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Fenoldopam for Parenteral Treatment of Severe Hypertension



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Am Fam Physician. 1998 Sep 15;58(4):978-980.

Fenoldopam, a peripheral dopamine-1 agonist, is labeled by the U.S. Food and Drug Association for parenteral treatment of severe hypertension. The drug induces arteriolar vasodilation mainly through stimulation of dopamine-1 receptors. Fenoldopam leads to an increase in renal blood flow. It also has direct natriuretic and diuretic properties mediated through effects on renal tubular cells, particularly in patients with hypertension. Medical Letter consultants review the information on this agent.

An intravenous infusion of fenoldopam produces effects in about five minutes, and plasma concentrations reach a steady state in about 20 minutes. The drug is metabolized in the liver and excreted in the urine. The plasma elimination half-life is about five minutes.

In a randomized trial of 153 patients, fenoldopam was found to be as effective as sodium nitroprusside in the treatment of severe hypertension (patients with diastolic pressure of 120 mm Hg or higher). Fenoldopam produced a dose-response reduction in arterial pressure for up to 24 hours, without evidence of tolerance, rebound on withdrawal of the agent or significant changes in the heart rate. However, partial tolerance over time has been observed in smaller studies. Fenoldopam has been shown to improve renal function in some patients with severe hypertension and renal impairment. Other studies have demonstrated that fenoldopam maintained or increased urine output better than nitroprusside in patients with postoperative hypertension following cardiac and noncardiac surgery.

Fenoldopam has been used in the treatment of congestive heart failure in a few patients. Although it decreased peripheral resistance and increased cardiac output in these patients, the increases in cardiac output were not accompanied by consistent reductions in pulmonary wedge pressure or right atrial pressure. The diuretic effects observed in hypertensive patients did not consistently occur in patients with congestive heart failure.

The most common adverse effects of fenoldopam are related to its vasodilatory properties. Hypotension, flushing, dizziness, headache and tachycardia have all occurred, along with nausea and hypokalemia. Fenoldopam increases intraocular pressure and should be used cautiously in patients with glaucoma.

Significant drug interactions have not been reported. Metabolism of fenoldopam does not involve the cytochrome P450 system. However, the natriuretic and diuretic properties could lead to worsening volume depletion, especially in some patients receiving diuretics. Concomitant use of beta-adrenergic blockers could inhibit reflex tachycardia in response to fenoldopam and result in severe hypotension. The safety of fenoldopam when used with beta blockers remains to be established.

Fenoldopam is diluted in normal saline or a 5 percent dextrose solution and given as a continuous infusion, usually for 48 hours or less, without a bolus dose. The effective dosage range is 0.1 to 1.6 μg per kg per minute. Although lower starting dosages produce less reflex tachycardia, the blood pressure response may be ineffective or only modestly effective. The dosage is titrated upward in increments of 0.05 to 0.1 μg per kg per minute at 15-minute intervals until blood pressure is controlled. The predominant effect of any dosage is usually apparent within 15 minutes. When blood pressure is stabilized, oral antihypertensive therapy can be started. The fenoldopam infusion can either be stopped abruptly or tapered.

Medical Letter consultants. Fenoldopam—a new drug for parenteral treatment of severe hypertension. Med Lett Drugs Ther. May 22, 1998;40(1027):57–8.



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