Drugs for the Treatment of Congestive Heart Failure ( CHF) 浙江大学医学院药理学系 张世红 shzhang713@zju.edu.cn
Drugs for the Treatment of Congestive Heart Failure （CHF） 1 浙江大学医学院药理学系 张世红 shzhang713@zju.edu.cn
Outlines ◆CHF概述 ◆CHF的治疗策略 ◆治疗cHF的药物
Outlines CHF概述 CHF的治疗策略 治疗CHF的药物 2
概述-CHF的定义和症状 ●充血性心力衰竭是指在静脉回流正常的情况下,由于原发的 心脏损害引起心排血量减少,不能满足组织代谢需要的一种 综合征。导致心衰的疾病包括冠心病,缺血性心脏病,心肌 病,高血压,心瓣膜病,肾病等。 ●临床上以肺循环和(体循环淤血以及组织血液灌注不足为 主要特征,包括无力、水肿、咳嗽、喘呜,咯血,头晕,心 律失常等
3 概述-CHF的定义和症状 ⚫充血性心力衰竭是指在静脉回流正常的情况下，由于原发的 心脏损害引起心排血量减少，不能满足组织代谢需要的一种 综合征。导致心衰的疾病包括冠心病，缺血性心脏病，心肌 病，高血压，心瓣膜病，肾病等。 ⚫临床上以肺循环和(或)体循环淤血以及组织血液灌注不足为 主要特征，包括无力、水肿、咳嗽、喘鸣，咯血，头晕，心 律失常等
概述-心力衰竭的类型 (1)收缩功能衰竭 the mechanical pumping action (contractility) and the ejection fraction of the heart are reduce d (2)舒张功能衰竭: stiffening and loss of adequate relaxation plays a major role in reducing cardiac output and ejection fraction may be normal. e. g Pericarditis(心包炎) (3)高输出型衰竭 can resu t from hyperthyroidism(甲亢 beriberi(脚气病), anemIa(贫血, and arteriovenous shunts(动静脉分流)
(1) 收缩功能衰竭: the mechanical pumping action (contractility) and the ejection fraction of the heart are reduced. (2) 舒张功能衰竭: stiffening and loss of adequate relaxation plays a major role in reducing cardiac output and ejection fraction may be normal. e.g. Pericarditis (心包炎) (3) 高输出型衰竭: can result from hyperthyroidism (甲亢), beriberi (脚气病), anemia (贫血), and arteriovenous shunts (动静脉分流). 概述-心力衰竭的类型 4
概述-心功能分级 根据症状对心功能分级: Class l: no limitation is experienced in any activities; no symptoms from ordinary activities Class l: slight, mild limitation of activity; the patient is comfortable at rest or with mild exertion Class l: marked limitation of any activity; the patient is comfortable only at rest Class IV: any physical activity brings on discomfort and symptoms occur at rest
概述-心功能分级 根据症状对心功能分级: Class I: no limitation is experienced in any activities; no symptoms from ordinary activities. Class II: slight, mild limitation of activity; the patient is comfortable at rest or with mild exertion. Class III: marked limitation of any activity; the patient is comfortable only at rest. Class IV: any physical activity brings on discomfort and symptoms occur at rest. 5
概述-心衰的分级 根据疾病进程对cHF分级: At risk/Stage A: a high risk HF in the future but no structural heart disorder. Stage B: a structural heart disorder but no symptoms at any stage Stage C: previous or current symptoms of heart failure in the context of an underlying HE structural heart problem, but managed with medical treatment Stage D: advanced disease requiring hospital-based support, a heart transplant or palliative care
根据疾病进程对CHF分级: Stage A: a high risk HF in the future but no structural heart disorder; Stage B: a structural heart disorder but no symptoms at any stage; Stage C: previous or current symptoms of heart failure in the context of an underlying structural heart problem, but managed with medical treatment; Stage D: advanced disease requiring hospital-based support, a heart transplant or palliative care 概述-心衰的分级 At risk HF 6
Cardiac failure Cardiac output几 Blood pressure Venous pressure Renal blood flow Renin angiotension I Venous hyperemia Aldosterone Pulmonary Systemic circulation circulation Jugular vein Sodium and water (cough, emptysis,distension, edema) retention dyspnea) Changes of hemodynamics in CHF I
Cardiac failure Cardiac output Venous pressure Venous hyperemia Pulmonary circulation (cough, emptysis, dyspnea) Systemic circulation (jugular vein distension, edema) Blood pressure Renal blood flow Renin, angiotension II Aldosterone Sodium and water retention Changes of hemodynamics in CHF 7
概述CHF的病理生理学 心肌损害 心输出量减少 SNS和RAAS激活 心脏毒性 ANP 血管收缩,血流动 BNP 力学改变 心肌肥厚( hy pertrophy) 心血管重构( remodeling) 发病和死亡 左室功能进行性恶化心衰症状 Fonarow GC. Rev Cardiovasc Med 2001: 2: 7-12
心肌损害 心输出量减少 SNS和RAAS 激活 心脏毒性 心肌肥厚（hypertrophy） 心血管重构（remodeling） 发病和死亡 左室功能进行性恶化 心衰症状 ANP BNP Fonarow GC. Rev Cardiovasc Med..2001;2:7–12. 概述-CHF的病理生理学 8 血管收缩，血流动 力学改变
Actions of angiotensin Constricts vessels, increases peripheral resistance and returned blood volume Increases sympathetic tension, promotes release of sympathetic transmitter Stimulates release of aldosterone(醛固酮) Induces expression of c-fos、c-myc、ciun rapidly, promotes proliferation and remodeling
• Constricts vessels, increases peripheral resistance and returned blood volume. • Increases sympathetic tension, promotes release of sympathetic transmitter. • Stimulates release of aldosterone (醛固酮). • Induces expression of c-fos、c-myc、c-jun rapidly, promotes proliferation and remodeling. Actions of angiotensin II 9
Actions of aldosterone Pro-thrombotic Vascular inflammation Potassium effect Myocardial and injury and fibrosis magnesium loss Deleterious effects Central of aldosterone hypertensive effects Catecholamine potentiation Endothelial Sodium Ventricular dysfunction retention arrhythmias Cardiovascular disease McMahon EG 2001, Current Opinion in Pharmacology
10 Actions of Aldosterone McMahon EG 2001