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其他抗血小板药物

时间:2022-03-13 理论教育 版权反馈
【摘要】:Sosnowski等对药物抵抗进行研究,发现普拉格雷药物抵抗发生率明显低于氯吡格雷。目前检验其有效和安全性的临床试验仍在进行中。

除了阿司匹林和氯吡格雷以外,还存在其他新型抗血小板制剂,如血小板糖蛋白Ⅱb/Ⅲa受体拮抗药以及更新型的抗血小板药,如普拉格雷、替卡格雷洛、砍格雷洛及SCH530348等。

纤维蛋白原与激活的血小板结合是血小板聚集的最后通路,这种结合可完全由糖蛋白Ⅱb/Ⅲa介导,因此抑制血小板糖蛋白Ⅱb/Ⅲa整合素可以抑制由“所有”激活剂引起血小板聚集的最后途径。而Ⅱb/Ⅲa是最大的血小板表面糖蛋白,因此对于血小板而言非常独特。目前血小板糖蛋白Ⅱb/Ⅲa受体拮抗药有阿昔单抗、替罗非班等。此类药物和活化血小板上糖蛋白Ⅱb/Ⅲa受体结合,可有效用于ACS的治疗,但临床对于开发口服的血小板糖蛋白Ⅱb/Ⅲa抑制药用来进行长期治疗很不理想,是将来研究的领域。

ADP受体拮抗药中除了噻氯匹定、氯吡格雷外,目前尚开发了第三代噻吩吡啶类药物普拉格雷,普拉格雷不可逆地与血小板表面P2Y12受体结合而抑制ADP依赖血小板聚集。普拉格雷是一种前体药物,需在肝脏细胞色素P450同工酶催化转化成代谢产物R138727后才具有抗血小板作用,且其起效迅速,30min即可达到最大血药浓度。Sosnowski等对药物抵抗进行研究,发现普拉格雷药物抵抗发生率明显低于氯吡格雷。新完成的TRITON-TIMI38研究发现,普拉格雷降低血栓事件作用优于氯吡格雷,且出血风险也低于氯吡格雷。

替卡格雷洛(AZDM6140)是第一代环丙烷戊基三唑吡啶类活性抗血小板药物,与噻吩吡啶类相似,也可通过与血小板表面P2Y12受体结合抑制ADP促血栓作用,属于ATP衍生物。几乎完全抑制ADP诱导血小板聚集,且无须代谢激活。尽管替卡格雷洛有望克服氯吡格雷缺陷,但其临床应用安全性有待进一步研究。

砍格雷洛(ARC-69931MX)也属于ATP类似物,同样具有高亲和力和可逆性拮抗血小板表面P2Y12受体,并可完全抑制ADP依赖血小板聚集作用。目前检验其有效和安全性的临床试验仍在进行中。

SCH530348是第一代凝血酶受体拮抗药,通过与凝血酶竞争结合凝血酶受体而抑制血小板聚集,由于凝血酶受体拮抗药本身不干扰凝血酶对纤维蛋白的催化活性,因此与传统抗血小板药物相比,预计出血并发症更低和具有更低的副作用,但具体临床效果尚待进一步验证。

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