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?

Question

Accepted Answer

A. Type B (Bizarre) reaction. ## 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.

Answer

B. Type C (Chronic) reaction

Answer

C. Type A (Augmented) reaction

Answer

D. Type D (Delayed) reaction

Explanation

Type B (Bizarre) Adverse Drug Reactions

Defining Characteristics of Type B Reactions

Common Examples of Type B Reactions

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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