医学治疗慢性心衰的药物PPT培训课件.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,治疗慢性心衰的药物,Definition and Clinical Features,慢性心力衰竭,(,充血性心力衰竭,),心脏在正常充盈压时无法提供有效的前向射血，心脏收缩功能下降，同时心室舒张末压增加，心腔残余血液增加，导致肺循环和体循环淤血,Congestive heart failure(chronic heart failure,CHF)is a complex of symptoms-shortness of breath,tachycardia,fatigue,and congestion-that are related to,the inadequate perfusion of tissue,during exertion and to,the retention of fluid,.,慢性心衰的呼吸困难、心率增加、乏力、淤血等缘于组织灌注不足及体液潴留,Definition and Clinical Features,慢性心力衰竭,(,充血性心力衰竭,),Congestive heart failure,(,chronic heart failure,CHF,)is the pathophysiologic state in which the heart is unable to pump blood at a rate commensurate with,相称,the tissue requirements,or can do so only from an elevated filling pressure.,心输出量不能满足组织代谢需求,或需通过升高充盈压代偿,Its primary cause is that the heart,fails to provide adequate output at normal filling pressures,which is associated with a syndrome of reduced contraction capacity as well as pulmonary and systemic venous congestion.,主要原因是,心脏在正常充盈压时无法提供有效的前向射血，导致心脏收缩功能功能下降以及肺循环和体循环淤血,Systemic and Pulmonary Circulation,When left ventricle fails,Left ventricular end-diastolic pressure,左室舒张末压,LAP,左房压,Pulmonary cap wedge pressure,肺毛细血管锲压,Left ventricle,contraction,左室射血,Thickening of the respiratory membrane reduces O,2,exchange,Enlarged heart,(,Contraction,LVEDP,),and pulmonary congestion,(,O,2,Exchange,),Clinical FeaturesOrthopnea,特征与鉴别,Exertional dyspnea,nocturnal paroxysmal dyspnea and orthopneapulmonary congestion,早期,运动性呼吸困难、夜间阵发性呼吸困难，,急性加重呈,端坐呼吸,-,肺淤血 为左心衰特征,Hypertension,Myocardial Hypertrophy and Diastole Dysfunction,心肌肥厚与舒张功能障碍,Normal,Hypertension,Diastolic and Systolic Heart Failure,舒张性心衰与收缩性心衰均表现为呼吸困难,(,肺淤血,),78 yo Woman Recurrent Pul Edema,50 yo Man HCM,颈静脉怒张,肝脾肿大,下肢浮肿,肺淤血,运动性及,夜间阵发性,呼吸困难,肺水肿,端坐呼吸,心源性哮喘,心肌收缩力下降 心腔残余血增加 左室舒张末压增高,肾灌注下降,尿量减少,水钠潴留,头昏、乏力、运动耐力下降,反射性,SNS,及,RAAS,兴奋，血管痉挛、心率加快、回心血量,When the heart fails,arterial pressure reduces which causes the baroreceptor response and excitation of sympathetic nervous system(SNS)and renin-angiotensin-aldosterone system(RAAS).,心输出量下降导致反射性交感神经系统及肾素血管紧张素醛固酮系统兴奋,Compensation mechanisms during chronic heart failure,心衰代偿机制及其作用,AT1,Renin-Angiotensin-,Aldosterone System,Compensation mechanisms during chronic heart failure,心衰代偿机制的不利影响,The epinephrine/norepinephrine(SNS)and angiotensin/aldosterone(RAAS)enhance heart performance and contract peripheral vessel with water/sodium retention to compensate for reduced cardiac output and redistribution of blood to important organs such as the CNS.,肾上腺素、去甲肾上腺素、血管紧张素使心肌收缩增强、心率加快、外周血管收缩、水钠潴留，血流重新分配以保证重要脏器血流,In addition,the vasoconstrictive effectors of the SNS and RAAS lead to an increase in systemic vascular resistance,which contributes to an increased impedance,阻抗,to left ventricular ejection(increased afterload)and therefore myocardial oxygen consumption.,交感神经及肾素血管紧张素醛固酮系统兴奋增加外周阻力，进而导致心脏后负荷增加，心肌耗氧增加,颈静脉怒张,肝脾肿大,下肢浮肿,肺淤血,运动性及,夜间阵发性,呼吸困难,肺水肿,端坐呼吸,心源性哮喘,心肌收缩力下降,左室舒张末压增高,肾灌注下降,尿量减少,水钠潴留,头昏、乏力、运动耐力下降,反射性,SNS,及,RAAS,兴奋,，血管痉挛、心率加快、回心血量,强心,Digitalis,洋地黄类,降低心脏负荷与氧耗,-blocker ACEI,降低前后负荷,Vasodilator,扩血管药,利尿,Diuretics,减轻水钠潴留,Diuretics,利尿剂,减轻肺淤血,利用哪些途径和药物治疗慢性心力衰竭？,Pharmacotherapy of CHF,治疗慢性心衰的药物,Positive inotropic agents,正性肌力药,Digitalis,洋地黄,Diuretics,利尿药,氢氯噻嗪 呋塞米,Vasodilators,扩血管药,酚妥拉明,-adrenergic receptor blockers,肾上腺素能受体阻断药,Inhibitors of Renin-Angiotensin System,肾素血管紧张素系统抑制药,Therapeutic Aims of CHF,CHF is a major contributor to morbidity and mortality worldwide.Mortality in patients with advanced heart failure exceeds 50%at 1 year.,现代社会中慢性心衰高发病率和高死亡率,While,palliation of symptoms,缓解症状,and,improvement in the quality of life,改善生活质量,remain important goals,it is possible to approach therapy with the expectation that,disease progression,can,be attenuated,减缓病情进展,and,in many instances,survival prolonged,.,延长生存期,治疗目标：缓解症状、降低死亡率，缓解病情进展、改善生存质量,Clinical conditions that precipitate deterioration of CHF,Elevated blood pressure,血压升高,Arrhythmia,心律失常,Myocardial ischemia,心肌缺血,Mental and physical stress,心理与躯体应激,Valve lesion and regurgitation,先心或瓣膜病变所致的分流与反流,Infection,esp.lung infection,各类感染尤其是肺部感染,High salt intake,高盐饮食,慢性心衰治疗同时纠正诱因同样重要,Pharmacotherapy of CHF,治疗慢性心衰的药物,Positive inotropic agents,正性肌力药,Diuretics,利尿药,Vasodilators,扩血管药,-adrenergic receptor blockers,肾上腺素能受体阻断药,Inhibitors of Renin-Angiotensin System,肾素血管紧张素系统抑制药,化学结构,基本骨架,William Withering,1741,1799,Positive inotropic agents,正性肌力药,Cardiac glycosides,强心苷,Digitalis,洋地黄类,abstracts from plant digitalis,Digoxin,地高辛,cidellannid,西地兰,Positive inotropic agents,正性肌力药,Cardiac glycosides,强心苷,Digoxin,地高辛,po,cidellannid,西地兰,iv,Actions and usages,The cardiac effects are,:,increasing force of contraction,增强心肌收缩力,positive inotropic action,正性肌力作用,cardiac slowing(negative chronotropic action),负性频率作用,and reduced rate of conduction through the AV node,负性传导作用,disturbances of rhythm,对心肌电生理的影响,especially,-block of AV conduction,抑制房室传导,-increased ectopic pacemaker activity,尤其是蒲氏纤维,Used in,chronic heart failure and for controlling ventricular rate in atrial fibrillation,MechanismCardiac glycosides,强心苷,Mechanisms of positive inotropic action,Inhibition of Na,+,K,+,-ATPase,.Cardiac glycosides are potent and highly selective inhibitors of the active transport of Na,+,&K,+,across cardiac cell membranes.They binds to a subunit of Na,+,K,+,-ATPase,increasing cytosolic Na,+,which in turn through Na,+,-Ca,2+,exchange increases the level of cytosolic Ca,2+,available to interact with the contractile proteins,thereby increasing the force of contraction.,抑制钠钾,ATP,酶，增加细胞内游离钙水平,洋地黄体内过程与给药特点,地高辛口服生物利用度,60%-80%,，但个体差异及不同厂家产品生物利用度差异很大,地高辛以原型主要经肾脏排泄,，易蓄积中毒，应随时根据患者尿量调整药物剂量,地高辛小剂量口服，西地兰静脉给药起效快,奎尼丁、胺碘酮、维拉帕米等均可升高地高辛血药浓度,利尿药疗效显著时可能导致患者血容量不足、血液浓缩 使地高辛血药浓度升高,Adverse Effects of Cardiac glycosides,强心苷的不良反应,强心苷安全范围小 过量易中毒 小剂量个体化用药,Adverse effects,One of the main drawbacks of glycosides is the narrow margin between effectiveness and toxicity.Adverse effects are common and can be severe.,容易导致中毒,Cardiac adverse effects:AV blockade,ventricular premature contraction(PVC)and even ventricular fibrillationlidocaine and potassium should be given for,室性心律失常与传导阻滞,Extracardiac adverse effects:nausea,vomiting,diarrhea,blurred vision,and confusion,The recognition of digoxin toxicity is important in the differential diagnosis of,arrhythmias,and,neurological,and,gastrointestinal,symptoms.,Positive inotropic agents,正性肌力药,Cardiac glycosides,强心苷,Regulation of Sympathetic Nervous System Activity.,洋地黄对交感神经活性的影响,When CO declines to a level that is inadequate to meet the tissue demands,increased SNS activity occurs as a compensatory response.This is due in part to a reduction in the sensitivity of the baroreflex response to BP,resulting in a decline in baroreflex-mediated tonic suppression of CNS-directed sympathetic activity,。,A direct effect of digitalis on carotid baroreflex response to changes in carotid sinus pressure has been demonstrated in isolated preparations from heart failure animals.In patients with moderate-to-advanced heart failure,infusion of a digitalis increased forearm blood flow and cardiac index and decreased HR;skeletal muscle sympathetic nerve activity,an indicator of the CNS tone,was markedly reduced.,洋地黄降低心衰时的代偿性交感兴奋,地高辛的应用与血药浓度监测,Use of Digoxin in Clinical Practice and Monitoring of Serum Levels.,It is recommended that digoxin be reserved for patients with heart failure with atrial fibrillation,or for patients in sinus rhythm who remain symptomatic despite maximal therapy with ACE inhibitors and antagonists.Digoxin may be unique among inotropic drugs by virtue of its neurohumoral effects,including attenuation of sympathetic activation and renin release.,Most studies suggest that the maximal increase in contractility is apparent at serum levels of digoxin around 1.4 to 1.8 nmol.The neurohormonal benefits of digoxin may occur at lower serum levels of 0.5-1 ng/ml;higher concentrations are not associated with further clinical benefit.,Use of S,ympathomimetics,in CHF,交感激动药在慢性心衰中的应用与争议,The use of,sympathomimetic drugs,拟交感药,such as,dobutamine,多巴酚丁胺,and,dopamine,多巴胺,was found to provide,short-term,relief of heart failure symptoms in patients with advanced ventricular dysfunction.It was presumed that the development of oral congeners of these sympathomimetic agents would represent a major advance in the pharmacotherapy of heart failure.,This mechanistic hypothesis has been discredited by the results of a number of trials that have addressed the longer-term use of positive inotropic agents.These trials have been concordant in demonstrating increased mortality in CHF patients treated with drugs that amplify the receptor/cyclic AMP-modulated Ca,2+,signaling that underlies myocardial contraction and relaxation.,拟交感强心药治疗急性心功能障碍效果尚好，,但治疗慢性心衰仅暂时缓解缓解症状仍增加其死亡率,Diuretics,利尿剂,Diuretics retain a central role in the pharmacological management of the“congestive”symptoms in patients with heart failure.,慢性心衰通常伴有水钠潴留，肺淤血与外周循环受阻，利尿药始终是治疗心衰最重要的药物之一。,Diuretics reduce blood volume through diuresis,利尿,leading to lowered preload and blood pressure.,利尿剂通过利尿作用降低血容量，亦可降低血压，同时降低心脏前后负荷。,They are useful in relieving the pulmonary and peripheral edema as well as hypertension.,利尿剂对肺水肿及外周水肿缓解作用显著，同时也能有效地治疗高血压。,急性左心衰发生肺水肿用药举例,Diuretics,利尿剂,利尿剂通常分为强效、中效和弱效三类，常用的强效利尿药为呋塞米又称袢利尿剂,(,loop diuretics,),，中效为氢氯噻嗪，弱效利尿剂也为保钾,(,K,+,-Sparing,),利尿剂，如螺内酯，可根据病情选用或联合应用,Usage:Furosemide,is injected to relieve the pulmonary edema quickly and efficiently,while,hydrochlorothiazide,is the most choices for oral administration.,呋塞米为强效利尿剂，可静脉给药有效缓解水肿包括肺水肿，口服通常选用氢氯噻嗪,Adverse effects,:Diuretics could cause depletion of blood volume and reflex SNS activation,low serum potassium,which are detrimental to heart failure and may lead to severe arrhythmias.,过度利尿可导致水电解质平衡紊乱，低血容量可致反射性交感兴奋，低血钾、低血镁等易致心律失常，应注意避免过度利尿，及时补充钾，或与保钾利尿药合用。,Vasodilators,扩血管药,-adrenergic blocker,酚妥拉明（,受体阻断药）,sodium nitroprusside,硝普钠,(NO donor),Usage:,used for short-term release of symptoms,by reducing preload and afterload,酚妥拉明用药举例,Adverse effects,:tachycardia(reflex SNS activation),avoid long-term and large doses use,硝普钠须避光使用，过量可致氰化物中毒,Use of-blocker in CHF,受体阻断药在慢性心衰中的应用,Heart failure is characterized by sympathetic hyperactivation,a neurohumoral state that reflects biological responses that can be both,compensatory,and,maladaptive,.,既是代偿又有适应不良 增加心肌耗氧,While many of sympathomimetics increased mortality in CHF patients,an unexpected mortality benefit was seen with the administration of adrenergic blocking drugs.,adrenergic blockers reduce the heart work load and catecholamines myocardial toxicity,producing long-term benefits in patients with CHF.,Start blocker at lose dose and with digitalis or diuretics.,小剂量开始启用逐渐增加至最大耐受剂量，常常需合用强心苷和,/,或利尿剂,Heart function changes with the use of-blocker in CHF,The direct hemodynamic effect of a antagonist in patients with heart failure is to depress contractile function.An increase in left ventricular systolic function between 2 and 4 months after initiation of therapy is seen consistently.,Inhibitors of Renin-Angiotensin System,抑制肾素血管紧张素系统的药物,Angiotensin converting enzyme(ACE)Inhibitors,:ACE inhibitors suppress Ang II and aldosterone production,decrease sympathetic nervous system activity,and potentiate the effects of diuretics in heart failure.,However,Ang II levels frequently return to baseline values following chronic treatment with ACE inhibitors,due in part to production of Ang II through ACE-independent enzymes such as chymase,a tissue protease.,Pharmacotherapy of CHF,治疗慢性心衰的药物,Positive inotropic agents,正性肌力药,Digitalis,洋地黄类,:Digoxin,地高辛,-adrenergic agonists:dopamine,多巴胺,dobutamine,多巴酚丁胺,Diuretics,利尿药,Loop diuretics,袢利尿药 强效利尿药：,furosemide,呋塞米,Thiazide diuretics,中效利尿药：,hydrochlorothiazide,氢氯噻嗪,Vasodilators,扩血管药,-adrenergic blocker,酚妥拉明,sodium nitroprusside,硝普钠,-adrenergic receptor blockers,肾上腺素能受体阻断药,Carvedilol,卡维地洛,(,兼有,受体阻断作用,),bisoprolol,比索洛尔,ACEIs and ARB,血管紧张素转化酶抑制剂及,AT1,受体阻断剂,Captopril,卡托普利,losartan,洛沙坦,Pharmacotherapy of CHF,治疗慢性心衰的药物,Positive inotropic agents,正性肌力药,Cardiac glycosides(,强心苷类,digitalis,洋地黄类,):Digoxin,地高辛,Phosphodiesterase III(PDE)inhibitors,磷酸二酯酶峰抑制剂,and,-adrenergic agonists,：,dopamine,多巴胺,dobutamine,多巴酚丁胺,Diuretics,利尿药,Loop Diuretics,袢利尿药，强效利尿药,furosemide,呋塞米,Thiazide Diuretics,噻嗪类利尿药，中效利尿药：,hydrochlorothiazide,K,+,-Sparing diuretics and aldosterone antagonists,保钾利尿药及醛固酮拮抗剂，弱效利尿,Vasodilators,扩血管药,-adrenergic blockers,酚妥拉明,sodium nitroprusside,硝普钠,(Mixed),-adrenergic receptor blockers,肾上腺素能受体阻断药、,Carvedilol,卡维地洛,bisoprolol,比索洛尔,Inhibitors of Renin-Angiotensin System:ACE Inhibitors and AT,1,Receptor Antagonists,血管紧张素转化酶抑制剂及,AT1,受体阻断剂,Captopril,卡托普利,losartan,洛沙坦,(,沙坦类,),US guidelines for adult CHF,美国成人慢性心力衰竭治疗指南解读,NYHA,心功能分类方法 传统,1,级 日常活动无明显受限，心功能代偿期,2,级 日常活动水平时出现心衰症状,3,级 稍活动出现心衰症状,4,级 静息状态下有心衰症状,心力衰竭新的分类方法：一个对疾病过程进行客观评价的分期系统 对,NYHA,功能分级的补充,A,期 心衰高危但没有器质性心脏病或心力衰竭症状,B,期 器质性心脏病但没有心衰症状,C,期 器质性心脏病并且既往或目前有心衰症状,D,期 需要特殊干预治疗的难治性心力衰竭,US guidelines for adult CHF,美国成人慢性心力衰竭治疗指南解读,心力衰竭新的分类方法,图示,Try mild exercise therapy for your CHF patients after symptom relief,Plants in my hometown Nanping,FujianProvince,补充幻灯,Cecil Medicine,24,th,edition,开篇第一段,Medicine is a profession that incorporates science and the scientific methods with the art of being a physician.,The art of attending to the sick is as old as humanity itself.Even in the modern times,the art of caring and comforting guided by millennia of common sense as well as a more recent,systemic approach to medical ethics,remains the cornerstone of medicine.,Without these humanistic qualities,the application of the modern science of medicine is suboptimal,ineffective,or even detrimental.,Feb 16,2004,A Patient f,rom Unstable Angina Pectoris to Myocardial Infarction,Coronary interference vs drug therapy associated complications,Feb 14,2004,Osmotic Diuretics,渗透性利尿药,(,脱水利尿药,),甘露醇,mannitol,特点,甘露醇易经肾小球滤过而不易被重吸收,在体内不易被代谢，不进入细胞,不易从血管透入组织液中,作用,脱水,静脉注射后迅速提高血浆渗透压,使组织间液水分向血浆转移而使组织脱水,利尿,提高肾小管滤过率及肾小管内渗透压,产生渗透利尿,应用：用于组织脱水，如脑水肿脱水,Osmotic Diuretics,渗透性利尿药,(,脱水利尿药,),甘露醇,mannitol,临床应用,脑水肿,静注后迅速提高血浆渗透压,使脑组织水分向血浆转移并随尿排出，从而使脑组织脱水,迅速减低颅压,青光眼,减少房水,减低眼压,不良反应,血容量增加,增加心肺负担，心衰患者慎用,肾脏损伤,尿液浓缩时甘露醇可在肾小管形成结晶，损害肾小管功能，肾功能障碍者慎用,抗心力衰竭药物复习案例,一,60,岁男性顽固性心绞痛住院治疗中，该组医疗工作,忙,患者有高脂血症，心电图检查显示广泛,ST,段压低,主治医师考虑到患者体内高凝血状态可能加重心肌缺血，决定给患者输注低分子右旋糖酐抗凝，希望能改善心绞痛，下午查房后开出医嘱：输注低分子右旋糖酐,250ml,接班查体见患者可平卧，深吸气时可闻及双下肺少量细湿罗音。约两小时后患者突然出现明显呼吸困难，不能平卧，听诊双肺满布湿罗音，心电图显示窦性心动过速,突然出现心衰加重的原因？应采取何种治疗措施？,静推呋塞米无利尿作用，多巴酚丁胺静脉滴注维持心功能，第三天患者突然出现室颤，除颤无效死亡,充血性心力衰竭患者治疗中的部分问题,低分子右旋糖酐、甘露醇等可扩充血容量的药物慎用或禁用,肾上腺素、异丙肾上腺素等显著增加心肌耗氧量的药物禁用,使用洋地黄治疗的患者禁用钙剂（如不能用葡萄糖酸钙注射治疗过敏）,大剂量硝普钠及与硝酸甘油合用应限制,Once a year,go some place you have never been before.,Many thanks for your attention,