## Mechanism of Action **Key Point:** Pyrimethamine is a dihydrofolate reductase (DHFR) inhibitor that disrupts folate metabolism in Plasmodium parasites, preventing DNA synthesis and cell division. ## Antimalarial Classification by Mechanism | Drug Class | Mechanism | Examples | |---|---|---| | **Folate antagonists** | DHFR inhibition | Pyrimethamine, Proguanil | | **Quinolines** | Heme polymerization inhibition | Chloroquine, Quinine | | **Artemisinin derivatives** | Endoperoxide cleavage | Artemether, Artesunate | | **Atovaquone-proguanil** | Dual: cytochrome bc1 + DHFR | Combination drug | ## Clinical Use **High-Yield:** Pyrimethamine is used in combination with sulfadiazine or dapsone for: - Acute malaria treatment (especially P. falciparum) - Malaria prophylaxis in pregnancy (safe alternative to other agents) - Treatment of toxoplasmosis (off-label but important) **Clinical Pearl:** Pyrimethamine requires concurrent folic acid supplementation (folinic acid, not folic acid) to prevent bone marrow suppression and megaloblastic anemia. **Mnemonic:** PRIM = **P**yrimethamine **R**educes **I**nhibits **M**alaria (via DHFR block)
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