1、治疗充血性心力衰竭的药物Drugs used in Congestive Heart Failure,Chapter 26,慢性心功能不全, CHF,心肌重构,超负荷性心肌病心肌重量增加、心室容量增加、心室形状改变(横径增加呈球型),CHF病理生理变化,心功能障碍,收缩功能,舒张功能,输出量,血管收缩,神经激素,心肌受体下调,水钠潴留,血容量,静脉淤血(左、右心淤血),阻抗,顺应性,后负荷,血管肥厚变形,心肌收缩力,顺应性,心肌肥大变形,前负荷室壁张力,( RAA CA ), , ,外周水肿、肺水肿,1. 增加心肌收缩力 正性肌力药 强心苷: 地高辛 非苷类:米力农、维司力农2. 减轻心脏前后
2、负荷 利尿药:氢氯噻嗪、 7天连锁酒店会员呋塞米、螺内酯 血管扩张药:硝普钠、硝酸甘油、 肼屈嗪等3.调节神经-体液系统功能http:/ ACEI抑制药、AT1拮抗药:卡托普利、氯沙坦 受体阻断药:美托洛尔、卡维地洛,治疗CHF药物的分类,一、强心苷 cardiac glycosides,地高辛(digoxin)、洋地黄毒苷(digitoxin),极性:洋地黄毒苷地高辛毒毛花苷维持时间:洋地黄毒苷地高辛毒毛花苷,红霉素、四环素提高血药浓度,药理作用1)正性肌力作用(positive inotropic action)心肌收缩性、心输出量、耗氧量加快心肌纤维缩短速度,相对延长舒张期刺激主动脉弓,
3、颈动脉窦压力感受器 迷走N兴奋相对降低耗氧量,2)负性频率,反射性兴奋迷走N抑制窦房结,心率减慢,治疗阵发性室上性心动过速,降低窦房结自律性,增高浦氏纤维自律性 减慢房室结传导性 缩短心房、浦氏纤维的ERP,3)对心肌电生理特性的影响,房颤、房扑,4) 对肾脏的作用,明显利尿正性肌力作用,增加肾血流量抑制肾小管Na+-K+-ATP酶 ,减少Na+重吸收,5) 神经体液影响兴奋延脑催吐化学感受区抑制RAAS,减少AngII及醛固酮释放,1CHF 最佳适应症:伴房颤、房扑或心室率快的CHF 良好:瓣膜病、风心病、高血压、先心病、冠心病 效差:甲亢及严重贫血、肺心病、伴机械阻塞的CHF CHF基础用
4、药:地高辛+ 7天会员利尿药2.某些心律失常房颤:减慢房室结传导,增加隐匿性传导房扑:缩短心房ERP,使房扑转为房颤阵发性室上性心动过速,临床应用,不良反应 安全范围小胃肠道反应: 兴奋CTZ神经系统反应:眩晕、头痛、疲倦、失眠、黄视症、绿视症 心脏毒性:窦性心动过缓、房室阻滞,快速型室性心律失常:室早,室颤http:/,停药指征,中 毒 救 治静脉滴注、口服钾盐:快速性心律失常者房室传导阻滞或高血钾时禁用苯妥英钠、利多卡因:室早、室速和严重室颤阿托品:心动过缓或房室阻滞地高辛抗体:致死性中毒,用 法全效量 “洋地黄化”, 用药先给获足够效应的药量,后逐日给维持量补充每日消除的药量无负荷量no
5、-loading dose,逐日给恒定剂量的7天酒店会员药物,经45个t1/2后在血中达到稳态浓度,取得稳定疗效,明显降低中毒发生率,肾功能减退者、老人减量,用量个体化,二、肾素-血管紧张素-醛固酮系统抑制剂,血管紧张素I转化酶抑制药卡托普利(captopril)、依那普利(enalapril)等血管紧张素受体拮抗药氯沙坦(losartan)等抗醛固酮药物螺内酯(spironolactone),AT1受体,ACE局部及循环,血管内皮B2受体,PGI2,NO,缓激肽,失活肽,AngI,AngII,ACEI,ACE,血管舒张降低负荷,麋酶,促生长促心肌肥厚,AT1阻断药,醛固酮,醛固酮受体,螺内酯
6、,改善心舒张功能增加肾血流量运动耐力增加,ACEI治疗CHF的药理作用1. 减少循环中AngII生成a. 扩张血管,降低前后负荷b. 降低儿茶酚胺、加压素含量,降低交感活性c. 降低左室舒张末期压力和容量,改善舒张功能2. 减少心肌局部AngII生成a. 防止心肌细胞增生,减轻心室扩张,改善恢复心脏形状b. 降低醛固酮生成,减轻其引起的心肌纤维变性3. 减少缓激肽降解,降低后负荷,ACEI临床应用缓解或消除CHF症状,提高运动耐力,防止和逆转心肌肥厚,降低病死率 与利尿药、地高辛合用为治疗CHF的基础药物,尤其对舒张性心衰效果好不良反应:低血压、肾功能下降、干咳、血管神经性水肿等,药理作用消除
7、水肿排Na+、水,减少体液量,降低心脏前负荷排Na+,减少Na+-Ca2+交换,减少Ca2+, 降低心脏后负荷临床应用轻度CHF:噻嗪类中度CHF:口服呋噻米等或与噻嗪类和留钾利尿药合用重度CHF、慢性CHF急性发作、急性肺水肿或全身浮肿者:静注呋噻米、布美他尼等,三、利尿药,四、受体阻断药 美托洛尔(metoprolol)、卡维地洛(carvedilol)药理作用1.上调心肌受体,增加机体对儿茶酚胺的敏感2. 阻断儿茶酚胺对心肌毒性3. 抑制PG或肾素产生的缩血管作用4.减慢心率,减少心肌耗氧量,改善心肌缺血及心室舒张功能务必与常规治疗CHF的药物联用,用于慢性心衰的长期治疗,1、是否可以取
8、代CHF的某种常规治疗2、 治疗CHF是改善症状,还是可以挽救生命3、 是减少泵衰竭引起的死亡,还是减少心律失常所致的死亡4、早期应用,可否阻抑心衰进程,推迟心衰的到来5、严重CHF患者(NYHA 级),治疗风险较大是否应作为其的适应症,受体阻滞剂治疗心力衰竭尚有待探索的问题,五、血管舒张药,扩张小静脉,降低前负荷:硝酸酯类扩张小动脉,降低后负荷:肼曲嗪降低前后负荷:硝普钠、哌唑嗪,危重CHF,长效钙拮抗药氨氯地平1.促进NO产生2.防止及逆转心肌肥厚3.左室功能障碍伴有高血压、心绞痛者,多巴酚丁胺、米力农(milrinone)临床应用仅用于严重CHF者短期静脉滴注,六、儿茶酚胺类磷酸二酯酶(
9、PDE III)抑制药cAMP降解酶,一、硝酸异山梨醇酯+肼苯哒嗪二、钙通道阻滞剂三、cAMP依赖性的正性肌力药物四、抗心律失常药物,目前有争议或不主张用治疗心衰的药物,CASE STUDY,A 50-year-old man has developed shortness of breath with exertion several weeks after experiencing a viral illness. This is accompanied by swelling of the feet and ankles and some increasing fatigue. On p
10、hysical examination he is found to be mildly short of breath lying down, but feels better sitting upright. Pulse is 105 and regular, and blood pressure is 90/60 mm Hg. His lungs show crackles at both bases, and his jugular venous pressure is elevated. A third heart sound is present but no murmurs ar
11、e heard on auscultation of the heart. The liver is enlarged, and there is 3+ edema of the ankles and feet. An echocardiogram shows a dilated, poorly contracting heart with a left ventricular ejection fraction of about 20% (normal: 60%). Because of an abnormal ECG, he undergoes a coronary angiogram,
12、which shows normal coronary arteries. The presumptive diagnosis is dilated cardiomyopathy secondary to a viral infection with stage C heart failure. He is placed on a low-sodium diet and treated with a diuretic (furosemide 40 mg twice daily) and digoxin 0.25 mg daily. On this therapy, he is less sho
13、rt of breath on exertion and can also lie flat without dyspnea. An angiotensin-converting enzyme (ACE) inhibitor is added (enalapril 20 mg twice daily), and over the next few weeks he continues to feel better. Three months after the first visit, the man is asymptomatic at rest and with mild exercise
14、. Heart rate is 80, and blood pressure is 110/70. A repeat echocardiogram shows that his heart is smaller (though not back to normal) and his left ventricular ejection fraction has improved to 40%. What other pharmacologic options are available if this mans disease remains stable? What treatments are available if his heart failure suddenly,