1. Pharmacotherapy of heart failure 台大藥理所 蘇銘嘉老師

2. Introduction Heart failure Etiology 1.Hypertension 2.Valvular disease 3.Congenital abnormalities 4.Ischemic cardiomyopathy Pathophysiological changes 1.Activation of RAAS A.Exercise intolerance B.Hypertrophy & Cardiac remodeling 2.Congestion of blood in venous system A.Pulmonary edema B.Reduced tissue perfusion C.Increase in end diastolic pressure

3. Introduction Heart failure Goals 1.Reduce symptom of dyspnea & fatigue 2.Arrest ventricular hypertrophy & remodeling 3.Increase survival Strategy 1.Reduce weight & Na + restriction 2.Drugs for reducing preload 3.Drugs for reducing afterload 4.Drugs preventing cellular hypertrophy A.Neurohormonal antagonists B.β-blockers 5.Inotropic agents (Nitroprusside 、 Diuretics) (Vasodilator 、 Diuretics) (ACEI & ARB) (Carvedilol 、 Bisoprolol 、 Metoprolol)

4. Inotropic agents Classification 1.Cardiac glycosides 2.Sympathomimetics A.Dopamine B.Dobutamine C.Other β-agonists 3.Phosphodiesterase inhibitor A.Amrinone (Type III PDE inhibitor) 4.Drugs increasing myofibrillar calcium sensitivity A.Sulmazole B.Pimobendan

5. Inotropic agents Cardiac glycosides 1.Mechanism of action A.Inhibition of Na + -K + -ATPase 2.Pharmacological action A.Increase cardiac output B.Reduce Na + reabsorption C.Sensitize baroreceptor reflex 3.Hemodynamic effects A.Cause immediate decrease of cardiac filling pressure B.Increase of cardiac output & LVEF C.Reduce plasma renin & noradrenaline

7. Inotropic agents Cardiac glycosides 1.Clinical implications A.Low LVEF (Systolic dysfunction) B.PSVT 、 AF 、 Af 2.Adverse effects A.GI discomfort 1)Nausea & Vomiting B.Neurologic complaints 1)Visual disturbance (Green or Yellow vision) 2)Confusion 、 Disorientation C.Others 1)VT 、 Vf 2)Gynecomastia

8. Inotropic agents Cardiac glycosides 1.Enhance toxicity of cardiac glycosides A.Hemodialysis (Increase K + & Mg 2+ loss) B.Increasing extracellular Ca 2+ C.Hypomagnesemia D.Thiazide & Furosemide 2.Reduce toxicity of cardiac glycosides A.Spironolactone

9. Inotropic agents Cardiac glycosides (Antidote) 1.K + salt 2.Cholestyramine 3.Lidocaine 、 Dilantin 4.Electric shock 5.Fab fragment of digoxin antibody

10. Inotropic agents Cardiac glycosides (Effects of digitalis on cardiac electrical functions) 1.Atrial muscle A. ↓ ERP B. ↑ Conduction velocity & automaticity 2.AV node A. ↑ ERP B. ↓ Conduction velocity C. ↑ Automaticity & PR interval 3.Purkinje fiber & Ventricles A. ↓ ERP (Less effect on conduction) B. ↑ Automaticity C. ↓ QT interval D. T wave inversion E. ST segment depression

11. Chronic heart failure Rational steps – Reduce workload & Sodium restriction Control body weight Control hypertension Reduce activity – Pharmacotherapy Give diuretic Give ACEI or β-blocker Give β-blockers or ACEI + Digitalis Give vasodilators – Hydralazine(Arteriole dilator) – Nitrates(Vein & Venules dilator) – ACEI & ARB(Arteriole & Vein dilator)

12. Acute heart failure Therapeutic strategy – Hypovolemia Give fluid to increase LV filling pressure up to 15 mmHg – Pulmonary congestion LV filling pressure > 20 mmHg Cardiac index > 2.5 L/min/m 2 Diuretics – Peripheral vasodilation Vasoactive drugs if BP is very low

13. Acute heart failure Therapeutic strategy – Power failure SBP < 100 mmHg Cardiac index < 2.5 L/min/m 2 LV filling pressure > 20 mmHg Vasodilator Inotropic agents – Severe shock SBP < 90 mmHg Cardiac index < 2 L/min/m 2 LV filling pressure > 20 mmHg Dopamine followed by Na nitroprusside Circulatory assist

14. Acute heart failure Therapeutic strategy – RV infarct Volume infusion Inotropic agent Avoid diuretics – Mitral regurgitation & Ventricular septal defect Vasodilator Inotropic drugs Circulatory assist Surgery