## Dapsone and G6PD Deficiency **Key Point:** Dapsone is the classic antitubercular/antimicrobial agent contraindicated in patients with G6PD deficiency due to its well-established risk of causing hemolytic anemia through oxidative stress on red blood cells. ### Mechanism of Hemolysis 1. **Oxidative stress**: Dapsone and its hydroxylamine metabolite (dapsone hydroxylamine) are potent oxidizing agents that generate reactive oxygen species 2. **G6PD role**: Glucose-6-phosphate dehydrogenase is essential for maintaining reduced glutathione (GSH) via the hexose monophosphate shunt, which protects RBCs from oxidative damage 3. **Hemolysis in G6PD deficiency**: Without adequate GSH, RBCs cannot neutralize oxidative stress from dapsone metabolites, leading to Heinz body formation and hemolytic anemia ### Clinical Context **High-Yield:** Dapsone is used in multidrug therapy (MDT) for leprosy (a mycobacterial disease) and is also used in Pneumocystis jirovecii pneumonia (PCP) prophylaxis. It is a **classic, well-established contraindication** in G6PD deficiency — this is a standard high-yield fact in pharmacology (KD Tripathi, Goodman & Gilman). **Clinical Pearl:** G6PD deficiency is more common in populations from Africa, the Mediterranean region, and Southeast Asia — the same populations with high leprosy burden — making this drug-disease interaction clinically very relevant. ### Antitubercular/Antimycobacterial Drugs and G6PD | Drug | G6PD Safe? | Mechanism if Unsafe | Notes | | --- | --- | --- | --- | | Rifampicin | Yes | — | No significant oxidative hemolysis | | Pyrazinamide | Yes (generally) | — | Not a classic G6PD contraindication | | Ethambutol | Yes | — | No oxidative hemolysis | | **Dapsone** | **No** | Oxidative stress via hydroxylamine metabolite → Heinz body hemolysis | **Contraindicated** | **Mnemonic:** **Dapsone = Danger in G6PD** — Dapsone causes hemolytic anemia in G6PD-deficient patients due to its oxidizing metabolites. *Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed., Chapter on Antileprosy Drugs; Goodman & Gilman's Pharmacological Basis of Therapeutics.*
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