Anti Hypertensive Drugs Dr.hasem mansour

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

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

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

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

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

The Nephron

Loop diuretics The loop diuretics (furosemide, torsemide) Block sodium and chloride reabsorption in the kidneys, even in patients with poor renal function. Loop diuretics cause decreased renal vascular resistance and increased renal blood flow. The net result hypotension.

Treatment mild to moderate HTN First drug of treatment is thiazide. 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).

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

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

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

Optimal time to admin.= AM Accurate intake and output Daily weights Implications for use Optimal time to admin.= AM Accurate intake and output Daily weights Monitor electrolyte imbalances Pregnancy risk : c

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

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.

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

2nd and 3rd degree heart block Pregnancy category: C C.I and pregnancy Cardiogenic shock. CHF 2nd and 3rd degree heart block Pregnancy category: C

ACE INHIBITORS Captopril, enalapril, and ramipril ACE inhibitors decrease angiotensin II causing Vasodilation of both arterioles and veins. Also decrease the secretion of aldosterone, resulting in decreased sodium and water retention. ACE inhibitors reduce cardiac work

ACEI and ARB mechanism of action

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.

Orthostatic hypotension-infrequent Dry Cough 10- 20 % of pts. 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

ANGIOTENSIN II RECEPTOR BLOCKERS The ARBs, such as losartan and irbesartan 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.

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

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

Mechanism of action of B blockers Blockade of β1-adrenoceptors in heart reduces heart rate and myocardial contractility. Blockade of renal β1- receptors reduces renin secretion(vasoconstrictor). Blockade of presynaptc β2-adrenoceptors inhibits exocytose of NA. Carvedilol and labetalol also block a-receptors and produce vasodilation.

Beta Adrenergic Blocking Agents The nonselective β-blockers, such as propranolol and nadolol. Selective blockers of β1 receptors, such as metoprolol, bisoprolol and atenolol .

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.

Warning and contra indication Asthma (nonselective β-blockers) Second- and third-degree heart block Severe peripheral vascular disease.

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

Most β-blockers raise plasma concentration Side effects Most β-blockers raise plasma concentration of triglycerides and lower concentration of antiatherogenic HDL. Sudden withdrawal syndrome: beta-blockers should be stopped gradually. Pregnancy category: C

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

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

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

Direct Acting Vasodilators Action: direct arteriolar smooth muscle relaxation, decreasing peripheral venous resistance Uses: HTN, renal dx., toxemia of pregnancy Minoxidil is used topically to treat male pattern baldness

Direct Acting Vasodilators Apresoline(hydralasine), Minoxidel SE: tachycardia, orthostatic hypotension,dizziness, palpitations, nausea, nasal congestion These undesirable side effects can be blocked by concomitant use of a diuretic and a β-blocker

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

CLINICAL RELEVANCE FOR REHABILITATION Adverse Drug Reactions • Orthostatic hypotension is a common problem with some classes of antihypertensive drugs (prazosin). • Broncho constriction is a problem with beta-receptor antagonists. • Beta-receptor antagonists blunt the early manifestations of hypoglycemia. • Several antihypertensive drug classes depress heart rate and contractility. Loop and thiazide diuretics can cause hypokalemia. • Potassium-sparing diuretics and ACEI can cause hyperkalemia.

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. • Heart rate cannot be used as a marker of exertion for patients taking beta-receptor antagonists. • 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.

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.

Possible Therapy Solutions • Use percieved exertion ( Borg rating of Perceived Exertion Scale) when determining aerobic activity in 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.