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III. ARTERIAL VASODILATORS The important vasodilators in the therapy of moderate hypertension are hydralazine and the calcium channel blockers. In severe hyperten- sion, minoxidil may be used. A. Hydralazine Hydralazine relaxes arterial smooth muscle by an un- known mechanism. It should always be used with a sympathoplegic and a diuretic to counteract the compensatory responses it evokes (tachycar- dia and salt and water retention). Indications: * Hypertension. * Congestive heart failure (unlabeled). * Severe aortic or mitral regurgitation (unlabeled). Contraindications and Warnings: * Coronary artery disease (eg, angina) and mitral stenosis (because hydralazine evokes significant tachycardia). Adverse Reactions and Overdose Toxicity: * Fluid retention (compensatory) is common unless used with a diuretic) * Tachycardia (compensatory) is common unless a sympathoplegic is used concomitantly. Anginal pain may occur in patients with coronary disease. Overdose can result in severe hypotension and reflex tachycardia with myocardial ischemia. (PgDn for more text) * A lupus erythematosus-like syndrome may occur in patients receiving more than 200 mg/d of hydralazine, especially if they are "slow acetylators." It is usually reversible. * Peripheral neuropathies resembling pyridoxine deficiency and blood dyscrasias (rare). * Treatment of overdosage should be directed towards maintenance of ade- quate blood pressure (fluids are usually sufficient). Interactions: * Additive actions with other antihypertensive drugs. * Increase in oral bioavailability of beta-blockers normally subject to large first-pass metabolism has been reported when hydralazine was given, but is of dubious significance. 2. Minoxidil: Minoxidil is a powerful arterial vasodilator with an un- known mechanism of action. Because of its toxicity, it is usually reserved for severe hypertension. Indications: * Hypertension. * Topical use in treatment of baldness under the name Rogaine. (PgDn for more text) Contraindications and warnings: * Pheochromocytoma * Acute myocardial infarction * Dissecting aneurysm of the aorta. Adverse reactions and Overdosage Toxicity: * Compensatory sympathetic discharge may cause significant tachycardia. * Compensatory fluid retention. * Pleural or pericardial effusion. Tamponade has been reported but it is rare. * Hirsuitism in women has been reported. * Overdosage is likely to cause significant hypotension. This is best managed with fluids. Interactions: Additive effects with other hypotensive agents. 3. Calcium Channel Blockers: Verapamil, Diltiazem, Nifedipine Verapamil is labeled for the treatment of hypertension and it appears likely that the other members of this group will soon be approved for this indication since all are effective. Additional details are provided in Chapter 2 (Antianginal Drugs). Many newer calcium channel blockers are being investigated as potential antihypertensive agents. (Home key to return to top of file)

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