Pharmacotherapy of Heart Failure
DEFINITION
A pathophysiological condition where the heart
is incapable of maintaining a cardiac output
adequate to accommodate metabolic requirements and the venous return."
E. Braunwald
The principal goals of Treatment are; 1. Improve / prevent symptoms from worsening 2. To improve / maintain quality of life & to delay death.
3. Avoid side effects of treatment & decrease occurrence of major morbid events
Types of Heart Failure
Acute & Chronic heart failure Left & Right heart failure Systolic & Diastolic heart failure Low & High output failure
Symptoms & Signs of HF:
Fatigue (low cardiac out-put) Shortness of breath JVP Rales Edema Radiologic congestion Cardiomegaly
DIET Approach to the Patient With Heart Failure
Diagnose
Etiology Severity (LV dysfunction)
Educate
Diet Exercise Lifestyle CV Risk
Initiate
Diuretic/ACE inhibitor -blocker Spirololactone Digoxin
Titrate
Optimize ACE inhibitor Optimize diuretics
Drugs used for Tt of Heart Failure
Positive inotropic drugs Cardiac Gylcosides Digoxin, Digitoxin -Phosphodiesterase inhibitors: cAMP dependent --Milrinone, Inamrinone. ACE Inhibitors Enalapril, Lisinopril Angiotensin II Receptor Blockers (ARBs)- Losartan, Diuretics Frusemide, Spironolactone Vasodilators--Hydralazine, Sodium Nitropruside
Cardiac glycosides
Foxglove - Digitalis purpurea Extract called digitalis Long history as a folk remedy for congestive heart failure William Withering investigated this remedy from 17751785 - first scientific study of a medicinal plant
Currently available cardiac glycosides
Digoxin, digitoxin & ouabain
Digoxin is the most preferred
Digitalis purpurea
Mechanism of Action
Na-K ATPase
K+
Na-Ca Exchange
Na+
Ca++
Na+
Myofilaments
Ca++
CONTRACTILITY
DIGOXIN
Na-K ATPase
Na-Ca Exchange
Na+ Ca2+
K+
Na+ Na+
Ca2+
SR
Ca2+
Ca2+
Mechanism of Action
Inhibit Na-K ATPase, intracellular Na Ca through Na-Ca exchange which causes contraction of the myocardium.
Pharmacologic Actions
1. Increases Cardiac Output 2. Indirectly decreases sympathetic nervous system activity
Arteriolar dilation Venous dilation
3. Causes Vagal stimulation
Cardiac glycosides
As a positive inotropic drug, digitalis improves myocardial contractility
Useful in systolic heart failure
Still the drug of choice for patients with CHF and rapid atrial fibrillation
Electrophysiological Effects
Decrease conduction velocity Decreases action potential duration: decreases refractory period in ventricles
Enhances automaticity due to
Steeper phase 4 Afterdepolarizations
Parasympathomimetic Effects
Decreases conduction velocity in the AV node Increases effective refractory period in the AV node Causes Heart block (toxic concentrations)
Digitalis
Uses 1. Chronic Heart Failure 2. Atrial fibrillation
Overall Benefit of Digitalis to Myocardial Function cardiac output cardiac efficiency heart rate cardiac size
Digitalis Adverse Effects
Cardiac AV block Bradycardia Ventricular extrasystole Arrhythmias Extra-Cardiac GI Nausea, Vomiting, Anorexia CNS Disorientation, Hallucinations Misc - Gynecomastia
Serum Electrolytes & Digoxin
K+
Digitalis competes for K binding at Na/K ATPase Hypokalemia: increase toxicity Hyperkalemia: decrease toxicity
Mg2+
Hypomagnesemia: increases toxicity
Ca2+
Hypercalcemia: increases toxicity
Treatment of Digitalis Toxicity
Stop/Reduce digoxin dose: Atropine- Corrects heart block KClAntiarrythmics- ventricular arrhythmiasLignocaine or Phenytoin
Antidigoxin Immunotherapy -Fab antibodies-
Heart Failure Therapeutic Goal
Mild-Moderate Heart Failure Primary goal = Reduce mortality ACE inhibitors Diuretics Prevent progression to symptoms Prevent progressive LV dysfunction
Heart Failure Therapeutic Goal
Moderate-Severe Heart Failure Primary goal = Reduce symptoms Improve quality of life (QOL) Reduce hospitalizations Prevent sudden death