Anti hypertensive Drugs

OVERVIEW Hypertension is defined as a sustained diastolic blood pressure greater than 90 mm Hg accompanied by an elevated systolic blood pressure (>140 mm Hg).

can lead to congestive heart failure, myocardial infarction, renal damage, and cerebrovascular accidents.

ETIOLOGY OF HYPERTENSION more than 90% of patients have essential hypertension, a disorder of unknown origin affecting the blood pressure-regulating mechanism. Inheritance factors Environmental factors such as a stressful lifestyle, high dietary intake of sodium, obesity,

MECHANISMS FOR CONTROLLING BLOOD PRESSURE In both normal and hypertensive individuals, cardiac output and peripheral resistance are controlled mainly by two overlapping control mechanisms: the baroreflexes mediated by the sym- pathetic nervous system, and the renin-angiotensin-aldosterone system

TREATMENT STRATEGIES Mild hypertension can often be controlled with a single drug. More severe hypertension may require treatment with several drugs that are selected to minimize adverse effects of the combined regimen. Treatment is initiated with any of four drugs depending on the individual patient: a diuretic, a beta-blocker, an ACE inhibitor, or a calcium channel blocker.

DIURETICS Diuretics are currently recommended as the first-line drug therapy for hypertension. Low-dose diuretic therapy is safe and effective in preventing stroke, myocardial infarction, congestive heart failure and total mortality.

Thiazide diuretics All oral diuretic drugs are effective in the treatment of hypertension, but the thiazides have found the most widespread use.

Actions hydrochlorothiazide lower blood pressure, initially by increasing sodium and water excretion. This causes a decrease in extracellular volume, resulting in a decrease in cardiac output and renal blood flow. With long-term treatment, plasma volume approaches a normal value, but peripheral resistance decreases.

Therapeutic uses in both the supine and standing positions; postural hypotension is rarely observed. useful in combination therapy with a variety of other antihypertensive agents including beta-blockers and ACE inhibitors. are particularly useful in the treatment of black or elderly patients, and in those with chronic renal disease. Thiazide diuretics are not effective in patients with inadequate kidney function

Pharmacokinetics Thiazide diuretics can be administered orally. They induce considerable disturbances in electrolyte balance. For example, blood levels of K + and Mg ++ are reduced, and Ca ++ is retained by the body

Adverse effects induce hypokalemia and hyperuricemia in 70% of patients, and hyperglycemia in 10% of patients. Serum potassium levels should be monitored closely in patients who are predisposed to cardiac arrhythmias Diuretics should be avoided in the treatment of hypertensive diabetics or patients with hyperlipidemia.

beta-ADRENOCEPTOR BLOCKING AGENTS beta-Blockers and/or diuretics are currently recommended as first-line drug therapy for hypertension. These drugs are efficacious but have some contraindications.

Actions The beta-blockers reduce blood pressure primarily by decreasing cardiac output. They may also decrease sympathetic outflow from the CNS and inhibit the release of renin from the kidneys, thus decreasing the formation of angiotensin II and secretion of aldosterone.

Therapeutic uses Subsets of the hypertensive population: The beta-blockers are more effective for treating hypertension in white than in black patients, and in young patients compared to the elderly. Conditions that discourage the use of beta-blockers (for example, severe chronic obstructive lung disease, chronic congestive heart failure, severe symptomatic occlusive peripheral vascular disease) are more commonly found in the elderly and in diabetics.]

Therapeutic uses Hypertensive patients with concomitant diseases: The beta-blockers are useful in treating conditions that may coexist with hypertension, such as supraventricular tachyarrhythmia, previous myocardial infarction, angina pectoris,

Adverse effects Drug withdrawal: Abrupt withdrawal may cause rebound hypertension, probably as a result of up-regulation of beta-receptors.

ACE INHIBITORS These drugs block the angiotensin converting enzyme that cleaves angiotensin I to form the potent vasoconstrictor, angiotensin II

Actions: The ACE inhibitors lower blood pressure by reducing peripheral vascular resistance without reflexly increasing cardiac output, rate, or contractility.

Therapeutic uses Like beta-blockers, ACE inhibitors are most effective in hypertensive patients who are white and young. However, when used in combination with a diuretic, the effectiveness of ACE inhibitors is similar in white and black hypertensive patients. Unlike beta-blockers, ACE inhibitors are effective in the management of patients with chronic congestive heart failure. ACE inhibitors are now a standard in the care of a patient following a myocardial infarction. Therapy is started 24 hours after the end of the infarction.

CALCIUM CHANNEL BLOCKERS Diphenylalkylamines: Benzothiazepines: Dihydropyridines:

Actions Calcium channel antagonists block the inward movement of calcium by binding to L-type calcium channels in the heart and in smooth-muscle of the coronary and peripheral vasculature. This causes vascular smooth muscle to relax, dilating mainly arterioles.

Therapeutic uses have an intrinsic natriuretic effect; therefore, they do not usually require the addition of a diuretic. are useful in the treatment of hypertensive patients who also have asthma, diabetes, angina, and/or peripheral vascular disease.

CENTRALLY-ACTING ADRENERGIC DRUGS Clonidine

actions diminishes central adrenergic outflow. Clonidine is used primarily for the treatment of mild to moderate hypertension that has not responded adequately to treatment with diuretics alone. does not decrease renal blood flow or glomerular filtration and therefore is useful in the treatment of hypertension complicated by renal disease.

Clonidine is absorbed well after oral administration and is excreted by the kidney. Because it causes sodium and water retention, clonidine is usually administered in combination with a diuretic.

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