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治疗慢性心功能不全药物课件

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治疗慢性心功能不全药PPT 慢性心功能不全药 课件 治疗慢性心功能不全 慢性心功能不全药 慢性心功能不全药ppt
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With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 第19章 治疗慢性心功能不全药物 中国医科大学 药学院 主讲:郝丽英 教授 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 心力衰竭:由于初始的心肌损害(心肌细胞 数量的减少和/或收缩期或舒张期心室负荷过 重,导致心肌肥厚和心室扩张(心室重构) ,继之心室舒缩功能障碍发展而成。 充血性心力衰竭(CHF):静 脉回流正常,心输出量减少 和心室充盈压升高,临床上 表现组织血液灌注不足以及 肺循环和(或)体循环淤血 的一种综合征。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 分为四类: 一、强心药:强心苷类,非强心苷类。 二、减负荷药:扩血管药,ACEI, AT1受体阻断药,醛固酮受体阻断药 。 三、利尿药:噻嗪类,袢利尿药。 四、受体阻断药: 第一节 抗心力衰竭药物分类 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 一、强心药 正性肌力药: 心肌收缩力增强、心输出量增加; 心肌耗氧量降低。 主要有强心苷类和磷酸二酯酶抑制药。 第二节 常用的抗心力衰竭药物 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society (一)强心苷类 主要从紫花洋地黄和毛花洋地黄中提得, 故又称洋地黄类药物。 常用的: 地高辛(digoxin) 毒毛花苷K(strophanthin K) 毛花苷丙(cedilanide) With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【体内过程】 地高辛的极性小,脂溶性大,口服吸收良 好,但生物利用度个体差异大,不同制药厂 甚至不同批号的产品其吸收率都不同; 毒毛花苷K的极性大,脂溶性低,口服不易 吸收,只能静脉给药。 地高辛在肝脏代谢的较少,大部分以原形 经肾脏排泄,所以应注意肾功能低下者或老 年人容易过量中毒。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 不同强心苷类甾核上的羟基数与体内过程比较表 [体内过程 ] 药物 羟基吸收率 (%) 蛋白结合 (%) 肝肠 循环 (%) 生物转化 (%) 肾排出 (%) 血浆t1/2 洋地黄 毒苷 190~100972730~70105~7d 地高辛260~8530 6.8 5~1060~9033~36h 毛花苷 丙 多个20~405少极少90~10 0 33h 毒毛花 苷K 多个2~55少090~10 0 12~19h With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 1. 增强心肌收缩力(正性肌力作用): ① 明显增强衰竭心脏的收缩力; ② 使收缩动作敏捷,舒张期相对延长; ③ 心排出量增加; 作用机制: 抑制心肌细胞膜上的Na+-K+-ATP酶使Na+ 和K+ 交换减少,使心肌细胞内Ca2+增多, 心肌收缩力增强。 【药理作用和机制】 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ①  Na+  i↑→ 交换进入细胞内的Ca2+↑, ②  Na+ 0↓→交换出细胞外的Ca2+↓ With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 细胞内Na+ 和细胞外Ca2+交换增多,增加了 细胞内Ca2+的含量,同时细胞外Na+的减少,也 使细胞内Ca2+交换到细胞外减少,通过这个双 向机制,使细胞内钙增多,心肌收缩力增强。 钠钾 ATP酶 钠钙交换 AP 2K+ 3Na+ [K+]i [Na+]i [Ca2+]i 强心苷的 作用机制 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 2. 减慢心率(负性频率作用): 继发于强心苷的正性肌力作用 特点: 对正常心率影响小; 对心率加快者可显著减慢心率; 机制: 1) 输出量↑-- 交感神经↓ --心率↓ 2) 增加心肌对迷走神经敏感性 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 3. 降低衰竭心脏的耗氧量 由于心排出量增加,使心室腔内的血液排 出完全,心室容积缩小,室壁张力降低,并 且心率减慢,所以总体结果心肌耗氧量减低 。 对正常心脏因收缩力的增加可增强心肌耗 氧量,故没有心衰的心绞痛患者不能用强心 苷治疗。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 4.对神经激素的作用 • 中毒量可兴奋交感神经中枢而引起快速心 律失常; • 兴奋脑干副交感神经中枢而引起心率减慢 和房室传导减慢; • 能降低血浆肾素水平,减少血管紧张素Ⅱ 和醛固酮的含量。 5.利尿作用: 与肾血流量增加和抑制 Na+-K+-ATP 酶→ Na+ 再吸收↓有关。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 6.对心肌电生理特性的影响 增强迷走神经活性,促进K+外流。 ①缩短心房ERP,静息电位增大,传导加快, 是治疗房扑转为房颤的机制; ②增加窦房结的最大舒张电位,自律性降低 ,是减慢心率作用的依据; ③使房室结传导减慢,ERP延长,也是治疗房 颤和房扑的作用依据, ④提高浦肯野纤维的自律性,是强心苷引起 室早、室性心律失常的原因之一。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 7.心电图的影响 治疗剂量强心苷使 S-T段下降呈钓鱼钩 状,T波低平, Q-T 间期缩短, P-R 间 期延长。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society • 对高血压、心瓣膜病、先天性心脏病引起 的心衰疗效最好,尤其伴有心房纤颤和心 室率快的心衰效果更好; • 对继发于严重贫血、维生素B1缺乏、甲状 腺功能障碍所致的心衰疗效较差; • 对肺源性心脏病、严重心肌损伤、活动性 心肌炎所致的心衰疗效差; • 对机械性梗阻如严重二尖瓣狭窄、缩窄性 心包炎所致的心衰无效。 【临床应用】 1、充血性心力衰竭 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 2、心房纤颤和心房扑动 目的是减慢心室率。 通过阻滞房室传导 可减少心房的过多冲动传到心室而减少心 室频率。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 强心苷治疗范围小,个体差异大,不良反应多 。 1、胃肠道反应:最常见的早期中毒症状,停药 指征之一,注意与强心苷用量不足鉴别; 2、C.N.S反应:视觉障碍(色视障碍),早期 中毒症状,停药指征之一; 【不良反应】 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 3.心脏反应:最重最危险的反应 各种心律失常: 1)快速型心律失常 室早是早期中毒症状 2)房室传导阻滞 3)窦性心动过缓:60次/分以下, 停药指征之一。 心脏毒性是抑制Na+-K+-ATP 酶所致 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society • 快速型心律失常:室性早搏、二联律、三 联律,严重并发室性心动过速甚至室颤。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【注意事项】 用药期间注意血压,心电图,心率及心律 ,钾、钙、镁等电介质的浓度和肾脏功能的 变化。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 〔中毒的预防〕 l注意中毒的早期症状,一旦出现立即停药 。 l监测地高辛的血药浓度; l避免诱发中毒的因素:低血钾、高血钙、 l低血镁、缺氧、酸血症、碱血症; 肝肾功能障碍; l合并用药:奎尼丁使地高辛血药浓度增加1 倍,维拉帕米使之增加70%;排钾利尿药和 拟肾上腺素药加重强心苷中毒。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 〔中毒的治疗〕 ① 氯化钾: 快速型心律失常。与强心苷竞 争Na+-K+-ATP酶,减少强心苷与酶结合; ② 苯妥英钠: 强心苷引起的室性心动过速, 苯妥英钠可使与强心苷结合的Na+-K+-ATP酶 解离下来,恢复酶活性; ③ 利多卡因: 室性心动过速和室颤; ④ 阿托品: 房室传导阻滞、窦性心动过缓; ⑤ 0地高辛抗体: 极严重中毒。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【中毒的防治】 • 氯化钾可阻止强心苷与Na+-K+-ATP酶的结 合,减轻毒性作用,对早搏和二联律患者 可口服氯化钾3~6g/日,如果病情危急或 血钾低于正常者可用氯化钾1.5~3g溶于5% 葡萄糖液500ml中缓慢静滴。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 〔用药方法〕 全效量(即洋地黄化),维持量 1.全效量的两种给予方法: 速给法:病情紧急,且两周未用过强心苷。 缓给法:病情较轻,且两周未用过强心苷。 2.每日维持量法: 地高辛 0.25mg/日,6~7天(4~5个t1/2) 达稳态血药浓度。 特点:毒性反应低,不适于急症。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 【用法和剂量】 地高辛 口服 成人常用量:0.125~0.5mg,每日一次 ,七天可达稳态 血药浓 度;如若快速达到稳 态血药浓 度,可每6~8小时给 0.25mg,总剂 量为每日0.75~1.25mg;维持量每天一次为 0.125~0.5mg。儿童常用量:一个月~2岁 0.05~0.06mg/kg,2~5岁 0.03~0.04mg/kg,5~10 岁 0.02~0.035mg/kg,10岁以上按成人量,将 该药 的总量分3次或6~8小时给 予,维持量为 总量的1/5~1/3,每12小时一次或每日一次。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 注射剂 成人常用量:静脉注射0.25~0.5mg, 用5%葡萄糖注射液稀释后缓慢注射,以后可 用0.25mg,每隔4~6小时按需要注射,每日总 量不超过1mg,维持量0.125~0.5mg,每日一 次。儿童常用量:静脉注射 1个月~2岁 0.04~0.05mg/kg,2~5岁 0.025~0.035mg/kg,5~ 10岁 0.015~0.03mg/kg,10岁以上按成人量, 将该药 的总量分3次或6~8小时给 予,维持量 为总 量的25%~35%,每日一次。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 毒毛花苷K 静脉注射 成人常用量:首剂0.125~ 0.25mg加入5%葡萄糖液20~40ml后缓慢注射 (不少于5分钟),2小时后根据需要可重复 给一次,每日总量0.25~0.5mg,极量为每次 0.5mg,每日1mg。儿童常用量:0.007~ 0.01mg/kg,首剂给一半的剂量,其余分成 几个相等部分,间隔半小时到2小时给予。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 磷酸二酯酶抑制药 抑制PDE Ⅲ → cAMP↑→SR释放Ca2+正性肌 力作用和扩血管→外周阻力↓→心输出量↑。 用于心衰时短时间的支持疗法,尤其对强心苷 、利尿药、扩血管药反应差者。 氨力农(armirinone)、米力农(milrinone) 维司立农(vesnarinone) 具有正性肌力 和扩血管作用。 抑制PDE Ⅲ ,激活 Na+通 道,抑制K+通道,延长APD 。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 正性肌力作用 抑制PDE Ⅲ → Ca2+内流↑ 延长APD → Ca2+内流↑ 心肌对Ca2+敏感性↑ 匹莫苯(pimobendan) 正性肌力作用 抑制PDE Ⅲ → Ca2+内流↑ 心肌对Ca2+敏感性↑ 特点: 不增加Ca2+ i即可提高心肌收缩力 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 不作为常规治疗药应用。只用于强心苷治 疗效果不佳或禁忌者,适用于伴有心率减慢 或有传导阻滞者。 多巴胺(dopamine) 小剂量激动DA受体→肾血流量↑→外周阻 量↓,中剂量激动β1受体→收缩力↑ (三)儿茶酚胺类 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 多巴酚丁胺(dobutamine) 激动β1受体→心肌收缩力↑→心排出量↑ 激动β2受体→扩血管→心脏后负荷↓ 异布帕明 激动D1、D2、β、 受体。 心肌收缩力↑→心排出量↑, 显著利尿、改善肾功能。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 其他治疗CHF药 扩血管药 〔治疗CHF机制〕 扩张静脉→回心血↓→心脏前负荷↓→ 肺楔压↓ 、左室舒张末压↓ ; 扩小动脉→外周阻力↓→心脏后负荷↓→ 心排血量↑。 硝酸甘油:主要扩V。肼屈嗪:主要扩A。 硝普钠:扩A、V。哌唑嗪:扩A、V。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 钙通道阻滞药 • 降低心脏前后负荷,同时激活交感神经, 具有负性肌力作用 • 最适于治疗冠心病、高血压和舒张功能障 碍的CHF • 目前不作为治疗CHF的常规用药 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 血管紧张素Ⅰ转化酶抑制药(angotensin converting enzyme inhibitor,ACEI) 卡托普利(captopril)、依那普利(enalapril)等 [治疗CHF的作用机制] 1) 扩血管、降负荷:AngⅡ↓, 缓激肽降解↓→NO和PGI2↑。 2) 抑制心肌及血管重构:AngⅡ↓、醛固酮↓ 3) 血流动力学改变:全身血管阻力↓ → 心输出量↑,改善心室舒张功能; With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 4)抑制交感神经活性 : 血管紧张素II受体(AT1)拮抗药 氯沙坦、缬沙坦、厄贝沙坦 作用同ACEI且不良反应少。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society ACEI治疗CHF的机制 收缩血管 升高血压 ACE局 部及循环 血管内皮 B2受体 PGI2NO 缓激肽失活肽 AngIAngII ACEI ACE局 部及循环 血管舒张 血压下降 AngII减少 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 螺内酯(spironolacton) 保钾利尿药-醛固酮拮抗药 〔治疗CHF机制〕 醛固酮的效应: • 保 Na+ 排 K+ →水肿→ 心脏负荷↑ • 促进纤维细胞的增殖→心肌、血管重构 • NA游离浓度↑→室性心律失常和猝死↑ 螺内酯拮抗醛固酮的作用,改善上述病变, 降低CHF发病率和死亡率。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 三、利尿药 促进Na+和水的排泄 → 心脏前、后负荷↓ 轻度CHF单独应用利尿药效果良好 • 中度CHF,可口服袢利尿药或与噻嗪类和留 钾利尿药合用。 • 严重CHF、慢性CHF急性发作、急性肺水肿 或全身浮肿者,宜连续静脉注射呋塞米。 • 严重CHF伴腹水者,常与ACEI及地高辛合用 。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 利尿药在CHF的治疗中起关键作用 1.迅速环境CHF的症状,在数小时或几天内消 除肺水肿和外周水肿; 2.是唯一能够最充分控制CHF体液潴留的药物; 3.合理应用利尿药是成功治疗CHF的关键因素 之一。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 四、受体阻断药 治疗CHF的理论基础: CHF时NA的浓度已经足以产生对心肌细胞 的损伤。NA作用于1受体通路使心肌细胞凋 亡,肾上腺素能神经活性增强介导心肌重构 ,1受体信号转导的致病性明显大于2和1 受体。 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 可选用的受体药物: 美托洛尔(metoprolol) 卡维洛尔(carvedilol) 比索洛尔(bisoprolol) 卡维地洛(carvedilol)效果显著 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 〔作用及机制〕 1.抗交感神经作用:减慢心率,抑制RAAS, 减轻心脏前后负荷,降低心肌耗氧量, 抑制心肌重构; 2.上调1受体; 3.阻断1受体,抗氧化作用; 4.长期应用明显改善心脏功能; 5.抗心律失常和抗心肌缺血 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 〔应用〕 扩张型心肌病 缺血性心脏病所致的心衰 〔注意〕 1.不能突然停药 2.急性心衰,伴有哮喘、低血压、心动过缓、 Ⅱ度房室传导阻滞者禁用或慎用 3.宜从小剂量开始应用 4.宜与其他CHF治疗药合用 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society •强心苷的药理作用是什么。 •强心苷正性肌力作用的原理是什么? •强心苷的主要不良反应及其中毒的防治是 什么? •强心苷治疗心房纤颤和心房扑动的目的是 减慢心房频率吗? •强心苷的早期中毒症状有哪些? •强心苷的体内过程有什么特点? 复习思考题 With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society • 目前临床上常用的强心苷类药物有什么? • 米力农和维司力农的强心机理是什么? • 多巴酚丁胺的适应症和禁忌证是什么? • 通过减轻心脏负荷治疗CHF的药物有哪些? • 应用利尿药治疗CHF时要注意什么? • β受体阻滞药治疗CHF的机理是什么? 临床应用和禁忌证是什么? With the improving quality of life as well as the ever-accelerating pace of life, the quality of people's food needs and rate also changing.In order to meet the needs of society 谢 谢
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