Dopamine

Introduction Overview

Generic Name

dopamine

Brand Name

Intropin

Dosage Form

Injection

Drug Class

Catecholamines, Inotropic agents, Vasopressors

Pharmacokinetics

Absorption:
Dopamine is administered exclusively by intravenous infusion, which bypasses gastrointestinal absorption and allows immediate bioavailability. When injected, dopamine achieves rapid onset of action, generally within minutes, which is essential for emergency management of acute hemodynamic compromise such as shock and heart failure. Because it is not absorbed orally and undergoes extensive first-pass metabolism if taken orally, clinical use is limited to parenteral administration.

Distribution:
Following intravenous administration, dopamine distributes primarily within the vascular compartment and extracellular fluid due to its hydrophilic nature. Dopamine has a relatively small volume of distribution, approximately 2–4 L/kg, reflecting limited tissue binding. Dopamine does not readily cross the blood-brain barrier under normal conditions. Plasma protein binding is minimal. Its distribution is influenced by tissue blood flow, which can be altered in shock states.

Metabolism:
Dopamine is extensively metabolized by enzymatic degradation in the liver, kidneys, and plasma. The primary metabolic pathways involve monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), which convert dopamine into inactive metabolites such as homovanillic acid (HVA). Rapid metabolism contributes to dopamine's short plasma half-life of approximately two minutes. Co-administration or recent use of MAO inhibitors can significantly potentiate dopamine's effects by inhibiting its metabolism, leading to increased toxicity risk.

Elimination:
Dopamine and its metabolites are primarily excreted via the kidneys. Less than 2% of the dose is excreted unchanged in urine. Renal function profoundly affects elimination kinetics; impaired renal function may reduce clearance of dopamine metabolites. The drug's brief half-life necessitates continuous infusion to maintain therapeutic plasma concentrations. Hemodynamic responses diminish rapidly upon cessation due to rapid elimination.

Dosage Forms

Available Dosage Forms:
Dopamine injection is commercially available as a sterile concentrate for intravenous use.
- Injection concentrate: Commonly supplied at concentrations such as 40 mg/mL or 160 mg/mL (varies by manufacturer), intended for dilution before infusion.

Dosages for Adults and Adolescents:
- Initial dose for treatment of shock or nonobstructive oliguria: 1 to 5 mcg/kg/min continuous IV infusion.
- Titrated according to response; infusion rates may be increased to more than 50 mcg/kg/min in emergent situations under close monitoring.
- Dose-dependent hemodynamic effects: low doses increase renal perfusion, intermediate doses enhance cardiac output and blood pressure, and high doses elicit vasoconstriction.

Specific Patient Populations:
- Pediatric dosing: for neonates and children, 1 to 20 mcg/kg/min continuous IV infusion titrated to hemodynamic response, with some cases administering up to 50 mcg/kg/min cautiously.
- Patients with renal impairment: dosing titrated carefully as altered elimination of metabolites may impact effect and toxicity.
- Patients with cardiac conditions require cautious titration to avoid arrhythmias.

Clinical dosing requires continuous hemodynamic monitoring to adjust infusion rates for optimal therapeutic effect and minimal adverse events.

Mechanism Of Action

Dopamine acts primarily as a naturally occurring endogenous catecholamine neurotransmitter and vasopressor agent with dose-dependent pharmacodynamic effects mediated through stimulation of multiple adrenergic and dopaminergic receptors. At low doses (1–5 mcg/kg/min), dopamine primarily activates dopaminergic D1 receptors located in renal, mesenteric, coronary, and cerebral vascular beds, causing vasodilation and increased blood flow, particularly enhancing renal perfusion and promoting diuresis. This effect comes from relaxation of vascular smooth muscle via increased cyclic AMP.

At intermediate doses (5–15 mcg/kg/min), dopamine additionally stimulates beta-1 adrenergic receptors predominantly in cardiac tissue, resulting in positive inotropic and chronotropic effects. Activation of beta-1 receptors enhances myocardial contractility and heart rate, thus increasing cardiac output and improving perfusion in states of heart failure or shock.

At higher doses (>15 mcg/kg/min), dopamine predominantly stimulates alpha-1 adrenergic receptors on vascular smooth muscle, inducing vasoconstriction, increased systemic vascular resistance, and elevated blood pressure. This vasopressor effect can be beneficial in hypotensive states but carries risk of excessive vasoconstriction and tissue ischemia.

Dopamine's pharmacological profile allows tailored therapy through dose titration, targeting specific receptor subsets to balance improved cardiac function, renal perfusion, and vascular tone. Clinical studies have demonstrated efficacy in treating shock, heart failure, and oliguria by these mechanisms. Comparative to other catecholamines, dopamine's unique receptor selectivity and dose-dependent receptor activation provide advantages in certain clinical scenarios, although emerging evidence has refined its utilization in modern critical care.

Pharmacological Actions

Dose-dependent receptor agonist activity including dopaminergic (D1), beta-1, and alpha-1 adrenergic receptors.
Positive inotropic and chronotropic effects increasing cardiac output and heart rate.
Vasodilation of renal, mesenteric, coronary, and cerebral vessels at low doses improving blood flow and urine output.
Vasoconstrictive properties at high doses to elevate systemic vascular resistance and blood pressure.
Improvement of myocardial contractility and cardiac performance in heart failure and shock.
Enhancement of renal perfusion aiding in prevention or treatment of nonobstructive oliguria.
Sympathomimetic activity mimicking endogenous catecholamines released during stress.
Rapid onset and short duration of action allowing precise titration and control of hemodynamic parameters.
Potential to increase heart rate and oxygen consumption, necessitating cautious use in patients with ischemic heart disease.
Minimal plasma protein binding facilitating rapid pharmacodynamic effects.
Metabolism influenced by monoamine oxidase and catechol-O-methyltransferase enzymes.
Ability to stimulate dopaminergic pathways with central and peripheral physiological implications.
Utility as a vasopressor in critical care settings for management of hypotension and shock states.

Therapeutic Or Clinical Uses

Management of various types of shock including cardiogenic, septic, and hypovolemic shock to improve hemodynamic stability.
Treatment of heart failure by increasing myocardial contractility and cardiac output.
Management of nonobstructive oliguria and acute kidney injury to enhance renal perfusion and urine output.
Acute management of hypotension unresponsive to fluid resuscitation.
Support of blood pressure during and after cardiac surgery or trauma.
Use in intensive care settings to maintain vital organ perfusion.
Treatment of certain states of low cardiac output where inotropic support is necessary.
Occasionally used as adjunct therapy in renal failure to improve renal blood flow.
Improvement of systemic perfusion in critical illness requiring vasopressor support.
Use in emergency medicine for rapid stabilisation of hemodynamics.
May serve as a temporizing agent prior to more definitive interventions.
Adjunct to resuscitation protocols in selected hypotensive patients.
Clinical situations requiring both inotropic and vasopressor support.
Use in neonates and pediatric patients with shock or compromised cardiac function.
Exploratory uses in some off-label indications under specialist supervision.

Side Or Adverse Effects

Tachyarrhythmias including ventricular and supraventricular arrhythmias due to beta-1 receptor stimulation.
Chest pain or angina from increased myocardial oxygen demand in patients with coronary artery disease.
Hypertension secondary to alpha-1 mediated vasoconstriction, especially at higher doses.
Extravasation injury at IV injection site causing tissue necrosis due to potent vasoconstriction.
Headache and anxiety related to sympathomimetic stimulation.
Nausea and vomiting possibly from central nervous system stimulation.
Peripheral ischemia presenting as coldness, numbness, cyanosis, or skin changes in extremities.
Possible development of ischemic complications such as gangrene in predisposed patients.
Increased myocardial workload potentially worsening ischemia in susceptible individuals.
Hypokalemia and metabolic acidosis may occur secondary to enhanced beta-adrenergic effects.
Rare allergic reactions including anaphylaxis although uncommon.
Fluctuations in blood pressure necessitating close cardiovascular monitoring.
Potential for reduced renal perfusion if excessive vasoconstriction occurs.
Shivering, chills, or goosebumps as nonspecific sympathomimetic adverse events.
Dizziness or lightheadedness that might indicate hemodynamic instability.

Precautions

Use cautiously in patients with underlying arrhythmias or ischemic heart disease due to risk of exacerbation.
Monitor infusion site closely to prevent and manage potential extravasation injuries.
Avoid use in patients with pheochromocytoma because of risk of hypertensive crisis.
Caution in patients with metabolic acidosis; dopamine may exacerbate acid-base disturbances.
Close monitoring of blood pressure, heart rate, urine output, and tissue perfusion during administration.
Consider alternative vasopressors in patients with known hypersensitivity to dopamine or catecholamines.
Adjust dosing carefully in patients with impaired renal function.
Assess for concomitant use of MAO inhibitors which can potentiate dopamine effects and toxicity.
Pregnancy and breastfeeding patients should be managed with care, balancing benefit versus potential risks.
Discontinue or adjust therapy if signs of peripheral ischemia develop.
Monitor electrolyte levels, especially potassium, due to adrenergic effects on cellular shifts.
Avoid abrupt discontinuation to prevent hemodynamic instability.
Use only under intensive care or monitored settings by trained healthcare professionals.
Evaluate for potential drug interactions and adjust therapy accordingly.
Educate caregivers and patients about signs of adverse effects requiring urgent medical attention.

Warnings

Risk of tissue necrosis and gangrene from extravasation of intravenous dopamine infusion.
Potential for severe hypertension in patients with pheochromocytoma or when combined with MAO inhibitors.
May precipitate life-threatening cardiac arrhythmias including ventricular tachycardia and fibrillation.
Use with extreme caution in patients with cardiovascular disease, particularly coronary artery disease.
Monitor closely for signs of compromised peripheral circulation such as limb ischemia and blue discoloration.
Not recommended for use in the absence of adequate intravascular volume repletion.
Careful dose titration necessary to avoid abrupt changes in blood pressure and heart rate.
Discontinue if hypersensitivity or anaphylactic reaction occurs.
Neurologic side effects such as anxiety, headache, or tremor may occur requiring dose adjustment.
May interact with other sympathomimetic drugs leading to additive effects.
Reports of severe ischemic injury at infusion site necessitate immediate intervention if suspected.
Patients with metabolic acidosis may experience worsening acid-base status with dopamine use.
Use caution in elderly and frail patients due to variable pharmacodynamics and increased sensitivity.
Dopamine administration should be restricted to hospitals or settings with full resuscitation capabilities.
Sudden discontinuation can lead to rebound hypotension or hemodynamic deterioration.

Contraindication

Known hypersensitivity or allergy to dopamine or any component of the formulation.
Pheochromocytoma, as dopamine can cause hypertensive crisis via excessive catecholamine release.
Uncorrected tachyarrhythmias or ventricular fibrillation due to risk of worsening arrhythmia.
Use with monoamine oxidase inhibitors (MAOIs) within the previous 14 days unless under strict medical supervision.
Patients with uncorrected hypovolemia prior to volume resuscitation, as dopamine may worsen ischemia.
Avoid in patients with severe peripheral vascular disease or risk factors for limb ischemia unless benefits outweigh risks.
Do not use if signs of extravasation or infiltration at IV site are present.
Relative contraindication in patients with hypertrophic cardiomyopathy due to increased myocardial workload.
Contraindicated for administration by routes other than intravenous infusion.
Avoid use in patients with sulfite allergy if the preparation contains sulfites.
Contraindicated in patients with untreated adrenal tumors producing catecholamines.
Should not be used as first-line therapy when other inotropes or vasopressors are indicated specifically.
Patients with severe metabolic acidosis should be carefully evaluated before use.
Infants with immature metabolic pathways require specialist assessment before use.
Contraindicated in situations where benefit to risk ratio is unfavorable as per medical judgment.

Drug Interactions

Monoamine oxidase inhibitors (MAOIs) can potentiate dopamine effects leading to hypertensive crisis and severe toxicity.
Concomitant use with other sympathomimetic drugs can result in additive alpha and beta adrenergic effects, increasing risk of hypertension and arrhythmias.
Tricyclic antidepressants may enhance vasopressor effects of dopamine, increasing risk of cardiovascular adverse events.
Beta-blockers may antagonize the beta-adrenergic effects of dopamine, potentially blunting inotropic and chronotropic responses.
Alpha-adrenergic antagonists may reduce vasoconstrictive effects, leading to altered hemodynamic response.
General anesthetics may sensitize myocardium to arrhythmogenic effects of dopamine.
Diuretics may interact by affecting electrolyte balance, which can be influenced by dopamine therapy.
Drugs that prolong QT interval may have heightened risk when combined with dopamine-induced arrhythmias.
Other vasopressors or inotropes require careful co-administration to avoid overlapping toxicities.
Agents that increase intracellular cyclic AMP may potentiate dopamine effects.
Concomitant use with linezolid or methylene blue may increase risk of hypertensive episodes due to MAO inhibition.
Herbal supplements and over-the-counter medications with sympathomimetic activity may interact adversely.
Drugs affecting renal function can alter dopamine clearance or associated metabolite profiles.
Caution with drugs metabolized by COMT or MAO enzymes as pharmacokinetics may be altered.
Monitoring for interactions is essential during initiation, discontinuation, or dosage changes of concomitant therapies.

Preparations Of The Drug

Dopamine Hydrochloride Injection Concentrate in strengths such as 40 mg/mL and 160 mg/mL for intravenous infusion after dilution.
Premixed Dopamine injection formulations diluted in 5% Dextrose or normal saline for ready-to-use intravenous infusion.
Multi-dose vials intended for hospital use, stored under refrigeration or controlled room temperature conditions.
Single-use vials to reduce risk of contamination and dosing errors in critical care.
Formulations free of preservatives for neonatal and pediatric use where required.
Sterile, pyrogen-free preparations conforming to USP standards for parenteral administration.
Formulations may contain sulfites as stabilizers; labeled appropriately for allergy precautions.
Available commercially under brand name Intropin and generics with equivalent bioequivalence and potency.
Packaging includes multiple vial sizes to accommodate various dosing regimens from small pediatric doses to high adult infusion rates.
Instructions specify dilution and administration protocols to ensure stability and efficacy.
Availability through hospital pharmacies, critical care units, and specialty drug suppliers.
Accompanying prescribing information includes detailed warnings, contraindications, and administration guidance.
Documentation includes compatibility data with various IV fluids and other co-administered drugs in infusion.
Storage and handling recommendations emphasize protection from light and temperature extremes.
Specialty formulations such as dopamine with dextrose for combined fluid and vasopressor therapy in select clinical scenarios.