2. Heart failure Results from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood to meet the body, s needs at rest or during exercise.

3. Low out put failure

4. Factors affecting cardiac output Intrinsic factors which regulate myocardial contractility. Extrinsic factors including contractile state of arterioles & veins.

5. Pathophysiology of cardiac performance in heart failure - Intrinsic changes. - Extrinsic changes. Intrinsic changes: Myocardial hypertrophy to maintain cardiac performance in the face of adverse effects as decrease in myocardial contractility.

6. Continue Extrinsic changes: Decrease in cardiac output  renal blood flow  renin release,  angiotensin 11   in after load, preload,sympathetic discharge  cardiac output Remodeling: Proliferation of connective tissue cells, abnormal myocardial cells.

8. Clinical manifestations of heart failure Tachycardia, decreased exercise tolerance with rapid muscular fatigue, dyspnea ( pulmonary congestion) peripheral edema, cardiomegaly.

9. Classification of Low out put Failure Left Heart Failure :Most common due to L.V.S. Dysfunction Right Heart Failure : In Pulmonary hypertension

10. Classification of Heart Failure According to NYHA Class 1: No limitations on ordinary activities and symptoms occur only with greater than ordinary exercise. Class11: Slight limitation of ordinary activities, that result in fatigue & palpitation

11. Continue Class 111: No symptoms at rest, fatigue occur with less than ordinary physical activity Class 1V : Is associated with symptoms even at rest

12. High output failure Even though there is an increase in cardiac output; still not enough to meet all the body needs as in hyperthyroidism, anemia.

13. Drugs used in treatment of heart failure Drugs with positive inotropic effect as : Cardiac glycosides Phosphodiesterase inhibitors β- adrenoceptor agonist

14. Drugs without positive inotropic effect Diuretics Aldosterone antagonist ACEI & Angiotensin receptor blockers Vasodilators β- adrenoceptor blockers

15. Vasodilators The chose of vasodilators according to signs and symptoms and hemodynamic changes : Selective venodilators as nitrate group is used when the main symptoms is dyspnea due to pulmonary congestion. Selective arteriodilators as hydralazine is used when the main complain is rapid fatigue due to low cardiac output. Non-selective vasodilators as ACEI

16. Clinical uses of vasodilators 1. Acute heart failure 2. Chronic heart failure Long-term use of hydralazine & isosorbide dinitrate can reduce remodeling of heart

17. ACEI & Angiotensin11 receptor blockers  afterload  preload  sympathetic activity  remodeling  mortality rate

18. β-adrenoceptor blockers Antagonism the enhancing action of sympathetic overactivity. Reduce mortality ( reduce the remodeling changes through inhibition the mitogenic activity of catecholamines. Inhibit renin release Some of them have antioxident activity E.g. carvedilol & metoprolol

19. Diuretics Reduce salt and water retention  ventricular preload. Reduction of edema and its symptoms Reduction of cardiac size  improve cardiac performance Spironolactone has two benefits:potassium sparing effect & inhibit the action of aldosterone.

20. β-agonist Dopamine :acts on α,β 1 and dopamine receptors. Dobutamine :selective β 1 - agonist.  Both of them are given intravenously & used in acute cardiac emergencies.  Dopamine is effective in patients with impaired renal function.

21. Adverse effects Tachycardia Angina Tachyphylaxis

22. Phosphodiesterase inhibitors Bipyridines : (Amrinone,Milrinone ) They are given only intravenously. Half-life 3-6hrs. 10-40% excreted in urine.

23. Mechanism of action Inhibit phosphodiesterase enzyme (isozyme 3) in both cardiac & smooth muscles resulting an ↑ in cAMP leading to: - Positive inotropism. - Dilation in both resistance & capacitance vessels (reduction in after load & preload.)

24. Therapeutic uses Used only for acute heart failure ( Short term use )

25. Adverse effects Nausea,vomiting Arrhythmias (less than digitalis ) Thrombocytopenia Liver toxicity Milrinone less hepatotoxic and less bone marrow depression than amrinone.

26. Digitalis (cardiac glycosides ) Origin Chemistry Preparations

27. Structure o of cardiac glycoside

28. Pharmacokinetics Oral availability Ouabain Digoxin Digitoxin 0 75 > 90 Half- life 21 40 168 Plasma protein binding 0 20-40 > 90 Percentage metabolized 0 80

29. Pharmacodynamics At the molecular level cardiac glycosides inhibit Na + / K + ATP ase (sodium pump ). Cardiac effects : A) Mechanical B) Electrical

30. Mechanism of action

31. (A) MECHANICAL EFFECT Increase in myocardial contractility

32. (B) ELECTRICAL EFFECTS

33. At Therapeutic Doses A)  Slow conduction through S.A.N. & A.V.N.  prolong conduction time between atrium and ventricles ( prolong P-R interval in ECG.). B)  Short duration of action potential & refractory periods of both atrium & ventricles (Short in QT interval ).

34. At Toxic Doses  in automaticity of ectopic focus  All forms of arrhythmias can be detected : - - Second-degree of A-V block. - In Purkinje conducting system leading bigeminy rhythm.

35. Extra cardiac effects GIT :Anorexia, nausea,vomiting, diarrhea. C.N.S. :Disorientation,hallucination,visual disturbances, agitation, convulsions. Gynecomastia Kidney : Diuretic effect I. Improve renal function. II. Inhibit Na + reabsorption from P.C.T.

36. Adverse effects Heart All forms of cardiac arrhythmias GIT C.N.S. Skin : rash Gynecomastia

37. Contraindications Toxic myocarditis Constrictive pericarditis Cardioversion Digitalis are effective in H.F. due to hypertension, atherosclerosis or ischemic heart diseases.

38. Factors increase digitalis toxicity Small Lean body mass Renal disease Hypothyroidism Hypokalemia Hypomagnesemia Hypercalemia

39. Treatment of digitalis toxicity Stop drug Potassium therapy Cholestyramine Atropine Lidocaine Fab antibodies in life-threating or severe cases.

40. Clinical uses Heart failure ( LVSD) 2-Atrial flutter or fibrillation

41. Drug interactions Diuretics  hypokalemia (arrhythmia) Quinidine :  plasma level of digitalis through (1) displaces from protein binding sites (2)  renal clearance. Antibiotics that alter intestinal flora  digoxin bioavailability Agents that release catecholamines sensitize myocardium to digitalis to induce arrhythmias.

42. Management of chronic heart failure Reduce work load of the heart Limit activity Reduce weight Control hypertension Restrict sodium Diuretics ACEI or receptor blockers

43. Cont. Digitalis β- blockers ( class II-IV stable HF) Vasodilators

44. Management of acute heart failure Volume replacement Diuretics Positive inotropic drugs Vasodilators