indication

For the in-hospital, short-term (up to 48 hours) management of severe hypertension when rapid, but quickly reversible, emergency reduction of blood pressure is clinically indicated, including malignant hypertension with deteriorating end-organ function.

pharmacology

Fenoldopam is an agonist at D₁-like dopamine receptors, binds to α₂-adrenoceptors, increasing renal blood flow.

mechanism of action

Fenoldopam is a rapid-acting vasodilator. It is an agonist for D₁-like dopamine receptors and binds with moderate affinity to α₂-adrenoceptors. It has no significant affinity for D₂-like receptors, α₁ and β-adrenoceptors, 5_HT1 and 5_HT2 receptors, or muscarinic receptors. Fenoldopam is a racemic mixture with the R-isomer responsible for the biological activity. The R-isomer has approximately 250-fold higher affinity for D₁-like receptors than does the S-isomer. In non-clinical studies, fenoldopam had no agonist effect on presynaptic D₂-like dopamine receptors, or α or β -adrenoceptors, nor did it affect angiotensin-converting enzyme activity. Fenoldopam may increase norepinephrine plasma concentration.

toxicity

The most likely reaction of overdose would be excessive hypotension which should be treated with drug discontinuation and appropriate supportive measures.

biotransformation

Elimination is largely by conjugation, without participation of cytochrome P-450 enzymes. Methylation, glucuronidation, and sulfation are the main routes of conjugation.

half life

The elimination half-life is about 5 minutes in mild to moderate hypertensives, with little difference between the R (active) and S isomers.

route of elimination

Radiolabeled studies show that about 90% of infused fenoldopam is eliminated in urine, 10% in feces. Elimination is largely by conjugation, without participation of cytochrome P-450 enzymes. Only 4% of the administered dose is excreted unchanged.