Fenoldopam

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Fenoldopam
Fenoldopam.svg
Fenoldopam 3d balls.png
Systematic (IUPAC) name
(RS)-6-chloro-1-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol
Clinical data
Trade names Corlopam
AHFS/Drugs.com monograph
Pregnancy cat. B (US)
Legal status -only (US)
Routes IV
Pharmacokinetic data
Metabolism Hepatic (CYP not involved)
Half-life 5 minutes
Excretion Renal (90%) and fecal (10%)
Identifiers
CAS number 67227-57-0 YesY
ATC code C01CA19
PubChem CID 3341
IUPHAR ligand 939
DrugBank DB00800
ChemSpider 3224 YesY
UNII HA3R0MY016 YesY
KEGG D07946 YesY
ChEBI CHEBI:5002 YesY
ChEMBL CHEMBL588 YesY
Chemical data
Formula C16H16ClNO3 
Mol. mass 305.76 g/mol
 YesY (what is this?)  (verify)

Fenoldopam mesylate (Corlopam) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist.[1] Fenoldopam is used as an antihypertensive agent.[2] It was approved by the Food and Drug Administration (FDA) in September 1997.[3]

Indications[edit]

Fenoldopam is used as an antihypertensive agent postoperatively, and also intravenously (IV) to treat a hypertensive crisis.[4] Since fenoldopam is the only intravenous agent that improves renal perfusion, it may be exceptionally beneficial in hypertensive patients with concomitant renal insufficiency.[5]

Pharmacology[edit]

Fenoldopam causes arterial/arteriolar vasodilation leading to a decrease in blood pressure by activating peripheral D1 receptors.[6] It decreases afterload and also promotes sodium excretion via specific dopamine receptors along the nephron. The renal effect of fenoldopam and dopamine may involve physiological antagonism of the renin-angiotensin system in the kidney.[7] In contrast to dopamine, fenoldopam is a selective D1 receptor agonist with no effect on beta adrenoceptors, although there is evidence that it may have some alpha-1 [8] and alpha-2 adrenoceptor antagonist activity.[6] D1 receptor stimulation activates adenylyl cyclase and raises intracellular cyclic AMP, resulting in vasodilation of most arterial beds, including renal, mesenteric, and coronary arteries.[9] to cause a reduction in systemic vascular resistance. Fenoldopam has a rapid onset of action (4 minutes) and short duration of action (< 10 minutes) and a linear dose response relationship at usual clinical doses.[10]

Side effects[edit]

Adverse effects include headache, flushing, nausea, hypotension, reflex tachycardia, and increased intraocular pressure.[4][11]

Contraindications, warnings and precautions[edit]

Fenoldopam mesylate contains sodium metabisulfite, a sulfite that may rarely cause allergic-type reactions including anaphylactic symptoms and asthma in susceptible people. Fenoldopam mesylate administration should be undertaken with caution to patients with glaucoma or raised intraocular pressure as fenoldopam raises intraocular pressure.[11] Concomitant use of fenoldopam with a beta-blocker should be avoided if possible, as unexpected hypotension can result from beta-blocker inhibition of sympathetic-mediated reflex tachycardia in response to fenoldopam.[11]

References[edit]

  1. ^ Grenader A, Healy DP (July 1991). "Fenoldopam is a partial agonist at dopamine-1 (DA1) receptors in LLC-PK1 cells". J. Pharmacol. Exp. Ther. 258 (1): 193–8. PMID 1677038. 
  2. ^ Oliver WC, Nuttall GA, Cherry KJ, Decker PA, Bower T, Ereth MH (October 2006). "A comparison of fenoldopam with dopamine and sodium nitroprusside in patients undergoing cross-clamping of the abdominal aorta". Anesth. Analg. 103 (4): 833–40. doi:10.1213/01.ane.0000237273.79553.9e. PMID 17000789. 
  3. ^ http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory accessed November 14, 2011
  4. ^ a b Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 9. ISBN 1-59541-101-1. 
  5. ^ USMLE WORLD 2009 Step1 QBanks, Pharmacology, Pharma50q, Q NO 18
  6. ^ a b Nichols AJ, Ruffolo RR, Brooks DP (June 1990). "The pharmacology of fenoldopam". Am. J. Hypertens. 3 (6 Pt 2): 116S–119S. PMID 1974439. 
  7. ^ Gildea JJ (January 2009). "Dopamine and angiotensin as renal counterregulatory systems controlling sodium balance". Curr. Opin. Nephrol. Hypertens. 18 (1): 28–32. doi:10.1097/MNH.0b013e32831a9e0b. PMC 2847451. PMID 19077686. 
  8. ^ Martin SW, Broadley KJ (May 1995). "Renal vasodilatation by dopexamine and fenoldopam due to alpha 1-adrenoceptor blockade". Br. J. Pharmacol. 115 (2): 349–55. doi:10.1111/j.1476-5381.1995.tb15884.x. PMC 1908310. PMID 7670737. 
  9. ^ Hughes AD, Sever PS (1989). "Action of fenoldopam, a selective dopamine (DA1) receptor agonist, on isolated human arteries". Blood Vessels 26 (2): 119–27. PMID 2474340. 
  10. ^ Epstein, Murray MD, "Diagnosis and Management of Hypertensive Emergencies," clinical Cornerstone. Hypertension Vol2. No 1.
  11. ^ a b c NDA 19-922/S-005: Corlopam RA06497-R1-9/03 brand of Fenoldopam Mesylate Injection, USP