Drug acting on the Heart

1. Drug acting on the Heart Heart failure

2. Lecture objectives 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

3. 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

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

6. 70 ml 75 beat/min 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

7. 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

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

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

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

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

12. 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%

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

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

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

17. 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

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

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

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

21. 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

23. Side effects of ACE inhibitors • Angioedema • Hypotension • Renal insuffiency • Rash • cough

24. 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

25. 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

26. 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

27. 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

28. 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

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

30. 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

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