FENOLDOPAM - A NOVEL, PERIPHERALLY ACTING DOPAMINE-1 AGONIST FOR PARENTERAL TREATMENT OF HYPERTENSION

Fenoldopam mesylate is a novel, peripherally acting dopamine-1 recepto r agonist that induces potent arteriolar vasodilatation of renal, mese nteric, coronary and skeletal muscle vasculature. Clinical studies ind icate that fenoldopam reduces blood pressure in a linear, dose-depende nt fashion in healthy subjects and in patients with mild, moderate or severe hypertension. The reduction in blood pressure is attributable p rimarily to a reduction in peripheral vascular resistance. In hyperten sive subjects with and without renal insufficiency, fenoldopam tends t o increase renal blood flow and has significant natriuretic and diuret ic properties, as indicated by substantial increases in sodium and fre e water excretion and urine flow. Fenoldopam has a rapid onset of acti on (5 min) and short duration of action (30 min) when administered int ravenously. Little if any tachyphylaxis is observed in blood pressure reduction with up to 24 h of infusion, and no rebound hypertension occ urs upon abrupt cessation of therapy. Fenoldopam is metabolized quickl y, with no accumulation of toxic degradation products. Fenoldopam is w ell tolerated. The most common adverse events associated with the comp ound, flushing and headache, are attributable to its vasodilator actio n. In heart failure patients, fenoldopam reduces systemic vascular res istance while increasing cardiac output. Unlike nitroprusside, fenoldo pam is not a venodilator, and does not consistently reduce pulmonary c apillary wedge pressure. Interestingly, the natriuretic/diuretic prope rties of fenoldopam observed in hypertensive patients have not been co nsistently observed in heart failure patients. Fenoldopam has been sho wn 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 associa ted with nitroprusside were not seen with use of fenoldopam. In these same postoperative patients, nitroprusside use was associated with red uctions in pulmonary capillary wedge pressure while fenoldopam was not . Fenoldopam is a promising alternative to nitroprusside for intraveno us reduction of blood pressure. Clinical comparisons indicate antihype rtensive efficacy and safety similar to nitroprusside. Fenoldopam has a rapid but not abrupt onset of action such that use of an intraarteri al line to monitor blood pressure can be avoided. Compared with nitrop russide, fenoldopam tends to increase renal blood flow and to increase sodium and free water excretion, which may De clinically advantageous in certain subsets of patients. Fenoldopam will likely be more conven ient to use than nitroprusside as it is not photosensitive and none of its metabolites arts toxic.