浙江大学医学院：治疗充血性心力衰竭的药物 Drugs for Treatment of Congestive Heart Failure

浙孚 ZheJiang University Drugs for Treatment of Congestive Heart Failure

Drugs for Treatment of Congestive Heart Failure

Contents J Overview J ACE inhibitors(ACEr) J AT1 receptor blockers(ARB) J mineralocorticoid receptor blockers MRB) u Diuretics B receptor blockers J Cardiac gly coside Others

◼ Overview ◼ ACE inhibitors (ACEI) ◼ AT1 receptor blockers(ARB) ◼ mineralocorticoid receptor blockers(MRB) ◼ Diuretics ◼  receptor blockers ◼ Cardiac glycoside ◼ Others Contents

A. Overview 1. Pathophysiological changes of congestive heart failure(CHF) (1)Function and structure changes neuroendocrine changes (3)Changes of B receptor signal transduction

1. Pathophysiological changes of congestive heart failure (CHF) (1) Function and structure changes (2) Neuroendocrine changes (3) Changes of  receptor signal transduction A. Overview

art Failure Inotropes, digoxin Reduced cardiac output 阝- blockers, digoxin Renin Sympathetic nervous Elevated cardia c filling pressures s system activation t k Vasodilators I Angiotensin I Vasoconstriction ACE inhibitors Angiotensin‖l Sodium and water retention ARBs Diuretics Aldosterone Spironolactone Ho2 Cardiac Remodeling

↑ Preload Myocyte loss ↓ Energy supply Cellular Altered collagen hypertrophy matrix afterload Remodelling 小 Cardiac output ↑ Inotropy ↓ Baroreflex Neurohormonal sponse Natriuretic Renin-angiotensin peptides aldosterone Prostaglandins -Sympathetic nervous ↑Ca Arrhythmias Bradyki ↓ Response to system Sudden death Endothelin stress Arginine Fluid& salt tention Vasoconstriction, vascular remodelling, endothelial dysfunction ↑ Peripheral Maintains blood pressure s Perfusion Altered skeletal muscle resistance > Redistributes cardiac output /of vital blood flow and metabolism organs Dyspnea, edema, fatigue

Cardiac failure Cardiac output Blood supply Venous pressure Renal blood flow Renin- angiotensionⅡ Venous hyperemia Aldosterone Pulmonary circulation: Systemic circulation cough, emptysis Sodium and water perella retention dyspnea Jugular vein dIsTension dema Changes of hemodynamics in CHF

Cardiac 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 Ⅱ Aldosterone Sodium and water retention Changes of hemodynamics in CHF

A. Overview Changes of B-adrenergic receptors B1-receptor down-regulation uncoupling of B1-adrenergic receptors increased activity of the inhibitory G protein(Gi) increased activity of G-protein receptor nase

Changes of -adrenergic receptors – 1-receptor down-regulation – uncoupling of 1-adrenergic receptors – increased activity of the inhibitory G￾protein(Gi) – increased activity of G-protein receptor kinase A. Overview

A. Overview 2. Grades of CHF I(A): no symptoms II B): physical activities were limited and symptoms could be induced by general activity I(C): physical activities were markedly limited TV(D): symptoms appear even at rest

A. Overview 2. Grades of CHF Ⅰ(A): no symptoms Ⅱ(B): physical activities were limited and symptoms could be induced by general activity Ⅲ(C): physical activities were markedly limited Ⅳ(D): symptoms appear even at rest

A Overview 3. Therapeutic strategies in CHF (1)Increasing contractility of the cardiac muscles Cardiac remodeling (2)Inhibiting RAAS (3) Decrease sympathetic activity (4)Dilating vessels ecrease rload (5)Diuresis

3. Therapeutic strategies in CHF (1) Increasing contractility of the cardiac muscles (2) Inhibiting RAAS (3) Decrease sympathetic activity (4) Dilating vessels (5) Diuresis A. Overview  Cardiac remodeling Decrease overload

art Failure Inotropes, digoxin Reduced cardiac output 阝 blockers, digoxin Sympathetic nervous s Renin n system activation Elevated cardiac filling pressures Vasodilators Angiotensin I Vasoconstriction ACE inhibitors Angiotensin II I Sodium and water retention ARBs Diuretics Aldosterone Spironolactone Mo Cardiac v Remodeling