1. Heart Failure  Dfinition:  Clinical features  Underlying causes of HF include Arteriosclerotic heart disease, MI, hypertensive heart disease, valvular heart disease, dilated cardiomyopathy, and congenital heart disease.

4. Role of physiologic compensatory mechanisms in the progression of HF  1- Increased sympathetic activity: Baroreceptors sense a decrease in blood pressure and activate the sympathetic nervous system (increased heart rate and a greater force of contraction) and vasoconstriction enhances venous return and increases cardiac preload.  2- Activation of the renin-angiotensin system:  3-Myocardial hypertrophy.

6. Classes of heart failure:  Class I refers to no limitation of physical activity and no dyspnea or fatigue with ordinary physical activities.  Class II indicates mild limitation of physical activity and dyspnea or fatigue occurring with ordinary physical activities. The patient has no symptoms at rest.  Class III implies marked limitation of activity. Less than ordinary physical activities cause symptoms. The patient is asymptomatic at rest.  Class IV refers to symptoms at rest and with any physical exertion.

7. Decompensated HF  If the adaptive mechanisms adequately restore cardiac output, the HF is said to be compensated.

8.   Decrease after load: e.g. diuretics and vasodilators  Decrease preload: e.g. diuretics and venodilators  Decrease heart work: e.g. beta blockers and digoxin Therapeutic strategies in HF

9. ACEI and ARABs

10. β-BLOCKERS They improved systolic functioning and reverse cardiac remodeling. They decrease the heart rate and inhibiting the release of renin. Two β-blockers have been approved for use in HF, Carvedilol and long-acting metoprolol.

11.  Nitrates are commonly used as venodilators for patients with congestive HF.  Hydralazine is used as arteriodilator. DIRECT VASODILATORS

12. Diuretics Loop diuretics are the most commonly used diuretics in HF.

13. INOTROPIC DRUGS Positive inotropic agents enhance cardiac muscle contractility and, thus, increase cardiac output. They increase cytoplasmic calcium concentration that enhances the contractility of cardiac muscle. Digitalis glycosides: They have positive inotropic action. The digitalis glycosides have a low therapeutic index. The most widely used agent is digoxin

14. Mechanism of action  1- Inhibition of Na + /K + –adenosine triphosphatase

15. 2- Increased contractility of the cardiac muscle leads to reduced sympathetic activity, which then reduces peripheral resistance. 3- Vagal tone is also enhanced, so the heart rate decreases, and myocardial oxygen demand diminishes. 4- Digoxin slows down conduction velocity through the AV node, which accounts for its use in atrial fibrillation

16. Pharmacokinetics: Digoxin is very potent, with a narrow margin of safety and long half-life of around 36 hours. Digoxin is mainly eliminated intact by the kidney. Digitoxin has a much longer half-life and is extensively metabolized by the liver before excretion in feces Therapeutic uses: Digoxin’s major indication is HF with atrial fibrillation.

17. Adverse effects: a. Cardiac effects: The common cardiac side effect is arrhythmia, characterized by slowing of AV conduction associated with atrial arrhythmias. A decrease in intracellular potassium is the primary predisposing factor in these effects. b. GIT effects: Anorexia, nausea, and vomiting c. CNS effects: These include headache, fatigue, confusion, blurred vision, alteration of color perception, and halos on dark objects.

18. Factors predisposing to digoxin toxicity: a. Electrolytic disturbances: Hypokalemia Hypercalcemia and hypomagnesemia b. Drugs: Quinidine, verapamil, and amiodarone. Potassium-depleting diuretics, corticosteroids, c. Others: like Hypothyroidism, hypoxia, renal failure, and myocarditis

19. β-Adrenergic agonists They cause a positive inotropic effects and vasodilation. Dobutamine is the most commonly used inotropic agent other than digoxin. Dobutamine leads to an increase in intracellular cyclic adenosine monophosphate (cAMP), which results in the activation of protein kinase.

20. Phosphodiesterase inhibitors Inamrinone (formerly amrinone) and milrinone are phosphodiesterase inhibitors that increase the intracellular concentration of cAMP Both long-term Inamrinone and milrinone therapy may be associated with a substantial increase in the risk of mortality.

22. ALDOSTERONE ANTAGONISTS Patients with advanced heart disease have elevated levels of aldosterone due to angiotensin II stimulation and reduced hepatic clearance of the hormone. Spironolactone is a direct antagonist of aldosterone, thereby preventing salt retention, myocardial hypertrophy, and hypokalemia. Spironolactone therapy should be reserved for the most advanced cases of HF. Eplerenone reduces mortality in patients with left ventricular systolic dysfunction and HF after acute myocardial infarction