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Heart failure


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Heart failure

  1. 1. Drugs Used In the Treatment of Congestive heart failure Dr. Hiwa K. SaaedDr. Hiwa K. Saaed,, PhD PharmacologyPhD Pharmacology School of Pharmacy, University of SulaimaniSchool of Pharmacy, University of Sulaimani
  2. 2. Congestive Heart Failure (CHF) • Heart failure (HF) is a complex, progressive disorder in which the heart is unable to pump sufficient blood to meet the needs of the body. • Chronic CHF: the clinical condition in which an individual expels less than 40% of the blood from the left ventricle per heartbeat (ejection fraction [EF] 40%). • A normal individual expels about 55 to 65% of the blood from the left ventricle per heart- beat (EF 55–65%). • HF is due to an impaired ability of the heart to adequately fill (diastolic failure) with and/or eject blood (Systolic failure). • It is often accompanied by abnormal increases in blood volume and interstitial fluid, hence the term congestive HF.
  3. 3. • Can involve the heart: left side (usually), right side, or both side • Its cardinal symptoms are: Dyspnea, Fatigue, and Fluid retention. • symptoms include dyspnea from pulmonary congestion in left HF, and peripheral edema in right HF. • Underlying causes of HF include: – arteriosclerotic heart disease, – Myocardial Infarction, – hypertensive heart disease, – valvular heart disease, – dilated cardiomyopathy, – and congenital heart disease. Congestive Heart Failure (CHF)
  4. 4. The pathophysiology Reduce Cardiac output:  low renal perfusion   renin production   angiotensin  1- stimulation of aldosterne  Na+ and fluid retention  in venous return   in preload 2- peripheral vasoconstriction (  in after load and preload)  low carotid sinus flow   in the sympathetic activity to maintain ventricular contractility  tachycardia and in TPR.
  5. 5. In CHF, the impaired contractile function of the heart is exacerbated by compensatory increase in preload and afterload
  6. 6. Physiology of cardiac muscle contraction The myocardium, •like smooth and skeletal muscle, responds to stimulation by depolarization of the membrane. •However, the cardiac muscle cells are interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated. •unlike skeletal muscle, which shows graded contractions depending on the number of muscle cells that are stimulated,
  7. 7. Ion movements during the contraction of cardiac muscle. ATPase
  8. 8. Ion fluxes in cardiac cells
  9. 9. Therapeutic strategies in HF Chronic HF is typically managed by: • a reduction in physical activity, • fluid limitations (less than 1.5 to 2 L daily); • low dietary intake of sodium (<1500 mg/day), • treatment of comorbid conditions, and judicious use of: – diuretics, – inhibitors of the renin-angiotensin system, – and inotropic agents. Avoid Drugs that may precipitate or exacerbate HF, such as: • NSAIDs (nonsteroidal anti-inflammatory drugs), • alcohol, • Nondihydropyridine calcium-channel blockers, • some antiarrhythmic drugs, should be avoided if possible.
  10. 10. The therapeutic goal for CHF Increase cardiac output, relieve the symptoms of cardiac insufficiency, Slow disease progression, and improve survival do not reverse the underlying pathologic condition. 1.inhibitors of the renin-angiotensin system (RAS). 2.β-adrenoreceptor blockers. 3.diuretics; decease extracellular fluid volume, 4.inotropic agents; increase the strength of contraction of cardiac muscle vasodilators; reduce the load on the myocardium. 6.aldosterone antagonists
  11. 11. Angiotensin converting enzyme (ACE) inhibitors ex : captopril, lisinopril, enalapril ACE inhibitors decrease: 1. vascular resistance, 2. venous tone, 3. blood pressure, resulting in an increased cardiac output Adverse effects postural hypotension renal insufficiency persistent dry cough should not be used in pregnant women
  12. 12. Effects of (ACE) inhibitors.
  13. 13. Angiotensin receptor blockers (ARBs): Ex: losartan, valsartan, etc are nonpeptide, orally active compounds that are extremely potent competitive antagonists of the AT1 receptor. ARBs have the advantage of more complete blockade of angiotensin action, because ACE inhibitors inhibit only one enzyme responsible for the production of angiotensin II.
  14. 14. β-blockers Carvedilol, metoprolol and bisprolol • The benefit of β-blockers is attributed, in part, to their ability to prevent the changes that occur because of the chronic activation of the sympathetic nervous system, including decreasing the heart rate and inhibiting the release of renin. • In addition, β -blockers also prevent the direct deleterious effects of norepinephrine on the cardiac muscle fibers, decreasing remodeling, hypertrophy and cell death.
  15. 15. Diuretics bumetanide, furosemide, hydrochlorothiazide Thiazide diuretics are relatively mild diuretics and lose efficacy if patient creatinine clearance is less than 50 ml/min. Loop diuretics are used in patients with renal insufficiency Diuretics: •relieve pulmonary congestion and peripheral edema •useful in reducing the symptoms of volume overload including orthopnea and nocturnal dyspnea •↓ plasma volume: ↓preload→↓ cardiac work & O2 demand • ↓aftereload→ ↓ BP
  16. 16. Direct vasodilators Vasodilators are useful in reducing excessive preload and afterload as follow • venodilator→↓preload • arterial dilators →↓afterload • Nitrates are commonly employed venodilator in CHF • CCBs should be avoided
  17. 17. Inotropic agents • positive inotropic agents • enhance cardiac muscle contractility • increase cardiac output • although these drugs act by different mechanisms ,in each case the inotropic action is the result of an increased cytoplasmic calcium concentration that enhances the contractility of the cardiac muscle
  18. 18. Cardiac glycosides (Digitalis: foxglove) digoxin & digitoxin digoxin (lanoxin) is the most widely used agent Mechanism of action: Inhibit Na-K-ATPase
  19. 19. Therapeutic uses • digoxin is indicated in patients with severe left ventricular systolic dysfunction after initiation of diuretic and vasodilation therapy • NOT indicated in patient with diastolic or right sided heart failure • patients with mild to moderate heart failure will often respond to treatment with ACE inhibitors and diuretics and do not require digoxin N.B. The digitalis glycosides have low therapeutic index
  20. 20. Adverse effects • Cardiac effects: is arrhythmia (common), characterized by slowing of AV conduction associated with atrial arrhythmias. hypokalemia is the primary predisposing factor in these effects. Caused by thiazide or loop diuretics and prevented by use of a K sparing diuretics or supplementation with KCl • GIT effects: Anorexia, nausea, and vomiting. • CNS effects: headache, fatigue, confusion, blurred vision, alteration of color perception, and halos on dark objects.
  21. 21. Factors predisposing to digitalis toxicity a) Electrolytic disturbances – hypokalemia can preciptate serious arrhythmia – hypercalcemia and hypomagnesemia also predispose to digitalis toxicity. B) drugs: – Quinidine, verapamil, amiodarone: displacing digoxin from protein binding and by competing with digoxin for renal excretion – Erythromycin and tetracycline – Thiazide and loop diuretics C) Disease: hypothyroidism, hypoxia, renal failure, myocarditis
  22. 22. Another inotropic agent: β1-AGONISTS • ex : dobutamine →↑cAMP→ activation of protein kinase → slow Ca+2 channel phosphorylation → Ca+2 entry → enhancing contraction • improves cardiac performance by both positive inotropic effects and vasodilation • must be given by I.V. infusion and is primarily used in the treatment of acute heart failure in hospital setting
  23. 23. Phosphodiesterase inhibitors: Inamrinone and milrenone →↑cAMP → ↑ intracellular Ca+2 → contraction
  24. 24. Spirolactone (Aldosterone antagonists) Patients with advanced heart disease have elevated levels of aldosterone due to: – angiotensin II stimulation – reduced hepatic clearance of the hormone. Adverse effects include •gastric disturbances, such as gastritis and peptic ulcer •CNS effects, such as lethargy and confusion •endocrine abnormalities, such as – gynecomastia, – decreased libido, – menstrual irregularities.
  25. 25. Ventricular function curves in the normal heart, in heart failure (HF), and in HF treated with digitalis.
  26. 26. Treatment options for various stages of heart failure. Stage D (refractory symptoms requiring special interventions) is not shown.