Fenoldopam: A novel, peripherally acting dopamine-1 agonist for parenteral treatment of hypertension

Academic Article

Abstract

  • Fenoldopam mesylate is a novel, peripherally acting dopamine-1 receptor agonist that induces potent arteriolar vasodilatation of renal, mesenteric, coronary and skeletal muscle vasculature. Clinical studies indicate that fenoldopam reduces blood pressure in a linear, dose-dependent fashion in healthy subjects and in patients with mild, moderate or severe hypertension. The reduction in blood pressure is attributable primarily to a reduction in peripheral vascular resistance. In hypertensive subjects with and without renal insufficiency, fenoldopam tends to increase renal blood flow and has significant natriuretic and diuretic properties, as indicated by substantial increases in sodium and free water excretion and urine flow. Fenoldopam has a rapid onset of action (5 min) and short duration of action (30 min) when administered intravenously. Little if any tachyphylaxis is observed in blood pressure reduction with up to 24 h of infusion, and no rebound hypertension occurs upon abrupt cessation of therapy. Fenoldopam is metabolized quickly, with no accumulation of toxic degradation products. Fenoldopam is well tolerated. The most common adverse events associated with the compound, flushing and headache, are attributable to its vasodilator action. In heart failure patients, fenoldopam reduces systemic vascular resistance while increasing cardiac output. Unlike nitroprusside, fenoldopam is not a venodilator, and does not consistently reduce pulmonary capillary wedge pressure. Interestingly, the natriuretic/diuretic properties of fenoldopam observed in hypertensive patients have not been consistently observed in heart failure patients. Fenoldopam has been shown to safely reduce postoperative hypertension in patients undergoing both cardiac and noncardiac surgery. In a study of patients recovering from coronary artery bypass grafting, decreases in urine flow associated with nitroprusside were not seen with use of fenoldopam. In these same postoperative patients, nitroprusside use was associated with reductions in pulmonary capillary wedge pressure while fenoldopam was not. Fenoldopam is a promising alternative to nitroprusside for intravenous reduction of blood pressure. Clinical comparisons indicate antihypertensive efficacy and safety similar to nitroprusside. Fenoldopam has a rapid but not abrupt onset of action such that use of an intraarterial line to monitor blood pressure can be avoided. Compared with nitroprusside, fenoldopam tends to increase renal blood flow and to increase sodium and free water excretion, which may be clinically advantageous in certain subsets of patients. Fenoldopam will likely be more convenient to use than nitroprusside as it is not photosensitive and none of its metabolites are toxic.
  • Authors

    Published In

  • Drugs of Today  Journal
  • Digital Object Identifier (doi)

    Author List

  • Calhoun D; Oparil S; Mathur V; Luther R; Ellis D
  • Start Page

  • 729
  • End Page

  • 738
  • Volume

  • 33
  • Issue

  • 10