep induction
bronchospasms, - Skeletal muscle relaxation, anxiety relief
cough - Treatment of alcohol withdrawal
o GI? Nausea, vomiting, diarrhea - Agitation, depression, epilepsy
o Others? Agranulocytosis, vasodilation, - Balanced anesthesia
Benzodiazepines
Steven-Johnson syndrome,
Hypotension Drug Indications
 Toxicology:
- Overdose leads to respiratory depression  Alprazolam Anxiety, panic, and phobias
respiratory arrest
Anxiety, pre-operative sedation, muscle
- Therapeutic : anesthesia induction Diazepam
relaxation, and withdrawal states
uncontrollable seizures
(phenobarbital coma) Anxiety, pre-operative sedation, and
 Drug Interactions: Lorazepam
status epilepticus (IV)
- Additive? ETOH, antihistamines, narcotics,
benzodiazepines, Midazolam Pre-operative sedation, anesthesia (IV)
tranquilizers
Temazepam Sleep disorders
- Inhibited metabolism? MAOIs
(prolong its effects) Oxazepam Sleep disorders, and anxiety
- Increased metabolism? Reduces anticoagulant
response
 Side Effects:
(clots form)
- Mild and infrequent (HA, drowsiness, dizziness,
vertigo, lethargy, paradoxical excitement
Benzodiazepines
nervousness], “hangover effect”)
- Most commonly prescribed of the drug classes
 Nursing Implications:
- Favorable side effects
- Before beginning therapy, perform a thorough
- Better efficacy and safety
history regarding allergies, use
- Classified as either:
of other medications, health history, and
o Sedative-Hypnotic
medical history.
o Anxiolytic (relieves anxiety)
- Obtain baseline vital signs and I & O, including
 Sedative-Hypnotic:
supine and erect BPs.
- Long? Flurazepam (Dalmane)
- Assess for potential disorders or conditions that
Quazepam (Doral)
may be contraindications, and for potential drug
- Short? Estazolam (Prosom)
interactions.
Temazepam (Restoril)
- Patients should be instructed to avoid alcohol
and other CNS depressants.
Triazolam (Halcion) - Check with physician before taking any other
 Anxiolytics: medications, including OTC medications.
- Alprazolam (Xanax) - It may take 2 to 3 weeks to notice improved
- Chloridiazepoxide (Librium) sleep when taking barbiturates.
- Diazepam (Valium) - Abruptly stopping these medications, especially
- Lorazepam (Ativan) barbiturates, may cause rebound insomnia.
- Midazolam (Versed) - Safety is important
 (keep side rails up, do not allow smoking,  S-H drugs ideally should reduce anxiety without
assist patient with ambulation [especially affecting mental or motor function (but these get
the elderly], keep call light within reach) affected depending on the dose)
- Monitor for side effects  Most S-H drugs facilitate GABA action by binding to
- Monitor for therapeutic effects the GABAA receptor, which has one binding site for
o Increased ability to sleep at night barbiturates, and another for benzodiazepines.
o Fewer awakenings  Binding of drugs at these sites leads to increased Cl
o Shorter sleep induction time influx, potentiating the inhibitory transmitter effects
- Monitor for therapeutic effects of GABA.
o Few side effects, such as hangover  Differences in action in the various S-H drugs relate
effects to the differences in binding sites used. Along with
o Improved sense of well-being because BZ1 (sedation) and BZ2 (anti-anxiety and impairment
of improved sleep of cognition)
 Benzodiazepines are used to treat anxiety states and
Atypical Sedative-Hypnotics sleep disorders.
Buspirone  Dose-dependent CNS depression may occur but can
- Selective anxiolytic with minimal CNS be reversed by Flumazenil.
depressant effects (does not affect driving skills)  Chronic use can lead to tolerance and dependence
- No anticonvulsant or muscle relaxant properties with rebound effects upon withdrawal.
- Interacts with brain serotonin receptors as  Phenobarbital is used to treat seizures. Thiopental is
partial agonist used as an IV anesthetic. Barbiturates induce deep
- Specific mechanism of action for its anxiolytic CNS depression at high doses and there is no
effect is unknown antidote.
- Minimal tolerance with chronic use  Tolerance, dependence, and severe withdrawal
- Little rebound anxiety or withdrawal symptoms symptoms are associated with chronic barbiturate
upon discontinuance use.
- Safe in pregnancy  Zolpidem and Zaleplon are non-benzodiazepines that
bind to BZ1 receptors which make them more specific
Ramelteon hypnotics.
- Activates melatonin receptors (suprachiasmatic
nuclei of the CNS) and decreases latency of
sleep onset
- Minimal rebound insomnia or withdrawal Sympathomimetics and Sympatholytics
symptoms
- No direct effect on GABA-ergic Must Know Terms
neurotranmission in the CNS Anorexiant
- Minimal abuse liability (not a controlled Drug that decreases appetite
substance) Catecholamine
 Tasimelteon Dihydroxyphenlethylamine derivative readily
- Similar to Ramelteon metabolized by catechol-o-methyltransferase
- Similar melatonin receptor agonist Decongestant
- Recently approved Alpha agonist drug that reduces conjunctival, nasal,
or oropharyngeal mucosal vasodilation by
Orexin Antagonists constricting blood vessels in the submucosal tissue
 Orexin Mydriatic
- Peptide found in the hypothalamus Drug that causes dilation of the pupil; opposite of
- Involved in wakefulness miotic
 Suvorexant Selective alpha or beta adrenoceptor agonist
- Recently approved antagonist at orexin Drugs that have greater effects on alpha or beta
receptors adrenoceptors; none are absolutely specific
- Has hypnotic properties Sympathomimetic
Drug that mimics stimulation of the sympathetic
autonomic nervous system
Reuptake Inhibitor
Summary Drug that increases activity of transmitters in the
 Sedative-hypnotic-anxiolytic drugs include synapse by inhibiting their reuptake into the
benzodiazepines, barbiturates, and alcohols presynaptic nerve ending
 Receptors o beta receptors (moderate doses)
Sympathomimetics o alpha receptors (higher doses)
- Mimic the effects of norepinephrine (NE) and Mode of Action
epinephrine (EPI) - Direct activation (binds directly to the receptor and
- Located throughout the body causes a physiologic response)
- Receptors for sympathetic neurotransmitters - Indirect activation (increase concentration of the
o Alpha adrenergic receptors  endogenous catecholamine transmitter in the
norepinephrine synapse)
o Beta adrenergic receptors  epinephrine o Cause release of stored catecholamines
(amphetamines and tyramine)
Alpha Adrenergic Receptors o Inhibit reuptake of catecholamines (cocaine
- Divided into alpha1 and alpha2 receptors (based on and TCA)
their locations on nerves) o Increase stores of catecholamine;
o Alpha1  postsynaptic effector cells (cell, potentiates indirect acting agents (MAO
muscle, organ that nerves stimulate) inhibitors)
o Alpha2  presynaptic nerve terminals (control Pharmacokinetics
release of neurotransmitters) - Relatively inactive by oral route; must be given
- Predominant response: parentally
o Vasoconstriction o Epinephrine
o CNS stimulation o Norepinephrine
o Dopamine
Beta Adrenergic Receptors Mechanism of Action
- Divided based on their locations: - Alpha receptor effects
o Beta1 adrenergic receptors  heart (primarily) o Mediated by the trimeric coupling protein
o Beta2 adrenergic receprots  smooth muscles of G4.
bronchioles, arterioles, and visceral organs o G4 activation  phospholipase C activation
- Primary response:  release of inositol 1,4,5-triphosphate
o Smooth muscle relaxation (bronchial, (IP3) and diacylglycerol (DAG) from
gastrointestinal, and uterine smooth muscle membrane lipids  calcium released by
relaxation) IP3; enzymes activated by DAG
o Glycogenolysis - Beta adrenergic agents (B1)  cardiac stimulation
o Cardiac stimulation (myocardium, AV and SA nodes)
Dopaminergic Receptors
- Additional adrenergic receptor o Increased:
- Stimulated by dopamine  Force of contraction (positive
- Primary response: dilation (increased blood flow) inotropic effect)
o Renal  Heart rate (positive chronotropic
o Mesenteric effect)
o Coronary  Conduction through AV node
o Cerebral (positive dromotropic effect)
- Dopaminergic agents
Sympathomimetics o Depend on the dose (mixed activation of
Catecholamines receptors)
- Produce a sympathomimetic response Clinical Uses
o Endogenous (epinephrine, norepinephrine,  Anorexiant
dopamine) o Adjuncts to diet in the short-term
o Synthetic (isoproterenol, dobutamine, management of obesity
phenylephrine) o Drugs: benzphetamine
Classification phentermine
Spectrum of Action dextroamphetamine
- Alpha, beta, or dopamine receptors (further into Dexedrine
subgroups)  Anaphylaxis
- Prototypes: o Epinephrine (drug of choice for immediate
o epinephrine (alpha & beta agonist) treatment of anaphylactic shock
phenylephrine (alpha agonist) [hypotension, bronchospasm, and
isoproterenol (beta agonist) angioedema])
o little effect on dopamine receptors o Antihistamines and corticosteroids are also
- Dopamine (given as a drug itself) also activates: used but not as effective as epinephrine
  CNS o Slightly alpha1 selective
o Amphetamine (narcolepsy, and weight b. Phentolamine
reduction) o Reversible, short-acting
o Methylphenidate (ADHD) o Competitive antagonist
o Often abused for purposes of deferring o Does not distinguish between alpha1 and
sleep and mood-elevating, euphoria- alpha2 receptors
producing effect (cocaine) c. Prazosin
 Eye o Reversible
o Phenylephrine and tetrahydrozoline o Highly selective alpha1 blocker
(reduce conjunctival itching and congestion o Similar drugs: Doxazosin
 from allergy and irritation) Terazosin
o Phenylephrine (mydriatic) Tamsulosin
o Apraclonidine and brimonidine (glaucoma) d. Yohimbine
 Bronchi o Alpha2 selective blocker
o Drugs of choice for acute asthmatic o Used primarily in research applications
bronchoconstriction o Similar drug: Rauwolscine
o Drugs: albuterol
metaproterenol Pharmacokinetics (alpha blockers)
terbutaline - Active through oral and parenteral route
 Cardiovascular o Phentolamine (rarely given orally)
o Heart failure Mechanism of Action
o Septic and cardiogenic shock - Phenoxybenzamine covalently binds to the alpha
(norepinephrine) receptor
 Genitourinary o Irreversible blockade
o Ritodrine and terbutaline (beta2 agonists) - All the rest are competitive antagonists
are used to suppress labor o Effects can be counteracted by increased
 Cardiac stimulant effect may be concentrations of agonists
hazardous to the mother and child Note: important in the treatment of
o Ephedrine may be used for children pheochromocytoma (massive
(enuresis) and elderly (urinary incontinence) release of catecholamines may
overcome reversible
Toxicity blockade)
- Little toxicity to the CNS because of their limited Effects
ability to penetrate into the brain Non-selective blockers:
- Effects are more evident in the periphery - Most important are on the cardiovascular system
(reduction in vascular tone  decrease in arterial
ADRENOCEPTOR BLOCKERS and venous pressures)
Adrenergic Blockers - No significant direct cardiac effects
- Bind to adrenergic receptors but inhibit or block - Cause baroreceptor-mediated tachycardia (due to
stimulation of the sympathetic nervous system drop in mean arterial pressure)
- Have opposite effect of adrenergic agents o May be exaggerated
- Adrenergic antagonists or sympatholytics o Alpha2 receptors in the heart (which
- Sympatholytics reduce the net release of norepinephrine)
o Inhibit or lyse sympathetic are also blocked
neurotransmitters (norepinephrine and Selective alpha blockers
epinephrine) - Because they block alpha1 receptors more effectively
Sympatholytics than alpha2 receptors, induce less reflex tachycardia
- Classified as either: (than non-selectives)
o α1 and α2 receptor blockers - Useful in relaxing smooth muscles in the prostate
o β1 and β2 receptor blockers
- Other classifications depend on reversibility and Clinical Uses
duration of action Non-selective alpha blockers
- Limited clinical applications
Alpha Blockers - Pre-surgical management of pheochromocytoma
Classifications (may have severe hypertension and reduced blood
a. Phenoxybenzamine volume  must be corrected prior to surgery)
o Irreversible, long-acting o Phenoxybenzamine (preparatory phase)
o Prototype alpha blocker
 o Phentolamine (occasionally used during o Advantageous in treating patients with
surgery) asthma
- For reversal of accidental local infiltration of alpha o In theory, less likely to cause bronchospasm
agonists (epinephrine) may cause severe tissue o Drugs: Pindolol
ischemia and necrosis (uses phentolamine) Acebutolol
- Substance abuse/overdose (amphetamines, cocaine,
or phenylpropanolamine) may be reversed Local Anesthetic Activity
- Raynaud’s phenomenon (sometimes responds) but A. Membrane-stabilizing activity
efficacy is not well-documented o Disadvantage when beta blockers are used
- Erectile dysfunction on the eye (decreases protective reflexes 
o Phentolamine increases risk of ulceration)
o Yohimbine  Timolol (only one with absent local
anesthetic effects, and used in
Selective alpha blockers glaucoma)
- Hypertension (prazosin, doxazosin, and terazosin)
- Prevent urinary distention in benign prostatic Effects and Clinical Uses
hyperplasia (+ tamsulosin, and silodosin) - Remarkably broad:
o Eye (open angle glaucoma)
Toxicity o Heart(hypertension, angina, arrhythmia)
- Orthostatic hypotension  maybe heart failure  labetalol,
- Reflex tachycardia (non-selective alpha blockers) carvedilol, and metoprolol
o Pheochromocytoma  combined alpha
BETA BLOCKERS and beta blocker agents (when producing
Classification norepinephrine and epinephrine)
- All are competitive antagonists o Infantile hemangioma  propanolol
- Prototype drug is propanolol Toxicity
- Subgroups: - Bradycardia
o Receptor selectivity - AV blockade
o Partial agonist activity - Heart failure
o Local anesthetic action
o Lipid-solubility

ANTI-MALARIALS
Receptor Selectivity
A. Beta1 selective Malaria
o Advantageous in treating asthma patients - One of the most common diseases worldwide and a
(functioning B2 receptors are necessary to leading cause of death
prevent bronchospasm) - King of Tropical Diseases
o Drugs: Acebutolol - Leads to RBC deformities, increased fragility, and
Atenolol decreased oxygen transport
Esmolol - Caused by protozoan parasites:
Metoprolol o P falciparum
B. Non-selective o P malariae
o Nadolol o P ovale
o Propanolol o P vivax
o Timolol - Clinical Manifestations:
o Fever and chills
o Note: except for those starting with o Sweating
“c” and “l”, all blockers o Anemia
starting with letters from “a” to o Organomegaly (spleen and liver)
“m” are beta1 selective o Malaise

o Carvedilol and Labetalol have combined

alpha and beta-blocking activity Anti-malaria drugs
Types of Anti-Malarial Agents
Partial Agonist Activity  Tissue schizonticides
A. Intrinsic sympathomimetic activity o Kill schizonts in liver
 Blood schizonticides
 o Kill schizonts in the erythrocyte o No evidence of increase in congenital
 Sporonticides abnormalities, stillbirths, and abortion in
o Prevent sporogony and multiplication in the the pregnant
mosquito
Drugs: Quinine
 Chloroquine - Rapidly absorbed orally (and metabolized before
 Artemisinin derivates renal excretion)
 Quinine - IV forms are available (for severe infections)
 Mefloquine - Not routinely used for chemoprophylaxis (to delay
 Primaquine emergence of resistance)
 Other Drugs - MOA: complexes with double-stranded DNA to
prevent strand separation, resulting in a block in DNA
Chloroquine replication and RNA transcription
- Rapidly absorbed orally (widely distributed to - Type: blood schizonticide
-tissues, and large volume of distribution) - Uses:
- Antacids decrease oral absorption o P falciparum infections resistant to
- Excreted largely unchanged in the kidney chloroquine (in patients who can tolerate
- MOA: accumulates in the food vacuole of the oral treatment)
plasmodia and prevents polymerization of the o Shorter duration of therapy if combined
hemoglobin breakdown product heme into with doxycycline or clindamycin (and limits
hemozoin toxicity)
o accumulation of this substance is toxic to o Severe falciparum infection (uses Quinidine
the parasite form)
 any resistance is due to increased - Toxicity:
activity of excretion of this o GI distress, headache, vertigo, blurred
substance vision, and tinnitus (clinical entity:
- Type: blood schizonticide cinchonism)
- Uses: o Cardiac conduction disturbances and
o Chemoprophylaxis for malaria-endemic hematotoxic effects in G6PD patients
regions (except those with resistant strains) (hemolysis)
o Also for autoimmune disorders (rheumatoid o Blackwater fever  rare but fatal
arthritis) complication in quinin-sensitized persons
- Toxicity:
o GI irritation, skin rash, and headaches (low Mefloquine
doses) - Uses:
o Severe skin lesions, peripheral neuropathy, o First-line medication (taken weekly) as
myocardial depression, auditory prophylaxis in all geographic areas with
impairment, and psychosis (high doses) chloroquine resistance
o May also trigger porphyria attacks o Alternative drug to quinine in acute attacks
and uncomplicated infections (P falciparum)
Artemisinin Derivatives - Toxicity:
- Ex. Artesunate, Artemether, Dihydroartemisinin o GI distress, skin rash, headache, and
- Type: blood schizonticide dizziness (low doses)
- MOA: metabolized in the food vacuole which then o Cardiac conduction defects, psychiatric
forms toxic free radicals disorders, neurologic effects such as
- Uses: seizures (high doses)
o Active against P falciparum (including
resistant strains) Primaquine
o Severe infections (IV form available) - Type: tissue schizonticide
o 1st line agent for chloroquine-resistant Gametocide
malaria (in most countries) - MOA: forms quinoline-quinolone metabolites
 Best used in combination with (which act as cellular oxidants)
other agents (also because of short - Uses:
half-life 1-3 hours) o Eradicates liver stages of P vivax and P ovale
- Adverse Effects: (should be used in conjunction with a blood
o Nausea, vomiting, and diarrhea (all are schizonticide)
mild) o Alternative (daily) prophylactic for primary
prevention
 - Toxicity: - Appropriate treatment needs antibiotic susceptibility
o GI distress, pruritus, and headache (mild) testing (of samples from the patient)
o Methemoglobinemia, and RBC hemolysis in - Regimens are 3 or 4-drug combinations
G6PD patients (severe)
o Contraindicated in pregnancy
Anti-Tuberculosis
Other Drugs:  Isoniazid
 Rifampin
Lindane  Ethambutol
- MOA: unknown (may stimulate parasite CNS,  Pyrazinamide
leading to seizures and eventual death)  Streptomycin
- SE: local skin irritation  Alternative Drugs
- Nursing Considerations:
o Administer twice ( 1st immediately after dx;
2nd one week after the initial) Isoniazid
o Administer to all household members - Structural congener of pyridoxine
o Wear gloves to remove nits by using fine- - MOA: inhibition of mycolic acid synthesis
toothed comb with vinegar (essential components of mycobacterial)
o Apply to all body areas (except the face) o Resistance emerges rapidly if used alone
- Uses:
Doxycycline o Single most important drug used in
- Daily chemoprophylactic for travelers in geographical tuberculosis
areas (those with multidrug-resistant strains of P o Given as single agent for those in close
falciparum) contact with diseased patients
- Mainly used as prophylaxis for leptospirosis - Toxicity:
o Neurotoxic (peripheral neuritis,
Lumefantrine restlessness, muscle twitching, and
- Used in fixed combination with artemether for insomnia)
uncomplicated falciparum malaria in many countries o Hepatotoxic (abnormal liver function tests,
- Related to halofantrine (but this has minimal jaundice, and hepatitis)
cardiotoxicity instead) o Lupus-like syndrome
o All of these can be mitigated through use of
pyridoxine at 25-50mg/day orally

Anti-Mycobacterials
Rifampin
Mycobacterium - MOA: inhibits DNA-dependent RNA polymerase in
- Rod-shaped, aerobic M tuberculosis
- Do not form spores o Resistance rapidly emerges if used as single
- Weakly gram (+) agent
o primarily acid-fast bacilli - Well absorbed orally, and is distributed into other
- Have very thick bacterial walls: body tissues (including the CNS)
o Lipids (mostly) - Undergoes enterohepatic cycling and is excreted
 Mycolic acid (main) mainly in the feces as orange-colored products
- Responsible for: - Uses:
o Tuberculosis o Can be used as single agent in INH-resistant
o Leprosy cases for people in close contact with
o Mycobacterium Avium Complex (MAC) diseased patients (PTB)
- Remember: o Given monthly for leprosy patients (this
o Tuberculin test delays resistance to dapsone)
 (+) result means previous infection o Used in combination with vancomycin for
 Does not imply active disease or MRSA or PRSP strains
immunity o Also used for meningococcal and
Anti-Tuberculosis staphylococcal carrier states
- Actions are either bacteriostatic or bactericidal - Toxicity:
o Depends on: blood concentration o Light-chain proteinuria and may impair
strain susceptibility antibody responses
 o Skin rash, thrombocytopenia, nephritis, o Used more frequently due to increased
abnormal liver function (occasional) prevalence of strains of M. tuberculosis
o Flu-like syndrome and anemia (if given less resistance to other drugs
than 2x a week) o Used principally in life-threatening
o Induces liver enzymes to enhance tuberculous diseases
elimination of other drugs which include: o Used principally in life-threatening
 Anti-convulsants, contraceptive tuberculous diseases:
steroids, cyclosporine,
ketoconazole, methadone,  TB meningitis
terbinafine, and warfarin  Miliary dissemination
- Other forms of Rifampin:  Severe organ tuberculosis
o Rifabutin – equally effective as
antimycobacterial agent (and has less drug TB Conditions
interactions than rifampin)  preferred for  TB meningitis
AIDS patients  Miliary TB Dissemination
o Rifaximin – not abosrbed in GI tract  used  Pott’s disease
for traveler’s diarrhea  TB of the cervix

Ethambutol OTHER DRUGS

- MOA: inhibits arabinosyl transferases involved in Amikacin
the synthesis of arabinogalactan (cell wall - For streptomycin-resistance cases of PTB
component) in mycobacterium
o Resistance is rapid if used alone as a single Ciprofloxacin and Ofloxacin
agent - For cases resistant to first-line agents
- Pharmacokinetics:
o Well-absorbed orally and distributed to Ethionamide
most tissues (including the CNS) - Cogener of INH (but has no cross-resistance)
o Eliminated mostly unchanged in the urine - Major disadvantages  GI irritation, and neurologic
o Reduce dosage in renal impairment effects (at the higher doses needed to achieve
- Uses: effective plasma levels)
o Tuberculosis (in combination with other
drugs) P-Aminosalisylic acid (PAS)
- Toxicity: - Rarely used because of primary resistance
o Visual disturbances (dose-dependent)  - Causes GI irritation, peptic ulceration,
decreased visual acuity, red-green hypersensitivity reactions, and adverse effects on
colorblindness, and retinal damage with kidney, liver, and thyroid function
prolonged use at high dosages
o Effects regress when drug is stopped Drugs with Limited Use
 Capteomycin (ototoxicity and renal dysfunction)
 Cycloserine (peripheral neuropathy, and CNS
Pyrazinamide dysfunction)
- Mechanism of Action: unknown
o but its bacteriostatic action may require
metabolic conversion via pyrazinamidases in
M tuberculosis
o Resistance develops rapidly if used as a
TREATMENT REGIMENS
single agent
Regimens:
- Pharmacokinetics
A. Standard
o Well-absorbed orally (and penetrates most
B. Alternative
body tissues, including CNS)
C. Resistance
o Excreted in the urine
- Uses:
o Component of short-course treatment
Standard Regimen
regimens of PTB (with other drugs) - Empiric treatment of PTB (in areas <4% INH
Streptomycin resistance)
- An Aminoglycoside
- Uses:
 o Initial 3-drug regimen (INH, Rifampin, and - Phenazine dye (interacts with DNA)
Pyrazinamide) - Causes GI irritation, and skin discoloration
o Discontinue pyrazinamide after 2 months (if o Red-brown to black
patient is HIV-negative and PTB strain is fully
susceptible)
o Continue treatment for another 2 months DRUGS FOR ATYPICAL MYCOBACTERIAL INFECTION

Alternative Regimen Atypical Mycobacterial Infection Agents:

- For fully susceptible PTB strains:
Mycobacterium avium complex (MAC)
o INH + Rifampin (for 9 months) - Causes disseminated infections in AIDS patients
o INH + Ethambutol (for 18 months) - Treatment:
o 4-drug regimen of high doses intermittently o azithromycin/clarithromycin
(2 or 3x weekly) plus ethambutol and rifabutin

Resistance Regimen
- In areas where resistance to INH is >4%:
o Include ethambutol or streptomycin (in
initial drug regiment) Anti-Fungals
o If resistant to INH only, treat with rifampin + Fungi
pyrazinamide + ethambutol or streptomycin  80,000 species described
(for 6 months) o 400 medically important
- In multidrug resistance (to both INH and Rifampin):
o <50 cause more than 90% of human infections
o 18 months treatment (3-drug regimen) plus
12 months after sputum cultures become
 Infections are difficult to treat (especially in
negative immunocompromised patients)
 Mostly resistant to conventional antimicrobial
agents
DRUGS FOR LEPROSY o Only few agents are available for systemic
Anti-Leprosy fungal infections (amphotericin B, azoles, and
a. Sulfones echinocandins)
b. other Agents o Local agents also available
 Primary agents work through inhibiting synthesis of
Sulfones
Dapsone ergosterol (unique to fungal cell membranes)
- Diaminodiphenylsulfone o Selectively toxic to fungi only
- Most active drug against M leprae
- MOA: inhibition of folic acid synthesis
- Used in combination with rifampin and/or Anti-Fungals
clofazimine (due to increasing resistance)
- Given orally, penetrates tissues well
- Undergoes enterohepatic recycling, with renal Alter cell Block beta-
Block nucleic
Disrupt
excretion membrane glucan microtubule
acid synthesis
permeability synthesis functions
- Adverse Effects:
o GI irritation, fever, skin rashes, and
methemoglobinemia
Azoles,
o Hemolysis (G6PD patients) Polyenes, Echinocandins Flucytosine Griseofulvin
Terbinafine
Acedapsone
- Repository form of Dapsone
- Provides inhibitory plasma concentrations for several
months
- Alternative drug for Pneumocystis jiroveci
pneumonia in AIDS patients

Other Agents:

Clofazimine
 o Suspension  mouth or throat fungal infection
o Ointment, suppository, cream  vaginal
 SE: Fever, nausea and vomiting, diarrhea (large
doses)

Azoles
 Azoles
o MOA: interfere with formation of ergosterol
o 2 types:
 Imidazole  ketoconazole
 Triazole  fluconazole, itraconazole,
posaconazole, and voriconazole
o Toxicity:
 Vomiting, diarrhea, rash, and sometimes
Polyenes hepatotoxicity (pre-existing liver function)
 Amphotericin B  Endocrine dysfunction (ketoconazole)
o MOA: binds to fungal cell membrane to form  Transient and immediate visual
open channels  increase cell permeability and disturbances (voriconazole)
leakage of intracellular proteins  Ketoconazole
 Potent but severe side effect (renal failure) o Narrow antifungal spectrum and causes more
o Uses: DOC for severe systemic infection (given adverse effects than other azoles
IV)  Rarely used for systemic mycoses
o SE/AE: fever, nausea, vomiting, hypotension, o First effective antifungal  orally absorbed
paresthesia, thrombophlebitis, nephrotoxicity,  Used to treat same mycoses with
hypersensitivity, electrolyte imbalances amphotericin B
(hypokalemia and hypomagnesemia)  Requires normal gastric acidity (with food
and no antacids)
o Uses: chronic mucocutaneous candidiasis and
dermatophytes  shampoo (Nizoral)
o SE: dizziness, and blurred vision
o AE: hepatomegaly and photosensitivity
 Fluconazole
o Brand: Diflucan
o Uses:
 DOC for esophageal and oropharyngeal
candidiasis (also treatment and prophylaxis
for cryptococcal meningitis)
 Single dose enough for vaginal candidiasis
 Itraconazole
o Brand: Sporanox
o Uses:
 DOC for systemic infection (blastomyces
and sporothrix) and subcutaneous
chromoblastomycosis
 Alternative agent for aspergillus,
conccidioides, histoplasma, and
cryptococcus
Nystatin
 Voriconazole
 Brand: MYCOSTATIN
o Wider spectrum of activity than itraconazole
 MOA: increases permeability of fungal cell
membranes o Uses:
 Uses:  Co-DOC for invasive aspergillosis
o oral  intestinal candidiasis (poor absorption)
  Reportedly greater efficacy than o Related to cancer drug, 5-fluorouracil
amphotericin B o Effective orally and crosses into the CNS
 Alternative for candidemia and those with o Eliminated through the urine (dose must be
resistance against fluconazole reduced in patients with renal impairment)
 Candidial esophagitis and stomatitis (AIDS o MOA: accumulates in fungal cells through a
patients) permease and converted into 5-FU (thymidylate
 Posaconazole synthase inhibitor)
o Broadest spectrum triazole  Mammalian species are protected because
o Uses: of low levels of permease, unlike fungal
 Activity against most species of Candida and cells
Aspergillus  Given with amphotericin B, or triazoles, to
 Only azole with activity against Rhizophus decrease resistance
 Prophylaxis for cancer chemotherapy o Uses:
 Salvage therapy for invasive aspergillosis  cryptococcus neoformans
 Terbiniafine  systemic candidal infections (possible)
o MOA: Inhibits the fungal enzyme, squalene  chromoblastomycosis due to molds
epoxidase, which causes accumulation of o Toxicity:
squalene (interferes with ergosterol synthesis)  reversible bone marrow depression,
o Uses: Dermatophytoses (more effective than alopecia, and liver dysfunction (all in
Griseofulvin)  prolonged high plasma levels)
o Toxicity:
 GI upset, rash, headache
 Taste disturbances
Griseofulvin
 Griseofulvin
o MOA:
 Interferes with microtubule function in
dermatophytes (and may inhibit the
synthesis and polymerization of nucleic
acids)
 Fungistatic
o Pharmacokinetics
 Oral forms are better absorbed aided by
fatty food
 Transported to the stratum corneum and
binds to keratin
 Excreted in the bile
o Uses:
Echinocandins  Not active topically
 Caspofungin  Oral form for dermatophytoses of skin and
o Uses: Disseminated and mucocutaneous hair (but has since been replaced largely by
candida infections (who fail to respond to azoles and terbinafine)
amphotericin B and in mucormycosis) o Toxicity:
 Anidulafungin  Liver dysfunction
o Uses: Candidiasis (esophageal and invasive)  Contraindicated for porphyria
 Micofungin  Disulfiram-like reaction to alcohol
o Uses:
 Mucocutaneous candidiasis (prophylaxis) NURSING CONSIDERATIONS
 Candidasis in bone marrow transplant  GSCS
patients (prophylaxis)  Monitor IV sites
 Check liver enzymes, creatinine, BUN, I/O
Anti-metabolite  Take with meals- oral forms (NAVDA)
 Flucytosine (5-Fluorocytosine [5-FC])
 Check for hypersensitivity reaction (rash) Amphoterrible is a monster. He treats monster
 For topical: wash hands before & after application infections such as histoplasmosis and other life-
 For athletes’ foot: wear cotton socks, change 2-3 threatening fungal infections. He has a terrible habit of
times daily creating irregularities in the heart (arrhythmias). The X
 Jock itch worm or ring worm: wear well fitting, non- marks the spot of the kidney since 80% of clients
constrictive, ventilated clothing receiving this drug may develop some nephrotoxicity.
 Intravaginal
o Read instructions carefully BETA-LACTAM ANTIBIOTICS
o Insert high into the vagina Penicillins
Cephalosporins
o Continue use through menstruation
Carbapenems - Not really a beta-lactam but retains its
o Wear a minipad to avoid staining clothing, do ring structure
not use tampon
o Wash applicator with mild soap and rinse A. Penicillins
thoroughly after each use  Derivatives of 6-aminopenicillanic acid
o Avoid sexual intercourse while using the drug  Contains a beta-lactam ring essential for
antibacterial activity
Note: How to Remember “ZOLE”  Have additional chemical substituents which
 ZOLE – many drug interactions can occur confer differences (antimicrobial activity,
 Observe hygiene measures to control infections susceptibility to acid, enzymatic hydrolysis,
and biodisposition)
 Liver Function Tests – monitor
 Pharmacokinetics
 Educate to take with food o Vary in resistance to gastric acid (and
Meet “ZOLE” the toad who destroys fungal infections, thus have variable bioavailability)
such as ringworm. “ZOLE” will help you remember o Not metabolized extensively (in
some key points with these drugs. It will also help you effect excreted unchanged in the
remember the medication used for these infections, urine via glomerular filtration and
since they have the letters zole in them. tubular secretion)
o Tubular secretion is inhibited by
probenecid
o Nafcillin (excreted mainly in bile)
o Ampicillin (undergoes enterhepatic
recycling)
o half-lives of mostly 30 minutes to 1
hour
o Procaine and Benzathine have longer
half-lives (given IM  active drug has
slow release into the bloodstream)
o Note:most penicillins are able to
cross the blood-brain barrier only
when meninges are inflamed
 Mechanism of Action: bactericidal
- Inhibits cell wall synthesis by the
following steps:
 Drug binds to specific enzymes
(penicillin-binding proteins [PBPs]
located in the bacterial cytoplasmic
membrane
 Inhibition of the transpeptidation
reaction that crosslinks the linear
peptidoglycan chain constituents
of the cell wall
 Activation of autolytic enzymes
that cause lesions in the bacterial
cell wall
 Resistance:
 o Enzymatic hydrolysis of the beta-lactam ring – Clinical use similar to penicillin G, as well as
results in the loss of antibacterial activity against:
o Formation of beta-lactamases (penicillinases) • Enterococci, L. monocytogenes, E.
by mostly staphylococci and many gram- coli, P. mirabilis, H. influenzae, and M.
negative organisms is the major cause of catarrhalis
resistance (Some resistant strains have
o To combat this development, inhibitors of developed)
these bacterial enzymes are often used in – Activity is enhanced when used with
combination with penicillins to prevent their penicillinase inhibitors (e.g. clavulanic acid 🡪
inactivation Co-Amoxiclav)
1. Clavulanic acid – Synergistic with aminoglycosides in
2. Tazobactam enterococcal and listerial infections (ampicillin)
3. Sulbactam
o In the case of MRSA 🡪 structural changes in  Piperacillin and Ticarcillin:
the target PBPs (also in resistance to penicillin – Activity against some gram-negative rods,
G in pneumococci) including:
o In some gram-negative rods (pseudomonas), • Pseudomonas
changes in porin structures in the outer cell • Enterobacter
wall may contribute resistance (it prevents • Klebsiella
penicillins from accessing and binding to the – Often used with penicillinase inhibitors
PBPs) (tazobactam and clavulanic acid) to enhance
Clinical Uses their activity
Narrow spectrum Penicillinase-susceptible agents
 Penicillin G
– Prototype of a subclass of penicillins with
limited spectrum of antibacterial activity (and
susceptible to beta-lactamases) Penicillins
– Used against common streptococci,  Toxicity:
meningococci, gram-positive bacilli, and – Allergic reactions
spirochetes o Urticaria, severe pruritus, fever, joint
– Many strains of pneumococci are now resistant swelling, hemolytic anemia, nephritis, and
to penicillins (PRSP) anaphylaxis
– Most strains of S. aureus and N. gonorrhea are o Allergic response occurs if given penicillin
resistant due to beta-lactamse production again (in 5-10% of persons)
– No longer DOC for gonorrhea, but still for o Maculopapular skin rash (but mimics an
syphilis allergic reaction) 🡪 ampicillin
– enhanced by co-administration of
aminoglycosides – Gastrointestinal disturbances
o Nausea and diarrhea (oral penicillins)
 Penicillin V o May be due to direct irritation or by
– Used for oropharyngeal infections (given orally) overgrowth of gram-positive organisms
or yeasts
Very Narrow Spectrum Penicillinase-Resistant o Pseudomembranous colitis (ampicillin)
 Subclass of penicillins which includes:
– Methicillin (prototype, but rarely used due to
its nephrotoxic potential) – Miscellaneous:
– Nafcillin o Neutropenia (nafcillin)
– Oxacillin o Interstitial nephritis (methicillin)
 Primary use: staphylococcal infections
 Note: MRSA and MRSE (S. epidermidis) are
resistant to all penicillins, and often against B. Cephalosporins
multiple antimicrobials  Derivatives of 7-aminocephalosporanic acid and
contain the beta-lactam ring structure
Wider Spectrum Penicillinase-Susceptible  Many members are in clinical use
 Ampicillin and Amoxicillin: – Vary in antimicrobial activity and are
– Subgroup that has wider spectrum of designated according to their generations
antibacterial activity compared to penicillin G (in order of their introduction into clinical
(but still susceptible to penicillinase) use)
  Pharmacokinetics:
– Many are available for oral use (mostly 3rd Generation
parenteral)  Increased activity against gram-negative microbes
– Those with sidechains may undergo resistant to other beta-lactam medications
heptaic metabolism but majority undergo – Plus the ability the penetrate the blood-brain
renal excretion via active tubular secretion barrier (except for cefoperazone and cefixime)
• Only Cefoperazone and  Most active against:
Ceftriaxone are excreted mainly in the – Providencia, serratia marcescens, and beta-
bile lactamase-producing strains of H. influenzae
– Most cephalosporins do not enter the and Neiserria
cerebrospinal fluid even when meninges  Less active against:
are inflamed – Enterobacter strains that produce extended-
spectrum beta-lactamases
 Most drugs in this class are reserved usually for serious
infections:
 Mechanism of Action – Pseudomonas  cefoperazone, ceftazidime
– Bind to penicillin-binding proteins to – B. fragilis cetizoxime
inhibit bacterial cell wall synthesis (just like  Except for: ceftriaxone (parenteral) and
penicillins) cefixime (oral) for gonorrhea
• bactericidal
– Some structural differences make them 4th Generation
less susceptible to penicillinase produced  Cefepime more resistant to beta-lactamases
by staphylococci produced by gram-negative microorganisms:
• Resistance – Enterobacter, haemophilus, neisseria, and
– Some bacteria are able to produce beta- some penicillinase-resistant pneumococci
lactamases which can inactivate – combines:
cephalosporins o Gram-positive activity of 1st generation
– May occur from decreases in membrane o Wider gram-negative spectrum of 3rd
permeability to cephalosporins or from generation
changes in PBPs 5th Generation
– MRSA is resistant  Indicated for treating bacteria which are otherwise
resistant to commonly used antibiotics
1st Generation  Ceftaroline – has broad spectrum activitiy against
 Cefazolin (parenteral) and Cephalexin (oral) MRSA (others: MRSE, VRE)
– Active against gram-positive cocci - Not effective against Pseudomonas
(staphylococcus and common streptococci)  Ceftobiprole – this drug has been called a 5th gen
– Effective against many strains of E. coli and K. cephalosporin, but the terminology is not universally
pneumoniae accepted.
– Usually used as surgical prophylaxis - has powerful antipseudomonal activity, and
– Minimal activity against: binds strongly to PBP 2a
• Gram-negative cocci - has activity against MRS, S. pneumonia,
• Enterococci enterococci
• MRSA - newer medication used for healthcare-
• most gram-negative rods associated pneumonia (HCAP) or HAP

2nd Generation
 Lesser activity against gram-positive microbes versus  Cephalosporins Toxicity:
1st generation drugs – Allergies (skin rashes to anaphylactic shock)
– But have extended gram-negative coverage • Between cephalosporins is
– Marked differences between usefulness complete (100%)
between drugs in the group • Between a cephalosporin and
 Examples: penicillin is incomplete (5-10%)
– Bacteroides fragilis (cefotetan and cefoxitin)  Other Adverse Effects:
– Sinus, ear, and respiratory infections caused by – May cause pain at IM injections (as well as
H. influenzae or M. catarrhalis (cefamandole, phlebitis if given IV)
cefuroxime, and cefaclor) – May increase nephrotoxicity of
aminoglycosides (if given together)
 – Some may cause: hypoprothrombinemia and – Enterobacter, citrobacter, and serratia spp
disulfiram-like actions with ethanol
(cefamandole, cefoperazone, and cefotetan) Imipenem
• Due to their methylthiotetrazole • Rapid inactivation by renal dehydropeptidase I
group • Administered in fixed combination with cilastatin (an
• Disulfuram-like action: inhibitor of the enzyme above)
- reaction to alcohol leading – Increases its half-life and inhibits the formation
to nausea, vomiting, of a metabolite toxic to the kidneys
flushing, dizziness, Note: other carbapenems are not significantly
throbbing headache, chest degraded by the kidneys
and abdominal discomfort,
and general hangover- Imipenem-Cilastatin
like symptoms among  Partial cross-allergenicity with penicillins
others  Adverse effects:
– GI distress, and skin rash
– CNS toxicity 🡪 confusion, encephalopathy, and
seizures (at very high plasma levels)
Other Beta-Lactam Drugs
 Aztreonam Meropenem
 Carbapenems (Imipenem, Meropenem, and  Similar to imipenem but not metabolized by renal
Ertapenem) dehydropeptidases
 Beta-Lactamase Inhibitors (Clavulanic acid, Sulbactam,  Less likely to cause seizures
and Tazobactam)

Aztreonam Ertapenem
 monobactam resistant to beta-lactamases produced  Long half-life but less active against enterococci and
by some gram-negative rods (including Klebsiella, pseudomonas
pseudomonas, and serratia)  Intramuscular route causes pain and irritation
 No activity against gram-positive bacteria or anaerobes
 Cell wall synthesis inhibitor (preferentially binds with
penicillin-binding protein (PBP3) Beta-Lactamase Inhibitors
 Synergistic with aminoglycosides (Clavulanic acid, Sulbactam, Tazobactam)
 Given intravenously and is eliminated via renal tubular  Used in fixed combinations with certain hydrolyzable
secretion penicillins
 Half-life is prolonged in renal failure  Most active against plasmid-encoded beta-lactamases
 Adverse effects include GI upset with possible (produced by gonococci, streptococci, E. coli, and H.
superinfection, vertigo, headache, and rarely influenzae)
hepatotoxicity  Not useful against enterobacter, pseudomonas, and
– Skin rash may occur but there is no cross- serratia
allergenicity with penicillins – Their type of beta-lactamase is chromosomal
(and not plasmid-encoded)
Carbapenems
(Imipenem, Doripenem, Meropenem, Ertapenem)
• Chemically different from penicillins but retain the OTHER CELL WALL OR MEMBRANE-ACTIVE AGENTS
beta-lactam ring structure (Vancomycin, Fosfomycin, Bacitracin, Cycloserine,
• Have low susceptibility to beta-lactamases which Daptomycin)
makes them useful against:
– Gram-positive cocci Vancomycin
– Gram-negative rods  Bactericidal glycoprotein which inhibits
– anaerobes transglycosylation
 All are active against P. aeruginosa and acinetobacter – Prevents elongation of the peptidoglycan chain
spp, except for ertapenem and interferes with cross-linking
– Often paired with an aminoglycoside if used – Resistance  due to decreased affinity for the
against pseudomonas binding site
 Given parenterally, are useful against microbes  Narrow spectrum of activity
resistant to other antibiotics – Used for serious infections caused by drug-
- But is not effective against MRSA resistant gram-positive organisms
 Co-drugs of choice for:
 • Methicillin-resistant staphylococci Antimicrobials and Antibacterials
(MRSA) ANTIMICROBIALS – inhibit the growth of or kill bacteria/
• Penicillin-resistant pneumococi microorganisms outright (e.g. bacteria, fungi, parasites and
(PRSP) 🡪 in combination with a 3rd some viruses)
generation cephalosporin (usually
ceftriaxone) ANTIBACTERIAL/Antibiotics – chemicals that specifically kills
– Used for serious infections caused by drug- bacteria; destructive or inhibiting the growth of bacteria
resistant gram-positive organisms
• Backup drug for Clostridium PHARMACOKINETICS
difficile infection  Must only penetrate the bacterial cell wall in
 Not absorbed in the GI tract (and may be given orally sufficient concentration; must have affinity to the
for bacterial enterocolitis) binding sites
 Given parenterally, it penetrates most tissues and is  TIME drug remains at the binding site = INCREASE
eliminated unchanged in the urine EFFECT;
• Dosage modification is mandatory in renal failure  Controlled by DISTRIBUTION, HALF-LIFE &
patients ELIMINATION
• Toxicity:  Most are not highly CHON bound = longer HALF-LIFE
– Chills, fever, phlebitis, ototoxicity, and greater concentration at binding sites; mostly
nephrotoxicity eliminated from the body through URINE after the 7 th
– Rapid intravenous infusion 🡪 Red Man half-life
Syndrome (due to histamine release)
RESISTANCE to Antibacterials
Fosfomycin INHERENT or NATURAL – occurs without previous exposure to
 Antimetabolite inhibitor of cytosolic enolpyruvate the antibacterial drug
transferase ACQUIRED - caused by PRIOR exposure to antibacterial
– Prevents formation of N-acetylmuramic acid  Responsible for causing Penicillin resistance =
(an essential precursor for peptidoglycan chain PENICILLINASE (enzyme that metabolizes PenG =
formation) drug is ineffective)
– Resistance 🡪 decreased intracellular  CAUSES :
accumulation of the drug o mutant bacteria- grown a thicker cell wall
 Excreted by the kidney in urinary levels higher than o transfer of genetic instruction to another
minimum inhibitory concentrations (MIC) makes it bacterial species
useful against UTIs To beat the problem:
 In multiple dosing, diarrhea is common  New antibiotics are developed 
 May be synergistic with beta-lactam and quinolone  Development of ANTIBIOTIC RESISTANT DISABLERS
antibiotics in some infections (disable antibiotic-resistant mechanism in the
bacteria)
Bacitracin  Bacterial Vaccines (e.g. DPT, Flu Vaccine, TT)
 Peptide antibiotic which interferes with a late stage in  Prevent antibiotic abuse
cell wall synthesis in gram-positive organisms  COMPLIANCE and MULTI ANTIBIOTIC THERAPY
 Limited to topical use because of its marked
nephrotoxicity Antibiotic Combinations
• ADDITIVE EFFECT
Cycloserine  equal to the SUM of the effects of 2
 Antimetabolite that blocks incorporation of amino antibiotics
acids into the side chain of the peptidoglycan • POTENTIATIVE (SYNERGISTIC) EFFECT
 Highly neurotoxic (tremors, seizures, and psychosis)  one antibiotic potentiates the effect of
– Limited use to tuberculosis that is resistant to the 2nd antibiotic
first-line antituberculosis drugs • ANTAGONISTIC
 combination of a drug that is
Daptomycin BACTERICIDAL PENICILLIN + drug that is
 Novel cyclic lipopeptide with spectrum similar to BACTERIOSTATIC, TETRACYCLINE =
vancomycin (but active against vancomycin-resistant desired effect may be reduced
strains of enterococci and staphylococci)
 Eliminated via the kidney SPECTRUM
 Monitor creatinine since it causes myopathy  NARROW SPECTRUM
o against one type of organism
 o Penicillin & Erythromycin – for gram (+)  Killing action continues even after plasma levels have
bacteria declined below measurable levels
 Aminoglycosides have greater efficacy if given as a
 BROAD SPECTRUM large single dose (compared to multiple smaller
o against both gram (+) & gram (-) doses)
o Tetracyline & Cephalosporins o Toxicity depends on both actual increased
plasma concentration and duration the level
General Adverse Reactions is exceeded
1) HYPERSENSITIVITY – rash, pruritus & hives ; severe o Leads to: once daily dosing  more
anaphylactic shock advantageous
TX: antihistamine, epinephrine, bronchodilators

2) SUPERINFECTION – secondary infection due to disturbed Pharmacokinetics

normal flora; occur with use of broad spectrum  Structurally related amino sugars attached by
antibiotics glycosidic linkages
 Must be given thru IM or IV (for systemic effect)
3) ORGAN TOXICITY – damage to organs that are involved in o Not absorbed well through oral
drugs metabolism & excretion (liver & kidneys) administration (and have limited tissue
aminoglycosides = OTOTOXIC & NEPHROTOXIC penetration in CNS)
 
Pharmacokinetics
NURSING CONSIDERATIONS  Undergoes renal excretion (plasma levels are greatly
 Monitor for superinfections affected by renal function)
 Evaluate renal [BUN & creatinine] & liver [AST,ALT]
functions  Excretion is proportional to creatinine clearance
 Diarrhea r/t superinfections (mgt: take yogurt, more  Dosage adjustments necessary in renal dysfunction
fluids)
 Inform physician before taking other meds Mechanism of Action
 Cultures- prior to 1st dose  Aminoglycosides are bactericidal inhibitors of
 Alcohol is OUT!/ ask about allergies protein synthesis
 Take full course of meds  May be enhanced by bacterial cell wall synthesis
 Evaluate cultures, WBC, C&S inhibitors
 Binds to 30s ribosomal subunit and interferes with
protein synthesis in at least three (3) ways:
o Block formation of initiation complex
o Cause misreading of code in the mRNA
template
Anti-Bacterials I o Inhibit translocation
Aminoglycosides o May also disrupt polysomal structure,
resulting in non-functional monosomes
Modes of Antibacterial Action (possible 4th MOAas proposed)
 Multiple daily dosage regimens are traditionally used  Streptococci (S pneumoniae) and Enterococci 
o to maintain serum concentrations above relatively resistant (due to drug’s inability to
minimum inhibitory concentration (MIC) penetrate their cell walls)
 Minimum inhibitory concentrations
(MICs) are defined as the lowest Clinical Uses
concentration of an antimicrobial  Main differences due to activities against specific
that will inhibit the visible growth microorganisms: gram (-) rods
of a microorganism after overnight  Gentamicin, Tobramycin, and Amikacin  serious
incubation infections of aerobic gram-negative bacteria
 As plasma levels increase, aminoglycosides kill an o E. coli, Enterobacter, Klebsiella, Proteus,
increased proportion of bacteria at a more rapid rate Providencia, Pseudomonas, and Serratia
 Same with penicillins and cephalosporins o alternative medications for:
 *time-dependent killing (more bacteria are killed  H. influenzae, M. catarrhalis, and
the longer drugs are maintained above the MIC  Shigella spp
same moment it becomes independent of  not reliably effective against gram-positive cocci
concentration) (instead, combined with cell wall inhibitors e.g.
 Aminoglycosides are capable of post-antibiotic effect penicillins)
  Streptomycin  used in regimens against:  Monitor I & O, hydrate well before and during
o Enterococcal carditis (Infective therapy (flush in between)
endocarditis) - infection in the heart valves  If anorexia or nausea occurs, SFF meals
or endocardium  Establish plan for safely if vestibular nerve effects
o Plague - a contagious bacterial disease occur.
characterized by fever and delirium,  Administer other antibiotics 1 hour before/after
typically with the formation of buboes amino
( bubonic plague ) and sometimes infection  Recommend using sunblock & protective clothing
of the lungs ( pneumonic plague ) when exposed to the sun.
o Tularemia
o Pulmonary tuberculosis (if resistant to
streptomycin, use amikacin instead)
CHLORAMPHENICOL
Spectinomycin  administered thru IM Classification and Pharmacokinetics
 Single dose for treatment of gonorrhea  Has a simple and distinctive structure (the only one
 not an aminoglycoside (but a related drug  it is an discovered in its chemical class)
 Effective orally, parenterally, and is widely distributed
aminocyclitol)
 Readily crosses the placenta and the blood-brain barrier
 Undergoes enterohepatic recycling (but a small fraction is
excreted in the urine unchanged
Toxicity  Most of the drug is inactivated by hepatic
 Ototoxicity glucoronyltransferase
o Two (2) main possible conditions: Antimicrobial Activity
 Auditory damage (amikacin and  Wide spectrum of antimicrobial activity (and usually
kanamycin) bacteriostatic)
 Vestibular damage (gentamicin  May be bactericidal in some microbes:
and tobramycin) H. influenzae
N. gonorrhea
 BOTH ARE IRREVERSIBLE (may be
Bacteroides
decreased with use of loop
 Not active against Chlamydia
diuretics)  Resistance:
o Contraindicated in pregnancy (due to Formation of acetyltransferase  inactivates the drug
damage to hearing of fetus after exposure) Clinical Uses
o Unless potential benefits outweigh risks  Few uses as a systemic drug (due to its toxicity):
 Nephrotoxicity o Backup drug caused by severe infections of
o Acute tubular necrosis  reversible but Salmonella
more common in: o Pneumococcal and meningococcal meningitis (in
beta-lactam sensitive persons)
 Elderly
 Commonly used as a topical agent
 Taking other medications Toxicity
(amphotericin B, cephalosporins,  GI disturbances  direct irritation and superinfection
or vancomycin) (esp. candidiasis)
o Most nephrotoxic:  Bone marrow  inhibits maturation of red blood cells
gentamicin (leads to a decrease in circulating RBCs)
tobramycin o Dose-dependent and reversible
 Neuromuscular Blockade o Rare idiosyncratic reaction  aplastic anemia
o Rare, but may result in respiratory paralysis (irreversible and fatal)
o Reversible: calcium and neostigmine  Gray Baby syndrome
o Occurs in infants
o May require a mechanical ventilator
o Characterized by:
 Skin Reactions  Decreased RBCs
o Most likely to cause these reactions   Cyanosis
Neomycin  Cardiovascular collapse
o Allergic skin reactions
o Contact dermatitis  Neonates (esp. the premature) are more prone
NURSING RESPONSIBILITIES o Lesser amounts of hepatic glucoronyltransferase
 Monitor periodical audiograms, BUN/creatinine & (makes them more sensitive to chloramphenicol
at doses infants may be able to tolerate)
vestibule function studies over 10 days therapy
Drug Interactions
 Adjust for renal insufficiency  Chloramphenicol inhibits hepatic drug-metabolizing
 Monitor VS, peak and serum levels enzymes
 For IV admin., dilute and administer slowly to  Increases elimination half-lives of drugs including:
prevent toxicity Phenytoin, tolbutamide, and warfarin
 o Disturbances in normal flora  candidiasis (oral
TETRACYCLINES and vaginal)
Classification o bacterial superinfection (S. aureus, or C. difficile)
 broad spectrum bacteriostatic antibiotics with only minor  Bony structures and teeth
differences in their activities against susceptible o Tooth enamel dysplasia (and other irregularities
microorganisms in bone growth)  fetal exposure
Pharmacokinetics  Though usually contraindicated, some
 Variable oral absorption (especially for the older drugs) cases may justify its use in pregnant
which may be impaired by: patients
o Food  Hepatic toxicity
o Multivalent cations (iron, calcium, and o Impaired liver function  hepatic necrosis (if in
aluminum) high doses)
 Wide tissue distribution (and crosses placental barrier) o Common in pregnant and those with preexisting
 All tetracyclines undergo enterohepatic cycling liver disease
 Excretion: mainly in urine  Renal toxicity
o doxycycline (feces o Fanconi’s syndrome (form of renal tubular
o tigecycline (bile) acidosis)
Antibacterial Activity o Not directly nephrotoxic but enhances
 Broad spectrum with activity against: preexisting renal dysfunction
o Gram-negative and positive bacteria  Photosensitivity
o Rickettsia o Enhanced skin activity to ultraviolet light
o Mycoplasma (demeclocyline)
o Protozoa  Vestibular toxicity
 Resistance  wide-spread o Dose-dependent reversible dizziness
o Development of efflux pumps (for active (doxycycline and minocycline)
expulsion of the drug from the bacteria) ___________________________________________
o Formation of ribosomal protection proteins
(prevent tetracycline from binding) MACROLIDES AND OTHER DRUGS
o Note both do not work against Tigecycline Classification and Pharmacokinetics
(except for the multidrug efflux pumps of  Macrolides are large cyclic lactone ring structures with
Proteus and Pseudomonas) attached sugars
Clinical Uses  Good oral bioavailability
 Primary: o Absorption of azithromycin is impeded by food
o Mycoplasma pneumoniae (in adults)  Distributed to most body tissues
o Chlamydia, rickettsia, vibrio, and some o Azithromycin  unique because its levels are
spirochetes higher in tissues and in phagocytes
o Note: also alternative drug to macrolides in the  Elimination differs:
empirical treatment of CAP o Erythromycin (biliary excretion)
 Secondary: o Clarithromycin (hepatic metabolism and urinary
o Alternative to drugs for treatment of syphilis excretion of intact drug)
o Prophylaxis against infection in chronic bronchitis o More rapid:
o Leptospirosis  Erythromycin (biliary excretion at 2
o Acne hours)
 Selective uses:  Clarithromycin (urinary excretion at 6
o GI ulcers (caused by H. pylori)  tetracycline hours)
o Lyme disease  doxycycline o Slower:
o Also for prevention of malaria and treatment of  azithromycin (urinary excretion at 2-4
amebiasis days)
o Meningococcal carrier state  minocycline o Erythromycin  has activity against most
o Patients with antidiuretic hormone-secreting species of:
tumors  demeclocycline  Campylobacter, chlamydia, and
o Inhibits renal actions of antidiuretic hormone mycoplasma
o Tigecycline (only IV)  Legionella, gram-positive cocci, and
- It includes microbes resistant to standard some gram-negative microbes
tetracyclines: o Azithromycin & Clarithromycin  same
 gram-positive cocci resistant to spectrum of activity as erythromycin but greater
methicillin (MRSA) activity against species of:
 Vancomycin-resistant enterococci  Chlamydia, mycobacterium avium
(VRE) complex (MAC), and toxoplasma
 Beta-lactamase producing bacteria o Azithromycin  alternative for STDs
Toxicity  Gonorrhea/Gonococcal UTI
 GI disturbances (alternative to ceftriaxone)
o Mild nausea and diarrhea to severe life-  Syphilis (alternative to penicillin G)
threatening enterocolitis Resistance
  Development of efflux pumps (mostly in gram-positive  Inhibits bacterial protein synthesis via mechanisms similar
bacteria) to macrolides (but not chemically related)
 Assume complete cross-resistance between individual Resistance:
macrolides  Methylation of binding site on 50s subunits and enzymatic
Clinical Uses inactivation
 Erythromycin  effective in infections caused by:  gram-negative microbes are intrinsically resistant (poor
o M. pneumoniae, Corynebacterium, penetration through the outer membrane)
Campylobacter jejuni, Chlamydia trachomatis,  Cross-resistance between clindamycin and macrolides is
Chlamydophila pneumonia, Legionella common
pneumonia, Ureaplasma urealyticum, and Pharmacokinetics
Bordetella pertussis  good tissue penetration (after oral absorption)
 Clarithromycin  similar spectrum and clinical uses as  Undergoes hepatic metabolism
erythromycin, but may be used as prophylaxis for:  Eliminated via biliary and renal excretion
o M. avium complex Clinical Uses
o H. pylori (GI ulcers)  Mainly used as treatment for severe infections by certain
 Azithromycin  similar in spectrum but more active anaerobes (Bacteroides)
against:  Backup drug against gram-positive cocci, as it is active
o H. influenza against:
o M. catarrhalis o community-acquired strains of MRSA
o Neisseria o Prophylaxis for endocarditis (in patients allergic
 because of a long half-life, it can be effective as: to penicillin)
o Single dose (for C. trachomatis)  Also used as treatment for:
o 4-day regimen (CAP) o PCP (P. jirovecii)
 Fidaxomicin  narrow-spectrum macrolide o AIDS-related toxoplasmosis (in combination with
o Inhibits protein synthesis and selectively active pyrimethamine)
against gram-positive aerobes and anaerobes Toxicity:
o Given orally (to ensure minimal systemic  GI irritation, skin rashes, neutropenia, hepatic dysfunction
absorption)  Possible superinfection (C. difficile  pseudomembranous
o Proven to be as effective as vancomycin for colitis)
pseudomembranous colitis (C. difficile infection) ________________________________________________
Toxicity STREPTOGRAMINS
 Erythromycin: Quinupristin-Dalfopristin
o GI irritation (stimulation of motolin receptors),  Combination of two (2) streptogramins
skin rashes, and eosinophilia  Bactericidal
o Acute cholestatic hepatitis (hypersensitivity-  Exhibits postantibiotic effects
based)  Useful against:
- inhibits multiple isoforms of cytochrome P450  leads to o Penicillin-resistant pneumococci (PRPC)
increase in plasma levels of many drugs such as: o Methicillin-resistant S. aureus (MRSA)
o Anticoagulants o Vancomycin-resistant staphylococci (VRSA)
o Carbamazepine  Given intravenously
o Cisapride  May cause pain and arthralgia-myalgia syndrome
o Digoxin  Potent inhibitors of CYP3A4  increases plasma levels of
o Theophylline many drugs:
 Azithromycin  lactone ring structure is slightly different o Astemizole
compared to other macrolides o Cisapride
o Drug interactions are not common (does not o Cyclosporine
inhibit CP450) o Diazepam
___________________________________________ o NNRTI
TELITHROMYCIN o Warfarin
 Ketolide (structurally related to macrolides) ________________________________________________
 Same MOA as erythromycin and similar spectrum of LINEZOLID
activity  First of a novel class of antibiotics (oxazolidinones)
o But some strains resistant to macrolides are  Active against drug-resistant gram-positive cocci, including
vulnerable because it binds tighter to ribosomes those resistant to:
(and a poor substrate for bacterial efflux pumps o Penicillins (MRSA, and PRSP) and vancomycin
which mediate resistance) (VRE)
 Given orally (once a day)  Also active against L. monocytogenes and corynebacterium
 Eliminated in the bile and urine  MOA  binds to a unique site located at 23S ribosomal
 May induce hepatic dysfunction and prolongation of QT RNA of the 50s ribosomal subunit
interval (ECG)  No cross-resistance with other protein synthesis inhibitors
 Inhibits CYP3A4 drug-metabolizing system  Possible resistance:
___________________________________________ o Decreased affinity to its binding site
 Available in both oral and parenteral forms
CLINDAMYCIN
  Must be reserved for those infections caused by multidrug  some of the effects may be due to systemic
resistant gram-positive bacteria absorption of disintegrating parasite
 Metabolized by the liver (half-life of 4-6 hours)
 May cause thrombocytopenia and neutropenia (in
antigens
immunocompromised patietns) o Avoid alcohol for 24-48 hours
 Implicated in serotonin syndrome (when used in patients
taking SSRIs) Trematodes (Flatworms)
 980 million at risk in Southeast Asia and Western
Pacific
o Chlonorchis
Anti-Helminthics o Fasciola
Anti-Helminthics
o Paragonimus
Nematodes Trematodes Cestodes  200 million cases (schistosomiasis)
(Roundworms) (Flatworms) (Tapeworms) Drugs Against Trematodes
Mebendazole, Praziquantel, Mebendazole,  Praziquantel
Albendazole, Biothionol, Albendazole, o MOA: increases membrane permeability to
Diethylcarbazine, Metrifonate, Niclosamide, calcium (causes marked contraction, then
Ivermectin, Oxamniquine Praziquantel
Pyrantel pamaoate paralysis of muscles, followed by vacuolization
and parasite death)
Helminthiasis o Uses: wide spectrum of action against
 caused by helminths (large parasitic worms) which trematodes and cestodes (DOC for
food through host tissues schistosomiasis, chlonorchiasis, paragonimiasis,
o Lymphatics and for flukes)
o GI tract (especially hepatobiliary system) o Pharmacokinetics:
o Cardiopulmonary system  Rapid absorption in the gut
 Metabolized in the liver to inactive products
Cestodes (Tapeworms) o Toxicity:
o Bladder-like larvae (approximately the size of  Headache, dizziness, drowsiness, malaise
peas) (common)
o Develop into adult worms of several meters in  GI irritation, skin rash, fever
the intestines  Neurologic effects in treatment of
o Egg-filled terminal segments break off from neurocysticercosis (intracranial
adult worm hypertension and seizures)
o Pass out with the human feces  Bithionol
o Mostly asymptomatic o Co-DOC with triclabendazole for fascioliasis
o Usual symptoms are mild: (sheep liver fluke) and alternative agent for
 Diarrhea paragonimiasis
 Abdominal pain o MOA: unknown
 4 medically important tapeworms: o Effective orally, and eliminated through urine
o Taenia solium o Toxicity: Nausea, vomiting, abdominal cramps,
o Taenia saginata dizziness, headache, skin rash (reaction to dying
o Diphyllobothrium latum worms), and phototoxicity
o Echinococcus granulosus Other Drugs Against Trematodes
Drugs Against Cestodes (Tapeworms)  Metrifonate
 Niclosamide o Organophosphate prodrug converted to
o MOA: uncouples oxidative phosphorylation (or dichlorvos (cholinesterase inhibitor)
activating ATPase) o Only for bilharziasis (s. haematobium)
o Alternative drug to praziquantel o Contraindicated in pregnancy
o Not effective for:  Oxamniquine
 cysticercosis (use albendazole or o Only for intestinal bilharziasis (s. mansoni)
praziquantel) o Unknown MOA but causes paralysis in
 hydatid disease (use albendazole) immature male worms and both adult worms
o Toxicity: headache, rash, fever, GI distress o No driving for 24 hours (dizziness)
 o Not advisable for pregnant and patients with  Not for pregnancy
history of seizures  Mebendazole
o MOA: inhibits mictotubule synthesis and
Nematodes (Roundworms) glucose uptake in nematodes
 1.5 billion cases (ascariasis) o Uses: primary drug for ascariasis, pinworm, and
 1.3 billion cases (hookworms) whipworm infections.
 800 million cases (whipworm) o Backup drug for visceral larva migrans
 Benign manifestations (unless high worm burdens) o Toxicity:
 Acquired via oral-fecal route (also autoinfections)  Limited to GI irritation
 Reflect poor sanitation, dietary preparation, and  granulocytopenia and alopecia (high doses)
hygiene practices
o Eggs require incubation in the soil (several days  Thiabendazole
to weeks) o MOA: similar to mebendazole and albendazole
o Warm, tropical climates o Uses: alternative drug for strongyloidiasis and
Drugs Against Nematodes (Roundworms) trichinosis (adult worms)
 Albendazole o Also has anti-inflammatory and
o MOA: inhibition of microtubule assembly immunorestorative actions in the host
o Uses: ascariasis, hookworm, pinworm, and o Toxicity:
whipworm infections,  More toxic than the structural congener
o threadworm, filariasis, visceral and cutaneous (mebendazole)  other drugs are preferred
larva migrans (alternative drug)  GI irritation, drowsiness, leukopenia,
o Toxicity: allergic reactions, intrahepatic cholestasis
 Leukemia, alopecia, and elevation of liver  Irreversible liver failure and Stevens-
function enzymes in prolonged use of >3 Johnson syndrome
days (reversible)  Avoid in pregnant and hepatic/renal failure
 Safety for pregnancy and young children patients
not established  Pyrantel Pamoate
 Diethylcarbamazine o MOA: stimulates nicotinic receptors at
o MOA: immobilizes microfilariae through neuromuscular junctions of nematodes
unknown mechanism, increasing susceptibility (contraction then depolarization-induced
to host defenses paralysis)
o Uses: DOC for filarial infections  Kills adult worms in the colon (but not eggs)
 Wuchereria bancrofti  No effect on flukes or tapeworms
 Brugia malayi o Toxicity: Use with caution in hepatic
 Loa loa failure/dysfunction patients
o Toxicity:  Piperazine
 Headache, malaise, weakness, and anorexia o MOA: paralyzes ascaris by acting as GABA
 Fever, rashes, ocular damage, joint and agonist (worms are then expelled live by
muscle pain, and lymphangitis (reaction to normal peristalsis)
dying worms) o Uses: alternative drug for ascariasis
 Ivermectin o Toxicity:
o MOA: increases GABA-mediated  mild GI irritation (most common)
neurotransmission in nematodes which cause  Not for pregnant and liver/renal failure pts
paralysis, and then removal through the
reticuloendothelial system Nursing Considerations
o Uses: DOC for onchocerciasis, cutaneous larva  Assess history (food eaten)
migrans, strongyloidiasis, and some forms of  Collect stool specimen
filariasis  Take drug with food, small frequent feeding
o Toxicity:  Avoid driving, change position slowly
 Fever, headache, dizziness, rashes, pruritus,  Take drug as prescribed
tachycardia, hypotension, joint and muscle  Inform health care provider about OTC meds taking
pains, and lymphangitis (reaction to dying
worms)
 For intestinal infection, some measures that help o Antivirals work by inhibition of viral enzymes
prevent worm reinfection or help prevent spread to (selective toxicity)
other family members  One of the most important trends in antiviral
 Vigorous use of soap and water after use of toilet treatment  combination drug therapy
 Showering in the morning to wash away any ova
Anti-Virals
deposited in the anal area during the night
 Anti-Herpes
 Changing and laundering undergarments, bed linens
 Anti-Influenza
and pajama daily
 Anti-viral Hepatitis
 Disinfecting toilet & toilet seats, bathroom and
 Anti-HIV
bedroom floors periodically
 Anti-herpes agents
 Proper handling of food and food preparation
 Control flies Anti-Herpes
 Avoid sexual intercourse or use condom in with Acyclovir
vaginal infection  Mechanism of Action:
o Guanosine analog active against HSV-1 and 2,
Anti-Virals VZV
Viruses o Competitive substrate of DNA polymerase
 Smallest infectious agents  Uses:
 Contain only one kind of nucleic acid o Mucocutaneous and genital herpes, VZV,
o DNA Shingles
o RNA o AIDS prophylaxis and in other
 Obligate intracellular parasites immunocompromised patients (for organ
 Replication depends on the host cell’s synthetic transplantation)
processes o Neonatal HSV infection
o Based on the nucleic acid  Toxicity:
 Infection may have: o GI distress and headache (oral)
o Little or no effect o Delirium, tremor, seizures, hypotension, and
o Cell damage nephrotoxicity (IV)
o Cell death
Ganciclovir
 Mechanism of Action:
o Guanine derivative
o Inhibits DNA polymerases of CMV, and HSV
 Uses:
o CMV retinitis prophylaxis and treatment
o Other CMV infection in immunocompromised
patients
 Toxicity:
o Systemic (leukopenia, thrombocytopenia,
mucositis, hepatic dysfunction, and seizures)

Cidofovir
 Mechanism of Action:
Anti-virals o Inhibits DNA polymerase of HSV, CMV,
 Exert their actions at several stages of the adenovirus, and HPV
replication of the virus  Uses:
o Early stages (viral entry, nucleic acid synthesis, o CMV retinitis
late protein synthesis, and processing) o Mucocutaneous HSV infections (resistant to
o Late stages (viral packaging and virion release) acyclovir)
 Most agents active against herpesvirus and HIV are o Genital warts
antimetabolites  Toxicity: nephrotoxicity
Foscarnet Anti-influenza agents
 Mechanism of Action: Amantadine and Rimantadine
o Phosphonoformate derivative that does not  Mechanism of Action:
require phosphorylation for anti-viral activity o Inhibit an early step in replication of influenza-A
o Inhibits viral RNA polymerase, DNA polymerase, (but not B) virus
and HIV reverse transcriptase o Prevents viral uncoating by binding to a proton
 Uses: channel
o CMV prophylaxis and treatment (alternative o Prevents acidification of viral core (necessary to
drug) activate viral RNA transcriptase)
o For CMV strains resistant to ganciclovir  Uses:
o Herpes in AIDS patients o Prophylactic against influenza-A virus (and
 Toxicity: reduces duration of infection if given within 48
o Nephrotoxicity (30% of cases) hours of contact/exposure)
o Electrolyte imbalance o Not for H3N22 and H1N1 (resistant)
o Genitourinary ulceration  Toxicity:
o CNS effects (headache, hallucinations, and o GI irritation, dizziness, ataxia, slurred speech
seizures)

Other Agents Oseltamivir and Zanamivir

 Vidarabine (adenine analogue)  Mechanism of Action:
o Has activity against HSV, VZV, and CMV o Inhibit neuraminidase produced by influenza-A
o Topical agent for herpes keratitis but no effect and B
on genital lesions o Cleave sialic acid residues from viral proteins
 Idoxuridine and Trifluridine (pyrimidine analogy) and surface proteins of infected cells
o Topical agent for herpes keratitis (HSV-1) o Responsible for virion release and prevents
o Too toxic for systemic use clumping of newly released virions
 Fomivirsen (anti-sense oligonucleotide)  Uses:
o Binds to mRNA of CMV (inhibiting early protein o Influenza-A and B
synthesis) o H3N2 and H1N1
o Injected intravitreally for CMV retinitis  Toxicity:
o Eye problems (iritis, vitreitis, increased IOP, and o GI symptoms (oseltamivir)
vision disturbances) o Cough, throat discomfort, and bronchospasm
(zanamivir)
Nursing Considerations:
 Extreme caution to children (carcinogenic); Nursing Considerations:
foscarnet (affect bone growth & development)  Start regimen as soon after the exposure to the
 Good hydration (decrease toxic effects of the virus as possible (achieve best effectiveness and
kidney) decrease the risk of complications)
 Administer as soon as possible, compliance  Administer the full course of drug
 Wear protective gloves when applying the dug  Provide safety measures (protect patient from
topically (decrease risk of exposure to the drug and injury)
inadvertent absorption)
 Safety precautions = CNS effects (orientation, Anti-viral hepatitis agents
siderails, lighting, assistance) Interferon-alpha
 Warn that GI upset, N/V can occur (prevent undue  Mechanism of Action:
anxiety, increase awareness of the importance of o Cytokine that acts through host cell surface
nutrition) receptors to increase production of anti-viral
 Monitor renal function proteins
 Avoid sexual intercourse if with genital herpes o Preferential degradation of viral mRNA
 Avoid driving and hazardous tasks if with dizziness o Promotes formation of natural killer cells
& drowsiness (destroys infected liver cells)
 Uses:
 o Chronic HBV infection (as single agent or in o Inhibits replication of DNA and RNA viruses
combination with other drugs) (influenza A and B, respiratory syncytial virus,
o Kaposi’s sarcoma paramyxovirus, HCV, and HIV)
o Papillomatosis o Precise mechanism is unknown
o Genital warts (topical)  Uses:
 Toxicity: o Chronic HCV (along with IFN-α)
o GI irritation, flu-like syndrome, neutropenia, o Viral hemorrhagic fevers (early administration
profound fatigue and myalgia decreases mortality)
o Reversible hearing loss  Toxicity:
o Thyroid dysfunction, mental confusion, severe o Hemolytic anemia (dose-dependent)
depression o Teratogenic (contraindicated in pregnancy)
o Contraindicated for pregnancy
Newer Agents
Adefovir Dipivoxil  Hepatitis B
 Mechanism of Action: o Telbivudine and Tenofovir
o Competitively inhibits HBV DNA polymerase and  Hepatitis C
results into chain termination after o Sofosbuvir and Boceprevir
incorporation into viral DNA  Telbivudine
o Prodrug of adefovir o Nucleoside analog that inhibits HBV DNA
 Uses: polymerase (as effective as lamivudine)
o HBV infection (suppresses replication and  Tenofovir
improves liver histology and fibrosis) o Antiretroviral drug also for HBV (for strains
o HBV DNA activity reappears after cessation of resistant to lamivudine and entecavir)
therapy  Sofosbuvir
o For strains resistant to lamivudine o Inhibits RNA polymerase in HCV (alone or with
 Toxicity: interferon-alpha/ribavirin)
o Nephrotoxicity (dose-limiting)  Boceprevir
o Lactic acidosis o Protease inhibitor in HCV (in combination with
o Severe hepatomegaly (with steatosis) ribavirin)

Entecavir Nursing Considerations:

 Mechanism of Action:  Extreme caution to children (carcinogenic);
o Inhibits HBV DNA polymerase foscarnet (affect bone growth & development)
 Uses:  Good hydration (decrease toxic effects of the
o HBV infection (similar to lamivudine and there is kidney)
cross-resistance between the 2 agents)  Administer as soon as possible, compliance
 Toxicity:  Wear protective gloves when applying the dug
o Headache, dizziness, fatigue, and nausea topically (decrease risk of exposure to the drug and
inadvertent absorption)
Lamivudine  Safety precautions = CNS effects (orientation,
 Mechanism of Action: siderails, lighting, assistance)
o Nucleoside inhibitor of HIV reverse  Warn that GI upset, N/V can occur (prevent undue
transcriptase (but more active in cells affected anxiety, increase awareness of the importance of
by HBV than HIV) nutrition)
 Uses:  Monitor renal function
o HBV infection (rapidly suppresses viral  Avoid sexual intercourse if with genital herpes
replication)  Avoid driving and hazardous tasks if with dizziness
 Toxicity: & drowsiness
o None (in low doses)
Anti-HIV agents
Ribavirin Anti-HIV
 Mechanism of Action:  Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
 Nonnucleoside Reverse Transcriptase Inhibitors core
(NNRTIs) • Tox:
 Protease Inhibitors nephrotoxicity
 Entry Inhibitors • Possible
 Integrase Strand Transfer Inhibitors insulin resistance
• MOA: blocks
attachment of HIV-
1 infection to host
Entry cell
Maraviroc
Inhibitors • Tox:
increased hepatic
transaminases
(liver enzymes)
• MOA: binds
integrase, which
inhibits transfer of
Integrase
reverse-
Strand
transcribed
Transfer Raltegravir
proteins into host
Inhibitors
chromosomes
Prototype (INSTs)
Subclass Description • Tox:
Drug
myopathy and
• MOA: rhabdomyolysis
inhibits viral
Nucleoside reverse
Reverse transcriptase
Transcriptase Zidovudine • Tox: Bone
Inhibitors marrow
(NRTIs) suppression
• High risk of
resistance
• MOA: Bind
to a different site
than NRTIs but still
inhibit viral
Nonnucleoside reverse
Reverse transcriptase
Delavirdin
Transcriptase • Tox: skin
e
Inhibitors rash, and
(NNRTIs) teratogenic in
animals (avoid in
pregnancy)
• Less risk of
resistance
Protease Indinavir • MOA:
Inhibitors inhibits protease,
an enzyme
required to
produce final
structure of virion
 Psychosis
- Major emotional disorder that impairs mental
function
- Individual cannot participate in everyday life
- Hallmark? Loss of contact with reality

Affective Disorders
- Major emotional disorder that impairs mental
function
- Individual cannot participate in everyday life
- Mania
o Abnormally pronounced emotions
- Depression
o Abnormally reduced emotions
- Bipolar affective disorder
o Exhibits both mania and depression

Antipsychotics
- Drugs used to treat schizophrenia are also
effective in the treatment of other psychoses
and agitated states
- Affinity:
older à D2 receptors
newer à 5HT2 receptors

Schizophrenia
- Clinical syndrome of variable but profoundly
disruptive, psychopathology that involves
cognition, emotion, perception, and other
aspects of behavior.
- Usually begins before 25 years old (lasts
throughout life)
- Affects persons of all social classes
- Both patients and families suffer from poor care
and ostracism (due to ignorance about the
disorder)
I DID NOT INSERT ANTI HPN1 AND HPN2 - Often discussed as a single disease entity
- May comprise a group of disorders with
Anti arrhythmics and cardiac glycosides anti anginals
heterogenous etiologies.
- Not cured by drug therapy
Schizophrenia
PSYCHOTHERAPEUTICS - Symptoms may be ameliorated:
Psychotherapeutics o Thought disorder
- Therapy of emotional and mental disorders o Emotional withdrawal
Normal human emotions: o Hallucinations
o Grief o Delusions
o Anxiety Unfortunately:
o Depression o Protracted therapy is needed (many
- Ability to cope can range from depression or years)
anxiety, to constant emotional distress o Result in severe toxicity
- To the point of interfering with the ability to - Positive symptoms:
function or normal daily living o Hallucinations
- When this happens, treatments with these
o Delusions
medications is a possible option
o Confusion and disorganized speech
o Movement disorders
Psychotherapeutics
- Negative symptoms:
Three (3) main emotional and mental disorders:
o Lack of pleasure
Psychoses, Affective disorders, Anxiety
o Lack of speech
 o Flat affect/voice o Many antipsychotic drugs block
o Withdrawal dopamine receptors (D2)
o Struggles with ADLs o Dopamine agonist drugs
o No follow-through (amphetamines, and levodopa)
exacerbate schizophrenia
Bipolar Affective Disorder o Increased density of dopamine
- Mainstay drug is Lithium receptors observed in untreated
- Use of other drugs are increasing schizophrenics
o Antipsychotic agents - not fully satisfactory:
o Antiseizure drugs o Antipsychotic medications are only
_________________________________________ partially effective in most patients
o Other effective drugs have higher
ANTIPSYCHOTICS affinity for other receptors (than D2)
o Phencyclidine (PCP) causes psychotic
Classification of Antipsychotics syndrome without any effect on
- Can be divided into: dopamine receptors [dissociative
o Typical (first generation) anesthetic]
o Atypical (second generation)
B. Dopamine Receptors
First Generation Antipsychotics - There are five (5) different receptors for
Three (3) major clinical subgroups: dopamine
o D2 is found in the caudate putamen,
A. Phenothiazines: nucleus accumbens, cerebral cortex,
a. Chlorpromazine and hypothalamus
b. Thioridazine - Negatively coupled to adenylyl cyclase
c. Fluphenazine - Efficacy of older drugs (neuroleptics) correlates
B. Thioxanthenes: with their affinity for D2 receptors
a. Thiothixene - Problem à D2 blockade also correlates with
C. Butyrophenones extrapyramidal dysfunction
a. Haloperidol
C. Other Receptors
Second Generation Antipsychotics - Most of newer antipsychotics have higher
- Varied heterocyclic structures but effective in affinities for other receptors (than D2) or have
schizophrenia: no affinity at all for D2
o Clozapine - For example:
o Loxapine o Affinity for D4 and 5HT2A only
o Olanzapine (Clozapine)
*Aripiprazole: third generation à dopamine partial o High affinity for 5HT2A but may interact
agonist with D2 and other receptors
(Olanzapine, Quetiapine, and
Pharmacokinetics Risperidone)
- Well-absorbed orally o Antagonist at D2, 5HT2A, and 5HT1D;
- Readily enter into the CNS and most other agonist at 5HT1A receptor (Ziprasidone)
tissues (lipid solubility) o Partial agonist at D2 and 5HT1A; strong
- Have long plasma half-lives (permits once a day antagonist at 5HT2A receptors
dosing) (Aripiprazole)
- Parenteral forms are available for some agents - Receptor binding characteristics of the newer
(for rapid initiation of therapy and depot drugs led to another NT as a suspect:
treatment): o Serotonin synthesis
o Fluphenazine - Most atypical drugs cause less EPS than
o Haloperidol standard drugs
- All antipsychotics block H1 receptors up to some
Mechanism of Action degree (except Haloperidol)
A. Dopamine Synthesis - Major effect that correlates with therapeutic
- Proposes that schizophrenia is due to an excess benefit à dopamine receptor blockade (older
of dopaminergic activity (in specific neuronal antipsychotics)
tracts of the brain)
- Basis: D. Dopaminergic pathways:
 - Mesocortical-mesolimbic pathway (mentation
and mood) Tardive dyskinesia
- Chemoreceptor trigger zone (emesis) - Choreoathetoid movements of muscles of the
- Nigrostriatal tract (extrapyramidal function) lips and buccal cavity (may be irreversible)
- Tuberoinfundibular pathway (prolactin release) - Tend to develop after several years (but appear
as early as 6 months)
**Note: all antipsychotic agents block both α1 and histamine - No effective drug treatment
H1 receptors (to some extent)
Neuroleptic malignant syndrome
Clinical Uses for Antipsychotics - Patients too sensitive to extrapyramidal effects
A. Treatment for Schizophrenia may develop this (muscle rigidity, impairment of
- Reduce some positive symptoms (hyperactivity, sweating, hyperpyrexia, and autonomic
hallucinations, delusions, and bizarre ideations) instability)
- Can facilitate functioning in both in-patient and - Treatment à Dantrolene, Diazepam, and
out-patient environments Diphenhydramine
- May take several weeks to develop beneficial
effects Miscellaneous
- Older drugs are used more (due to cheaper - Thioridazine: low dose à visual
cost), but have little to no effect on negative impairments
symptoms (retinal deposits)
- Newer drugs reportedly improve negative high doseàventricular
symptoms (emotional blunting, social arrhythmias
withdrawal, and lack of motivation) - Clozapine: low doseà agranulocytosis (1-2%)
- Some patients respond more with specific drugs high dose à seizures
- Clozapine is effective for patients who are
resistant to other antipsychotics _______________________________________________

B. Other Psychiatric & Neurologic Conditions BIPOLAR DRUGS

- 2nd generation antipsychotics are often used Principle to remember for Lithium effectiveness:
with lithium (initial treatment of mania) - Manic phase
- Several are approved for treatment of acute - Acute-phase illness
mania (aripiprazole and olanzapine) à - Prevention of recurrent and depressive episodes
maintenance treatment of bipolar disorder
- Also for: Pharmacokinetics
o Schizoaffective disorders (psychotic - Absorbed completely from the gut
symptoms) - Cleared by the kidneys at 1/5th the rate of
o Gilles de la Tourette syndrome creatinine
(Molindone) - Half-life is 20 hours
o Overdose of CNS stimulants - Can increase lithium in the blood:
o Alzheimer’s and Parkinsonism (2nd o Dehydration
generation) o Thiazides
o ACE inhibitors
C. Non-Psychiatric Indications o Loop diuretics
- Anti-emetics - Increases renal clearance:
o Most phenothiazines (especially o Caffeine
prochlorperazine à sole indication) o Theophylline
o Except thioridazine
- Antipruritics and sedatives (H1 receptor Mechanism of Action
blockade) - Not well-defined
- Inhibits several enzymes involved in the
Toxicity recycling of neuronal membrane
Reversible neurologic effects phosphoinositides
- Dose-dependent EPS dysfunction (parkinson- - Depletes source of 2nd messengers (which is
like syndrome) important in amine transmission)
o Commonly occurs with haloperidol (but
also fluphenazine, and trifluoperazine) Clinical Use
- Others (akathisia and dystonia) - Treatment for bipolar disorder:
o diphenhydramine - Lithium carbonate (main drug)
 o Reduces manic behavior, as well as
frequency and magnitude of mood
swings (maintenance therapy)
o Antipsychotic agents (and maybe
benzodiazepines) may be used at start
of therapy because of their faster onset
(Olanzapine and Quetiapine à
monotherapy for mania)
o Protective against suicide and self-
harm (with antidepressants)
- Valproic acid and carbamazepine (equally
effective)

Toxicity
- Adverse neurologic effects:
o Tremors
o Sedation
o Ataxia
o Aphasia
- Possible thyroid enlargement (but no
hyperthyroidism)
- In pregnancy, may increase incidence of
Ebstein’s anomaly (cardiac abnormality)
- Teratogenic risk is low (but low APGAR scores)
- Lithium should be withheld 24-48 hours prior to
delivery (and contraindicated for nursing
mothers)

Other Drugs for BPD

- Manic phase (olanzapine and quetiapine à
monotherapy)
- Valproic acid (anti-mania  USA)
o Often as first choice (and for those who
fail to respond to lithium)
- Carbamazepine and lamotrigine (anti-seizure
drugs) for: Acute mania and Prophylaxis (during
depressive phase)

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