Anti Hypertensive Drugs

1. Anti Hypertensive Drugs Dr.hasemmansour

4. Drugs used to treat Hypertension • HTN = BP > 140/90 • complications: premature death vascular disease of brain, heart,kidneys

7. Goal of treatment • Improve life expectancy. • Preventing cardiovascular problems by reducing BP < 140/90 • Prevent cerebrovascular accidents and kidney damage

8. Initial treatment of hypertension • Lifestyle modification first including exercise. • No smoking • Weight control • Reduce alcohol intake • Decrease stress • Sodium control

9. Drugs to treat hypertension • Diuretics • Calcium channel blockers • Angiotesin converting enzyme inhibitors (ACEI). • Angiotensin receptor blockers (ARB). • Autonomic nervous system agents • Direct acting vasodilators

10. Diuretics action • Thiazide diuretics, such as hydrochlorothiazide lower blood pressure by increasing sodium and water excretion. • This causes in extracellular volume, resulting in cardiac output & renal blood flow . • The net result is hypotensive.

11. The Nephron

13. Loop diuretics • The loop diuretics (furosemide) • Block sodium and chloride reabsorption in the kidneys, even in patients with poor renal function. • The net result hypotension.

14. Diuretics use • Treatment mild to moderate HTN • First drug of treatment is thiazide. • Treatment heart failure or kidney disease(loop diuretics). • Reduce edema associated with CHF (loop diuretics).

15. Diuretics side effects • Loop diuretics: ototoxicity, blood dyscriasis, hypokalemia, hyperurecemia, hypotension. • Thiazide diuretics: Hypokalemia, headache, hepatotoxicity, hyperglycemia , hypotension and hyperurecemia.

16. Potassium sparing diuretics • Spironolactone (inhibits sodium transport at the late distal and collecting ducts) • Spironolactone prevent potassium loss. • Used to treat resistant HTN • Used in combination with other diuretic.

17. Side effects • Orthostatic hypotension • Dry mouth, irritation • Hyperkalemia • Disorientation • Dehydration • Gynecomastia

19. Calcium Channel Blockers • Block the inward movement of calcium in the heart and in smooth muscle of the peripheral arteriolar vasculature. • This causes smooth muscle to relax, dilating mainly arterioles.

20. Calcium Channel Blockers types • Non dihydropyridine: Verapamil and Diltiazem • Have a much greater affinity for heart. • Dihydropyridines: nifedipine , amlodipine. • Have a much greater affinity for vascular calcium channels.

21. SIDE EFFECTS • Decrease BP • Bradycardia extremely • May precipitate A-V block • Headache, flushing and dizziness • Abdominal discomfort • Peripheral edema • Constipation with verapamil

22. ACE INHIBITORS • Captopril, enalapril • ACE inhibitors decrease angiotensin II causing Vasodilation of both arterioles and veins. • Also decrease sodium and water retention. • ACE inhibitors reduce cardiac work

23. ACEI and ARB mechanism of action

24. Therapeutic uses • Treatment of HTN. • Prevention of ventricular remodeling after MI. • ACE inhibitors are first-line drugs for treating heart failure, hypertensive patients with chronic kidney disease. • ACE inhibitors slow the progression of diabetic nephropathy.

25. Side effects • Headache • Rash, angioedema • Orthostatic hypotension-infrequent • Dry Cough 10- 20 % of pts. • GI distress and disturbance of taste. • Hyperkaleemia • Need frequent monitoring of renal function

26. ANGIOTENSIN II RECEPTOR BLOCKERS • The ARBs, such as losartan and valsartan are alternatives to the ACE inhibitors. • Their pharmacologic effects, use are similar to those of ACE inhibitors • Adverse effects are similar to those of ACE inhibitors, except the risks of cough and angioedema are significantly decreased.

28. ACEI and ARB • These agents are also teratogenic and should not be used by pregnant women.

29. Adrenergic receptors • Sympathetic Nervous System • Alpha 1 = vasoconstriction • Alpha 2 = vasodilation • Beta 1 = increases heart rate • Beta 2 = bronchodilation

30. Mechanism of action of B blockers • Blockade of β1-adrenoceptors in heart reduces heart rate and myocardial contractility. • Carvedilol and labetalol also block a-receptors and produce vasodilation.

32. Therapeutic uses • The primary therapeutic benefits of β-blockers are seen in hypertensive patients with concomitant heart disease, such as • Arrhythmia : (atrial fibrillation), • Previous myocardial infarction, angina pectoris, and chronic heart failure.

33. Side effects • Bradycardia, AV block • Intermittent claudication. • Bronchospasm, wheezing • Hypoglycemia. • Heart failure: edema,dyspnea • Insomnia • Fatigue • Sexual dysfunction

34. Alpha-1 Adrenergic Blocking Agents • Block postsynaptic alpha-1 adrenergic receptors to produce arteriolar and venous vasodilation • Reduces peripheral-vascular resistance

35. Side effects • Drowsiness • Headache • Dizziness,tachycardia,fainting • Weakness,lethargy • Palpitation. • Pancreatitis.

36. Centrally Acting Alpha-2 Agonists • Stimulate Alpha-2 receptors in brainstem • Decreases HR, SBP and DBP • More frequent side effects – drowsiness, dry mouth, dizziness • Never suddenly stop = rebound HTN • Clonidine. • Methyldopa : the safest drug in pregnancy

38. Renin IV: V: Resistant HT / Intolerance Add / substitute alpha blocker Re-consider 20 causes  trial of spironolactone AB/CD Rule – HT Treatment ACEi, Beta-blocker Ca++-blocker, Diuretic) (AB/CD = AGE Younger (< 55) High Renin HT Older (> 55) Low Renin HT I ACEi BB CCB Diuretic I III III A + B A + B + D D + C + A II D + C II Dickerson et al. Lancet 353:2008-11;1999

39. CLINICAL RELEVANCE FOR REHABILITATION • Adverse Drug Reactions • • Orthostatic hypotension is a common problem with • some classes of antihypertensive. • • Broncho constriction is a problem with beta-receptor • antagonists. • • Beta-receptor antagonists blunt the early manifestations • of hypoglycemia. • Loop and thiazide diuretics can cause hypokalemia. • • Potassium-sparing diuretics and ACEI can cause hyperkalemia.

40. Effects Interfering with Rehabilitation • Orthostatic cause patients to faint when position change, exiting from a warm aquatherapy area, or if aerobic exercise is terminated without an appropriate cool-down period. • Dyspnea may decrease aerobic capacity. • Manifestations of hypoglycemia occurring during aerobic activities may be delayed. • Cardiac output may be depressed during aerobic activities by several drug groups. • Altered plasma potassium levels can cause paresthesias, decrease skeletal muscle function, increase cramps, and increase the risk of cardiac dysfunction.

41. Possible Therapy Solutions • • Check blood pressure and heart rate prior to and following aerobic activities. • • Monitor heart rate during aerobic activities. • • To prevent fainting associated with orthostatic hypotension , assist patients with positional changes and when exiting a warm pool. • Always provide a cool-down period following exercise. • • Allow increased time to complete aerobic tasks to prevent dyspnea and account for depressed cardiac activity.

42. Possible Therapy Solutions • Use percievedexertion ( Borg rating of Perceived Exertion Scale) when determining aerobic activityin patients being treated with beta– receptor antagonists. • Check glucose levels prior to aerobic activities if the patients are taking hypoglycemic drugs. • Review the clinical manifestations of altered plasma potassium levels and determine if patients are taking medications that may alter these levels.