## Primaquine and G6PD Deficiency **Key Point:** Primaquine is the most notorious antimalarial for triggering acute hemolytic anemia in G6PD-deficient individuals. This is a classic, high-yield association in NEET PG pharmacology. ### Mechanism of Hemolysis 1. Primaquine is oxidized to reactive metabolites (quinone imine and semiquinone radicals) in red blood cells. 2. In G6PD-deficient RBCs, reduced glutathione (GSH) cannot be regenerated efficiently (G6PD catalyzes the first step of the pentose phosphate pathway). 3. Oxidative stress accumulates → hemoglobin denatures → Heinz bodies form → RBC membrane damage → hemolysis. **High-Yield:** Primaquine is the **only antimalarial with activity against hypnozoites** (dormant liver forms of P. vivax and P. ovale), making it essential for radical cure — but its use requires G6PD screening. ### Clinical Features of Primaquine-Induced Hemolysis | Feature | Details | |---------|----------| | Onset | 24–72 hours after first dose | | Severity | Mild (self-limited) in heterozygous females; severe in hemizygous males | | Hemoglobinuria | Dark urine ("black water") | | Reticulocytosis | Marked (>10%) as bone marrow compensates | | Heinz bodies | Visible on supravital staining | **Clinical Pearl:** G6PD screening is **mandatory before prescribing primaquine** in endemic regions (Africa, Mediterranean, Southeast Asia, India). Variants differ in severity — African variant (A–) is usually mild; Mediterranean variant is severe. **Mnemonic:** **PQ = Primaquine + G6PD = Quinidine-like hemolysis** — the 8-aminoquinoline core structure of primaquine is the oxidant culprit. ### Why Other Drugs Don't Cause This - **Chloroquine:** Does not generate oxidative metabolites; safe in G6PD deficiency. - **Artemether:** Peroxide-based mechanism; minimal hemolytic risk in G6PD deficiency. - **Mefloquine:** Arylmethanol structure; no known association with G6PD-triggered hemolysis.
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