This document discusses various drug treatments for congestive heart failure. It describes how beta blockers, ACE inhibitors, angiotensin II inhibitors, vasodilators like nitrates, and other drugs work to impact factors like preload, contractility, cardiac output, and afterload. It outlines the mechanisms of action, hemodynamic effects, advantages, and potential undesirable side effects of different classes of heart failure drugs.

1. Drugs Used In the Treatment of Congestive Heart Failure(Cont)

3.  BLOCKERS AT 1 BLOCKERS

4. DETERMINANTS OF VENTRICULAR FUNCTION STROKE VOLUME PRELOAD CONTRACTILITY CARDIAC OUTPUT HEART RATE AFTERLOAD - Synergistic LV contraction - LV wall integrity - Valvular competence

9. Venous Vasodilatation MIXED  -adrenergic Blockers ACEI Angiotensin II inhibitors K + channel activators Nitroprusside VENOUS Nitrates Molsidomine ARTERIAL Minoxidil Hydralazin VASODILATORS CLASSIFICATION Arterial Vasodilatation

10. 1- VENOUS VASODILATATION Preload 2- Coronary vasodilatation Myocardial perfusion 3- Arterial vasodilatation Afterload 4- Others Pulmonary congestion Ventricular size Vent. Wall stress MVO 2 NITRATES HEMODYNAMIC EFFECTS • Cardiac output • Blood pressure

13. Placebo Enalapril 12 11 10 9 8 7 6 5 PROBABILITY OF DEATH MONTHS 0.1 0.8 0 0.2 0.3 0.7 0.4 0.5 0.6 p< 0.001 p< 0.002 CONSENSUS N Engl J Med 1987;316:1429 ACEI SURVIVAL 4 3 2 1 0

14. VASOCONSTRICTION VASODILATATION Kininogen Kallikrein Inactive Fragments Angiotensinogen Angiotensin I RENIN Kininase II Inhibitor ALDOSTERONE SYMPATHETIC VASOPRESSIN PROSTAGLANDINS tPA ANGIOTENSIN II BRADYKININ ACEI MECHANISM OF ACTION A.C.E.

15. ACEI HEMODYNAMIC EFFECTS Arteriovenous Vasodilatation - PCWP and LVEDP - SVR and BP - CO and exercise tolerance No change in HR / contractility MVO 2 Renal, coronary and cerebral flow Diuresis and natriuresis

17. ACEI UNDESIRABLE EFFECTS Inherent in their mechanism of action - Hypotension - Hyperkalemia - Angioneurotic edema Due to their chemical structure - Cutaneous eruptions - Neutropenia, thrombocytopenia - Digestive upset - Dry cough - Renal Insuff. - Dysgeusia - Proteinuria

18. ANGIOTENSIN II INHIBITORS MECHANISM OF ACTION RENIN Angiotensinogen Angiotensin I ANGIOTENSIN II ACE Other paths Vasoconstriction Proliferative Action Vasodilatation Antiproliferative Action AT1 AT2 AT1 RECEPTOR BLOCKERS RECEPTORS

19. AT1 RECEPTOR BLOCKERS DRUGS Losartan Valsartan Irbersartan Candesartan Competitive and selective blocking of AT1 receptors

20. 0.6 PROBABILITY OF DEATH 0 Placebo (273) Prazosin (183) Hz + ISDN (186) MONTHS 0.7 0.5 0.3 0.4 0.2 0.1 VHefT-1 N Engl J Med 1986;314:1547 NITRATES SURVIVAL 0 6 12 18 24 30 36 42

26. Inamrine&Mirinone

27. 3. Nesiritide:  natriuretic peptide a. New treatment for acute congestive heart failure and dyspnea at rest

33. ß-ADRENERGIC BLOCKERS INDICATIONS and UTILIZATION Not clearly established Begin with very low doses Slow augmentation of dose Slow withdrawal ?

34. ß-ADRENERGIC BLOCKERS POSSIBLE BENEFICIAL EFFECTS  Density of ß 1 receptors Inhibit cardiotoxicity of catecholamines  Neurohormonal  activation  HR Antihypertensive and antianginal Antiarrhythmic Antioxidant Antiproliferative

35. ALDOSTERONE Retention Na + Retention H 2 O Excretion K + Excretion Mg 2+ Collagen deposition Fibrosis - myocardium - vessels Spironolactone Edema Arrhythmias Competitive antagonist of the aldosterone receptor (myocardium, arterial walls, kidney) ALDOSTERONE INHIBITORS

36.  BLOCKERS AT 1 BLOCKERS