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Pharmacological management of heart failure
Heart failure is caused by decreased cardiac output and increased sympathetic discharge. Drugs used to treat heart failure include diuretics to reduce preload, ACE inhibitors to reduce afterload, beta blockers to attenuate sympathetic activation, and digitalis for its inotropic effects. Newer drugs target vasodilation and myosin activation to further increase cardiac efficiency while reducing energy demands. Combination therapy following an assessment of cardiac function and volume status provides the best approach for management of heart failure.
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Introduction to pharmacological management of heart failure; basic definition of heart failure.
Detailed pathophysiology involving factors like FOC, COP, renal perfusion, and resulting cardiac remodeling.
Objectives for managing heart failure, including drug groups, mechanism of action, and strategies for treatment.
Major drug groups for chronic & acute heart failure, including diuretics, ACE inhibitors, and other agents.
List of drugs used, including diuretics and ACE inhibitors. Specifics on drug types and actions.
Detailed mechanism of action of Digoxin: effects on cardiac output, heart rate, and other systems.
Adverse effects of Digoxin toxicity and treatment; use of pacemakers and digitalis antibodies.
Use of phosphodiesterase inhibitors like Amrinone and Milrinone, their mechanism and effects.
Importance of diuretics, especially Furosemide, in managing heart failure-related symptoms.
The impact of spironolactone on mortality in heart failure patients along with its mechanisms.
Mechanism and benefits of ACE inhibitors in reducing afterload and preload in heart failure.
Similar hemodynamic benefits of Angiotensin receptor blockers compared to ACE inhibitors.
Utility of hydralazine and isosorbide dinitrate in heart failure treatment, especially when ACE-i cannot be used.
Specific beta blockers that have proven beneficial in heart failure management and their mechanisms.
Approach for assessing left ventricular function and managing fluid status in heart failure patients.
Treatment protocols for acute left ventricular failure with pulmonary edema; specific drug administration.
Introduction to newer drug classes like vasopeptidase inhibitors and their potential impacts.
Key strategies for managing heart failure, focusing on efficiency of various drug classes.
Citing the reference text for the pharmacological information provided throughout the presentation.
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Pharmacological management of heart failure
- 1. Pharmacological management of HeartFailure Dr Naser Ashraf Tadvi
- 2. What is heartfailure
- 3. Pathophysiology of heartfailure Heart failure ↓ FOC ↓ COP↑ Sympathetic discharge ↓ Renal perfusion •Vasoconstriction •β1 activation ↑ preload ↑ afterload ↑ FOC ↑ HR ↑ Renin release ↓ GFR Cardiac remodelling Ventricular dilation Back pressure Oedema Na & water retention (Oedema) ↑ AT-II ↑ AT-1 ↑ Aldosterone Initially ↑CO Later ↓ CO
- 4. Objectives • List majordrug groups used in treatment of heart failure • Explain mechanism of action of digitalis and its major effects • Explain the nature and mechanism of digitalis toxic effects • Describe the clinical implications of diuretics, vasodilators, ACE inhibitors and other drugs that lack positive inotropic effects in heart failure • Describe the strategies used in the treatment of heart failure
- 5. Major drug groupsused in heart failure Chronic Heart Failure • Diuretics • Aldosterone receptor antagonists • Angiotensin converting enzyme inhibitors • Angiotensin receptor blockers • Beta blockers • Cardiac glycosides • Vasodilators Acute Heart failure • Diuretics • Vasodilators • Oxygen • Morphine • Bipyridines • Beta receptor agonist: Dobutamine
- 6. Drugs used inheart failure • Diuretics: – Loop diuretic: Furosemide – Thiazide diuretic: Hydrochlorthiazide – Spironolactone: Potassium sparing diuretic and aldosterone antagonist • Angiotensin converting enzyme inhibitors – Enalapril, lisinopril, captopril • Angiotensin receptor blockers – Losartan, telmisartan
- 7. • Beta blockers –Bisoprolol, Carvedilol, Metoprolol, Nebivolol • Vasodilators – Hydralazine, Isosorbide dinitrate, Nesiritide • Drugs which increase cardiac contractility: (Ionotropic drugs) – Cardiac glycosides: Digoxin – Beta agonist: Dobutamine – Bipyridines (Phosphodiesterase inhibitors) : Milrinone Drugs used in heart failure
- 8. Mechanism of actionof Digoxin
- 9. CARDIAC • ↑force ofcontraction & Cardiac Output • Heart rate • ↑ Refractory period & conduction velocity in AV node • Increased automaticity • ECG: ↑PR interval , QT interval , Flattening or inversion of T wave EXTRA CARDIAC • Kidney: – Increased renal perfusion – Retained salt and water is gradually excreted • CNS: – Nausea, vomiting Major effects of digoxin (Pharmacological actions) Cardiotonic drugs Uses of Digoxin • Congestive heart failure • Atrial fibrillation • Atrial flutter • Paroxysmal atrial tachycardia
- 10. Digoxin adverse effects(Toxicity) • Visual changes:(Visual disturbance, disturbance in color vision, blurring, photophobia) • Gastrointesinal toxicity: anorexia, nausea, vomiting • Cardiac adverse effects: – Bradycardia – Extrasystoles – A-V Block – Paroxysmal atrial Tachycardia – Sino Atrial arrest – Ventricular tachycardia • Miscellaneous toxicity – Gynaecomastia, Skin Rashes Contraindication to digoxin therapy is digoxin toxicity
- 11. • Prompt insertionof a temporary cardiac pacemaker & administration of digitalis antibodies (digoxin immune fab) • These antibodies recognize cardiac glycosides from many plants in addition to digoxin. They are extremely useful in reversing severe intoxication with most glycosides • Oral or parenteral potassium supplements : – contraindicated in presence of hyperkalemia • For ventricular arrhythmias: – Lidocaine IV drug of choice • For supraventricular arrhythmia: – Propranolol may be given IV or orally • For AV block and bradycardia – Atropine 0.6 -1.2 mg IM Treatment of digoxin toxicity
- 12. • Amrinone &milrinone : selective phosphodiesterase III inhibitors • ↑ cAMP levels • The PDE III isoenzyme is specific for intracellular degradation of cAMP in heart, blood vessels and bronchial smooth muscles. • Inodilator action: Inotropic effect with vasodilation • IV administration for short term treatment of severe heart failure • Common adverse effect of amrinone is thrombocytopenia • Milrinone is more potent & doesn’t cause thrombocytopenia Phosphodiesterase inhibitors in heart failure
- 13. • Diuretics, especiallyfurosemide, are drugs of choice in heart failure • Almost all symptomatic Patients treated with a diuretic • High ceiling diuretics (loop diuretics) preferred – Low dose therapy for maintenance • They increase salt and water excretion & reduce blood volume – Reduce preload & venous pressure – Improve cardiac performance & relieve edema Role of diuretics in heart failure
- 14. Role of spironolactonein heart failure • Aldosterone antagonist & potassium sparing diuretic • ↓ mortality by 30% when added to in patients receiving ACE inhibitors and other standard therapy. • Possible mechanism for this benefit is prevention of aldosterone induced myocardial and vascular fibrosis and baroreceptor dysfunction in addition to its renal effects.
- 15. • ↓ peripheralresistance (↓ afterload) • ↓reduce salt and water retention by ↓ aldosterone secretion (↓ preload). • ↓ long-term remodeling of the heart and vessels an effect that may be responsible for the observed reduction in mortality and morbidity • Drug of first choice in left ventricular dysfunction without edema ACE Inhibitors in heart failure
- 16. • Losartan ,telmisartan • Block AT1 receptor on the heart, peripheral vasculature and kidney • Produce beneficial hemodynamic effects similar to those of ACE inhibitors. • large clinical trials suggest that angiotensin receptor blockers are best reserved for patients who cannot tolerate ACE inhibitors (usually because of cough) Angiotensin receptor blockers in heart failure
- 17. Role of vasodilatorsin heart failure • The combination of hydralazine and isosorbide dinitrate should be used if intolerant of ACE-i and ARBS as it reduces mortality. • It also reduces mortality when added to standard therapy.
- 18. Role of Betablockers in heart failure • Not all β blockers have proved useful, but bisoprolol, carvedilol, metoprolol, and nebivolol have been shown to reduce mortality. • The beneficial effect may be due attenuation (↓) of adverse effects of activated sympathetic drive • Useful even though they have negative inotrophic action
- 19. Approach to thePatient with Heart Failure Assessment of LV function (echocardiogram) EF < 40% Assessment of volume status Signs and symptoms of fluid retention No signs and symptoms of fluid retention Diuretic (titrate to euvolemic state) ACE Inhibitor b-blocker Digoxin
- 20. Management of acuteLVF with pulmonary edema • Semi-upright posture • Oxygen : 6-8 litres/min • Furosemide: 40-80 mg IV • Morphine • Aminophylline: if associated bronchospasm • Sublingual nitroglycerine • Digoxin IV in patients with Atrial fibrillation/SVT/ Heart failure • Continued management of heart failure /heart disease after resolution of acute heart failure
- 21. Newer drugs forheart failure • Vasopeptidase inhibitors: – Omapatrilat – Nesiritide • Omecamtiv mecarbil: selective cardiac myosin activator
- 22. Summary Reduce the numberof sacks on the wagon Limit the speed, thus saving energy Like the carrot placed in front Increase the efficiency Inotrops Vasodilators b blockers Diuretics, ACE inhibitors
- 23. KATZUNGS BASIC ANDCLINICAL PHARMACOLOGY 13TH EDITION references
Editor's Notes
- #3 Types: systolic heart failure: pump failure and diastolic heart failure (contractility) and reduced ejection fraction<40%. Causes IHD, mi, Cardiomyopathy The remaining group has diastolic failure: Inability of the ventricle to relax and fill normally causing ioncreased filling pressure, ejection fraction is >50%. Constrictive pericarditis, tamponade, restrictive cardiomyopathy,
- #6 Vasodilators used in AHF: ntg, nesiritide, nitroprusside.
- #10 Decrease heart rate due to Increased vagal tone Decreased sympathetic overactivity due improved circulation By direct action on SA and AV nodes Increases force of contraction and shortens the duration of systole allowing greater time for ventricular filling and rest, reduces diastolic heart size Systole is shortened, diastole is prolonged Ventricles more completely emptied due to forceful contractions
- #12 K contraindicated in presence of hyperkalemia K tends to antagonize digitalis induced enhanced automaticity and decreases binding of glycosides to sodium potassium ATPase by favouring a conformation of enzyme that has low affinity to digitalis Mild cases – 5 g daily in divided doses , infusion = 20 m.mol/hr
- #14 They have no direct effect on cardiac contractility; their major mechanism of action in heart failure is to reduce venous pressure and ventricular preload. The reduction of cardiac size, which leads to improved pump efficiency, is of major importance in systolic failure. In heart failure associated with hypertension, the reduction in blood pressure also reduces afterload.
- #16 Also ↓ sympathetic activity by ↓ angiotensin’s presynaptic effects on norepinephrine release.
- #17 IV sodium nitroprusside, and nitroglycerine are used fro severe heart failure