充血性心衰药物

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,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,*,治疗充血性心力衰竭药物,Drugs for Congestive Heart Failure,心力衰竭（heart failure）是各种原因引起的心肌舒缩障碍，导致心输出量不能满足机体需求的一组临床综合征。充血性心衰是其中最主要的一种。,慢性或充血性心力衰竭（,congestive heart failure,CHF,）是各种病因所引起的多种心脏疾病（冠心、高心、肺心、风心、心肌病等）的终末阶段，当静脉回流足够的情况下，心脏排出量绝对或相对减少，不能满足机体组织需求的,一种临床或病理综合征,。,心衰病人运动耐量下降，寿命缩短。,Concept:,CHF is a complex clinical syndrome characterized by impaired ventricular performance,exercise intolerance,a high incidence of ventricular arrhythmias,and shortened life expectancy,The signs and symptoms,The signs and symptoms of heart failure include tachycardia,decreased exercise tolerance and shortness of breath,peripheral and pulmonary edema,and cardiomegaly.,动脉系统缺血,-,乏力，气短，头晕,静脉系统淤血,-,水肿，颈静脉怒张，肝脾肿大，呼吸困难,静脉淤血所致的症状为主。,心衰的分级（,NYHA,标准）,级：心功能代偿完全，体力活动不受限，日常活动无乏力，心悸，呼吸困难等症状；,级：轻度代偿不全，活动轻度受限，休息时无症状；,级：中度代偿不全，体力活动明显受限，日常活动即可产生症状。限于室内活动；,级：严重代偿不全，休息时亦有症状，不能从事任何体力活动。,心力衰竭不是一种独立的疾病，而是由多种原因引起的心肌收缩和,/,或舒张功能障碍的综合征。近年来的研究发现，心力衰竭虽然主要表现为心肌收缩和舒张功能障碍，但神经内分泌的改变对其恶性循环的形成和维持有重要的作用。这些变化导致心脏出现不可逆的重构,(remodeling),，使衰竭的心脏一步步恶化。,Pathophysiology,心力衰竭时机体的代偿机制,:,Augmented sympathetic activity,Sodium and water retention,Myocardial hypertrophy,Ventricular dilatation,1,心脏本身的代偿,心率加快、心肌收缩加强,-,快速发生,心脏扩大和肥大,缓慢发生,是心脏本身储备功能的动员。,2,心脏外的代偿,血容量增加,血液重分配及红细胞增多,等几方面的心脏外代偿作用。,机体的代偿机制虽然有助于维持机体所需的心输出量要求，但长时间代偿机制的激活可加重心脏的负担。,在,CHF,的长期发病过程中，各种代偿机制对心脏和动脉血管等的影响可产生恶性循环，加重心脏负担，最终加重心力衰竭。,实际上慢性心衰的发展过程就是在,心肌氧供不足和维持机体循环血供需求之间不断平衡的矛盾发展过程,。,神经体液系统主要改变,Increased,sympathetic nervous system activity,(and increased plasma catecholamines,b,-receptor down regulation,),Increased activity of the,renin-angiotensin-aldosterone system,Increased release of,arginine-vasopressin,心衰的一些代偿机制,In addition to the effects shown,angiotensin II increases sympathetic effects by facilitating norepinephrine release.,慢性心衰的药物治疗：,应减轻负荷，降低能耗，保护心脏,。达到,改善血流动力学；改善运动耐量；延长生命。,而不是病马加鞭，只增强心肌收缩力,心衰的血流动力学指标：,压力指标：,LVEDP,，,dP/dtmax,；,容积指标：,SV,，,CO,，,CI,，,EF,（正常,0.67,心衰,0.45,严重心衰,0.3,）,时间指标：,PEP,，,LVET,，,T-dP/dtmax,抗心衰药物的发展和演变,洋地黄时代（从民间的治疗水肿药物而来）,利尿药（噻嗪类、汞撒利）,非苷类强心药（儿茶酚胺类，磷酸二酯酶抑制剂-氨力农、米力农）,扩血管药物,血管紧张素转化酶抑制剂 ACEIs，ARBs,受体阻断剂,醛固酮受体阻断剂,使用抗心衰药物后心功能曲线的改变,(I)正性肌力药物 positive inotropic agents,(V)舒血管药Vasodilators,(D)利尿药Diuretics,pharmacologic intervention in CHF,抗心衰药物是主要用于治疗,CHF,的药物，主要有,强心苷、非甙类正性肌力药、利尿药、,ACEI,和,受体阻断药,等。,Improving hemodynamics with inotropic drugs does not decrease mortality;,（病马加鞭）,long-term treatment directed towards neurohormonal factors with ACE inhibitors and beta-blockers can decrease mortality,Consensus recommendations for the management of CHF,Patients with heart failure should first be evaluated to assess LV ejection fraction.Patients with systolic dysfunction(EF,40%)should then undergo the following treatment:,水钠潴留：利尿药,ACEIs,，ARBs,和/或 beta-blocker,室率快的房颤：强心苷（地高辛）,重症患者延长寿命：醛固酮受体拮抗剂,fluid retention-a,diuretic,.,ACE inhibitor,and,beta-blocker,should be initiated and maintained unless specifically contraindicated.,（,Patients with severe heart failure should probably not receive a,beta-blocker,）,Digoxin,-in patients with rapid atrial fibrillation.,Spironolactone,an,aldosterone antagonist,may reduce mortality in patients with severe heart failure,ACE inhibitors,first-line therapy in all patients with heart failure,improve symptoms,slow progression of the disease,reduce mortality,and decrease the incidence of hospitalization,The most common adverse effects of ACE inhibitors are directly related to lowering angiotensin II concentrations(hypotension and renal insufficiency)and increasing concentrations of kinins(cough and angioneurotic edema),血管紧张素原,Angiotensin,收缩血管,肾素,激肽原,缓激肽,降解失活,Ang,ACE,ACEIs,Ang,分泌醛固酮,NO PGI,(,-,),ACE和ACEIs作用示意图,舒张血管,Captopril,第1个在临床上广泛应用的ACEI。含巯基，可致味觉异常。,Enalapril,前体药，不含巯基。药效和作用时间比cartopril强。,ARBs-,angiotensin receptor blockers,angiotensin receptor antagonists(,AT1 Receptor Antagonists,)are as effective as ACE inhibitors in treating heart failure,but it appears that therapeutic efficacy may be comparable,losartan,candesartan,valsartan,Inotropic Drugs-digitalis,The beneficial effects of cardiac glycosides in the treatment of heart failure have been attributed to a positive inotropic effect on failing myocardium and efficacy in controlling the ventricular rate response to atrial fibrillation.The cardiac glycosides also modulate autonomic nervous system activity,and it is likely that this mechanism contributes substantially to their efficacy in the management of heart failure.,Positive Inotropic Effect,（抑制,Na+,K+-ATPase,）,Electrophysiological Actions,（加上增强迷走）,Regulation of Sympathetic Nervous System Activity,There is evidence that digitalis may act directly to,sensitization of,baroreceptor response and thereby exert some of its beneficial effects through reduction of sympathetic tone,The recent Digitalis Investigation Group(DIG)clinical trial indicated digoxin did not reduce overall mortality in patients with heart failure(who were receiving di