Which P2Y12 inhibitors are irreversible?

• A. Clopidogrel and Prasugrel
• B. Ticagrelor and Cangrelor
• C. Clopidogrel and Ticagrelor
• D. Prasugrel and Ticagrelor

Answer: (A)

P2Y12 inhibitors can either bind irreversibly or reversibly to the receptor on platelets. Clopidogrel and prasugrel are irreversible because their active metabolites covalently modify the P2Y12 receptor, permanently inactivating it for the life of the platelet. Since platelets don’t synthesize new receptors, the antiplatelet effect lasts until new platelets are produced, typically several days. In contrast, ticagrelor and cangrelor bind reversibly, so their platelet-inhibiting effect diminishes after the drug is cleared; ticagrelor is a reversible, non-prodrug inhibitor, and cangrelor is an intravenous agent with rapid offset. Thus, the irreversible inhibitors are clopidogrel and prasugrel.