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Chapter: Clinical Anesthesiology: Clinical Pharmacology: Hypotensive Agents

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Non-Nitrovasodilator Hypotensive Agents: Fenoldopam

Fenoldopam mesylate causes rapid vasodilation by selectively activating D 1-dopamine receptors.

Non-Nitrovasodilator Hypotensive Agents

FENOLDOPAM

Mechanism of Action

Fenoldopam mesylate causes rapid vasodilation by selectively activating D 1-dopamine receptors. It has also demonstrated moderate affinity for α2-adrenoceptors. The R-isomer is responsible for the racemic mixture’s biological activity due to its much greater receptor affinity, compared with the S-isomer.

Clinical Uses

Fenoldopam mesylate (infusion rates studied in clinical trials range from 0.01–1.6 mcg/kg/min) reduces systolic and diastolic blood pres-sure in patients with malignant hypertension to an extent comparable to nitroprusside. Side effects include headache, flushing, nausea, tachycardia, hypokalemia, and hypotension. The onset of the hypotensive effect occurs within 15 min, and dis-continuation of an infusion quickly reverses this effect without rebound hypertension. Some degree of tolerance may develop 48 hr after the infusion. Studies are conflicted as to fenolodopam’s ability to “protect” and “maintain” renal function in periop-erative patients with hypertension at risk of periop-erative kidney injury.

Metabolism

Fenoldopam undergoes conjugation without par-ticipation of the cytochrome P-450 enzymes, and its metabolites are inactive. Clearance of fenoldopam remains unaltered despite the presence of renal or hepatic failure, and no dosage adjustments are nec-essary for these patients.

Eects on Organ Systems

Fenoldopam decreases systolic and diastolic blood pressure. Heart rate typically increases. Low ini-tial doses (0.03–0.1 mcg/kg/min) titrated slowly have been associated with less ref lex tachycardia than higher doses (>0.3 mcg/kg/min). Tachycardia decreases over time but remains substantial at higher doses.

Fenoldopam can lead to rises in intraocular pressure and should be administered with caution or avoided in patients with a history of glaucoma or intraocular hypertension.

As would be expected from a D 1-dopamine receptor agonist, fenoldopam markedly increases renal blood flow. Despite a drop in arterial blood pressure, the glomerular filtration rate is well main-tained. Fenoldopam increases urinary flow rate, uri-nary sodium extraction, and creatinine clearance compared with sodium nitroprusside.

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