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,
but potential benefits may warrant use of the drug
in pregnant women despite potential risks.
 Category D - There is positive evidence of human
fetal risk based on adverse reaction data from
investigational or marketing experience or studies
in humans, but potential benefits may warrant use
of the drug in pregnant women despite potential
risks.
 Category X - Studies in animals or humans have
demonstrated fetal abnormalities and/or there is
positive evidence of human fetal risk based on
adverse reaction data from investigational or
marketing experience, and the risks involved in use
of the drug in pregnant women clearly outweigh
potential benefits.
NOTE: A= Absolutely use it. B=Better to use it or
benefits outweigh the risks. C=Cutting too
close. Could use it. D= Don’t use it. X= Cross it out. It’s
contraindicated.
Drug Names
 Chemical
o systematically derived name which identifies
the chemical structure of the drug; shows the
exact chemical constitution of the drug and
exact placing of atoms
o e.g. N- Acetyl-para-aminophenol
 Generic
o given before drug becomes official; reflects
some important pharmacological or chemical
characteristic of the drug
o e.g. acetaminophen
 Brand
o followed by the symbol ®
o indicates the name is registered, that its use is
restricted to the owner of the drug (usually the
manufacturer of the product)
o Tylenol
Sources of drug information
 Sources of Drug Information
o Pharmacopoeia
o Formulary
o Nursing textbook
o Package insert
o Reference books
o PDR
o Drug facts & comparisons
o Nursing drug guide/ handbook
o Journals
 Medical letter
 American Journal of Nursing
 Internet
The Nursing Process in Pharmacology
 Assessment
o Forms basis on which the care is:
 Planned
 Implemented
 Evaluated
o Assess for:
 Findings/Cues
 Subjective cues
 Objective cues
 Drug history
o Drug History
 to evaluate the patient’s need for
medication
 to obtain current and past use of medicines
(OTC medicines, prescribed medicines,
herbal products, illicit drugs)
 to identify problems related to drug therapy
 to identify risk factors in drug therapy
 Diagnosis
o Based on analysis of the assessment data
o May be actual or potential
o Examples:
 KNOWLEDGE DEFICIT r/t LACK OF
EXPERIENCE WITH MEDICATION REGIMEN
AND SECOND GRADE READING LEVEL AS AN
ADULT AS EVIDENCED BY INABILITY TO
PERFORM A RETURN DEMONSTRATION
AND INABILITY TO STATE ADVERESE
EFFECTS TO REPORT TO THE PRESCRIBER
 RISK for INJURY R/T forgetfulness
 INEFFECTIVE THERAPEUTIC REGIMEN
MANAGEMENT R/T lack of finances
 Planning
o characterized by goal setting (or expected
outcomes) which represent effectiveness of
nursing care:
 patient goals
 state of desired patient behaviors or
responses
o Include:
 identification of the therapeutic intent for
every medication
 side effects to be expected and reported
 identification of the recommended dosage
and route of administration
 scheduling of the administration of
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 Amphetamine (narcolepsy, and weight
reduction)
o Methylphenidate (ADHD)
o Often abused for purposes of deferring
sleep and mood-elevating, euphoria-
producing effect (cocaine)
 Eye
o Phenylephrine and tetrahydrozoline
(reduce conjunctival itching and congestion
 from allergy and irritation)
o Phenylephrine (mydriatic)
o Apraclonidine and brimonidine (glaucoma)
 Bronchi
o Drugs of choice for acute asthmatic
bronchoconstriction
o Drugs: albuterol
metaproterenol
terbutaline
 Cardiovascular
o Heart failure
o Septic and cardiogenic shock
(norepinephrine)
 Genitourinary
o Ritodrine and terbutaline (beta2 agonists)
are used to suppress labor
 Cardiac stimulant effect may be
hazardous to the mother and child
o Ephedrine may be used for children
(enuresis) and elderly (urinary incontinence)
Toxicity
- Little toxicity to the CNS because of their limited
ability to penetrate into the brain
- Effects are more evident in the periphery
ADRENOCEPTOR BLOCKERS
Adrenergic Blockers
- Bind to adrenergic receptors but inhibit or block
stimulation of the sympathetic nervous system
- Have opposite effect of adrenergic agents
- Adrenergic antagonists or sympatholytics
- Sympatholytics
o Inhibit or lyse sympathetic
neurotransmitters (norepinephrine and
epinephrine)
Sympatholytics
- Classified as either:
o α1 and α2 receptor blockers
o β1 and β2 receptor blockers
- Other classifications depend on reversibility and
duration of action
Alpha Blockers
Classifications
a. Phenoxybenzamine
o Irreversible, long-acting
o Prototype alpha blocker
o Slightly alpha1 selective
b. Phentolamine
o Reversible, short-acting
o Competitive antagonist
o Does not distinguish between alpha1 and
alpha2 receptors
c. Prazosin
o Reversible
o Highly selective alpha1 blocker
o Similar drugs: Doxazosin
Terazosin
Tamsulosin
d. Yohimbine
o Alpha2 selective blocker
o Used primarily in research applications
o Similar drug: Rauwolscine
Pharmacokinetics (alpha blockers)
- Active through oral and parenteral route
o Phentolamine (rarely given orally)
Mechanism of Action
- Phenoxybenzamine covalently binds to the alpha
receptor
o Irreversible blockade
- All the rest are competitive antagonists
o Effects can be counteracted by increased
concentrations of agonists
Note: important in the treatment of
pheochromocytoma (massive
release of catecholamines may
overcome reversible
blockade)
Effects
Non-selective blockers:
- Most important are on the cardiovascular system
(reduction in vascular tone  decrease in arterial
and venous pressures)
- No significant direct cardiac effects
- Cause baroreceptor-mediated tachycardia (due to
drop in mean arterial pressure)
o May be exaggerated
o Alpha2 receptors in the heart (which
reduce the net release of norepinephrine)
are also blocked
Selective alpha blockers
- Because they block alpha1 receptors more effectively
than alpha2 receptors, induce less reflex tachycardia
(than non-selectives)
- Useful in relaxing smooth muscles in the prostate
Clinical Uses
Non-selective alpha blockers
- Limited clinical applications
- Pre-surgical management of pheochromocytoma
(may have severe hypertension and reduced blood
volume  must be corrected prior to surgery)
o Phenoxybenzamine (preparatory phase)
 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
 Sporonticides
o Prevent sporogony and multiplication in the
mosquito
Drugs:
 Chloroquine
 Artemisinin derivates
 Quinine
 Mefloquine
 Primaquine
 Other Drugs
Chloroquine
- Rapidly absorbed orally (widely distributed to
-tissues, and large volume of distribution)
- Antacids decrease oral absorption
- Excreted largely unchanged in the kidney
- MOA: accumulates in the food vacuole of the
plasmodia and prevents polymerization of the
hemoglobin breakdown product heme into
hemozoin
o accumulation of this substance is toxic to
the parasite
 any resistance is due to increased
activity of excretion of this
substance
- Type: blood schizonticide
- Uses:
o Chemoprophylaxis for malaria-endemic
regions (except those with resistant strains)
o Also for autoimmune disorders (rheumatoid
arthritis)
- Toxicity:
o GI irritation, skin rash, and headaches (low
doses)
o Severe skin lesions, peripheral neuropathy,
myocardial depression, auditory
impairment, and psychosis (high doses)
o May also trigger porphyria attacks
Artemisinin Derivatives
- Ex. Artesunate, Artemether, Dihydroartemisinin
- Type: blood schizonticide
- MOA: metabolized in the food vacuole which then
forms toxic free radicals
- Uses:
o Active against P falciparum (including
resistant strains)
o Severe infections (IV form available)
o 1st line agent for chloroquine-resistant
malaria (in most countries)
 Best used in combination with
other agents (also because of short
half-life 1-3 hours)
- Adverse Effects:
o Nausea, vomiting, and diarrhea (all are
mild)
o No evidence of increase in congenital
abnormalities, stillbirths, and abortion in
the pregnant
Quinine
- Rapidly absorbed orally (and metabolized before
renal excretion)
- IV forms are available (for severe infections)
- Not routinely used for chemoprophylaxis (to delay
emergence of resistance)
- MOA: complexes with double-stranded DNA to
prevent strand separation, resulting in a block in DNA
replication and RNA transcription
- Type: blood schizonticide
- Uses:
o P falciparum infections resistant to
chloroquine (in patients who can tolerate
oral treatment)
o Shorter duration of therapy if combined
with doxycycline or clindamycin (and limits
toxicity)
o Severe falciparum infection (uses Quinidine
form)
- Toxicity:
o GI distress, headache, vertigo, blurred
vision, and tinnitus (clinical entity:
cinchonism)
o Cardiac conduction disturbances and
hematotoxic effects in G6PD patients
(hemolysis)
o Blackwater fever  rare but fatal
complication in quinin-sensitized persons
Mefloquine
- Uses:
o First-line medication (taken weekly) as
prophylaxis in all geographic areas with
chloroquine resistance
o Alternative drug to quinine in acute attacks
and uncomplicated infections (P falciparum)
- Toxicity:
o GI distress, skin rash, headache, and
dizziness (low doses)
o Cardiac conduction defects, psychiatric
disorders, neurologic effects such as
seizures (high doses)
Primaquine
- Type: tissue schizonticide
Gametocide
- MOA: forms quinoline-quinolone metabolites
(which act as cellular oxidants)
- Uses:
o Eradicates liver stages of P vivax and P ovale
(should be used in conjunction with a blood
schizonticide)
o Alternative (daily) prophylactic for primary
prevention
 - Toxicity:
o GI distress, pruritus, and headache (mild)
o Methemoglobinemia, and RBC hemolysis in
G6PD patients (severe)
o Contraindicated in pregnancy
Other Drugs:
Lindane
- MOA: unknown (may stimulate parasite CNS,
leading to seizures and eventual death)
- SE: local skin irritation
- Nursing Considerations:
o Administer twice ( 1st immediately after dx;
2nd one week after the initial)
o Administer to all household members
o Wear gloves to remove nits by using fine-
toothed comb with vinegar
o Apply to all body areas (except the face)
Doxycycline
- Daily chemoprophylactic for travelers in geographical
areas (those with multidrug-resistant strains of P
falciparum)
- Mainly used as prophylaxis for leptospirosis
Lumefantrine
- Used in fixed combination with artemether for
uncomplicated falciparum malaria in many countries
- Related to halofantrine (but this has minimal
cardiotoxicity instead)
- Appropriate treatment needs antibiotic susceptibility
testing (of samples from the patient)
- Regimens are 3 or 4-drug combinations
Anti-Tuberculosis
 Isoniazid
 Rifampin
 Ethambutol
 Pyrazinamide
 Streptomycin
 Alternative Drugs
Isoniazid
- Structural congener of pyridoxine
- MOA: inhibition of mycolic acid synthesis
(essential components of mycobacterial)
o Resistance emerges rapidly if used alone
- Uses:
o Single most important drug used in
tuberculosis
o Given as single agent for those in close
contact with diseased patients
- Toxicity:
o Neurotoxic (peripheral neuritis,
restlessness, muscle twitching, and
insomnia)
o Hepatotoxic (abnormal liver function tests,
jaundice, and hepatitis)
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,
abnormal liver function (occasional)
o Flu-like syndrome and anemia (if given less
than 2x a week)
o Induces liver enzymes to enhance
elimination of other drugs which include:
 Anti-convulsants, contraceptive
steroids, cyclosporine,
ketoconazole, methadone,
terbinafine, and warfarin
- Other forms of Rifampin:
o Rifabutin – equally effective as
antimycobacterial agent (and has less drug
interactions than rifampin)  preferred for
AIDS patients
o Rifaximin – not abosrbed in GI tract  used
for traveler’s diarrhea
Ethambutol
- MOA: inhibits arabinosyl transferases involved in
the synthesis of arabinogalactan (cell wall
component) in mycobacterium
o Resistance is rapid if used alone as a single
agent
- Pharmacokinetics:
o Well-absorbed orally and distributed to
most tissues (including the CNS)
o Eliminated mostly unchanged in the urine
o Reduce dosage in renal impairment
- Uses:
o Tuberculosis (in combination with other
drugs)
- Toxicity:
o Visual disturbances (dose-dependent) 
decreased visual acuity, red-green
colorblindness, and retinal damage with
prolonged use at high dosages
o Effects regress when drug is stopped
Pyrazinamide
- 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
single agent
- Pharmacokinetics
o Well-absorbed orally (and penetrates most
body tissues, including CNS)
o Excreted in the urine
- Uses:
o Component of short-course treatment
regimens of PTB (with other drugs)
Streptomycin
- An Aminoglycoside
- Uses:
o Used more frequently due to increased
prevalence of strains of M. tuberculosis
resistance to other drugs
o Used principally in life-threatening
tuberculous diseases
o Used principally in life-threatening
tuberculous diseases:
 TB meningitis
 Miliary dissemination
 Severe organ tuberculosis
TB Conditions
 TB meningitis
 Miliary TB Dissemination
 Pott’s disease
 TB of the cervix
OTHER DRUGS
Amikacin
- For streptomycin-resistance cases of PTB
Ciprofloxacin and Ofloxacin
- For cases resistant to first-line agents
Ethionamide
- Cogener of INH (but has no cross-resistance)
- Major disadvantages  GI irritation, and neurologic
effects (at the higher doses needed to achieve
effective plasma levels)
P-Aminosalisylic acid (PAS)
- Rarely used because of primary resistance
- Causes GI irritation, peptic ulceration,
hypersensitivity reactions, and adverse effects on
kidney, liver, and thyroid function
Drugs with Limited Use
 Capteomycin (ototoxicity and renal dysfunction)
 Cycloserine (peripheral neuropathy, and CNS
dysfunction)
TREATMENT REGIMENS
Regimens:
A. Standard
B. Alternative
C. Resistance
Standard Regimen
- Empiric treatment of PTB (in areas <4% INH
resistance)
 o Initial 3-drug regimen (INH, Rifampin, and
Pyrazinamide)
o Discontinue pyrazinamide after 2 months (if
patient is HIV-negative and PTB strain is fully
susceptible)
o Continue treatment for another 2 months
- Phenazine dye (interacts with DNA)
- Causes GI irritation, and skin discoloration
o Red-brown to black
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

Polyenes
 Amphotericin B
o MOA: binds to fungal cell membrane to form
open channels  increase cell permeability and
leakage of intracellular proteins
 Potent but severe side effect (renal failure)
o Uses: DOC for severe systemic infection (given
IV)
o SE/AE: fever, nausea, vomiting, hypotension,
paresthesia, thrombophlebitis, nephrotoxicity,
hypersensitivity, electrolyte imbalances
(hypokalemia and hypomagnesemia)
Nystatin
 Brand: MYCOSTATIN
 MOA: increases permeability of fungal cell
membranes
 Uses:
o oral  intestinal candidiasis (poor absorption)
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
hepatotoxicity (pre-existing liver function)
 Endocrine dysfunction (ketoconazole)
 Transient and immediate visual
disturbances (voriconazole)
 Ketoconazole
o Narrow antifungal spectrum and causes more
adverse effects than other azoles
 Rarely used for systemic mycoses
o First effective antifungal  orally absorbed
 Used to treat same mycoses with
amphotericin B
 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
 Voriconazole
o Wider spectrum of activity than itraconazole
o Uses:
 Co-DOC for invasive aspergillosis
  Reportedly greater efficacy than
amphotericin B
 Alternative for candidemia and those with
resistance against fluconazole
 Candidial esophagitis and stomatitis (AIDS
patients)
 Posaconazole
o Broadest spectrum triazole
o Uses:
 Activity against most species of Candida and
Aspergillus
 Only azole with activity against Rhizophus
 Prophylaxis for cancer chemotherapy
 Salvage therapy for invasive aspergillosis
 Terbiniafine
o MOA: Inhibits the fungal enzyme, squalene
epoxidase, which causes accumulation of
squalene (interferes with ergosterol synthesis)
o Uses: Dermatophytoses (more effective than
Griseofulvin)
o Toxicity:
 GI upset, rash, headache
 Taste disturbances
Echinocandins
 Caspofungin
o Uses: Disseminated and mucocutaneous
candida infections (who fail to respond to
amphotericin B and in mucormycosis)
 Anidulafungin
o Uses: Candidiasis (esophageal and invasive)
 Micofungin
o Uses:
 Mucocutaneous candidiasis (prophylaxis)
 Candidasis in bone marrow transplant
patients (prophylaxis)
Anti-metabolite
 Flucytosine (5-Fluorocytosine [5-FC])
o Related to cancer drug, 5-fluorouracil
o Effective orally and crosses into the CNS
o Eliminated through the urine (dose must be
reduced in patients with renal impairment)
o MOA: accumulates in fungal cells through a
permease and converted into 5-FU (thymidylate
synthase inhibitor)
 Mammalian species are protected because
of low levels of permease, unlike fungal
cells
 Given with amphotericin B, or triazoles, to
decrease resistance
o Uses:
 cryptococcus neoformans
 systemic candidal infections (possible)
 chromoblastomycosis due to molds
o Toxicity:
 reversible bone marrow depression,
alopecia, and liver dysfunction (all in
 prolonged high plasma levels)
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:
 Not active topically
 Oral form for dermatophytoses of skin and
hair (but has since been replaced largely by
azoles and terbinafine)
o Toxicity:
 Liver dysfunction
 Contraindicated for porphyria
 Disulfiram-like reaction to alcohol
NURSING CONSIDERATIONS
 GSCS
 Monitor IV sites
 Check liver enzymes, creatinine, BUN, I/O
 Take with meals- oral forms (NAVDA)
 Check for hypersensitivity reaction (rash)
 For topical: wash hands before & after application
 For athletes’ foot: wear cotton socks, change 2-3
times daily
 Jock itch worm or ring worm: wear well fitting, non-
constrictive, ventilated clothing
 Intravaginal
o Read instructions carefully
o Insert high into the vagina
o Continue use through menstruation
o Wear a minipad to avoid staining clothing, do
not use tampon
o Wash applicator with mild soap and rinse
thoroughly after each use
o Avoid sexual intercourse while using the drug
Note: How to Remember “ZOLE”
 ZOLE – many drug interactions can occur
 Observe hygiene measures to control infections
 Liver Function Tests – monitor
 Educate to take with food
Meet “ZOLE” the toad who destroys fungal infections,
such as ringworm. “ZOLE” will help you remember
some key points with these drugs. It will also help you
remember the medication used for these infections,
since they have the letters zole in them.
Amphoterrible is a monster. He treats monster
infections such as histoplasmosis and other life-
threatening fungal infections. He has a terrible habit of
creating irregularities in the heart (arrhythmias). The X
marks the spot of the kidney since 80% of clients
receiving this drug may develop some nephrotoxicity.
BETA-LACTAM ANTIBIOTICS
Penicillins
Cephalosporins
Carbapenems - Not really a beta-lactam but retains its
ring structure
A. Penicillins
 Derivatives of 6-aminopenicillanic acid
 Contains a beta-lactam ring essential for
antibacterial activity
 Have additional chemical substituents which
confer differences (antimicrobial activity,
susceptibility to acid, enzymatic hydrolysis,
and biodisposition)
 Pharmacokinetics
o Vary in resistance to gastric acid (and
thus have variable bioavailability)
o Not metabolized extensively (in
effect excreted unchanged in the
urine via glomerular filtration and
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
results in the loss of antibacterial activity
o Formation of beta-lactamases (penicillinases)
by mostly staphylococci and many gram-
negative organisms is the major cause of
resistance
o To combat this development, inhibitors of
these bacterial enzymes are often used in
combination with penicillins to prevent their
inactivation
1. Clavulanic acid
2. Tazobactam
3. Sulbactam
o In the case of MRSA 🡪 structural changes in
the target PBPs (also in resistance to penicillin
G in pneumococci)
o In some gram-negative rods (pseudomonas),
changes in porin structures in the outer cell
wall may contribute resistance (it prevents
penicillins from accessing and binding to the
PBPs)
Clinical Uses
Narrow spectrum Penicillinase-susceptible agents
 Penicillin G
– Prototype of a subclass of penicillins with
limited spectrum of antibacterial activity (and
susceptible to beta-lactamases)
– Used against common streptococci,
meningococci, gram-positive bacilli, and
spirochetes
– Many strains of pneumococci are now resistant
to penicillins (PRSP)
– Most strains of S. aureus and N. gonorrhea are
resistant due to beta-lactamse production
– No longer DOC for gonorrhea, but still for
syphilis
– enhanced by co-administration of
aminoglycosides
 Penicillin V
– Used for oropharyngeal infections (given orally)
Very Narrow Spectrum Penicillinase-Resistant
 Subclass of penicillins which includes:
– Methicillin (prototype, but rarely used due to
its nephrotoxic potential)
– Nafcillin
– Oxacillin
 Primary use: staphylococcal infections
 Note: MRSA and MRSE (S. epidermidis) are
resistant to all penicillins, and often against
multiple antimicrobials
Wider Spectrum Penicillinase-Susceptible
 Ampicillin and Amoxicillin:
– Subgroup that has wider spectrum of
antibacterial activity compared to penicillin G
(but still susceptible to penicillinase)
– Clinical use similar to penicillin G, as well as
against:
• Enterococci, L. monocytogenes, E.
coli, P. mirabilis, H. influenzae, and M.
catarrhalis
(Some resistant strains have
developed)
– Activity is enhanced when used with
penicillinase inhibitors (e.g. clavulanic acid 🡪
Co-Amoxiclav)
– Synergistic with aminoglycosides in
enterococcal and listerial infections (ampicillin)
 Piperacillin and Ticarcillin:
– Activity against some gram-negative rods,
including:
• Pseudomonas
• Enterobacter
• Klebsiella
– Often used with penicillinase inhibitors
(tazobactam and clavulanic acid) to enhance
their activity
Penicillins
 Toxicity:
– Allergic reactions
o Urticaria, severe pruritus, fever, joint
swelling, hemolytic anemia, nephritis, and
anaphylaxis
o Allergic response occurs if given penicillin
again (in 5-10% of persons)
o Maculopapular skin rash (but mimics an
allergic reaction) 🡪 ampicillin
– Gastrointestinal disturbances
o Nausea and diarrhea (oral penicillins)
o May be due to direct irritation or by
overgrowth of gram-positive organisms
or yeasts
o Pseudomembranous colitis (ampicillin)
– Miscellaneous:
o Neutropenia (nafcillin)
o Interstitial nephritis (methicillin)
B. Cephalosporins
 Derivatives of 7-aminocephalosporanic acid and
contain the beta-lactam ring structure
 Many members are in clinical use
– Vary in antimicrobial activity and are
designated according to their generations
(in order of their introduction into clinical
use)
  Pharmacokinetics:
– Many are available for oral use (mostly
parenteral)
– Those with sidechains may undergo
heptaic metabolism but majority undergo
renal excretion via active tubular secretion
• Only Cefoperazone and
Ceftriaxone are excreted mainly in the
bile
– Most cephalosporins do not enter the
cerebrospinal fluid even when meninges
are inflamed
 Mechanism of Action
– Bind to penicillin-binding proteins to
inhibit bacterial cell wall synthesis (just like
penicillins)
• bactericidal
– Some structural differences make them
less susceptible to penicillinase produced
by staphylococci
• Resistance
– Some bacteria are able to produce beta-
lactamases which can inactivate
cephalosporins
– May occur from decreases in membrane
permeability to cephalosporins or from
changes in PBPs
– MRSA is resistant
1st Generation
 Cefazolin (parenteral) and Cephalexin (oral)
– Active against gram-positive cocci
(staphylococcus and common streptococci)
– Effective against many strains of E. coli and K.
pneumoniae
– Usually used as surgical prophylaxis
– Minimal activity against:
• Gram-negative cocci
• Enterococci
• MRSA
• most gram-negative rods
2nd Generation
 Lesser activity against gram-positive microbes versus
1st generation drugs
– But have extended gram-negative coverage
– Marked differences between usefulness
between drugs in the group
 Examples:
– Bacteroides fragilis (cefotetan and cefoxitin)
– Sinus, ear, and respiratory infections caused by
H. influenzae or M. catarrhalis (cefamandole,
cefuroxime, and cefaclor)
3rd Generation
 Increased activity against gram-negative microbes
resistant to other beta-lactam medications
– Plus the ability the penetrate the blood-brain
barrier (except for cefoperazone and cefixime)
 Most active against:
– Providencia, serratia marcescens, and beta-
lactamase-producing strains of H. influenzae
and Neiserria
 Less active against:
– Enterobacter strains that produce extended-
spectrum beta-lactamases
 Most drugs in this class are reserved usually for serious
infections:
– Pseudomonas  cefoperazone, ceftazidime
– B. fragilis cetizoxime
 Except for: ceftriaxone (parenteral) and
cefixime (oral) for gonorrhea
4th Generation
 Cefepime more resistant to beta-lactamases
produced by gram-negative microorganisms:
– Enterobacter, haemophilus, neisseria, and
some penicillinase-resistant pneumococci
– combines:
o Gram-positive activity of 1st generation
o Wider gram-negative spectrum of 3rd
generation
5th Generation
 Indicated for treating bacteria which are otherwise
resistant to commonly used antibiotics
 Ceftaroline – has broad spectrum activitiy against
MRSA (others: MRSE, VRE)
- Not effective against Pseudomonas
 Ceftobiprole – this drug has been called a 5th gen
cephalosporin, but the terminology is not universally
accepted.
- has powerful antipseudomonal activity, and
binds strongly to PBP 2a
- has activity against MRS, S. pneumonia,
enterococci
- newer medication used for healthcare-
associated pneumonia (HCAP) or HAP
 Cephalosporins Toxicity:
– Allergies (skin rashes to anaphylactic shock)
• Between cephalosporins is
complete (100%)
• Between a cephalosporin and
penicillin is incomplete (5-10%)
 Other Adverse Effects:
– May cause pain at IM injections (as well as
phlebitis if given IV)
– May increase nephrotoxicity of
aminoglycosides (if given together)
 – Some may cause: hypoprothrombinemia and
disulfiram-like actions with ethanol
(cefamandole, cefoperazone, and cefotetan)
• Due to their methylthiotetrazole
group
• Disulfuram-like action:
- reaction to alcohol leading
to nausea, vomiting,
flushing, dizziness,
throbbing headache, chest
and abdominal discomfort,
and general hangover-
like symptoms among
others
Other Beta-Lactam Drugs
 Aztreonam
 Carbapenems (Imipenem, Meropenem, and
Ertapenem)
 Beta-Lactamase Inhibitors (Clavulanic acid, Sulbactam,
and Tazobactam)
Aztreonam
 monobactam resistant to beta-lactamases produced
by some gram-negative rods (including Klebsiella,
pseudomonas, and serratia)
 No activity against gram-positive bacteria or anaerobes
 Cell wall synthesis inhibitor (preferentially binds with
penicillin-binding protein (PBP3)
 Synergistic with aminoglycosides
 Given intravenously and is eliminated via renal tubular
secretion
 Half-life is prolonged in renal failure
 Adverse effects include GI upset with possible
superinfection, vertigo, headache, and rarely
hepatotoxicity
– Skin rash may occur but there is no cross-
allergenicity with penicillins
Carbapenems
(Imipenem, Doripenem, Meropenem, Ertapenem)
• Chemically different from penicillins but retain the
beta-lactam ring structure
• Have low susceptibility to beta-lactamases which
makes them useful against:
– Gram-positive cocci
– Gram-negative rods
– anaerobes
 All are active against P. aeruginosa and acinetobacter
spp, except for ertapenem
– Often paired with an aminoglycoside if used
against pseudomonas
 Given parenterally, are useful against microbes
resistant to other antibiotics
- But is not effective against MRSA
 Co-drugs of choice for:
– Enterobacter, citrobacter, and serratia spp
Imipenem
• Rapid inactivation by renal dehydropeptidase I
• Administered in fixed combination with cilastatin (an
inhibitor of the enzyme above)
– Increases its half-life and inhibits the formation
of a metabolite toxic to the kidneys
Note: other carbapenems are not significantly
degraded by the kidneys
Imipenem-Cilastatin
 Partial cross-allergenicity with penicillins
 Adverse effects:
– GI distress, and skin rash
– CNS toxicity 🡪 confusion, encephalopathy, and
seizures (at very high plasma levels)
Meropenem
 Similar to imipenem but not metabolized by renal
dehydropeptidases
 Less likely to cause seizures
Ertapenem
 Long half-life but less active against enterococci and
pseudomonas
 Intramuscular route causes pain and irritation
Beta-Lactamase Inhibitors
(Clavulanic acid, Sulbactam, Tazobactam)
 Used in fixed combinations with certain hydrolyzable
penicillins
 Most active against plasmid-encoded beta-lactamases
(produced by gonococci, streptococci, E. coli, and H.
influenzae)
 Not useful against enterobacter, pseudomonas, and
serratia
– Their type of beta-lactamase is chromosomal
(and not plasmid-encoded)
OTHER CELL WALL OR MEMBRANE-ACTIVE AGENTS
(Vancomycin, Fosfomycin, Bacitracin, Cycloserine,
Daptomycin)
Vancomycin
 Bactericidal glycoprotein which inhibits
transglycosylation
– Prevents elongation of the peptidoglycan chain
and interferes with cross-linking
– Resistance  due to decreased affinity for the
binding site
 Narrow spectrum of activity
– Used for serious infections caused by drug-
resistant gram-positive organisms
 • Methicillin-resistant staphylococci
(MRSA)
• Penicillin-resistant pneumococi
(PRSP) 🡪 in combination with a 3rd
generation cephalosporin (usually
ceftriaxone)
– Used for serious infections caused by drug-
resistant gram-positive organisms
• Backup drug for Clostridium
difficile infection
 Not absorbed in the GI tract (and may be given orally
for bacterial enterocolitis)
 Given parenterally, it penetrates most tissues and is
eliminated unchanged in the urine
• Dosage modification is mandatory in renal failure
patients
• Toxicity:
– Chills, fever, phlebitis, ototoxicity, and
nephrotoxicity
– Rapid intravenous infusion 🡪 Red Man
Syndrome (due to histamine release)
Fosfomycin
 Antimetabolite inhibitor of cytosolic enolpyruvate
transferase
– Prevents formation of N-acetylmuramic acid
(an essential precursor for peptidoglycan chain
formation)
– Resistance 🡪 decreased intracellular
accumulation of the drug
 Excreted by the kidney in urinary levels higher than
minimum inhibitory concentrations (MIC) makes it
useful against UTIs
 In multiple dosing, diarrhea is common
 May be synergistic with beta-lactam and quinolone
antibiotics in some infections
Bacitracin
 Peptide antibiotic which interferes with a late stage in
cell wall synthesis in gram-positive organisms
 Limited to topical use because of its marked
nephrotoxicity
Cycloserine
 Antimetabolite that blocks incorporation of amino
acids into the side chain of the peptidoglycan
 Highly neurotoxic (tremors, seizures, and psychosis)
– Limited use to tuberculosis that is resistant to
first-line antituberculosis drugs
Daptomycin
 Novel cyclic lipopeptide with spectrum similar to
vancomycin (but active against vancomycin-resistant
strains of enterococci and staphylococci)
 Eliminated via the kidney
 Monitor creatinine since it causes myopathy
Antimicrobials and Antibacterials
ANTIMICROBIALS – inhibit the growth of or kill bacteria/
microorganisms outright (e.g. bacteria, fungi, parasites and
some viruses)
ANTIBACTERIAL/Antibiotics – chemicals that specifically kills
bacteria; destructive or inhibiting the growth of bacteria
PHARMACOKINETICS
 Must only penetrate the bacterial cell wall in
sufficient concentration; must have affinity to the
binding sites
 TIME drug remains at the binding site = INCREASE
EFFECT;
 Controlled by DISTRIBUTION, HALF-LIFE &
ELIMINATION
 Most are not highly CHON bound = longer HALF-LIFE
greater concentration at binding sites; mostly
eliminated from the body through URINE after the 7 th
half-life
RESISTANCE to Antibacterials
INHERENT or NATURAL – occurs without previous exposure to
the antibacterial drug
ACQUIRED - caused by PRIOR exposure to antibacterial
 Responsible for causing Penicillin resistance =
PENICILLINASE (enzyme that metabolizes PenG =
drug is ineffective)
 CAUSES :
o mutant bacteria- grown a thicker cell wall
o transfer of genetic instruction to another
bacterial species
To beat the problem:
 New antibiotics are developed 
 Development of ANTIBIOTIC RESISTANT DISABLERS
(disable antibiotic-resistant mechanism in the
bacteria)
 Bacterial Vaccines (e.g. DPT, Flu Vaccine, TT)
 Prevent antibiotic abuse
 COMPLIANCE and MULTI ANTIBIOTIC THERAPY
Antibiotic Combinations
• ADDITIVE EFFECT
 equal to the SUM of the effects of 2
antibiotics
• POTENTIATIVE (SYNERGISTIC) EFFECT
 one antibiotic potentiates the effect of
the 2nd antibiotic
• ANTAGONISTIC
 combination of a drug that is
BACTERICIDAL PENICILLIN + drug that is
BACTERIOSTATIC, TETRACYCLINE =
desired effect may be reduced
SPECTRUM
 NARROW SPECTRUM
o against one type of organism
 o Penicillin & Erythromycin – for gram (+)
bacteria
 BROAD SPECTRUM
o against both gram (+) & gram (-)
o Tetracyline & Cephalosporins
General Adverse Reactions
1) HYPERSENSITIVITY – rash, pruritus & hives ; severe
anaphylactic shock
TX: antihistamine, epinephrine, bronchodilators
2) SUPERINFECTION – secondary infection due to disturbed
normal flora; occur with use of broad spectrum
antibiotics
3) ORGAN TOXICITY – damage to organs that are involved in
drugs metabolism & excretion (liver & kidneys)
aminoglycosides = OTOTOXIC & NEPHROTOXIC
NURSING CONSIDERATIONS
 Monitor for superinfections
 Evaluate renal [BUN & creatinine] & liver [AST,ALT]
functions
 Diarrhea r/t superinfections (mgt: take yogurt, more
fluids)
 Inform physician before taking other meds
 Cultures- prior to 1st dose
 Alcohol is OUT!/ ask about allergies
 Take full course of meds
 Evaluate cultures, WBC, C&S
Anti-Bacterials I
Aminoglycosides
Modes of Antibacterial Action
 Multiple daily dosage regimens are traditionally used
o to maintain serum concentrations above
minimum inhibitory concentration (MIC)
 Minimum inhibitory concentrations
(MICs) are defined as the lowest
concentration of an antimicrobial
that will inhibit the visible growth
of a microorganism after overnight
incubation
 As plasma levels increase, aminoglycosides kill an
increased proportion of bacteria at a more rapid rate
 Same with penicillins and cephalosporins
 *time-dependent killing (more bacteria are killed
the longer drugs are maintained above the MIC 
same moment it becomes independent of
concentration)
 Aminoglycosides are capable of post-antibiotic effect
 Killing action continues even after plasma levels have
declined below measurable levels
 Aminoglycosides have greater efficacy if given as a
large single dose (compared to multiple smaller
doses)
o Toxicity depends on both actual increased
plasma concentration and duration the level
is exceeded
o Leads to: once daily dosing  more
advantageous
Pharmacokinetics
 Structurally related amino sugars attached by
glycosidic linkages
 Must be given thru IM or IV (for systemic effect)
o Not absorbed well through oral
administration (and have limited tissue
penetration in CNS)
Pharmacokinetics
 Undergoes renal excretion (plasma levels are greatly
affected by renal function)
 Excretion is proportional to creatinine clearance
 Dosage adjustments necessary in renal dysfunction
Mechanism of Action
 Aminoglycosides are bactericidal inhibitors of
protein synthesis
 May be enhanced by bacterial cell wall synthesis
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
o Inhibit translocation
o May also disrupt polysomal structure,
resulting in non-functional monosomes
(possible 4th MOAas proposed)
 Streptococci (S pneumoniae) and Enterococci 
relatively resistant (due to drug’s inability to
penetrate their cell walls)
Clinical Uses
 Main differences due to activities against specific
microorganisms: gram (-) rods
 Gentamicin, Tobramycin, and Amikacin  serious
infections of aerobic gram-negative bacteria
o E. coli, Enterobacter, Klebsiella, Proteus,
Providencia, Pseudomonas, and Serratia
o alternative medications for:
 H. influenzae, M. catarrhalis, and
Shigella spp
 not reliably effective against gram-positive cocci
(instead, combined with cell wall inhibitors e.g.
penicillins)
  Streptomycin  used in regimens against:
o Enterococcal carditis (Infective
endocarditis) - infection in the heart valves
or endocardium
o Plague - a contagious bacterial disease
characterized by fever and delirium,
typically with the formation of buboes
( bubonic plague ) and sometimes infection
of the lungs ( pneumonic plague )
o Tularemia
o Pulmonary tuberculosis (if resistant to
streptomycin, use amikacin instead)
Spectinomycin  administered thru IM
 Single dose for treatment of gonorrhea
 not an aminoglycoside (but a related drug  it is an
aminocyclitol)
Toxicity
 Ototoxicity
o Two (2) main possible conditions:
 Auditory damage (amikacin and
kanamycin)
 Vestibular damage (gentamicin
and tobramycin)
 BOTH ARE IRREVERSIBLE (may be
decreased with use of loop
diuretics)
o Contraindicated in pregnancy (due to
damage to hearing of fetus after exposure)
o Unless potential benefits outweigh risks
 Nephrotoxicity
o Acute tubular necrosis  reversible but
more common in:
 Elderly
 Taking other medications
(amphotericin B, cephalosporins,
or vancomycin)
o Most nephrotoxic:
gentamicin
tobramycin
 Neuromuscular Blockade
o Rare, but may result in respiratory paralysis
o Reversible: calcium and neostigmine
o May require a mechanical ventilator
 Skin Reactions
o Most likely to cause these reactions 
Neomycin
o Allergic skin reactions
o Contact dermatitis
NURSING RESPONSIBILITIES
 Monitor periodical audiograms, BUN/creatinine &
vestibule function studies over 10 days therapy
 Adjust for renal insufficiency
 Monitor VS, peak and serum levels
 For IV admin., dilute and administer slowly to
prevent toxicity
 Monitor I & O, hydrate well before and during
therapy (flush in between)
 If anorexia or nausea occurs, SFF meals
 Establish plan for safely if vestibular nerve effects
occur.
 Administer other antibiotics 1 hour before/after
amino
 Recommend using sunblock & protective clothing
when exposed to the sun.
CHLORAMPHENICOL
Classification and Pharmacokinetics
 Has a simple and distinctive structure (the only one
discovered in its chemical class)
 Effective orally, parenterally, and is widely distributed
 Readily crosses the placenta and the blood-brain barrier
 Undergoes enterohepatic recycling (but a small fraction is
excreted in the urine unchanged
 Most of the drug is inactivated by hepatic
glucoronyltransferase
Antimicrobial Activity
 Wide spectrum of antimicrobial activity (and usually
bacteriostatic)
 May be bactericidal in some microbes:
H. influenzae
N. gonorrhea
Bacteroides
 Not active against Chlamydia
 Resistance:
Formation of acetyltransferase  inactivates the drug
Clinical Uses
 Few uses as a systemic drug (due to its toxicity):
o Backup drug caused by severe infections of
Salmonella
o Pneumococcal and meningococcal meningitis (in
beta-lactam sensitive persons)
 Commonly used as a topical agent
Toxicity
 GI disturbances  direct irritation and superinfection
(esp. candidiasis)
 Bone marrow  inhibits maturation of red blood cells
(leads to a decrease in circulating RBCs)
o Dose-dependent and reversible
o Rare idiosyncratic reaction  aplastic anemia
(irreversible and fatal)
 Gray Baby syndrome
o Occurs in infants
o Characterized by:
 Decreased RBCs
 Cyanosis
 Cardiovascular collapse
 Neonates (esp. the premature) are more prone
o Lesser amounts of hepatic glucoronyltransferase
(makes them more sensitive to chloramphenicol
at doses infants may be able to tolerate)
Drug Interactions
 Chloramphenicol inhibits hepatic drug-metabolizing
enzymes
 Increases elimination half-lives of drugs including:
Phenytoin, tolbutamide, and warfarin

TETRACYCLINES
Classification
 broad spectrum bacteriostatic antibiotics with only minor
differences in their activities against susceptible
microorganisms
Pharmacokinetics
 Variable oral absorption (especially for the older drugs)
which may be impaired by:
o Food
o Multivalent cations (iron, calcium, and
aluminum)
 Wide tissue distribution (and crosses placental barrier)
 All tetracyclines undergo enterohepatic cycling
 Excretion: mainly in urine
o doxycycline (feces
o tigecycline (bile)
Antibacterial Activity
 Broad spectrum with activity against:
o Gram-negative and positive bacteria
o Rickettsia
o Mycoplasma
o Protozoa
 Resistance  wide-spread
o Development of efflux pumps (for active
expulsion of the drug from the bacteria)
o Formation of ribosomal protection proteins
(prevent tetracycline from binding)
o Note both do not work against Tigecycline
(except for the multidrug efflux pumps of
Proteus and Pseudomonas)
Clinical Uses
 Primary:
o Mycoplasma pneumoniae (in adults)
o Chlamydia, rickettsia, vibrio, and some
spirochetes
o Note: also alternative drug to macrolides in the
empirical treatment of CAP
 Secondary:
o Alternative to drugs for treatment of syphilis
o Prophylaxis against infection in chronic bronchitis
o Leptospirosis
o Acne
 Selective uses:
o GI ulcers (caused by H. pylori)  tetracycline
o Lyme disease  doxycycline
o Also for prevention of malaria and treatment of
amebiasis
o Meningococcal carrier state  minocycline
o Patients with antidiuretic hormone-secreting
tumors  demeclocycline
o Inhibits renal actions of antidiuretic hormone
o Tigecycline (only IV)
- It includes microbes resistant to standard
tetracyclines:
 gram-positive cocci resistant to
methicillin (MRSA)
 Vancomycin-resistant enterococci
(VRE)
 Beta-lactamase producing bacteria
Toxicity
 GI disturbances
o Mild nausea and diarrhea to severe life-
threatening enterocolitis
o Disturbances in normal flora  candidiasis (oral
and vaginal)
o bacterial superinfection (S. aureus, or C. difficile)
 Bony structures and teeth
o Tooth enamel dysplasia (and other irregularities
in bone growth)  fetal exposure
 Though usually contraindicated, some
cases may justify its use in pregnant
patients
 Hepatic toxicity
o Impaired liver function  hepatic necrosis (if in
high doses)
o Common in pregnant and those with preexisting
liver disease
 Renal toxicity
o Fanconi’s syndrome (form of renal tubular
acidosis)
o Not directly nephrotoxic but enhances
preexisting renal dysfunction
 Photosensitivity
o Enhanced skin activity to ultraviolet light
(demeclocyline)
 Vestibular toxicity
o Dose-dependent reversible dizziness
(doxycycline and minocycline)
___________________________________________
MACROLIDES AND OTHER DRUGS
Classification and Pharmacokinetics
 Macrolides are large cyclic lactone ring structures with
attached sugars
 Good oral bioavailability
o Absorption of azithromycin is impeded by food
 Distributed to most body tissues
o Azithromycin  unique because its levels are
higher in tissues and in phagocytes
 Elimination differs:
o Erythromycin (biliary excretion)
o Clarithromycin (hepatic metabolism and urinary
excretion of intact drug)
o More rapid:
 Erythromycin (biliary excretion at 2
hours)
 Clarithromycin (urinary excretion at 6
hours)
o Slower:
 azithromycin (urinary excretion at 2-4
days)
o Erythromycin  has activity against most
species of:
 Campylobacter, chlamydia, and
mycoplasma
 Legionella, gram-positive cocci, and
some gram-negative microbes
o Azithromycin & Clarithromycin  same
spectrum of activity as erythromycin but greater
activity against species of:
 Chlamydia, mycobacterium avium
complex (MAC), and toxoplasma
o Azithromycin  alternative for STDs
 Gonorrhea/Gonococcal UTI
(alternative to ceftriaxone)
 Syphilis (alternative to penicillin G)
Resistance
  Development of efflux pumps (mostly in gram-positive
bacteria)
 Assume complete cross-resistance between individual
macrolides
Clinical Uses
 Erythromycin  effective in infections caused by:
o M. pneumoniae, Corynebacterium,
Campylobacter jejuni, Chlamydia trachomatis,
Chlamydophila pneumonia, Legionella
pneumonia, Ureaplasma urealyticum, and
Bordetella pertussis
 Clarithromycin  similar spectrum and clinical uses as
erythromycin, but may be used as prophylaxis for:
o M. avium complex
o H. pylori (GI ulcers)
 Azithromycin  similar in spectrum but more active
against:
o H. influenza
o M. catarrhalis
o Neisseria
 because of a long half-life, it can be effective as:
o Single dose (for C. trachomatis)
o 4-day regimen (CAP)
 Fidaxomicin  narrow-spectrum macrolide
o Inhibits protein synthesis and selectively active
against gram-positive aerobes and anaerobes
o Given orally (to ensure minimal systemic
absorption)
o Proven to be as effective as vancomycin for
pseudomembranous colitis (C. difficile infection)
Toxicity
 Erythromycin:
o GI irritation (stimulation of motolin receptors),
skin rashes, and eosinophilia
o Acute cholestatic hepatitis (hypersensitivity-
based)
- inhibits multiple isoforms of cytochrome P450  leads to
increase in plasma levels of many drugs such as:
o Anticoagulants
o Carbamazepine
o Cisapride
o Digoxin
o Theophylline
 Azithromycin  lactone ring structure is slightly different
compared to other macrolides
o Drug interactions are not common (does not
inhibit CP450)
___________________________________________
TELITHROMYCIN
 Ketolide (structurally related to macrolides)
 Same MOA as erythromycin and similar spectrum of
activity
o But some strains resistant to macrolides are
vulnerable because it binds tighter to ribosomes
(and a poor substrate for bacterial efflux pumps
which mediate resistance)
 Given orally (once a day)
 Eliminated in the bile and urine
 May induce hepatic dysfunction and prolongation of QT
interval (ECG)
 Inhibits CYP3A4 drug-metabolizing system
___________________________________________
CLINDAMYCIN
 Inhibits bacterial protein synthesis via mechanisms similar
to macrolides (but not chemically related)
Resistance:
 Methylation of binding site on 50s subunits and enzymatic
inactivation
 gram-negative microbes are intrinsically resistant (poor
penetration through the outer membrane)
 Cross-resistance between clindamycin and macrolides is
common
Pharmacokinetics
 good tissue penetration (after oral absorption)
 Undergoes hepatic metabolism
 Eliminated via biliary and renal excretion
Clinical Uses
 Mainly used as treatment for severe infections by certain
anaerobes (Bacteroides)
 Backup drug against gram-positive cocci, as it is active
against:
o community-acquired strains of MRSA
o Prophylaxis for endocarditis (in patients allergic
to penicillin)
 Also used as treatment for:
o PCP (P. jirovecii)
o AIDS-related toxoplasmosis (in combination with
pyrimethamine)
Toxicity:
 GI irritation, skin rashes, neutropenia, hepatic dysfunction
 Possible superinfection (C. difficile  pseudomembranous
colitis)
________________________________________________
STREPTOGRAMINS
Quinupristin-Dalfopristin
 Combination of two (2) streptogramins
 Bactericidal
 Exhibits postantibiotic effects
 Useful against:
o Penicillin-resistant pneumococci (PRPC)
o Methicillin-resistant S. aureus (MRSA)
o Vancomycin-resistant staphylococci (VRSA)
 Given intravenously
 May cause pain and arthralgia-myalgia syndrome
 Potent inhibitors of CYP3A4  increases plasma levels of
many drugs:
o Astemizole
o Cisapride
o Cyclosporine
o Diazepam
o NNRTI
o Warfarin
________________________________________________
LINEZOLID
 First of a novel class of antibiotics (oxazolidinones)
 Active against drug-resistant gram-positive cocci, including
those resistant to:
o Penicillins (MRSA, and PRSP) and vancomycin
(VRE)
 Also active against L. monocytogenes and corynebacterium
 MOA  binds to a unique site located at 23S ribosomal
RNA of the 50s ribosomal subunit
 No cross-resistance with other protein synthesis inhibitors
 Possible resistance:
o Decreased affinity to its binding site
 Available in both oral and parenteral forms
  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
history of seizures
Nematodes (Roundworms)
 1.5 billion cases (ascariasis)
 1.3 billion cases (hookworms)
 800 million cases (whipworm)
 Benign manifestations (unless high worm burdens)
 Acquired via oral-fecal route (also autoinfections)
 Reflect poor sanitation, dietary preparation, and
hygiene practices
o Eggs require incubation in the soil (several days
to weeks)
o Warm, tropical climates
Drugs Against Nematodes (Roundworms)
 Albendazole
o MOA: inhibition of microtubule assembly
o Uses: ascariasis, hookworm, pinworm, and
whipworm infections,
o threadworm, filariasis, visceral and cutaneous
larva migrans (alternative drug)
o Toxicity:
 Leukemia, alopecia, and elevation of liver
function enzymes in prolonged use of >3
days (reversible)
 Safety for pregnancy and young children
not established
 Diethylcarbamazine
o MOA: immobilizes microfilariae through
unknown mechanism, increasing susceptibility
to host defenses
o Uses: DOC for filarial infections
 Wuchereria bancrofti
 Brugia malayi
 Loa loa
o Toxicity:
 Headache, malaise, weakness, and anorexia
 Fever, rashes, ocular damage, joint and
muscle pain, and lymphangitis (reaction to
dying worms)
 Ivermectin
o MOA: increases GABA-mediated
neurotransmission in nematodes which cause
paralysis, and then removal through the
reticuloendothelial system
o Uses: DOC for onchocerciasis, cutaneous larva
migrans, strongyloidiasis, and some forms of
filariasis
o Toxicity:
 Fever, headache, dizziness, rashes, pruritus,
tachycardia, hypotension, joint and muscle
pains, and lymphangitis (reaction to dying
worms)
 Not for pregnancy
 Mebendazole
o MOA: inhibits mictotubule synthesis and
glucose uptake in nematodes
o Uses: primary drug for ascariasis, pinworm, and
whipworm infections.
o Backup drug for visceral larva migrans
o Toxicity:
 Limited to GI irritation
 granulocytopenia and alopecia (high doses)
 Thiabendazole
o MOA: similar to mebendazole and albendazole
o Uses: alternative drug for strongyloidiasis and
trichinosis (adult worms)
o Also has anti-inflammatory and
immunorestorative actions in the host
o Toxicity:
 More toxic than the structural congener
(mebendazole)  other drugs are preferred
 GI irritation, drowsiness, leukopenia,
allergic reactions, intrahepatic cholestasis
 Irreversible liver failure and Stevens-
Johnson syndrome
 Avoid in pregnant and hepatic/renal failure
patients
 Pyrantel Pamoate
o MOA: stimulates nicotinic receptors at
neuromuscular junctions of nematodes
(contraction then depolarization-induced
paralysis)
 Kills adult worms in the colon (but not eggs)
 No effect on flukes or tapeworms
o Toxicity: Use with caution in hepatic
failure/dysfunction patients
 Piperazine
o MOA: paralyzes ascaris by acting as GABA
agonist (worms are then expelled live by
normal peristalsis)
o Uses: alternative drug for ascariasis
o Toxicity:
 mild GI irritation (most common)
 Not for pregnant and liver/renal failure pts
Nursing Considerations
 Assess history (food eaten)
 Collect stool specimen
 Take drug with food, small frequent feeding
 Avoid driving, change position slowly
 Take drug as prescribed
 Inform health care provider about OTC meds taking
 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
 Mechanism of Action:
o Phosphonoformate derivative that does not
require phosphorylation for anti-viral activity
o Inhibits viral RNA polymerase, DNA polymerase,
and HIV reverse transcriptase
 Uses:
o CMV prophylaxis and treatment (alternative
drug)
o For CMV strains resistant to ganciclovir
o Herpes in AIDS patients
 Toxicity:
o Nephrotoxicity (30% of cases)
o Electrolyte imbalance
o Genitourinary ulceration
o CNS effects (headache, hallucinations, and
seizures)
Other Agents
 Vidarabine (adenine analogue)
o Has activity against HSV, VZV, and CMV
o Topical agent for herpes keratitis but no effect
on genital lesions
 Idoxuridine and Trifluridine (pyrimidine analogy)
o Topical agent for herpes keratitis (HSV-1)
o Too toxic for systemic use
 Fomivirsen (anti-sense oligonucleotide)
o Binds to mRNA of CMV (inhibiting early protein
synthesis)
o Injected intravitreally for CMV retinitis
o Eye problems (iritis, vitreitis, increased IOP, and
vision disturbances)
Nursing Considerations:
 Extreme caution to children (carcinogenic);
foscarnet (affect bone growth & development)
 Good hydration (decrease toxic effects of the
kidney)
 Administer as soon as possible, compliance
 Wear protective gloves when applying the dug
topically (decrease risk of exposure to the drug and
inadvertent absorption)
 Safety precautions = CNS effects (orientation,
siderails, lighting, assistance)
 Warn that GI upset, N/V can occur (prevent undue
anxiety, increase awareness of the importance of
nutrition)
 Monitor renal function
 Avoid sexual intercourse if with genital herpes
 Avoid driving and hazardous tasks if with dizziness
& drowsiness
Anti-influenza agents
Amantadine and Rimantadine
 Mechanism of Action:
o Inhibit an early step in replication of influenza-A
(but not B) virus
o Prevents viral uncoating by binding to a proton
channel
o Prevents acidification of viral core (necessary to
activate viral RNA transcriptase)
 Uses:
o Prophylactic against influenza-A virus (and
reduces duration of infection if given within 48
hours of contact/exposure)
o Not for H3N22 and H1N1 (resistant)
 Toxicity:
o GI irritation, dizziness, ataxia, slurred speech
Oseltamivir and Zanamivir
 Mechanism of Action:
o Inhibit neuraminidase produced by influenza-A
and B
o Cleave sialic acid residues from viral proteins
and surface proteins of infected cells
o Responsible for virion release and prevents
clumping of newly released virions
 Uses:
o Influenza-A and B
o H3N2 and H1N1
 Toxicity:
o GI symptoms (oseltamivir)
o Cough, throat discomfort, and bronchospasm
(zanamivir)
Nursing Considerations:
 Start regimen as soon after the exposure to the
virus as possible (achieve best effectiveness and
decrease the risk of complications)
 Administer the full course of drug
 Provide safety measures (protect patient from
injury)
Anti-viral hepatitis agents
Interferon-alpha
 Mechanism of Action:
o Cytokine that acts through host cell surface
receptors to increase production of anti-viral
proteins
o Preferential degradation of viral mRNA
o Promotes formation of natural killer cells
(destroys infected liver cells)
 Uses:
 o Chronic HBV infection (as single agent or in
combination with other drugs)
o Kaposi’s sarcoma
o Papillomatosis
o Genital warts (topical)
 Toxicity:
o GI irritation, flu-like syndrome, neutropenia,
profound fatigue and myalgia
o Reversible hearing loss
o Thyroid dysfunction, mental confusion, severe
depression
o Contraindicated for pregnancy
Adefovir Dipivoxil
 Mechanism of Action:
o Competitively inhibits HBV DNA polymerase and
results into chain termination after
incorporation into viral DNA
o Prodrug of adefovir
 Uses:
o HBV infection (suppresses replication and
improves liver histology and fibrosis)
o HBV DNA activity reappears after cessation of
therapy
o For strains resistant to lamivudine
 Toxicity:
o Nephrotoxicity (dose-limiting)
o Lactic acidosis
o Severe hepatomegaly (with steatosis)
o Inhibits replication of DNA and RNA viruses
(influenza A and B, respiratory syncytial virus,
paramyxovirus, HCV, and HIV)
o Precise mechanism is unknown
 Uses:
o Chronic HCV (along with IFN-α)
o Viral hemorrhagic fevers (early administration
decreases mortality)
 Toxicity:
o Hemolytic anemia (dose-dependent)
o Teratogenic (contraindicated in pregnancy)
Newer Agents
 Hepatitis B
o Telbivudine and Tenofovir
 Hepatitis C
o Sofosbuvir and Boceprevir
 Telbivudine
o Nucleoside analog that inhibits HBV DNA
polymerase (as effective as lamivudine)
 Tenofovir
o Antiretroviral drug also for HBV (for strains
resistant to lamivudine and entecavir)
 Sofosbuvir
o Inhibits RNA polymerase in HCV (alone or with
interferon-alpha/ribavirin)
 Boceprevir
o Protease inhibitor in HCV (in combination with
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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