1. CARDIOVASCULAR DRUGS

2. Reference: Pharmacology in Rehabilitation 4th Edition Charles D. Ciccone, PT, PhD

4. Diuretics

5. increase the formation and excretion of urine. increase the renal excretion of water and sodium, thus decreasing the volume of fluid within the vascular system.

6. Classification of Diuretics Thiazide Diuretics. act primarily on the early portion of the distal tubule of the nephron, where they inhibit sodium reabsorption. the most frequently used type of diuretic Loop Diuretics. act primarily on the ascending limb of the loop of Henle (hence the term inhibit the reabsorption of sodium and chloride from the nephron, thereby preventing reabsorption of the water that follows these electrolytes Potassium-Sparing Diuretics. prevent the secretion of potassium into the distal tubule. Normally, there is sodium-potassium exchange - sodium is reabsorbed and potassium is secreted. Potassium-sparing agents interfere with this exchange so potassium is spared from secretion and sodium is excreted. potassium sparing drugs have the advantage of reducing potassium loss and thus preventing hypokalemia.

7. Classification of Diuretics Potassium-Sparing Diuretics. prevent the secretion of potassium into the distal tubule. Normally, there is sodium-potassium exchange - sodium is reabsorbed and potassium is secreted. Potassium-sparing agents interfere with this exchange so potassium is spared from secretion and sodium is excreted. Potassium sparing drugs have the advantage of reducing potassium loss and thus preventing hypokalemia.

8. Adverse Effects of Diuretics fluid depletion and electrolyte imbalance. decreased extracellular fluid volume as well as produce sodium depletion (hyponatremia) and potassium depletion (hypokalemia).

10. Sympatholytic Drugs

12. an increase in sympathetic - a factor in essential hypertension. sympatholytic agents - drugs that interfere with sympathetic discharge classified according to where and how they interrupt sympathetic activity.

13. Sympatholytic drugs: beta-adrenergic blockers alpha-adrenergic blockers presynaptic adrenergic neurotransmitter depletors centrally acting drugs ganglionic blockers

14. Beta Blockers Beta-adrenergic blockers-a mainstay of antihypertensive exert their primary effect on the heart- decrease heart rate and force of myocardial contraction. (-) inotropic effect, (-) chronotropic effect = lowers BP

15. Adverse Effects Nonselective beta blockers (equal affinity for beta-1 and beta-2 receptors) may produce bronchoconstriction in patients with asthma Cardiovascular side effects include excessive depression of heart rate and myocardial contractility as well as orthostatic hypotension. may impair glucose and lipid metabolism

17. Alpha Blockers block the alpha-1–adrenergic receptor on vascular smooth muscle = decrease in vascular resistance. decreases total peripheral resistance

18. Adverse Effects When peripheral vascular resistance due to alpha blockers, the baroreceptor reflex often responds by generating a compensatory increase in heart rate (reflex tachycardia) To prevent reflex tachycardia, a beta blocker may be administered with the alpha blocker to negate the increase in heart rate

19. Presynaptic Adrenergic Inhibitors inhibit the release of norepinephrine from the presynaptic terminals of peripheral adrenergic neurons Adverse Effects Orthostatic hypotension gastrointestinal disturbances such as nausea, vomiting and diarrhea.

20. Centrally Acting Agents inhibit sympathetic discharge from the brainstem. Adverse Effects dry mouth, dizziness, and sedation.

21. Vasodilators

22. directly vasodilate the peripheral vasculature by decreasing peripheral vascular resistance. inhibit smooth-muscle Adverse Effects Reflex tachycardia dizziness, postural hypotension, weakness, nausea, fluid retention, and headache

24. Inhibition of the renin- angiotensin system

26. Renin-Angiotensin System Renin -formed in the renal juxtaglomerular cells in response to certain types of stimuli: salt depletion β2 stimulation decrease in renal perfusion that might be found in hypotension or hypovolemia.

27. renin mediates the formation of angiotensin-I in the liver. When angiotensin-I reaches the lungs, it is converted by the angiotensin converting enzyme into angiotensin-II. Angiotensin-II causes vasoconstriction, promotes the release of norepinephrine, and stimulates aldosterone production resulting in sodium and water retention.

28. Additional effects of angiotensin-II include increased systemic vascular resistance, arterial blood pressure, and intravascular volume.

29. Inhibition of the Renin-Angiotensin System two pharmacologic strategies: inhibit the enzyme that converts angiotensin I to angiotensin II = angiotensin converting enzyme (ACE) inhibitors. block angiotensin II receptors on various tissues = angiotensin II blockers

30. Result: a decrease in norepinephrine levels, prevention of systemic vasoconstriction and decreased blood pressure. aldosterone production is no longer stimulated by Angiotensin II, which results in decreased intravascular volume.

31. Adverse Effects allergic reaction - skin rash. persistent dry cough

33. Calcium channel blockers

35. Adverse Effects may cause excessive vasodilation as evidenced by swelling in the feet and ankles orthostatic hypotension.

37. Nitrates

38. Organic nitrates dilate vascular smooth muscle Nitrates are actually drug precursors (prodrugs) that become activated when they are converted to nitric oxide within vascular smooth muscle Nitroglycerin- the most well known antianginal drug.

39. Drugs Used for Overclotting

41. Antithrombotic Drugs anticoagulants affect the synthesis and function of clotting factors antithrombotics primarily inhibit the function of platelets prevent the formation of arterial clots, such as those that cause coronary artery occlusion or cerebral infarction.

42. Aspirin suppresses platelet aggregation by inhibiting the synthesis of prostaglandins and thromboxanes. inhibit the cyclooxygenase enzyme that initiates synthesis of prostaglandins and thromboxanes.

43. Certain prostaglandins and thromboxanes, especially thromboxane A2, have a potent ability to induce platelet aggregation. By inhibiting the synthesis of these proaggregation substances, aspirin prevents platelet-induced thrombus formation.

44. very low aspirin doses = meaningful antithrombotic effect adequate antithrombotic effects with one baby aspirin tablet each day During the acute phase of an infarction, aspirin is critical in helping to limit the progression of platelet-induced occlusion, reducing the extent of damage to the myocardium

45. Adverse Effects of Antithrombotic Drugs aspirin increases risk of bleeding may cause gastric irritation high doses of aspirin may be toxic to the liver and kidneys

46. Thrombolytic Drugs Thrombolytics facilitate the breakdown and dissolution of clots formed. activate conversion of plasminogen (profibrinolysin) to plasmin (fibrinolysin) used to dissolve clots that have already formed, thus reopening occluded blood vessels.

47. extremely valuable in treating acute myocardial infarction. When administered at infarction onset, these drugs can reestablish blood flow through occluded coronary vessels, preventing or reversing myocardial damage decreasing morbidity /mortality

48. can help reopen occluded coronary vessels when administered within 12 hours after symptom onset. Thrombolytics produce best results when administered soon after the symptom onset.

49. Streptokinase and Urokinase both cause activation of plasmin. Streptokinase indirectly activates plasmin (fibrinolysin) Urokinase directly converts plasminogen to plasmin

50. Adverse Effects of Thrombolytic Drugs Hemorrhage is the major adverse effect associated with thrombolytic agents.

51. Drugs That Increase Myocardial Contraction Force (Positive Inotropic Agents)

52. (Positive Inotropic Agents) Digitalis “digitalis" - term used to represent these drugs cardiac glycosides include digoxin, digitoxin one of the primary drugs used to treat congestive heart failure. digitalis improves cardiac pumping ability and therefore improves the primary symptoms of congestive heart failure.

55. Adverse Side Effects gastrointestinal distress (nausea, vomiting, diarrhea) and central nervous system (CNS) disturbances (drowsiness, fatigue, confusion, visual disturbances) arrhythmias such as premature atrial and ventricular contractions, paroxysmal atrial tachycardia, ventricular tachycardia, and high degrees of atrioventricular block

56. Agents Used to Treat Hyperlipidemia

57. Hyperlipidemia one of the primary causes of cardiovascular disease causes deposition of fatty plaquelike lesions on the walls of large and mediumsized arteries (atherosclerosis), which can lead to thrombosis and infarction. Hyperlipidemia is often caused by poor diet and lifestyle, as well as genetic conditions

58. Agents Used to Treat Hyperlipidemia are used when plasma lipid levels are unsuccessfully controlled by nonpharmacologic methods such as low-fat diets, weight reduction, regular exercise, and smoking cessation endogenous control of lipid metabolism

59. Adverse Effect of Antihyperlipidemia Agents gastrointestinal distress

61. THE END