## Mechanism of Action of Antiplatelet Agents **Key Point:** Clopidogrel is indeed a prodrug, but it is metabolized by **CYP2C19** (not CYP3A4) in a two-step hepatic process to generate its active thiol metabolite. This is a high-yield distinction because CYP2C19 polymorphisms are clinically significant — poor metabolizers have reduced antiplatelet response and higher cardiovascular event risk. ### Correct Statements Explained | Agent | Mechanism | Key Feature | |-------|-----------|-------------| | Aspirin | Irreversible COX-1 inhibition → ↓ TXA₂ | Permanent platelet dysfunction; effect lasts platelet lifespan (7–10 days) | | Clopidogrel | **CYP2C19-dependent** prodrug → P2Y12 antagonist | Requires activation; CYP2C19 loss-of-function variants reduce efficacy | | Ticagrelor | Direct, reversible P2Y12 antagonist | **No hepatic activation needed**; faster onset than clopidogrel | | Dipyridamole | Phosphodiesterase inhibition → ↑ cAMP | Synergistic with aspirin; used in secondary stroke prevention | **High-Yield:** The CYP2C19 polymorphism is tested frequently in NEET PG because it explains variable clopidogrel response and guides choice of P2Y12 inhibitor (ticagrelor or prasugrel preferred in poor metabolizers). **Clinical Pearl:** Patients on proton pump inhibitors (omeprazole, lansoprazole) have reduced clopidogrel efficacy because these drugs inhibit CYP2C19. This is a common exam trap. **Warning:** Do not confuse CYP2C19 (clopidogrel) with CYP3A4 (which metabolizes many other drugs but NOT clopidogrel's activation step).
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