Fenoldopam is used primarily for the lowering of blood pressure during episodes of severe hypertension.
Fenoldopam has a unique mechanism of action compared to other anti-hypertensive medications: it is a dopamine (D1) receptor agonist that results in decreased peripheral vascular resistance primarily in renal capillary beds thus promoting increased renal blood flow, natriuresis, and diuresis. Fenoldopam has minimal adrenergic effects.
It is important to understand the basics of vascular smooth muscle cell physiology and the role of D1 receptor agonism in severe hypertension. In arteries, the tunica media is composed of smooth muscle cells activated by various neurotransmitters, hormones, and mechanical perturbations. Examples of endogenous stimuli responsible for inducing arterial smooth muscle contraction include norepinephrine, angiotensin II, endothelin, and thromboxane-A2. Passive stretching also induces arterial smooth muscle contraction and can be of importance when describing the autoregulation of blood pressure. When an endogenous stimulus acts on a vascular smooth muscle cell, calcium (Ca++) is released from the sarcoplasmic reticulum or from an influx across the cell membrane and binds to cytoplasmic calmodulin. The Ca++/calmodulin complex subsequently activates myosin light chain kinase (MLCK). MLCK phosphorylates myosin heads in the presence of adenosine triphosphate (ATP) thus enabling actin-myosin cross-bridge formation and smooth muscle contraction.
Relaxation of smooth muscle occurs when there is decreased phosphorylation of myosin. There are three documented mechanisms by which this can occur: reduced entry or decreased release of Ca++ from the sarcoplasmic reticulum, inhibition of MLCK by increased cyclic guanosine monophosphate (cGMP), or dephosphorylation of MLCK by myosin phosphatase.
Removal of Ca++ ions from the cytoplasm is achieved by two mechanisms. The primary mechanism is a plasma membrane-bound sodium (Na+)/Ca++ antiporter that effluxes one Ca++ ion and influxes three Na+ ions by utilizing the electrochemical gradient created by the Na+/potassium (K+) ATPase. The second mechanism by which Ca++ is removed from the cytoplasm is by a Ca++/ATPase located on the sarcoplasmic reticulum.
The contraction and relaxation of vascular smooth muscle is the mechanism by which changes in systemic vascular resistance (SVR) occur. Contraction of vascular smooth muscle causes a decrease in the cross-sectional area of the arterial lumen, thus increasing SVR and afterload on the heart. Interpreting how changes in SVR affect blood pressure involve understanding the physiologic relationship between mean arterial pressure (MAP), cardiac output (CO), and SVR. MAP is equivalent to CO multiplied by SVR. Simply stated, this means that CO and SVR directly correlate with MAP such that increases in SVR cause a rise in MAP. This physiologic perturbation manifests clinically as high blood pressure. In contrast, by decreasing SVR, MAP decreases.
Dopamine D1 receptors are located in the tunica media of arteries and exert their effects through a G-alpha stimulatory second messenger system. Upon ligand binding to D1-receptors, the alpha subunit dissociates from the intracellular domain of the transmembrane receptor and activates adenylate cyclase (AC). AC subsequently converts ATP to cyclic adenosine monophosphate (cAMP). All downstream effects get mediated by cAMP, the chief second messenger in this pathway.
Inside the cell, cAMP activates protein kinase A (PKA). PKA phosphorylates MLCK thus causing its inactivation. Since myosin cannot undergo phosphorylated by MLCK, the cross-bridge formation between myosin and actin does not occur, rendering the arterial smooth muscle cell unable to contract. The result is the dilation of arteries producing decreased SVR, increased renal blood flow, natriuresis, and diuresis. These pharmacologic effects result in a decrease in blood pressure.
Fenoldopam administration is as a continuous intravenous (IV) infusion via infusion pump.
Neonatal Dosing (Full-term or at least 2 kg)
Central Nervous System
Central Nervous System
Endocrine and Metabolic
Hematologic and Oncologic
Neuromuscular and Skeletal
Risk C: Monitor
Increased hypotensive effects
Decreased Antihypertensive Effects
Risk D: Consider an alternate
Amifostine: Increased hypotensive effects; withhold antihypertensive therapy for 24 hours following infusion of amifostine if possible
Obinutuzumab: Increased hypotensive effects; withhold antihypertensive include for 12 hours before and 1 hour after infusion of obinutuzumab.
Risk X: Avoid
Bromperidol: Decreased effects of fenoldopam
Pregnancy: Risk factor B
Safety and efficacy data for use in pregnancy has not been established; however, no fetal harm was evident in animal studies.
Allergy to propylene glycol and/or sulfites.
In pediatric patients, tachycardia may occur and may last up to 4 hours at doses greater than 0.8 mcg/kg/minute.
Routine vitals such as blood pressure and heart rate in addition to serial electrocardiograms (ECGs), renal/hepatic function tests, and serum potassium require monitoring during fenoldopam infusion.
A hypertensive crisis must be treated expeditiously and with the appropriate medications. Managing a hypertensive emergency requires a team-based approach starting in the emergency department or the intensive care unit, which includes the active participation of nurses and physicians from many specialties. During a hypertensive crisis, the healthcare team must coordinate patient care, which includes:
Besides the physicians, the nurse and pharmacist must be fully aware of the drug's adverse reactions and monitor the patient. The pharmacist should be fully aware that the drug is not administered to patients with glaucoma and asthma or used in combination with a beta-blocker for fear of inducing severe hypotension. Nurses must administer the drug according to appropriate dosing and protocol, and report any adverse reactions to the healthcare team. All of the above represent examples of the type of collaborative interprofessional communication necessary for successful fenoldopam therapy to optimize patient outcomes. [Level V]
Once the patient has been stabilized, other healthcare personnel outside the emergency department will be involved in the patient's care. The type of providers involved in outpatient care differs based on etiology. However, a family practitioner or internist will always be responsible for initiating continuation of the patient's care.
Fenoldopam has been shown to have a renal protective effect in hypertensive patients with chronic kidney disease. However, a meta-analysis of many studies reveals that the drug can lower blood pressure effectively and decrease acute kidney injury, but in the long run, fenoldopam has no impact on renal replacement or the 30-day, in-patient mortality. (Level II)
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