Drugs for treating heart failure

1. Drugs for treating heart failure

2. A. Introduction • Heart failure (HF) is due to the inability of the ventricles to pump sufficient blood thru-out the body.

3. There are a number of causes of heart failure:

4. diabetes

5. from:http://www.nhlbi.nih.gov/health/dci/images/heart_coronary_artery.giffrom:http://www.nhlbi.nih.gov/health/dci/images/heart_coronary_artery.gif • coronary artery disease

6. chronic HT

7. MI

8. mitral stenosis (inability of mitral valve to open fully)

9. The incidence of heart failure increases with increasing age.

10. About 20% of patients diagnosed with heart failure die within 1 year of diagnosis, about 50% die within 5 years.

11. There is NO cure for heart failure. Treatment goals involve treating/removing the underlying causes in order to improve the quality of life and/or extend life expectancy.

12. B. Pathophysiology of heart failure • Two important factors which affect cardiac output, and therefore affect how heart failure is treated, are preload and afterload

13. 1. Preload • Immediately before the chambers of the heart contract they are filled to their maximum capacity with blood.

14. The degree to which heart fibers are stretched prior to contraction is known as preload.

15. The more these fibers are stretched, the more forcefully they will contract

16. 2. Afterload • For the left ventricle to pump blood out of the heart, it must overcome a fairly substantial pressure in the aorta.

17. Afterload is the pressure in the aorta that must be overcome for blood to be ejected from the left side of the heart.

18. In heart failure, the heart becomes weakened and cannot eject all the blood it receives.

19. This weakening can occur on the right side, on the left side or on both sides.

20. 3. Left heart failure aka CHF • If heart failure is on the left side (more common), excess blood accumulates in the left ventricle.

21. The wall of the left ventricle becomes thicker in an attempt to compensate for this extra blood.

22. It can only compensate so much, then the blood “backs up” into the lungs.

23. This results in classic symptoms: cough, shortness of breath, especially when a patient is prone

24. 4. Right heart failure • Here, blood “backs up” into peripheral veins.

25. This results in classic symptoms: swelling of feet, ankles (peripheral edema) and engorgement of organs such as liver

26. 5. Cardiac Output • Cardiac output (the amount of blood pumped by the heart per minute) is significantly decreased during heart failure.

27. This results in an inability of the cardiovascular system to meet the body’s demands for oxygen.

28. Patients with heart failure experience constant fatigue.

29. C. Drug class mechanisms of action in treating heart failure • There are a number of different mechanisms of action when considering how to treat heart failure:

30. 1. Certain drugs increase the force of contraction. This is called a positive inotropic effect and is characteristic of: • a. cardiac glycosides • b. phosphodiesterase inhibitors

31. 2. Certain drugs decrease the heart rate. This is characteristic of the adrenergic (beta) blockers.

32. 3. Certain drugs relax vascular smooth muscle which dilates blood vessels and lowers blood pressure. This is characteristic of the vasodilators.

33. 4. Certain drugs reduce blood volume. This is characteristic of the diuretics.

34. 5. Certain drugs affect the renin-angiotensin-aldosterone (RAA) system. This is characteristic of the ACE inhibitors

35. 6. Certain drugs reduce both preload and afterload. This is characteristic of the natriuretic peptides.

36. 1a. Cardiac glycoside therapy of heart failure • The cardiac glycosides are derived from the foxglove plants, Digitalis purpurea and Digitalis lanata

37. They have been used to treat heart disorders for over 2000 years, and were the mainstay of heart failure treatment until the discovery of the ACE inhibitors

38. Cardiac glycosides have 2 primary actions: • 1. Increasing the force of contraction allows the heart to eject more blood per beat which increases cardiac output and improves circulation.

39. 2. reduction in heart rate

40. Digoxin stimulates the vagus nerve, which slows the activity of the sinoatrial (SA) and atrioventricular (AV) nodes

41. This reduced heart rate (known as a negative chronotropic effect) is seen as a lengthening of the PR interval on an ECG.

42. The specific mechanism of action of the cardiac glycosides is inhibition of the Na1+- K1+-ATPase pump.

43. This pump normally removes Na1+ from the cell and brings K1+ in.

44. Inhibition of the pump leads to an accumulation of Na1+ inside heart muscle cells

45. The increased concentration of Na1+ stimulates the Na1+-Ca2+ exchange mechanism, leading to an increase in intracellular Ca2+.

46. Elevated Ca2+ results in an increase in the force of heart contraction

47. The primary cardiac glycoside available in the U.S. is digoxin (Digitek, Lanoxicaps, Lanoxin).

48. It’s ½ life is between 1-2 days, longer in older patients (those mostly likely to be taking it).

49. The antidote for digoxin is called digoxin immune fab (Digibind). It binds digoxin and has a rapid onset of action, less than 1 minute after IV infusion.

50. It is necessary to have an antidote available as nearly 1/3 of patients taking cardiac glycosides develop symptoms of toxicity.