Which of the following best describes the mechanism of action of clopidogrel?
ExplanationClopidogrel and ticlopidine are the two currently available members of the thienopyridine class of antiplatelet agents. As demonstrated in the figure below, the mechanism of action of these agents is to prevent ADP-induced platelet aggregation by irreversibly inhibiting the P2Y12 receptor. Both agents are prodrugs that require hepatic activation by the cytochrome P450 system; in the usual dose they require several days to reach maximal effectiveness. Clopidogrel is a more potent agent than ticlopidine with fewer associated side effects, and thus it has replaced ticlopidine in clinical practice. Other antiplatelet drugs act at other sites in the cascade that leads to platelet aggregation. Aspirin is the most commonly used antiplatelet agent. At the usual doses, aspirin inhibits COX-1 to prevent the production of thromboxane A2, a potent platelet agonist. Dipyridamole is a weak platelet inhibitor alone and acts as a phosphodiesterase inhibitor. In addition, dipyridamole blocks the uptake of adenosine by platelets. When combined with aspirin, dipyridamole has been shown to decrease the risk of stroke, but because it acts as a vasodilator, there is concern that it might increase the risk of cardiac events in severe coronary artery disease. A final class of antiplatelet agents is the glycoprotein IIb/IIIa inhibitors, which include abciximab, eptifibatide, and tirofiban. Each of these agents has a slightly different site of action, but all decrease the ability of platelets to bind adhesive molecules such as fibrinogen and von Willebrand factor. Thus, these agents decrease platelet aggregation. Abciximab is a monoclonal antibody directed against the activated form of GPIIb/IIIa. Tirofiban and eptifibatide are small synthetic molecules that bind to various sites of the GPIIb/IIIa receptor to decrease platelet aggregation.
