Drug Hypersensitivity Reactions

Drug Hypersensitivity Reactions

1. Definition, scope & terminology

• Drug allergy (drug hypersensitivity) = an immunologically mediated reaction to a drug, producing stereotyped symptoms that are unrelated to the pharmacodynamic profile of the drug; symptoms may appear with much smaller doses and follow a different time course of onset and duration from the drug's pharmacological effects (KDT 8e Ch.6, p.96).
• It is a subset of Type B (bizarre / unpredictable) adverse reactions — based on peculiarities of the patient, not on the drug's known actions; less common, often non–dose-related, generally more serious, and usually requiring drug withdrawal (KDT 8e Ch.6, p.92).
• "Hypersensitivity" here means an immune over-reaction; it does not mean supersensitivity (an increased pharmacodynamic response to the drug) — the two must not be conflated (KDT 8e Ch.6, p.96).
• In immunological terms, hypersensitivity reactions are immune responses mounted against generally innocuous antigens that, in predisposed individuals, cause tissue damage ranging from mild irritation to life-threatening anaphylactic shock; they are classified into four categories, type I–IV, distinguished by the cell types and effector molecules involved (the Gell & Coombs classification) (G&G 14e Ch.38, p.761).
• Target organs primarily affected in drug allergy: skin, airways, blood vessels, blood cells, and the gastrointestinal tract (KDT 8e Ch.6, p.96).
• Allergen = the antigen that triggers a (typically type I) hypersensitivity response; for drugs the trigger is usually the drug or a metabolite acting as a hapten (G&G 14e Ch.38, p.762; KDT 8e Ch.6, p.96).