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Published on July 1, 2009

Author: prakashmathewbio


TREATMENT FOR CONGESTIVE HEART FAILURE : TREATMENT FOR CONGESTIVE HEART FAILURE By MOHD SHAKEEL,B.Pharm Asst. CRA ALTREE LABS What is CCF? : What is CCF? A state in which the heart cannot provide sufficient cardiac output to satisfy the metabolic needs of the body. Causes: Coronary artery disease Hypertension Valvular heart disease Cardiomyopathy Cor pulmonale TREATMENT : TREATMENT The treatment of heart failure depends on several factors, such as: Its causes Its severity The patient’s health condition Mode of treatments : Mode of treatments Pharmacotherapy Surgery Life style modifications Pharmacotherapy of CCF : Pharmacotherapy of CCF Cardiac glycosides: Digoxin, Digitoxin, Deslanoside Vasodilators: ACE inhibitors: Captopril, Enalapril, Lisinopril, Benazipril, Ramipril. Angoitensin receptor blockers : Candesartan, Losartan,Valsartan Hydralazine and Isosorbide dinitrate Beta blockers : Carvedilol, Metoprolol, Bisoprolol. Diuretics: Benzothiazides, HCL diuretics, Potassium sparing diuretics, Osmotic diuretics APPROACH TO THE PATIENT WITH HEART FAILURE : APPROACH TO THE PATIENT WITH HEART FAILURE Assessment of LV function(echocardiography, MRI) EF < 40% Assessment ofvolume status Signs and symptoms of fluid retention No signs and symptoms offluid retention Diuretic ACE Inhibitor b-blocker Digoxin CARDIAC GLYCOSIDES : CARDIAC GLYCOSIDES Digoxin: increase force of cardiac contraction. MOA: Inhibits Na-K-ATPase enzyme. Indirectly accumulates Ca2+. Reduce the sympathetic out flow from the CNS. Reduce the heart rate and relief the symptom. Indications: LV dysfunction, atrial fibrillation Slide 9: PK: Lipid soluble, polar. Presence of food delays absorption. Volume of distribution is larger. Metabolised in liver. Primarily excreted unchanged by glomerular filtration. Therapeutic index: 1.5-3 Dose Oral: 0.0625mg,0.125mg,and 0.25mg Parentral: 0.25mg/ml Oral dose effective with in 35-45minutes Digitilizing dose, effect with in 35-45 minutes last for 2-6days Adverse effects : Adverse effects Cardiac : AV block ,Bradycardia ,Ventricular extrasystole , Arrhythmias Central Nervous System Gastro Intestinal . Contra indications: Hypokalemia, MI, Myxoedema, Ventricular tachycardia Interactions: Diuretics, Calcium, Adrenergic drugs Uses: CCF, Cardiac arrhythmias Brands available: Digitran Tab, Digox Tab, Digoxin Inj, Lanoxin Tab Only symptomatic relief, no survival benefit. Vasodilators : Vasodilators Venodialators: Isosorbide dinitrate, GTN Arteriolar dialators: Hydralazine, Nifedipine Mixed dialators: ACE inhibitors, ARBs Slide 12: MECHANISM OF ACTION Venodilators : Reduction of preload By venous dilation ? ? the venous return ?? the load on both ventricles. Arteriolar dilators: Reduction of after load by arteriolar vasodilatation ? reduce LVEDP, O2 consumption, improve myocardial perfusion. Usually the maximum benefit is achieved by using agents with both action. ACE Inhibitors : ACE Inhibitors Captopril, enalapril, lisinopril, benazepril, ramipril, fosinopril, etc. Mechanism of action of captopril Inhibits pressor action of A-I Blocks formation of A-II Block kinase-II decrease degradation of kinin prolong the effect of kinin (vasodilator) Slide 14: Pharmaco Kinetics: 70% orally. Presence of food decrease absorption. Poor BBB penetration. Partly metabolized and excreted unchanged in urine. Plasma t½ ~2hrs, action lasts for 6-12hrs. Adverse Effects: Hypotension, Cough, Hyperkalaemia, Fetal damage, Angioedemia, Rashes, Dysguesia, Acute renal failure. Interactions: NSAIDS, K+ sparing diuretics, Antacids. Uses: HTN, CHF, MI Brands available: Acezide Tab (captopril+hydrochlorothiazide), Aceten tab(wockhardt), Capotril Tab(lupin), Capotril-H Tab. Angiotensin Antagonists / ARBs : Angiotensin Antagonists / ARBs Losartan, candesartan, irbesartan, valsartan, telmisartan, etc. For patients who are unable to tolerate the ACE inhibitors (angioneurotic edema, cough). Act on the same hormonal pathway as the ACE inhibitors, but Block the action of angiotensin II at its receptor site directly.  Brands available: Adpace 4 Tab(sun), candesar Tab(rbxy), diovan cap(novartis), valent cap(lupin) {ramipril+losartan}, acord l tab(intra){amlodipine+losartan} ß – ADRENERGIC BLOCKERS : ß – ADRENERGIC BLOCKERS Carvedilol, Metoprolol,Bisoprolol, Bucindolol Mechanism of action: Reduction in damaging sympathetic influences in the heart (tachycardia, arrhythmias, LVEDP, remodeling, necrosis/apoptosis) inhibition of renin release Beta blockers improve EF peripheral vasodilatation via a1-adrenoceptor blockade (carvedilol) Slide 17: 3.125 mg bid 2 weeks Doubled every2 weeks Max dose 25 mg bid (<85 kg); 50 mg bid (>85 kg) Dosage guideline for Carvedilol Metoprolol: 12.5 to 50mg BD Bisoprolol : 2.5-10mg OD Bucindolol: 12.5-50mg BD The dose is increased every 2-4 weeks till a target dose is achieved Uses: CHF, HTN, Angina pectoris, cardiac arrhythmias, MI Slide 18: Brands available: Carvedilol Carca tab (intas), Cardivas tab( sun), Carloc tab(cipla) Metoprolol Betaloc H tab {hydrochlorothiazide+metoprolol(AZ)}, Betaone-xl tab, Ramic forte tab {metoprolol+ramipril} Bisoprolol lodoz tab{bisoprolol fumarate + hydrochlorothiazide} DIURETICS : DIURETICS Drugs used : Furosemide, Hydrochlorothiazide, Spironolactone, Triamterene Amiloride Indication: Prescribed for patients who have fluid retention Eliminate sign and symptoms of fluid retention Produce symptomatic relief more rapidly Mechanism of action: Block the reabsorption of Na+, K+, Cl- from glomerular filtrate at proximal tubule and ascending loop of Henle Spironolactone binds with with aldosterone lowering the blood pressure. Reduction of facilitation of sympathetic nervous system Slide 20: Dose: Therapy is initiated with a low dose of 20-40mg/day The dose is increased till signs and symptoms of patient is reduced Oral dose: 20-120mg/day, the action starts with in 2 hours and may last for 6-8hrs or more Acute pulmonary edema slow iv 4mg/min to a dose of 40 mg Slide 21: Brands Avilable: Amiloride+furosemide amifru tab(elder), amimide tab(gsk) amilochlor tab (finecure) {Amiloride hydrochloride+ hydrochlorothiazide}, Amiloride hydrochloride + atenolol + hydrochlorothiazide beta-biduret cap(gsk), benzthiazide + triamterene ditide tab(gsk) furosemide + triamterene furosemene tab SURGERY : SURGERY The Final Option Valve surgery Angioplasty Heart transplantation Implantation of artificial heart Life style Modifications : Life style Modifications Treatment should be started immediately Sodium intake should be reduced (2gm per day) Fluid consumption should be reduced (2 to 3 glass per day) Should take Diuretics Mild exercises CURRENT TRIALS : CURRENT TRIALS Effects of Exenatide in Type 2 Diabetic Patients With Congestive Heart Failure Phase IV This study is currently recruiting participants. Primary Outcome Measures:Cardiac Magnetic Resonance (CMR) will be used to assess global cardiac function (LV ejection fraction). VU University Medical Center, Amsterdam, Noord-Holland, Netherlands Eli Lilly and Company  Exenatide: ExperimentalDrug: exenatideExenatide 5 mcg BID for 4 weeks, subsequently increased to 10 mcg BID for the remainder of the study (total of 26 weeks). Estimated Enrollment:42. Study Start Date:May 2009. Estimated Study Completion Date:June 2011. Estimated Primary Completion Date:June 2011. Comparison of Long- and Short-Acting Diuretics in Congestive Heart Failure (J-MELODIC) : Comparison of Long- and Short-Acting Diuretics in Congestive Heart Failure (J-MELODIC) This study is ongoing, but not recruiting participants. Efficacy study. Hyogo College of Medicine, The Hospital of Hyogo College of MedicineNishinomiya, Hyogo, Japan,  Ministry of Health, Labour and Welfare Estimated Enrollment:300. Study Start Date:June 2006. Estimated Study Completion Date:August 2010. Estimated Primary Completion Date:August 2010. Drug: Furosemide, Azosemide Slide 26: Correlation of Intrathoracic Impedance Measures With Blood Plasma Volume in Congestive Heart Failure (Optivol) Observational This study is currently recruiting participants.  Blood Volume Analysis, Echocardiogram Estimated Enrollment:10. Study Start Date:January 2007. Estimated Study Completion Date:June 2009. Medical University of South Carolina United States, South Carolina Medical University of South Carolina Recruiting Charleston, South Carolina, United States Slide 27: Effect of Vildagliptin on Left Ventricular Function in Patients With Type 2 Diabetes and Congestive Heart Failure Phase IV This study is not yet open for participant recruitment. Estimated Enrollment:490. Study Start Date: May 2009. Estimated Primary Completion Date:May 2011. Primary Outcome Measures:To evaluate the effect of vildagliptin on left ventricular function in patients with T2DM and CHF by showing that vildagliptin is at least not inferior to placebo with respect to change in left ventricular ejection fraction (LVEF). Novartis Pharmaceuticals Questions ??? : Questions ???

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