Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fenoldopam is a selective dopamine1 (DA1) receptor agonist. Most of the DA1 receptor agonist activity of fenoldopam resides in the R-enantiomer, which also shows weaker alpha 2-adrenoceptor antagonist activity Fenoldopam produces vasodilation in vascular beds that are rich in vascular DA1 receptors, eg, renal and mesenteric receptors, and produces an increase in renal blood flow at doses that do not affect blood pressure. At higher doses, fenoldopam lowers blood pressure but still maintains renal perfusion. In addition to its renal vasodilator activity, fenoldopam is natriuretic, possibly resulting from a direct effect of DA1 receptors on the proximal convoluted tubule. In animals with spontaneous or drug-induced renal failure, fenoldopam improves renal function.
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PMID:The pharmacology of fenoldopam. 197 39

Fenoldopam (SK&F 82526) is a short-acting selective dopamine-1 agonist in clinical trials for the treatment of hypertension, congestive heart failure and renal failure. In the present study, we tested various N-ethyl carbamate esters of fenoldopam in the conscious dog instrumented with a femoral arterial Vascular-Access-Port and a renal artery flow probe. Oral administration of SK&F R-82526 at 1 and 3 mumol/kg resulted in transient (30-60 min) dose-dependent increases in plasma fenoldopam levels and renal blood flow. Administration of the 7,8-bis-N-ethyl carbamate ester of R-fenoldopam (SK&F R-106114) and the 4',7,8-tris-N-ethyl carbamate ester of R-fenoldopam (SK&F R-105058) at 1, 3 and 10 mumol/kg p.o. also resulted in dose-dependent increases in plasma fenoldopam levels and renal blood flow; however, both parameters remained elevated for at least 4 hr. Intravenous administration of SK&F R-105058 also resulted in sustained plasma fenoldopam levels and increases in renal blood flow, indicating that slow absorption was not the cause of the sustained effect. The present study indicates that N-ethyl carbamate esters of fenoldopam are fenoldopam prodrugs which result in sustained increases in renal blood flow and plasma fenoldopam levels.
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PMID:Identification of fenoldopam prodrugs with prolonged renal vasodilator activity. 197 20

Fenoldopam is an interesting orphan drug that is a variant of dopamine. It differs significantly from dopamine in that it is a specific agonist for the type I (DA-1) receptor. The DA-1 receptors are particularly prominent in the renal vasculature, renal tubules, mesenteric vasculature, and peripheral vessels. The DA-1 receptor stimulation vasodilates renal and peripheral vessels, causing a decrease in blood pressure and an increase in renal blood flow (RBF). Stimulation of the DA-1 receptors in the tubules causes an increase in sodium excretion, which gives rise to an increase in urine volume on the basis of a sodium natriuresis. Animal testing with fenoldopam has indicated that it is 6 times more potent than dopamine in its ability to decrease renal vascular resistance and increase RBF; this suggests that it could be a much more selective and potent renal protective agent against any toxin or stimulus that causes renal dysfunction by reducing RBF or increasing renal ischemia. The clinical activity of fenoldopam, which is administered intravenously, begins almost immediately and is clearly noticeable after 5 minutes. The drug has no rebound effect, and its use can be stopped at any time. The protocol for the use of fenoldopam as a renal protective agent (performed at the University of Minnesota) involves starting an intravenous fenoldopam infusion 2 hours before the procedure at a rate of 0.1 microg/kg/min and increasing the dose in increments of 0.1 microg/kg/min every 20 minutes, until a rate of 0.5 microg/kg/min is reached or the systolic blood pressure falls more than 40 mm Hg (or below 110 mm Hg). Any infusion level at or above 0.1 microg/kg/min is considered acceptable because the response in individual patients varies so widely. The fenoldopam infusion is maintained at the maximum rate throughout the procedure and for up to 4 hours after the end of the contrast administration. At the University of Minnesota, we have had anecdotal experience using the drug in 29 patients. The drug was used for patients who were thought to be at the highest risk for contrast-induced nephropathy, ie, patients who have both diabetes and pre-existing renal failure. In this small group of patients in whom hydration and other variables were not controlled, there was a startling lack of contrast-induced creatinine increase at any point during the 24 to 48 hours after the administration of contrast in all but 1 patient. Our experience suggests that fenoldopam may be of distinct benefit to high-risk patients who need intravascular contrast, especially those who may receive a large contrast dose, such as patients undergoing peripheral or coronary angiography and intervention and/or computed tomography. Although it is impossible on the basis of simple anecdotal case reports to determine whether or not the drug was the primary reason that such a marked protective effect was seen, the results are promising enough to indicate that a careful, prospective, randomized trial of fenoldopam versus hydration is warranted.
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PMID:Preventing contrast-induced nephropathy with fenoldopam. 1198 89

In the periphery, physiological dopamine increases renal blood flow, decreases renal resistance and acts on the kidney tubule to enhance natriuresis and diuresis. The loss of dopamine function may be involoved in the deterioration in kidney function associated with ageing and may have a role in the pathogenesis of hypertension and diabetes. Intravenous dopamine is used as a positive inotrope in the treatment of acute heart failure and cardiogenic shock and as a diuretic in renal failure. The clinical uses of dopamine are limited, as it must be given intravenously, and also has widespread effects. The levels of peripheral dopamine can be increased by the administration of L-dopa to increase synthesis, prodrugs to release dopamine (docarpamine, glu-dopa) or by inhibiting the breakdown of dopamine (nitecapone). Preliminary clinical trials suggest that docarpamine may be useful in patients with low cardiac output syndrome after cardiac surgery and in refractory cirrhotic ascites. Ibopamine is an agonist at dopamine D1 and D2 receptors, which may retard the progression of chronic renal failure. Glu-dopa is selective for the kidney, thus avoiding widespread side effects. The early clinical studies with ibopamine as a diuretic in heart failure were favourable but the subsequent large mortality study showed that ibopamine increased mortality. Fenoldopam is a selective dopamine D1 receptor agonist. Intravenous fenoldopam may be useful in the treatment of hypertension associated with coronary artery bypass surgery or in hypertensive emergencies. Although our understanding of physiological and pathological roles of peripheral dopamine has been increasing rapidly in recent times, we still need more information to allow the design of clinically useful drugs that modify these roles. One priority is an orally-active selective dopamine D1 receptor agonist.
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PMID:The therapeutic potential of dopamine modulators on the cardiovascular and renal systems. 1199 45

Postoperative acute renal failure (PO-ARF) is a serious complication resulting in a prolonged stay and high mortality. Patients may be at risk for this problem because of an underlying medical illness, nature of surgery, nephrotoxin exposure, or combinations of these factors. An increase in the intra abdominal pressure above 20-mm Hg is associated with an increase in the incidence of PO-ARF. Based on many clinical studies in high-risk surgical patients and patients undergoing renal transplantation, the only proven management strategies for prevention of PO-ARF are adequate volume expansion and avoidance of hypovolaemia. Drugs known to be nephrotoxic should be avoided or used with caution. Three main pharmacological agents namely mannitol, frusemide and dopamine have been extensively tried in the prevention of PO-ARF. Mannitol has proven of value only in the presence of adequate volume expansion in attenuating renal dysfunction in transplant patients. Frusemide converts oliguric renal failure to non-oliguric renal failure. The bulk of the data, including that from prospective studies indicate dopamine is only a diuretic. Fenoldopam, a dopamine analogue, has shown early promise in reports. Calcium channel blockers have not been shown to improve the outcome in renal transplantation or help in the prevention of contrast-induced nephropathy. Atrial natriuretic peptide has not been proven to be of benefit in established renal failure and its role in prevention has not been assessed.
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PMID:Prevention of postoperative acute renal failure. 1208 35

Low dose of dopamine is commonly used after kidney transplantation as a reno-protective agent, although its benefits are controversial. Dopamine may increase renal blood flow, decrease resistive index (RI), and induce urine output in normal kidneys. Many authors hypothesized that the vasculature of a denervated renal transplant may not respond to dopamine in the same fashion as healthy native kidneys, which led us to find other drugs to attenuate the ischemia-reperfusion (I/R) injury. Fenoldopam is a selective dopamine1 (DA1) receptor agonist, most of the activity of which resides in the R-enantiomer, which also shows weaker alpha 2-adrenoceptor antagonist activities. Fenoldopam produces a vasidilatory effect in vascular beds that are rich in vascular DA1 receptors, producing increased renal blood flow at doses that do not affect blood pressure. In addition to its renal vasodilator activity, fenoldopam is natriuretic, possibly resulting from a direct effect of DA1 receptors on the proximal convoluted tubule. In animals with spontaneous or drug-induced renal failure, fenoldopam improves renal function. The aim of this study was to investigate the possible effects of fenoldopan mesylate in recent kidney transplants. Creatinine, blood urea nitrogen, urine output, and renal vascular resistive index (IR) were measured using Doppler ultrasound. Two groups of patients with no statistical differences in demographic data were treated with dopamine or fenoldopan, showing no significant difference but a trend favoring the fenoldopan group.
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PMID:Dopamine "renal dose" versus fenoldopam mesylate to prevent ischemia-reperfusion injury in renal transplantation. 1618 14