Drugs for heart failure

Drugs for heart failure

1. DRUGS for congestive Heart failure ( cHf / ccf )

2. Congestive Heart Failure State where the heart cannot maintain an adequate cardiac output to meet metabolic demands of the body Almost all form of heart disease can lead to heart failure

3. Congestive heart failure (CHF) is a chronic progressive condition that affects the pumping power of your heart muscles. You have  four heart chambers . The upper half of your heart has two atria, and the lower half of your heart has two ventricles. The ventricles pump blood to your body’s organs and tissues, and the atria receive blood from your body as it circulates back from the rest of your body. CHF develops when your ventricles can’t pump blood in sufficient volume to the body. Eventually, blood and other fluids can back up inside your: -lungs -abdomen -liver -lower body

4. New York Heart Association (NYHA) Classification Drugs for CHF contd. ...…… Class I No symptoms with ordinary physical activity Class II Symptoms with ordinary physical activity but comfortable at rest Class III Symptoms with less than ordinary physical activity but comfortable at rest Class IV Cannot carry on any physical activity without symptoms. Symptoms may be present even at rest. The symptoms increases with increase physical activity

5. Left, right & biventricular heart failure Drugs for CHF contd. ...…… Left Heart Failure Right Heart Failure Cardiomegaly Pulmonary oedema Raised JVP +/++ Pitting oedema +/++ Pleural effusions Raised JVP +++ Hepatomegaly Ascites Pitting oedema +++

6. Therapy of CHF Drugs for CHF contd. ...…… Correction of reversible cause Diet and activity Salt restriction extremes of temperature & heavy physical exertion should be avoided. Drugs that worsen CHF should be avoided (including NSAIDs) Other Drugs therapy

7. Drugs for CHF Drugs for CHF contd. ...…… Inotropic drugs: Digoxin , Dobutamine , Dopamine, Amrinone , Milrinone Diuretics: Furosemide , Bumetanide , Thiazides , Spironolactone ( Aldosterone antagonist) Vasodilators: ACE Inhibitors /ARB, Hydralazine , Prazosin , Sod. Nitroprusside , Nitrates β Blocker: Metoprolol , Bisoprolol , Carvedilol

8. CARDIAC GLYCOSIDES (Digitalis) Drugs for CHF contd. ...…… E.g. Digoxin , Digitoxin ↑ Force of contraction and CO without ↑ ing HR- Cardiotonic Chemistry Glycosides consists of aglycone ring attached with one or more sugar moites Source: Digitalis lanata

9. Digitalis Contd ……… Drugs for CHF contd. ...…… Effect in Heart: In failing heart; it ↑ force of contraction (Dose dependent ) → ↑ CO Slow AV conduction → bradycardia More complete emptying of failing and dilated ventricles SA node and A-V node automaticity is reduced at therapeutic concentration They increase myocardial contractility and output in a hypodynamic heart without a proportionate increase in O2 consumption

10. Digitalis Contd ……… Drugs for CHF contd. ...…… Mechanism of action: Increase intracellular Ca 2+ by blocking Na + - K + ATPase

11. Digitalis Contd ……… Drugs for CHF contd. ...…… Mechanism of action: Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ 3Na + 2K +

12. Mechanism Contd ……… Drugs for CHF contd. ...…… Ca 2+ Ca 2+ Ca 2+ Ca 2+ Ca 2+ 3Na + 2K + Digoxin 3Na +

13. Digitalis Contd ……… Drugs for CHF contd. ...…… Effect in Blood vessels: No prominent effect in BP so can be given in hypertensive patient Effect CNS: Little effect in therapeutic dose Higher dose- activate CTZ, hyperapnoea , central sympathetic stimulation, mental confusion , disorientation, visual disturbances

14. Digitalis Contd ……… Drugs for CHF contd. ...…… PHARMACOKINETICS: Digitoxin : more lipid soluble ; slow & long acting Digoxin : Fast and short acting than digitoxin Relatively polar (……….) Bioavailability differ from manufacture to manufacturer Food delay absorption Concentrate in heart, Skeletal muscle, kidney and liver : large volume of distribution (6-8 L/Kg) t1/2 in elderly people………..?

15. Digitalis Contd ……… Drugs for CHF contd. ...…… ADVERSE EFFECTS: Toxicity is high Margin of safety is low (therapeutic index 1.5-3) Extracardiac : Initially: Anorexia, nausea, vomiting, diarrhoea and abdominal pain Fatigue, malaise, headache, mental confusion, restlessness, hyperapnoea , disorientation, psychosis, visual disturbances Skin rashes and gynaecomastia rarely Cardiac: Bradycardia , A-V block, any type of arrhythmias

16. Digitalis Contd ……… Drugs for CHF contd. ...…… TREATMENT OF DIGITALIS TOXICITY: Stop digitalis on earliest sign of toxicity Pot. Chloride administration (if toxicity is due to chronic use/ use of diuretics ) which is guided by serum pot. measurement Treatment of arrhythmias (if required) Ventricular arrhythmias: Lignocaine i.v . Supraventricular arrhythmias: Propranolol (oral/ i.v .) A-V block & bradycardia : Atropine ( i.m .) Digoxin antibody- very effective Orphan drug. NOT used in our part

17. Digitalis Contd ……… Drugs for CHF contd. ...…… CONTRAINDICATIONS: Hypokalemia Elderly, renal or severe hepatic disease (pt. more sensitive) Hypothyroidism (low elimination, cumulation ) Ventricular tachycardia Partial A-V Block

18. Digitalis Contd ……… Drugs for CHF contd. ...…… Interactions: Loop diuretics Thiazide diuretics Corticosteroids Hypokalemia Amiodarone Verapamil Erythromycin Displace digitalis from protein binding site Enhance digitalis Cardiotoxicity Catecholamines Succinylcholine Cause arrhythmias Calcium

19. Digitalis Contd ……… Drugs for CHF contd. ...…… Interactions: Antacids Sucralfate Neomycin Decrease absorption of digoxin Enzyme inducers Phenytoin Phenobarbitone Increase metabolism of digoxin Decreased digitalis Effect

20. Digitalis Contd ……… Drugs for CHF contd. ...…… USES: 1. Congestive Heart Failure: Not commonly used because: a. Have low margin of safety b. Inable to reverse/ retard the disease progression Drug of choice in CHF patient: a) With dilated heart and low ejection fraction b) With atrial fibrillation c) Not controlled by other drugs (resistant case) Prescribe in dose that provides plasma concentration (0.8 -1.2ng/dl)- digitalization Stable clinical state for 2-3 months, withdrawal of digitalis therapy can be attempted

21. Digitalis Contd ……… Drugs for CHF contd. ...…… 2. Cardiac arrhythmias: Atrial fibrillation (AF) Atrial flutter ( AFl ) Paroxysmal supraventricular tachycardia (PSVT)

22. Atrial flutter  and  atrial fibrillation  are both  abnormal heart rhythms .  In atrial fibrillation, the atria beat irregularly. In atrial flutter, the atria beat regularly, but faster than usual and more often than the ventricles Dose: 0.125-0.25 mg PO/IV

23. DIURETICS Drugs for CHF contd. ...…… High ceiling diuretics are preferred, but thiazide / spironolactone can be added to overcome resistance Mechanism: ↑ Na + & water excretion →↓ ECF volume → ↓ p reload & improve ventricular efficacy Remove oedema and congestion i.v furosemide increase venous capacitance Give quick symptomatic relief but DONOT influence the disease process Intermittently used when required at low dose

24. Diuretics contd ………… Drugs for CHF contd. ...…… Spironolactone ( aldesterone antagonist) – decrease morbidity and mortality in patient with severe heart failure Spironolactone is used in low dose (12.5-25mg/day) as add on therapy with ACEIs Beneficial effect of spironolactone is slow Spironolactone is contraindicated in renal insufficiency patient & pt. with hyperkalemia

25. Drugs for CHF contd. ...…… ACE Inhibitors/ ARBs: Orally active medium efficacy mixed dilator Vein dilation: ↓venous return → ↓ ventricular end diastolic pressure & volume → reduce ventricle size → improve systole (Laplace law) Arteriolar dilation: ↓ afterload → weaker ventricular contraction can pump more blood ↓ aldosterone release Recommended for all grades of CHF especially for patient with left ventricular dysfunction but no edema Advantages with ACEI: Afford symptomatic relief Retard/ reverse ventricular hypertrophy, myocardial cell apoptosis and remodeling

26. Drugs for CHF contd. ...…… ROLE OF OTHER VASODILATORS: Nitrates: Venodilator Hydralazine , Minoxidil : Arteriolar dilators Prazosin , Nitroprusside : Mixed dilators Hydralazine preferred in renal insufficiency patient

27. Drugs for CHF contd. ...…… Sympathomimetic inotropic drugs: DOBUTAMINE: Selective β 1 agonist given i.v . NOT commonly used b/c of potential to produce angina or arrhythmias Preferred in acute HF accompaning MI, cardiac surgery

28. Drugs for CHF contd. ...…… Phosphodiesterase III inhibitors: AMRINONE ( Inamrinone ) Increase myocardial cAMP & influx of Ca 2+ Inodilator : (+ ve inotropic and vasodilator) Given i.v. - action within 5 min & last for 2-3 hours Adverse effects: Thrombocytopenia (dose related, transient & asymptomatic), nausea, diarrhoea , abdominal pain, liver damage, fever and arrhythmias Uses: Severe and refractory CHF (Short term i.v . use along with other drugs)

29. Drugs for CHF contd. ...…… MILRINONE: More selective, more potent and short acting than amrinone Thrombocytopenia – NOT significant Preferred over amrinone for short term use

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