治疗充血性心衰的药物药学.pptxVIP

治疗充血性心衰的药物药学第1页/共63页第2页/共63页心力衰竭(heart failure,　HF）美国：2003年全部心血管疾病中心衰的发病率达到13%，发病人数达到50万人。中国：心衰占心血管病住院率的20%，病死率达到40%。A highly lethal condition with a 1-year mortality rate is about 50%. 5-year mortality rate is about 90%.心衰=没有癌细胞的恶性肿瘤第3页/共63页心力衰竭(heart failure,　HF）又叫慢性心功能不全(chronic cardiac insufficiency），是由多病因所致的心脏收缩功能降低和障碍，导致心输出量(cardiac output)降低，机体的组织供氧和代谢的血液供应明显减少，不能满足全身组织代谢需要的一种病理生理状态及临床综合征。常伴有显著的静脉系统充血状态，因此又叫充血性心力衰竭(congestive heart failure, CHF）第4页/共63页CHF临床表现冠脉血流量??加重心衰心率??心肌耗氧量?肾血流量??尿量?组织血液灌流不足心脏收缩?心脏舒张?心输出量?肾淤血：下肢水肿，颈V怒张肝淤血：肝脾水肿，肝腹水胃肠淤血：胃肠道症状体循环淤血肺循环淤血静脉淤血肺水肿，咳嗽端坐呼吸，呼吸困难第5页/共63页CHF Cardiac contractility cardiac outputRAAS?? AngⅡSympathetic system Down-regulation of β1-Gs systemHRvascular tonealdosteroneCardiac hypertrophy and remodeling Sodium and water retention afterloadpreload Pathophysiology第6页/共63页神经内分泌变化交感神经系统激活RAAS激活其他神经内分泌系统精氨酸加压素(AVP)增多内皮素( enclothelin,ET)增多肿瘤坏死因子(TNF-α)增多白介素(Interleukin, IL)增多肾上腺髓质(adrenomedullin, AM)增多EDRF(NO)减少第7页/共63页心肌肾上腺素β受体信号转导Adr βR1 ⊕Gs 心肌 ⊕AC PDE ˊcAMP AMPATP5- ˊ 促进Ca2+内流正性肌力作用 第8页/共63页心衰时β受体信号转导变化β1受体下调β1受体与兴奋性Gs脱耦联第9页/共63页心脏重构（remodeling，心脏构型重建）It is the most important intrinsic compensatory mechanism in CHF. It refers to the slow dilation and structural changes occurred in the stressed myocardium, including myocytes hypertrophy, proliferation of connective tissue cells (fibroblasts) and myocardial fibrosis. After an initial beneficial effect, myocardial remodeling can lead to ischemic changes, impairment of diastolic filling, and myocytes apoptosis. Angiotensin II and aldosterone can cause myocardial remodeling during CHF. CHF发病的内源性机制第10页/共63页基本病理生理学Pathophysiology神经内分泌变化交感神经系统激活RAAS系统激活心肌β受体信号转导下调心脏构型重建(remodeling)第11页/共63页CHF cardiac contractility cardiac outputRAAS?? AngⅡSympathetic system Down-regulation of β1-Gs systemHRvascular tonealdosteroneCardiac hypertrophy and remodeling Sodium and water retention afterloadpreload positive inotropic agents:Cardiac glycosides β- blockersRAASinhibitors β- b