利伐沙班作用机制及药理学性质课题.ppt

利伐沙班为什么一般无需监测? 使用利伐沙班时大多无需监测 药代动力学和药效学可预测 治疗窗宽 较少的药物、食物相互作用 1 Footnote Source: Source Subtitle or Unit of measure, when both Unit of measure goes into 2nd line TRACKER Legend1 Legend2 Legend3 Legend4 Legend1 Legend2 Legend3 Title Unit of measure ILLUSTRATIVE Legend1 Legend2 Legend3 Legend4 Legend5 首先我们先回顾一下抗凝药物的发展历程。 最早使用的抗凝药是上个世纪30年代问世的普通肝素，分子结构较为复杂，以从生物体内提取的制剂为主。 40年代，华法林应用于临床，80年代，低分子肝素问世，上述药物均作用于多个靶点，注射用制剂还需要ATIII的辅助； 到了21世纪，一系列新型的单靶点抗凝药物问世，包括2002年上市的静脉间接Xa因子抑制剂，2004年上市的口服直接凝血酶抑制剂和2008年上市的口服直接Xa因子抑制剂 可以看到，寻找单靶点、直接、有效、安全和方便的抗凝药物是抗凝药物发展的主线 下面我们依次介绍各种抗凝药物的作用机制 Properties of rivaroxaban * 利伐沙班是全球第一个口服单一靶点直接Xa因子抑制剂，说道这里我们需要再强调与一下人体内的两条凝血途径，图中可以看出，Xa因子是内源性和外源性凝血途径的共同通路，是一个特殊的抗凝靶点，其可将凝血酶原转化为凝血酶，一分子Xa因子可产生1000个凝血酶分子。凝血酶5分钟之内即可激活纤维斑块的形成。所以，抑制Xa因子可以抑制凝血酶爆发式的生成 The coagulation cascade is a complex process that results in the conversion of fibrinogen to fibrin – a reaction catalyzed by thrombin (Factor IIa) – and the formation of a thrombus or blood clot1,2 After it has been initiated, the coagulation cascade is a fast and self-propagating process1,2 Factor Xa is a particularly interesting target for effective anticoagulation, because Factor Xa catalyzes the conversion of prothrombin to thrombin, with one molecule of Factor Xa resulting in the generation of more than 1,000 thrombin molecules2 Clot formation is also a fast process, taking less than 5 minutes from activation to fibrin clot formation, and occurs at the inception of the propagation phase of thrombin generation, when only a small amount (5–10 nM) of thrombin has been generated2 Consequently, the vast majority (more than 95%) of thrombin is produced after clot formation, during the propagation phase of thrombin generation2 References 1. Brummel KE, Paradis SG, Butenas S, Mann KG. Thrombin functions during tissue factor-induced blood coagulation. Blood. 2002;100:148–152 2. Mann KG, Brummel K, Butenas S. What is all that thrombin for? J Thromb Haemost. 2003;1:1504–1514 Properties of rivaroxaban * Rivaroxaban 20 m