A drug causes severe hepatotoxicity in 1 in 10,000 patients regardless of dose, with no predictable dose-response relationship. The reaction is mediated by immune mechanisms in genetically predisposed individuals. According to Rawlins and Thompson classification, this is which type of adverse drug reaction?

Explanation

## Type B (Bizarre) Adverse Drug Reactions **Key Point:** Type B reactions are idiosyncratic, unpredictable, dose-independent, and occur in genetically susceptible individuals via immune or metabolic mechanisms. ### Defining Characteristics of Type B Reactions 1. **Dose-independence:** Occur at therapeutic or sub-therapeutic doses; no dose-response relationship 2. **Unpredictability:** Cannot be predicted from pharmacological properties of the drug 3. **Low incidence:** Rare (1 in 1,000 to 1 in 100,000 patients) 4. **Genetic susceptibility:** Associated with genetic polymorphisms in drug metabolism (e.g., HLA alleles, cytochrome P450 variants) 5. **Immune-mediated or metabolic:** Often involve: - Hypersensitivity reactions (Type I, II, III, IV) - Metabolic idiosyncrasy (abnormal drug metabolism) 6. **Severity:** Often serious and potentially fatal 7. **Irreversibility:** May not resolve even after drug withdrawal ### Common Examples of Type B Reactions | Drug | Reaction | Mechanism | |------|----------|----------| | Chloramphenicol | Aplastic anaemia | Idiosyncratic bone marrow suppression | | Carbamazepine | Stevens-Johnson Syndrome (SJS) | HLA-B*1502 association (Asian populations) | | Abacavir | Hypersensitivity syndrome | HLA-B*5701 association | | NSAIDs | Anaphylaxis | IgE-mediated hypersensitivity | | Penicillins | Anaphylaxis | Type I hypersensitivity | | Sulfonamides | Hemolytic anaemia | G6PD deficiency (metabolic idiosyncrasy) | | Isoniazid | Hepatotoxicity (in slow acetylators) | Genetic polymorphism in N-acetyltransferase | **Mnemonic:** **BIZARRE** = **B**one marrow suppression, **I**mmune-mediated, **Z**ero dose-response, **A**llergic, **R**are, **R**eversibility uncertain, **E**xceptional (genetically determined) **High-Yield:** Type B reactions account for ~15% of all ADRs but are responsible for the majority of serious/fatal ADRs. They are the focus of pharmacogenomics and precision medicine initiatives. **Clinical Pearl:** Genetic testing (e.g., HLA-B*5701 before abacavir, HLA-B*1502 before carbamazepine in Asian populations) can now predict and prevent some Type B reactions — a paradigm shift in ADR prevention.