Dopamine

Mechanism

Mechanism of Action

Immediate metabolic precursor of norepinephrine that exerts a direct agonist effect on dopamine receptors, β₁ and α₁ in a manner strictly dependent on the infusion dose administered:

Infusion Rate and Receivers

• Low Dose (0.5-2 µ g/kg/min): Selective activation of renal, mesenteric and coronary dopaminergic receptors D₁ and D₂, causing local vasodilation.
• Medium dose (2-10 µ g/kg/min): Direct stimulation of myocardial β₁ receptors and indirect release of presynaptic norepinephrine, predominantly increasing cardiac contractility and cardiac output.
• High dose (>10 µ g/kg/min): Predominant activation of α₁ adrenergic receptors that produces generalized vasoconstriction and increased SVR.

Physiological Consequences

• Renal Effect: The D₁ stimulus increases glomerular filtration through vasodilation of the afferent and efferent arterioles, although it has no impact on the reduction of established renal failure.
• Cardiac Effect: The β₁ stimulus increases stroke volume with a parallel increase in the risk of disruptive sinus tachycardia and atrial arrhythmias.
• Pressor Effect: The α₁ stimulus at maximum doses raises mean arterial pressure at the expense of an increase in myocardial afterload.

Pharmacokinetics

Key Pharmacokinetics

• Routes: Mandatory continuous IV infusion via central line to avoid necrosis due to tissue extravasation.
• Distribution: Wide in systemic tissues; does not cross the active blood-brain barrier at ordinary therapeutic doses.
• Metabolism: Hepatic, renal and plasma through the enzymes MAO and COMT towards homovanillic acid (AHV) and other metabolites. A fraction of 25% is hydroxylated to norepinephrine in sympathetic nerve endings.
• Half-life: Approximately 2 minutes.
• Excretion: Renal in the form of inactive metabolites.

Indicators and dose

Approved and Off-label Indications

Approved: Treatment of cardiogenic, distributive or septic shock once hypovolemia has been corrected, symptomatic bradycardia refractory to atropine or temporary pacemaker.

Off-label: Historically used at low doses for renal prophylaxis ("renal dose"), a practice currently proscribed and discouraged by available scientific evidence due to the absence of demonstrated clinical benefits.

Dosage and Adjustments

Shock / Bradycardia: Initial infusion of 2 to 5 µ g/kg/min IV, progressively titrated according to hemodynamic objectives up to a maximum of 20-50 µ g/kg/min.

Renal/hepatic adjustment: No specific dose adjustments are recommended based on standardized scales, closely monitoring renal clearance.

Security

Contraindications

Absolute: Pheochromocytoma (risk of catastrophic adrenergic discharge), uncontrolled ventricular or atrial tachyarrhythmias.

Relative: Occlusive peripheral vascular disease, active myocardial ischemia of recent evolution.

Adverse Effects (ADR)

Common: Limiting sinus tachycardia, frequent ventricular extrasystoles, dyspnea, pulsating headache, nausea and vomiting due to stimulation of the brain chemoreceptor trigger zone.

Serious: High ventricular response arrhythmias (atrial fibrillation with rapid response), refractory myocardial ischemia, severe focal tissue necrosis, peripheral dry gangrene in patients with compromised perfusion due to high doses.

Interactions

MAOI: Extreme and prolonged potentiation of the pressor effect; requires reduction of the dopamine dose to one tenth (1/10) of the conventional dose.

Phenytoin: Induction of dose-dependent profound hypotension and seizures has been described when co-administered intravenously.

Pregnancy and Breastfeeding

FDA Classification: Category C. Should be reserved only if the expected benefits outweigh the potential risk of fetal hypoxia secondary to generalized systemic vasoconstriction.