Adverse drug reactions Flashcards
describe adverse drug reaction
adverse drug reactions are a subset of adverse drug events, wherein harm is directly caused by
a drug under appropriate use (i.e., at normal
doses)
Therapeutic window parameters
MAX= minimum toxic concentration
MIN= minimum effective concentration
Describe the relevance of drug plasma concentration-time curve to adverse drug reactions
explain why elderly patients are at increased risk
of adverse drug reaction in the context of pharmacokinetics and pharmacodynamics
- polypharmacy: drug-drug interactions
- inappropriate prescribing
- AB: little clinical impact despite reduced surface area and slowed gastric emptying
- DIS: ↑ body fat and ↓ total body water, ↑ Vd
for lipophilic drugs but ↓ Vd
for hydrophilic drugs - MET: impaired CYP-mediated metabolism (conjugation is less affected), consideration for hepatically cleared drugs, Ph 1 met affected
- EXC: reduced GFR due to reduced renal size and nephron functions, consideration for renally cleared drugs
- ProB: decreased plasma albumin level, ↓ drug binding and therefore ↑ free drug level for action
- MORE SENSITIVE TO MEDICATIONS
explain why pregnant women are at increased risk of adverse drug reaction in the context of pharmacokinetics and pharmacodynamics
- the main concern is drug teratogenicity - prenatal toxicity
- AB: increased gastric pH alters ionisation of drugs, absorption of weak bases ↑ and weak acids ↓; slower GI mobility ↓ absorption
- DIS: ↑ body fat and total body water, can increase Vd
for lipophilic drugs and hydrophilic drugs - MET: ↑ cardiac output leads to ↑ hepatic metabolism; ↑ activity of drug-metabolising enzymes,
e.g., key CYP enzymes and UGT - EXC: ↑ cardiac output leads to ↑ renal clearance
- ProB: decreased plasma albumin level, ↓ drug binding and therefore ↑ free drug level for action
explain why pediatric patients are at increased risk of adverse drug reaction in the context of pharmacokinetics and pharmacodynamics
- capacity of drug-metabolising enzymes, receptors, and transporters
- lack of development of drug clearance capacity
- drugs are poorly studied in this group - off-label prescription
- polypharmacy: complex or multiple diseases, risk of drug-drug interactions
describe Type A ADR
- Augmented
often inherently linked to the pharmacological effects of a drug and show a dose-response relationship and, thus, can be predicted. e.g., respiratory depression with opioids (such as
morphine*)
Describe Type B ADR
- Bizarre
idiosyncratic and have no link with the pharmacological mechanism of action and are thus
unpredictable, e.g., anaphylaxis to penicillin*
Describe Type C
- Chronic
dose- (cumulative dose) and time-related, e.g., adrenal suppression with prolonged use of corticosteroids
Describe Type D ADR
- Delayed
time-related; occurs after the use of a drug, e.g., carcinogenesis (smoke), teratogenesis
(teratogens)*
Describe E ADR
- End of use
unwanted effect following the withdrawal of a drug, e.g., withdrawal syndrome with opioids or
benzodiazepines
Describe Type F ADR
- Failure
unexpected failure of a drug to produce therapeutic effects, e.g., antibiotic resistance*
Opioid use and Type A ADR
- G protein-dependent signalling pathways - analgesic effects (therapeutic effects)
- G protein-independent signalling pathways
!respiratory depression (most dangerous)! / miosis (pupillary constriction) / euphoria / sedation
/ reduced airway reflexes / nausea and vomiting / constipation
Type B and Drug hypersensitivity
- prior exposure
- delayed or immediate
- not completely unpredictable - ↑ risk due to immunogenetic predisposition
describe four types of drug hypersensitivity reaction
Type 1 - IgE-mediated, immediate (< 1hr after last dose)
Type 2 - antibody-mediated (e.g., IgG, IgM), delayed
Type 3 - immune complex-mediated, delayed
Type 4 - T cell-mediated, delayed
