抗凝药物发展ppt课件.ppt

Current methods of thromboprophylaxis * Anticoagulant agents have evolved over the last 80 years. Drugs are being aimed at more specific targets in the coagulation pathway. The goal has been to develop agents that are able to target factors and enzymes involved in coagulation more directly, ideally producing fewer triggers of the feedback loop. Current methods of thromboprophylaxis * Anticoagulant agents have evolved over the last 80 years. Drugs are being aimed at more specific targets in the coagulation pathway. The goal has been to develop agents that are able to target factors and enzymes involved in coagulation more directly, ideally producing fewer triggers of the feedback loop. Current methods of thromboprophylaxis * 肝素类抗凝药物主要就是通过强化抗凝血酶Ⅲ的作用来达到抗凝效果的，它们与凝血酶Ⅲ结合使其结构改变，从而使抗凝血酶Ⅲ灭活凝血因子的速度明显增加，戊糖的作用也是如此。 这张图解释了分子量为何影响肝素类药物的抗2a活性。 蚯蚓状分子为肝素片段，蓝色多边形为抗凝血酶，红色三角形为10a因子，黄色多边形是2a因子； 肝素对2a 因子灭活有赖于肝素-抗凝血酶和2a 因子三联复合物的形成，此时肝素同时结合于抗凝血酶和因子2a，肝素如要起到模板作用需要至少含有18 个糖单位，其中起桥梁作用需要13个单糖，另需5个单糖作为识别片段。每个单糖平均分子量为300，因此分子量一定要达到5400道尔顿以上才具有抗2a活性。普通肝素平均分子量15000道尔顿，绝大多数分子在5400道尔顿以上，具有相似的抗10a与2a活性；低分子肝素则要以5400以上的分子片段所占比例大小来衡量其抗2a活性，一般情况下其抗10a：抗2a活性约2-4：1；戊糖即磺达肝睽钠的分子量只有1700道尔顿左右，只有抗10a活性没有抗2a活性； Current methods of thromboprophylaxis * Anticoagulant agents have evolved over the last 80 years. Drugs are being aimed at more specific targets in the coagulation pathway. The goal has been to develop agents that are able to target factors and enzymes involved in coagulation more directly, ideally producing fewer triggers of the feedback loop. Current methods of thromboprophylaxis * Anticoagulant agents have evolved over the last 80 years. Drugs are being aimed at more specific targets in the coagulation pathway. The goal has been to develop agents that are able to target factors and enzymes involved in coagulation more directly, ideally producing fewer triggers of the feedback loop. Current methods of thromboprophylaxis * 这张图解释了分子量为何影响肝素类药物的抗2a活性。 蚯蚓状分子为肝素片段，蓝色多边形为抗凝血酶，红色三角形为10a因子，黄色