没有标题浙江大学教学信息化平台pp呢t课件.ppt
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1、Part 4 Drugs for Treatment of Congestive Heart Failure,Contents,Overview ACE inhibitors Diuretics receptor blockers Cardiac glycoside Others,Heart (cardiac) failure is said to have occurred when the heart is no longer able to maintain the circulation to the tissues for normal metabolism.,1. Pathophy
2、siological changes of congestive heart failure (CHF) (1) Function and structure changes (2) Increased sympathetic activity and down-regulation of receptor (3) Activated renin-angiotensin-aldosterone system (RAAS),A. Overview,Pathophysiological changes of CHF,Pathophysiological changes of CHF,Cardiac
3、 failure,Cardiac output,Venous pressure,Venous hyperemia,Pulmonary circulation: cough, emptysis, dyspnea,Systemic circulation hyperemia : jugular vein distension, edema,Blood supply,Renal blood flow,Renin - angiotension ,Aldosterone,Sodium and water retention,Changes in hemodynamics of CHF,A. Overvi
4、ew,2. Grades of CHF (A): no symptoms (B): physical activities were limited and symptoms could be induced by general activity (C): physical activities were markedly limited (D): symptoms appear even at rest,3. Therapeutic strategies in CHF (1) Increasing contractility of the cardiac muscles (2) Inhib
5、iting RAAS (3) Reducing sympathetic activity (4) Dilating vessels (5) Diuresis,A. Overview, Cardiac remodeling,Decrease overload,Drug therapy for CHF,ACEI: captopril 卡托普利 enalapril 依那普利 AT1 receptor antagonists: losartan 氯沙坦 irbesartan 伊白沙坦,B. Angiotensin converting enzyme inhibitors (ACEI) and angi
6、otensin receptor antagonists,Cardiovascular remodeling,vasodilatation,Systemic and local,ACEI 1. Pharmacological effects Inhibiting the production of Ang II vasoconstriction ; sodium retention ; cardiac remodeling (myocardial hypertrophy) Inhibiting the degradation of bradykinin vasodilatation Incre
7、asing ANP and scavenging free radicals,B. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists,Box Actions of angiotensin II through activating AT1 receptors Constricting vessels, increase peripheral resistance and returned blood volume. Increasing sympathetic tension
8、, promote release of sympathetic transmitter. Stimulating release of aldosterone. Rapidly inducing expression of c-fos, c-jun, Egr-1, c-myc, etc.,Cardiovascular effects Decrease resistance of peripheral vessels Dilate coronary artery, increase blood supply of heart and kidney, improve cardiac and re
9、nal function Reverse myocardial hypertrophy and ventricular remodeling,B. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists,B. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists,2. Clinical uses (1) CHF increase motor tolerance dec
10、rease mortality (2) Hypertension,3. Adverse effects Hypotension Cough and angioedema Hyperpotassemia Rashes and altered tastes Contraindications: pregnancy and stenosis of renal artery,B. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists,AT1 receptor antagonists Co
11、mpared with ACEI: Blocking actions of angiotensin II directly Not affecting bradykinin metabolism Protecting renal function Used for CHF and hypertension,B. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists,1. Pharmacological effects Reduce blood volume by increasi
12、ng Na+ and water excretion Reduce Na+-Ca2+ exchange in vascular smooth muscle cells 2. Clinical uses CHF: grand I IV (mainly used in II III), alone or combined with other drugs Edema, hypertension, etc. 3. Adverse effects imbalance of electrolytes/acid-base; plasma level of renin ; hypokalemia; hype
13、ruricemia; hyperglycemia/hyperlipidemia,C. Diuretics,Therapeutic effects of diuretics in CHF,Main diuretics,Thiazides,Loop diuretics,K+ sparing diuretics,Commonly used: carvedilol 卡维地洛, bisoprolol 比索洛尔, sustained-release metoprolol 缓释型美托洛尔 1. Pharmacological effects (1) Blocking effects of catechola
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