抗血小板药和抗凝药的临床合理应用讲解.ppt

* 目前的抗血小板药物包括： 血栓素 A2 抑制剂 乙酰水杨酸 (ASA) 磷酸二酯酶抑制剂 潘生丁 糖蛋白(GP) IIb/IIIa阻滞剂 胃肠外用药l: 阿昔单抗、eptifibatide, tirofiban 口服GPIIb/IIIa阻滞剂 (lotrafiban, orbofiban, sibrafiban, xemilofiban) 已经在大规模临床试验中进行了研究，但没能显示疗效优于ASA. ADP-受体拮抗剂 氯吡格雷 噻氯匹定 * 幻灯片9 血小板上含有许多激活介质的受体，如血栓素A2、凝血酶原、ADP及其他等。这些介质通过许多内在反应激活血小板，其最终反应为激活纤维蛋白原结合位点，也就是糖蛋白Ⅱb/IIIa受体。通过激活糖蛋白Ⅱb/IIIa受体与纤维蛋白原结合并最终引起血小板的聚集和血栓形成。 * 幻灯片12 氯吡格雷是一种新型的ADP受体拮抗剂，可阻断引起血小板激活和聚集的ADP通道。氯吡格雷的活性代谢产物与血小板上的低亲和力的ADP受体结合，从而抑制ADP与其结合。氯吡格雷能不可逆地阻断大部分ADP受体（75%）。因为血小板不能合成新的ADP受体，所以氯吡格雷的阻断作用可存在于整个血小板的生命周期（大约10天）。 * Clopidogrel undergoes rapid absorption after oral administration. Absorption is not affected by food or antacid consumption. The clopidogrel molecule needs to undergo extensive hepatic metabolism in order to be converted to an active metabolite (which is unstable and with a very short half-life). The pharmacokinetics of clopidogrel have been characterized by SR26334, the main but inactive metabolite in the plasma. The elimination half-life of SR26334 is approximately 8 hours but has an irreversible effect on platelets with a lifespan of approximately 7–10 days. After 5 days, 50% of the dose is eliminated in urine and 46% in the feces. The use of loading doses of clopidogrel significantly reduces the time required to achieve maximal inhibition of platelet aggregation in healthy volunteers and hastens platelet inhibition after coronary stent implantation. A 300 mg dose of clopidogrel provided significantly greater inhibition of ADP-induced platelet aggregation on the first day of treatment than either ticlopidine 500 mg/day or clopidogrel 75 mg/day. Reference: 1. Jarvis B, Simpson K. Drugs 2000; 60: 347–77. * No significant age and gender effects were noted during early clinical trials. There were no significant differences in platelet aggregation and bleeding time in elderly patients compared with young, healthy volunteers. After repeated doses of 75 mg clopidogrel per day, plasma levels of the main circulating metabolite were lower in p