How does clopidogrel work and what common interaction should be avoided?

• A. Inhibits platelet aggregation via P2Y12 receptor; avoid PPIs like omeprazole that may reduce activation.
• B. Directly inhibits COX-1 to prevent platelet aggregation.
• C. Activates plasmin to dissolve clots.
• D. Inhibits vitamin K epoxide reductase.

Answer: (A)

Clopidogrel works by blocking the P2Y12 ADP receptor on platelets, which prevents ADP from triggering platelet activation and aggregation. It is a prodrug that must be activated in the liver by cytochrome P450 enzymes, especially CYP2C19, to an active metabolite that irreversibly inhibits the P2Y12 receptor, giving a lasting antiplatelet effect for the life of the platelet. A common interaction to avoid is using proton pump inhibitors that inhibit CYP2C19—most notably omeprazole and esomeprazole—which can reduce the activation of clopidogrel and lessen its effectiveness. If gastric protection is needed, a PPI with less CYP2C19 inhibition (such as pantoprazole) may be preferred. For context, other options describe different drugs: direct COX-1 inhibition is aspirin, plasmin activation is a thrombolytic, and vitamin K epoxide reductase inhibition is warfarin.