Drug acting on the Heart Heart failure

Lecture objectives Describe basic anatomy of the heart. At the end of the this lecture, the student will able to: Describe basic anatomy of the heart. List determinants factor of cardiac out put. Describe main approach to the treatment of heart failure. List the names of drug used to treat heart failure and hypertension

A state in which the heart cannot provide sufficient cardiac output to satisfy the metabolic needs of the body. It is commonly termed congestive heart failure (CHF) since symptoms of increase venous pressure are often prominent

Cardiac Physiology (remember this?) CO = SV x HR HR: parasympathetic and sympathetic tone SV: preload, afterload, contractility

Cardiac Output Volume of blood ejected per minute Averages between 4-6L/min CO = Stroke volume X heart rate =70 ml X 60 beats/min =4,200 ml/min 70 75 beat/min ml

Preload Degree of stretch of myocardial fibers Determined by the volume of blood in left ventricle (LV) at end of diastole Increased volume –> increased preload-> increased cardiac output (CO) Decreased volume –> decreased preload –> decreased cardiac output (CO) Compliance of myocardial cells also affects preload

Factors on Cardiac Output More in More out Factors on Cardiac Output   Preload:  Preload   cardiac output (Starling-Frank Mechanism)

Factors Which Increase Preload IV fluids Blood Vasoconstriction Factors Which Decrease Preload Diuretics Dehydration Hemorrhage Vasodilation

Factors on Cardiac Output Afterload   Preload: 2) Afterload:    afterload   CO R

Afterload Related to arterial pressure or diameter of arteries As pressure increases, resistance increases, afterload increases As pressure decreases, resistance decreases, afterload decreases

Contractility Force generated by the myocardium when it contracts – inotropic property Ejection fraction (EF) - percentage of LV end-diastolic volume that is ejected with each contraction EF - normally approximately 50-55%

Factors on Cardiac Output   Preload: 2) Afterload:   3) Contractility:  contractility   CO

Left versus Right Failure Left Heart Failure - Dyspnea - Dec. exercise tolerance - Cough - Orthopnea - Pink, frothy sputum Right Heart Failure - Dec. exercise tolerance - Edema - JVD - Hepatomegaly - Ascites

Five main drugs are used Diuretics ACE inhibitors Positive isotropic drugs Vasodilator ß blockers

1) Diuretics Drugs that accelerate the rate of urine formation. Result: removal of sodium and water They relive distention of the heart by reducing blood volume

Side Effects Pre-renal azotemia Skin rashes Neutropenia Thrombocytopenia Hyperglycemia ↑ Uric Acid Hepatic dysfunction

More severe heart failure → loop diuretics Lasix (20 – 320 mg QD), Furosemide Bumex (Bumetanide 1-8mg) Torsemide (20-200mg)

2) Inhibitors of renin-angiotensin- aldosterone system Renin-angiotensin-aldosterone system is activation early in the course of heart failure and plays an important role in the progression of the syndrome Angiotensin converting enzyme inhibitors Angiotensin receptors blockers Spironolactone

Angiotensin Converting Enzyme Inhibitors They block the R-A-A system by inhibiting the conversion of angiotensin I to angiotensin II → vasodilation and ↓ Na retention

Side effects of ACE inhibitors Angioedema Hypotension Renal insuffiency Rash cough

3)Digitalis Glycosides (Digoxin, Digitoxin) The role of digitalis has declined somewhat because of safety concern Recent studies have shown that digitals does not affect mortality in CHF patients but causes significant Reduction in hospitalization Reduction in symptoms of HF

Digitalis (cont.) Mechanism of Action +ve inotropic effect by ↑ intracellular Ca & enhancing actin-myosin cross bride formation (binds to the Na-K ATPase → inhibits Na pump → ↑ intracellular Na → ↑ Na-Ca exchange Arrhythmogenic effect

Digitalis Toxicity Narrow therapeutic to toxic ratio Non and cardiac manifestations Anorexia, Nausea, vomiting, Headache, Disorientation Sinus bradycardia and arrest A/V block (usually 2nd degree) Atrial tachycardia with A/V Block Development of junctional rhythm in patients with a fib

4) β Blockers Has been traditionally contraindicated in pts with CHF Now they are the main stay in treatment on CHF & may be the only medication that shows substantial improvement in LV function In addition to improved LV function multiple studies show improved survival

Subdivisions of ANS Parasympathetic – acetylcholine produces inhibitory response Sympathetic – catecholamines stimulate Increase heart rate – Beta 1 receptors Dilate smooth muscles – Beta 2 receptors Vasoconstrict vessels – Alpha receptors

5) Vasodilators Reduction of afterload by arteriolar vasodilatation (hydralazin)  reduce LVEDP, O2 consumption,improve myocardial perfusion,  stroke volume and COP Reduction of preload By venous dilation ( Nitrate)  ↓ the venous return ↓ the load on both ventricles. Usually the maximum benefit is achieved by using agents with both action.

Positive inotropic agents These are the drugs that improve myocardial contractility (β adrenergic agonists, dopaminergic agents, phosphodiesterase inhibitors), dopamine, dobutamine, milrinone, amrinone Several studies showed ↑ mortality with oral inotropic agents So the only use for them now is in acute sittings as cardiogenic shock

thank you for listening Home work? Write the nursing implication to the drug that treat HF? Write two examples to each group of medication? thank you for listening