课件：抗血小板治疗-争议与选择.ppt

Reference: 1. Jarvis B, Simpson K. Drugs 2000; 60: 347–77. Clopidogrel is a potent, non-competitive inhibitor of adenosine diphosphate- (ADP) induced platelet aggregation, irreversibly inhibiting the binding of ADP to its platelet membrane receptors. Consequently, platelets exposed to clopidogrel are affected for the remainder of their lifespan (approximately 7–10 days). The inhibition is specific and does not significantly affect cyclo-oxygenase (COX) or arachidonic acid metabolism. Clopidogrel can also indirectly inhibit platelet aggregation induced by agonists other than ADP by blocking the amplification of platelet activation by released ADP: ADP binding is necessary for activation of the GPIIb/IIIa receptor, which is the binding site for fibrinogen. Fibrinogen links different platelets together to form the platelet aggregate. Clopidogrel thus ultimately inhibits the activation of the GPIIb/IIIa receptor, its binding to fibrinogen and further platelet aggregation. * In fact, immediately after absorption, prasugrel is hydrolyzed by an intestinal carboxylase, hCE2, that rapidly converts about 90% of the parent drug to the intermediate metabolite R-95913 (from which the active clopidogrel metabolite R-138727 is formed) [19]. Therefore, more than half of the administered dose of prasugrel is rapidly activated [19]. A minor quantity of prasugrel is transformed into M1, which is the main urine metabolite excreted * Wide inter-patient variability in the ex vivo measurement of the response to oral antiplatelet therapies has been recognized for nearly 40 years, although the clinical implications of this phenomenon have yet to be confirmed in large-scale clinical trials. This has led some clinicians to classify patients as “responders” and “non-responders,” implying that clopidogrel resistance is an all-or-none clinical phenomenon. Serebruany and colleagues conducted secondary post hoc analyses of an existing dataset consisting of volunteers with multiple risk factors (n