Adverse Drug Reactions
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Direct answer
Augmented (type A) reactions — dose-dependent, pharmacologically predictable, high incidence, low mortality — form the bulk of adverse drug events: beta-bradycardia, digoxin nausea, insulin hypoglycaemia. Bizarre (type B) reactions are the opposite: not dose-related, unpredictable, rare and dangerous — anaphylaxis, Stevens-Johnson syndrome, halothane hepatitis, chloramphenicol aplastic anaemia. The extended Rawlins classification adds chronic (C, steroid osteoporosis), delayed (D, teratogenesis and carcinogenesis), end-of-use (E, opiate withdrawal, beta-blocker rebound) and failure (F, oral contraceptive failure from enzyme inducers) reactions. WHO defines an ADR as a noxious, unintended response at normal doses used for prophylaxis, diagnosis or therapy. Causality is judged by the Naranjo algorithm and the dechallenge-rechallenge logic, and in India every suspected ADR should be reported to the Pharmacovigilance Programme of India — under-reporting, not rarity, is the national problem.
What you must remember
- Type A hallmarks: dose-related, predictable from pharmacology, usually manageable by dose reduction; examples — morphine respiratory depression, propranolol bradycardia, loop diuretic hypokalaemia.
- Type B hallmarks: idiosyncratic or immune-mediated, unrelated to dose, low incidence, high mortality — penicillin anaphylaxis, SJS/TEN, drug-induced lupus; withdraw and avoid re-exposure.
- Extended types: C = chronic cumulative (steroid-induced osteoporosis, analgesic nephropathy); D = delayed (phocomelia, DES-related clear-cell carcinoma); E = end-of-use withdrawal syndromes; F = therapy failure (enzyme-induced contraceptive failure).
- Causality assessment: Naranjo questionnaire scores dechallenge improvement, rechallenge recurrence, alternative causes and timing into definite, probable, possible or doubtful — the WHO-UMC categories used by PvPI.
- Risk amplifiers: extremes of age, polypharmacy, renal and hepatic impairment, atopy, G6PD deficiency (primaquine haemolysis — type B on a genotypic scaffold) and slow acetylator status (isoniazid neuropathy, procainamide lupus).
- Pharmacogenomic pairs that change prescribing: HLA-B5701 (abacavir hypersensitivity — screen before starting), HLA-B1502 (carbamazepine SJS, described in East Asian and reported Indian cohorts), HLA-B*5801 (allopurinol hypersensitivity).
- Severity triage: mild (tolerable, no intervention), moderate (requires treatment or dose change), severe (life-threatening, disabling, prolonged hospitalisation) — and every severity is reportable.
- Indian anchor: report suspected ADRs to PvPI via the toll-free helpline 1800-180-3024, the ADR reporting form or the PvPI mobile app; no causal proof is needed to report — suspicion suffices.
From bedside recognition to a filed report
A patient started on carbamazepine two weeks ago returns with fever, mucosal erosions and a spreading rash. This is a cutaneous severe adverse reaction — stop the drug immediately, never rechallenge, escalate care (SJS/TEN management is burns-like), and file a suspected ADR report to PvPI with the four essentials: patient details, suspected drug, reaction description and reporter identity. In the causality meeting, the timeline (two weeks of exposure, no other new drug, improvement on withdrawal) scores the case "probable" — rechallenge is ethically off the table for severe cutaneous reactions. The pharmacogenomic postscript: in a patient of East Asian or reported Indian ancestry with a family history of carbamazepine reactions, HLA-B*1502 screening before starting the drug is the guideline-sanctioned prevention.
Contrast the mundane cousin: a patient on digoxin and recently added furosemide develops nausea, xanthopsia and a slow pulse — type A toxicity at "normal" dose, precipitated by diuretic-induced hypokalaemia and renal function drift. Management is withdrawal, potassium correction and antibody fragments if severe; prevention is electrolyte surveillance. Same reporting duty, entirely different mechanism and outcome.
Where students slip
Classification questions turn on one hinge — predictability. A stem describing a dose-dependent, pharmacologically explicable effect is type A even when dramatic; a stem describing rarity and severity with no dose relationship is type B even when the drug is familiar. The second slip is confusing adverse drug reactions (normal doses) with toxicity (overdose) and with side effects used therapeutically (minoxidil hypertrichosis). Third, causality: candidates demand certainty before reporting, but pharmacovigilance runs on suspicion — the Naranjo categories explicitly accommodate doubt. Finally, the pharmacogenomic trio of HLA markers gets mismatched to its drugs; the pairs abacavir-B5701, carbamazepine-B1502 and allopurinol-B*5801 are worth overlearning.
Frequently asked questions
How do type A and type B reactions differ?
Type A reactions are dose-dependent, predictable from pharmacology, common and rarely fatal; type B reactions are dose-independent, unpredictable, rare and carry high mortality.
What are types C through F in the extended classification?
Chronic cumulative effects (C), delayed effects such as teratogenesis and carcinogenesis (D), end-of-use withdrawal phenomena (E) and unexpected therapeutic failure (F).
How is causality of an ADR assessed?
By the Naranjo algorithm or WHO-UMC criteria, weighing temporal relationship, dechallenge improvement, rechallenge recurrence and alternative explanations into definite, probable, possible or doubtful.
Which HLA markers predict severe drug reactions?
HLA-B5701 for abacavir hypersensitivity, HLA-B1502 for carbamazepine SJS/TEN in susceptible ancestries, and HLA-B*5801 for allopurinol hypersensitivity.
Where is a suspected ADR reported in India?
To the Pharmacovigilance Programme of India — through Adverse Drug Monitoring Centres, the ADR form, the mobile app, or the helpline 1800-180-3024 — suspicion is sufficient grounds.