## G6PD Deficiency and Antimalarials **Key Point:** Primaquine is an 8-aminoquinoline that generates oxidative stress in red blood cells. In G6PD-deficient patients, the lack of NADPH production impairs the glutathione antioxidant system, leading to hemolytic anemia when primaquine is administered. ## Pathophysiology **High-Yield:** G6PD deficiency reduces the cell's ability to regenerate reduced glutathione (GSH). Primaquine and other oxidant drugs deplete GSH, causing oxidative damage to RBC membranes and hemolysis. ## Antimalarials and G6PD Safety | Drug | G6PD Safe? | Mechanism if Unsafe | |---|---|---| | Primaquine | **NO** | Oxidant stress → hemolysis | | Pamaquine | **NO** | Oxidant stress → hemolysis | | Chloroquine | **YES** | Non-oxidant | | Quinine | **YES** | Non-oxidant | | Artemisinin derivatives | **YES** | Non-oxidant | | Atovaquone-proguanil | **YES** | Non-oxidant | ## Clinical Implications **Clinical Pearl:** Before prescribing primaquine (used for *P. vivax* and *P. ovale* hypnozoite eradication), G6PD screening is mandatory in at-risk populations (African, Mediterranean, Southeast Asian descent). **Warning:** Severe hemolytic episodes can occur within 24–48 hours of primaquine administration in G6PD-deficient patients, manifesting as jaundice, dark urine, and hemoglobinuria.
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