高血压3--课件.pptVIP

Figure of cardiac glycosides and Na+,K+/ATPase action Amrinone (氨力农) Amrinone is the first PDEI drug in clinical use in 1978. (1) The Development of NO donor drugs Organic nitrates have dominated the treatment of acute angina over 100 years after the antiaginal effect of amyl nitrite (亚硝酸异戊酯) was first observed in 1857. Although the introduction of the calcium channel blockers and the β-adrenergic blockers as antianginal agents has expanded the physician’s therapeutic arsenal, organic nitrates are still the class of choice to treat acute anginal episode. Chemistry of nitrates Organic nitrates are esters of simple organic alcohols or polyols with nitric acid. Nitrates in clinical use today The duration and onset of nitrates action (2) Action mechanism of Nitrates (3) Others NO donor drugs 硝酸酯与细胞中的巯基形成不稳定的S-亚硝基硫中间体，很快分解释放NO分子。 吗多明（molsidomine）在体内代谢后生成中间体，在碱催化下与分子氧反应释放NO分子。 吗多明（molsidomine） 钙通道 电压依赖的钙通道 (potential-dependent calcium channels) L(long-lasting) calcium channels 存在于心肌、血管平滑肌等组织，是钙通道阻滞剂的作用位点。 受体调控的钙通道(receptor-operated calcium channels) Section 3 Antiarrhythmic Drugs 心律失常是由于心脏搏动的自律性发生异常和障碍时，此时心房和心室正常激活和运动顺序发生障碍，其临床表现为心动过缓或心动过速，是一种后果严重的疾病。 2. Ion channel blockers (1) Ion channels A. ⅠA sodium channel blockers IA适度阻滞Na＋通道，减少除极时Na＋的内流，降低电子电位振幅，减慢传导速度；降低自律性；间接抑制K+外流。 Quinidine (奎尼丁) 化学名：(9S)-6’-甲氧基-脱氧辛可宁-9-醇 (9S)-6’-methoxy-cinchonan-9-ol B. IB sodium channel blockers IB：轻度阻滞钠通道，并促使K+外流，降低去极化速度，缩短复极化，提高颤动阈值。 C. Ic sodium channel blockers IC明显阻滞钠通道，明显减慢传导。 1) ACE Inhibitors (ACEI) 高血压药研究最为活跃的是ACEI，临床上ACEI主要用于高血压、充血性心力衰竭等心血管疾病的治疗。 Captopril (卡托普利) S-1-(3-mercapto-2-methyl-1-oxopropyl)-L-proline 稳定性 卡托普利晶体和甲醇溶液比较稳定，但水溶液易发生氧化反应，通过巯基生成二硫化合物。 溶液的pH、金属离子、药物浓度等因素均影响该反应。Ph3.5、浓度较高时，水溶液较稳定。 Action in the body 卡托普利为血管紧张素转化酶抑制剂，可口服，对各型高血压均有明显的降压作用，也用于急、慢性充血心力衰竭的治疗。 But its sulfhydryl group made it have two side effects: skin rashes and taste disturbances. (1) Classification and development of ACEIs A. Sulfhydryl-containing inhibitors B. Dicarboxylate-contai