Clinical Pharmacy · Short notes

Adverse Drug Reactions: Short Notes & Cheat Sheet

ADR definitions, the Rawlins–Thompson and hypersensitivity classifications, causality and severity assessment, risk factors and reporting.

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Short notes

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Rawlins–Thompson classification

Types A and B cover most reactions; the later letters describe timing and treatment failure.

Definitions

WHO defines an ADR as a response to a drug that is noxious and unintended and occurs at doses normally used in humans.
An adverse event is any harmful occurrence during treatment, whether or not the drug caused it.
A serious ADR causes death, is life-threatening, needs or prolongs hospital admission, causes disability, or causes a birth defect.
A side effect is any unintended effect at normal doses, which may even be beneficial.

Classification

Type A (augmented) reactions are dose-related extensions of the drug's pharmacology. They are common and predictable (bleeding with warfarin, hypoglycaemia with insulin).
Type B (bizarre) reactions are not dose-related and are unpredictable, often immune or genetic (penicillin anaphylaxis, malignant hyperthermia).
Type C (chronic) come from long-term use (steroid osteoporosis). Type D (delayed) appear later (teratogenicity, cancer).
Type E (end of use) are withdrawal reactions (rebound hypertension with clonidine, adrenal crisis after stopping steroids). Type F (failure) is unexpected treatment failure (oral contraceptive failure with enzyme inducers).
Hypersensitivity (Gell and Coombs): type I IgE-mediated anaphylaxis, type II cytotoxic (drug-induced haemolytic anaemia), type III immune complex (serum sickness) and type IV delayed T-cell (contact dermatitis, SJS/TEN).

Assessment and risk

Causality: the Naranjo algorithm scores ≥ 9 as definite, 5–8 probable, 1–4 possible and ≤ 0 doubtful. WHO–UMC categories run from certain to unassessable.
Dechallenge (improvement on stopping) and rechallenge (recurrence on restarting) strongly support causality.
Risk factors: old age, polypharmacy, female sex, kidney or liver impairment, and genetics (HLA-B*5701 with abacavir, HLA-B*1502 with carbamazepine, G6PD deficiency, TPMT deficiency).
Suspected ADRs in Pakistan are reported to DRAP's pharmacovigilance system. Report serious and unexpected reactions and all reactions to new drugs.

Cheat sheet

High-yield facts in one place. Cover the right-hand column and test yourself.

Rawlins–Thompson types

Type	Example
A — Augmented	Warfarin bleeding, insulin hypoglycaemia
B — Bizarre	Penicillin anaphylaxis, SJS
C — Chronic	Steroid osteoporosis
D — Delayed	Thalidomide birth defects, DES vaginal cancer
E — End of use	Clonidine rebound, benzodiazepine withdrawal
F — Failure	Pill failure with rifampicin

Naranjo score

Score	Category
≥ 9	Definite
5–8	Probable
1–4	Possible
≤ 0	Doubtful

Genetic risk markers

Marker	Drug · reaction
HLA-B*5701	Abacavir · hypersensitivity
HLA-B*1502	Carbamazepine · SJS/TEN
HLA-B*5801	Allopurinol · SJS/TEN
G6PD deficiency	Primaquine, dapsone · haemolysis
TPMT deficiency	Azathioprine · marrow suppression

Memory aids

A B C D E F: Augmented, Bizarre, Chronic, Delayed, End of use, Failure.

Exam traps

Type A reactions are the most common and are usually preventable by dose adjustment.
Anaphylaxis is type I hypersensitivity; SJS/TEN is type IV.
An adverse event is not automatically an ADR; causality must be assessed.
A positive rechallenge is strong evidence, but deliberate rechallenge after a serious reaction is unethical.

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