1. Heart Failure

2. Introduction It is the inability of the heart to pump sufficient blood to meet body requirement. HF can be due to 1.Increased preload. 2.Increased after load. 3.Disease of the heart.

3. Treatment 1.General measures Rest Sedatives Frequent small meals Salt restriction. Cardiac rehabilitation program 2.Treatment of the cause Hypertension Diabetes Myocardial infarction etc.

4. Pharmacological therapy 1.Diuretics; furosemide 2.Aldosterone antagonist: Spironolactone 3.Angiotensin converting enzyme inhibitors/angiotensin II receptor blockers. 4.Positive inotropic agents e.g. cardiac glycosides, dopamine, dobutamine and PDE inhibitors. 5.Vasodilators. 6.Beta blockers.

5. 1. Diuretics Pharmacological effects: – Reduce preload – Reduce afterload – Relive symptoms of congestion. A.Thiazides: In mild heart failure. B.Furosemide: In moderate - severe heart failure.

6. A.Potassium sparing diuretics: Aldosterone antagonist; spironolactone Significantly reduce mortality and hospitalization in patients with heart failure. It has a weak diuretic effects, used mainly to: – Counteract hypokalemia caused by furosemide and thiazide diuretics – Treat secondary hyperaldosteronemia. – Attenuate remodeling that occurs in heart failure

7. 2. Beta Blockers Beta blockers are considered dangerous in acute heart failure. They are only used in chronic heart failure Metoprolol, bisoprolol, carvidolol are one shown to reduce the mortality

8. B-blockers 1.Reduce excessive sympathetic stimulation which cause Tachycardia, increase myocardial oxygen demand, Cardiac remodeling effects caused by catecholamines Increase renin release and angiotensin formation, and angiotensin II may have adverse effects on the heart. 2.Up-regulation of beta 1 receptors (in heart failure there is down-regulation of receptors due to over- activity of sympathetic nervous system )

9. 3. Positive inotropic drugs A. Cardiac glycosides They are obtained from dried leaves of the foxgloves. The most important cardiac glycosides is Digoxin Mechanism of action They increase intracelluar Ca in cardiac myocyte by inhibiting the Na + /K + pump. More Ca ++ accumulates in the cytoplasm during depolarization and the myocardium will contract forcefully. This is known as positive inotropic effect Increased cardiac output Increased blood flow to the body organs e.g. kidney

10. Negative chronotropic effect: The heart rate is slowed due A.Vagal stimulation B.Direct depressive effect on SA C.Decreased conduction velocity through AV node D.Decreased rate of cellular repolarization

11. Pharmacological Effects 1. Cardiovascular System Positive inotropic effect Increased cardiac output due to better filling of the heart and increases in the systolic force. Reduced heart rate ↑ automaticity E.C.G.: – Long P-R interval – Short Q.R.S. and short Q-T interval – Depressed S-T segment – Arrhythmia.

12. 2. Kidney: In congestive heart failure, digitalis produces diuresis due to: – Increase renal plasma flow and glomerular filtration rate. – Inhibition of tubular sodium reabsorption. – competitive antagonism with aldosterone. 3.GIT It causes nausea, vomiting anorexia and diarrhea.

13. 4. CNS CNS stimulation, excitability and convulsions. Yellow vision. Stimulation of the chemoreceptor trigger zone. Therapeutic Uses Chronic congestive heart failure associated with atrial fibrillation. Rate control in atrial fibrillation, atrial flutter

14. Contraindications 1.Allergy 2.Ventricular dysrhythmias (reduce conduction through AV node, aggravate arrhythmias) 3.Heart block, Sick sinus syndrome (negative chronotropic effect) 4.Acute myocardial infarction (increase myocardial oxygen demand) 5.Aortic stenosis (reduce COP)

15. 6.Electrolyte imbalances: Hypokalemia, Hypomagnesemia, hypercalcemia (increase risk of digoxin toxicity) 7.Renal failure (cause accumulation of drug) 8.drugs which inhibit A.V. conduction e.g. beta- blockers. 9.It is best avoided in patient likely to require cardioversion.

16. Dosage and Administration It is necessary to establish and maintain an adequate concentration of digitalis in the heart “Digitalization”: Digitalization can be achieved by one of the following schedules: A. Slow digtitalization “Cumulative method”: A maximum effect will be achieved in 4-5 half-lives (i.e. one week for digoxin). Digitalization a can be also started with 0.5 mg twice per day for two days or 0.5 mg 3 times per day for one day followed by the maintenance dose.

17. B. Rapid digitalization “ Rapid loading method”: In emergency initial large loading dose “ digitalizing dose”. It is given in 3 or 4 divided doses at 6 hours intervals. Followed by maintenance doses. The main indications for urgent digitalization are AF with rapid ventricular response and severe acute left ventricular failure.

18. Adverse effects of digoxin Headache, weakness, seizures and drowsiness Signs of digitalis toxicity:anorexia, nausea & vomiting, visual changes – yellow halo around objects, palpitations, arrhythmias or bradycardia Management Stop digoxin Correct hypokalaemia Antiarrhythmic drugs:, Lignocaine, Phenytoin, Beta- blockers in tachyarrhythmia Fab fragments of digitalis: specific antibodies it permits high renal clearance of digitalis complex.

19. B. Dopamine, Dobutamine: Dobutamine: Selective agonist at B1 receptor Dopamine: Low dose: activation of D1 receptor (causes vasodilatation of renal, mesenteric coronary arteries) Intermediate dose: activate D1 plus B1 and B2 (positive inotropic) High dose: activation of S1, B1, B2 plus Alpha 1 and D2 (increase heart rate, hypertension)

20. Therapeutic uses Cardiogenic shock Neurogenic and septic shock (renal dose) Adverse effects: Arrhythmias Angina Hypertension Peripheral vasospasm

21. C. Phosphodiesterase inhibitors Milrinone It increases myocardial contractility and reduction of peripheral resistance. Mechanism of action: Inhibitor phosphodiesterase enzyme III which lead to increase cAMP in cardiac tissues and smooth muscle. Increase intracellular Ca causes positive inotropic effect Decrease phosphorylation of myosin light chain in smooth muscle causes vasodilatation

22. Side effects Hypotension, syncope Thrombocytopenia Hepatic enzymes abnormalities. Cardiac arrhythmias Therapeutic uses They are used in acute heart failure or acute exacerbation of chronic heart failure in patient who are not respond to other drugs.

23. 4. Vasodilators Vasodilators are effective in heart failure because they provide a reduction in preload (venodilation), or reduction in after load (arteriolar dilation), or both. Arteriodilators are preferred in patients with primary symptoms of low cardiac out put Venodilators is preferred in patients with primary symptoms is pulmonary congestion

24. Choice of vasodilators ACEIs. the, best, if not tolerated the second choice is → ARBs. If contraindicated the choice is → Nitrates, the oral preparations for CHF, and I.V. nitroglycerine for acute pulmonary edema.

26. ACEIs and ARB ACEIs are cornerstone therapy of all stages of heart failure They improve survival and quality of life (superior to other vasodilators) Their efficacy is mainly due to: – Reduction of preload; by reducing aldosterone secretion – Reduction of afterload; by reducing angiotensin II Other harmful effects of angiotensin II – Cardiac hypertrophy and ventricular remodeling – Myocardial fibrosis – Norepinephrine release

27. Atrial natriuretic peptide Nesiritide A recombinant brain natriuretic peptide Mechanism of action: Activate guanyl cyclase and increase cGMP Causes dilatation of both arteries and veins and increase diuresis Adverse effects Hypotension Renal failure Therapeutic uses: IV in acute decompensated heart failure

28. Treatment of cardiogenic acute pulmonary edema Hospitalization. Cardiac bed (patient lying at 45 0 ) Oxygen and supportive ventilation if necessary Treatment of the cause e.g. rapid atrial fibrillation, rapid rise of blood pressure etc. Low salt diet Reduce preload: – Nitrates – Morphine sulphate – Diuretics: Furosemide 40-60 mg. I.V. – Ultrafiltration if the patient has renal dysfunction – Nesiritide

29. Afterload reduction – ACEIs – ARB – Nitroprusside Inotropic support is usually used when preload- and afterload-reduction strategies are not successful or when hypotension precludes the use of these strategies. – Phosphodiesterase inhibitors – Dopamine and dobutamine

30. Good luck