## Dapsone: Mechanism and Role in Leprosy **Key Point:** Dapsone is a sulfone derivative that is a prodrug metabolized to DDS (diaminodiphenyl sulfone), the active metabolite responsible for its antimicrobial activity. ### Mechanism of Action 1. **Prodrug conversion:** Dapsone is rapidly absorbed and metabolized by hepatic acetylation to form DDS 2. **Bacteriostatic activity:** DDS inhibits dihydropteroate synthase, blocking folate synthesis in M. leprae 3. **Selectivity:** M. leprae is unable to utilize exogenous PABA, making it dependent on de novo folate synthesis ### Clinical Characteristics | Feature | Detail | | --- | --- | | **Spectrum** | Gram-positive cocci, M. leprae, P. jirovecii (PCP prophylaxis) | | **Bacteriostatic** | Yes (not bactericidal) | | **Absorption** | Rapid and complete from GI tract | | **Metabolism** | Hepatic acetylation (genetic polymorphism affects levels) | | **Half-life** | 24–30 hours | | **Protein binding** | High (70–80%) | **High-Yield:** Dapsone is the backbone of multidrug therapy (MDT) for leprosy and is also used for PCP prophylaxis in HIV patients with CD4 < 200 cells/μL. **Clinical Pearl:** Slow acetylators accumulate dapsone and are at higher risk of hemolytic anemia; fast acetylators may require higher doses. ### Adverse Effects - **Hemolytic anemia** (most common, especially in G6PD deficiency) - Methemoglobinemia - Agranulocytosis (rare but serious) - Peripheral neuropathy - Hepatotoxicity [cite:KD Tripathi 8e Ch 52]
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