DOPAMINE HCL FRESENIUS SOLUTION FOR INFUSION

Indications

• Acute heart failure
• Cardiogenic shock
• Septic shock
• Hypotension
• Renal failure (to enhance renal perfusion)

Dosage

Adults: Dopamine is typically administered as

Mechanism of action

Dopamine acts as a precursor to norepinephrine and exerts its effects through agonist action on beta-adrenoceptors, leading to positive chronotropic and inotropic effects on the heart. At low infusion rates (0.5-2 ug/kg/min), dopamine primarily stimulates dopaminergic receptors, enhancing renal and mesenteric blood flow. At higher doses (>4-6 ug/kg/min), it stimulates alpha-adrenergic receptors, causing vasoconstriction and increased afterload. The effects are mediated through increased cyclic adenosine monophosphate (cAMP) levels, enhancing calcium transport within cardiac cells.

Pharmacodynamics

Dopamine's pharmacodynamic profile includes its ability to increase heart rate and contractility via beta-1 receptor stimulation. It also improves renal perfusion at lower doses through D1 receptor activation. The physiological effects depend on the infusion rate, with lower rates promoting renal blood flow and higher rates leading to increased peripheral vascular resistance and blood pressure due to alpha-adrenergic receptor activation. The drug's action is dose-dependent, with significant implications for its clinical use in various forms of shock and heart failure.

Pharmacokinetics

Dopamine is administered intravenously and has a short half-life, typically around 2 minutes, due to rapid metabolism by monoamine oxidase and catechol-O-methyltransferase. It is distributed throughout the body, primarily affecting the central nervous system and cardiovascular system. The onset of action is immediate upon infusion, and the effects are closely tied to the infusion rate, requiring careful monitoring during administration to achieve the desired therapeutic outcomes.

Interactions

• antipsychotics, second generation (amisulpride, olanzapine, paliperidone, quetiapine, risperidone) + dopamine receptor agonists: Severe (decreases effects)
• benperidol + dopamine receptor agonists: Severe (decreases effects)
• droperidol + dopamine receptor agonists: Severe (decreases effects)
• flupentixol + dopamine receptor agonists: Severe (decreases effects)
• haloperidol + dopamine receptor agonists: Severe (decreases effects)
• phenothiazines + dopamine receptor agonists: Severe (decreases effects)
• pimozide + dopamine receptor agonists: Severe (decreases effects)
• sulpiride + dopamine receptor agonists: Severe (decreases effects)
• zuclopenthixol + dopamine receptor agonists: Severe (decreases effects)
• ergometrine + dopamine: Severe (increases risk of peripheral vasoconstriction)

Pregnancy

Dopamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dopamine is excreted in human milk. Caution is advised when administering to nursing women.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Indications

• Cardiogenic shock
• Severe hypotension
• Reversal of hypotension from spinal or epidural anaesthesia

Dosage

Children: Neonate: Initially 3 micrograms/kg/minute (maximum dose 20 micrograms/kg/minute), adjusted according to response.

Adults: Initially 2–5 micrograms/kg/minute, titrated according to response. The maintenance dose is typically between 3-10 micrograms/kg/minute, adjusted based on individual patient response.

Mechanism of action

Dopamine acts on specific adrenergic receptors, predominantly beta1 receptors in cardiac muscle, leading to increased myocardial contractility. At low doses, it also stimulates dopaminergic receptors, resulting in vasodilation of renal and mesenteric blood vessels, which enhances renal blood flow. As doses increase, dopamine's vasopressor effects become more pronounced due to its action on alpha-adrenergic receptors, causing peripheral vasoconstriction.

Pharmacodynamics

Dopamine's pharmacodynamics are dose-dependent. At low doses (1-5 micrograms/kg/min), it primarily acts on dopaminergic receptors, promoting renal vasodilation and enhancing glomerular filtration rate. At moderate doses (5-10 micrograms/kg/min), it increases cardiac contractility without significantly affecting heart rate. At high doses (>10 micrograms/kg/min), it predominantly stimulates alpha-adrenergic receptors, leading to increased systemic vascular resistance and blood pressure.

Pharmacokinetics

Dopamine is administered intravenously and has a rapid onset of action. It is metabolized in the body by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) to inactive metabolites. Its half-life is approximately 2 minutes, necessitating continuous infusion for sustained effects. The drug is excreted primarily in the urine as metabolites.

Contra-indications

• Phaeochromocytoma
• Tachyarrhythmias
• Severe peripheral vascular disease

Adverse effects

• Angina pectoris
• Anxiety
• Arrhythmias
• Azotaemia
• Cardiac conduction disorders
• Dyspnoea
• Headache
• Hypertension
• Mydriasis
• Nausea
• Palpitations
• Piloerection
• Polyuria
• Tremor
• Vomiting

Interactions

• Sympathomimetics
• Inotropic agents
• MAO inhibitors
• Certain antidepressants

Precautions

• Use the lowest effective dose to minimize the risk of peripheral ischaemia.
• Invasive monitoring is recommended during administration in critical care settings.
• Caution in patients with pre-existing cardiovascular disease.

Pregnancy

No evidence of harm in animal studies; manufacturer advises use only if potential benefit outweighs risk.

Breast-feeding

May suppress lactation; not known to be harmful.

Storage

Store in a refrigerator (2–8°C); consult product literature for storage conditions after dilution.

Formulations

• Dopamine hydrochloride solution for infusion

Mechanism of action

Dopamine is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings. In the brain, dopamine acts as an agonist to the five dopamine receptor subtypes (D1, D2, D3, D4, D5). Dopamine acts on cardiac beta-1-adrenergic receptors and has dosage-dependent effects on peripheral receptors. Dopamine receptors are activated at a low infusion rate (0.5-2 ug/kg/min). At a rate > 4-6 ug/kg/min, peripheral alpha-adrenergic receptors are activated, and vasoconstriction and increased afterload may occur. The effects that dopamine produces in the body are directly related to its actions on alpha, beta, and dopaminergic receptor sites. When these receptors are stimulated cyclic adenosine monophosphate levels increase, increasing calcium transport into the cell. The amount of dopamine determines which receptors are predominantly stimulated. At infusion rates more than 5 to 10 ug/kg/minute, alpha-receptor stimulation predominates, resulting in peripheral vasoconstriction, with a rise in blood pressure. At infusion rates greater than 20 ug/kg/minute, the vasoconstrictive effect can be greater than the beta1 effect. The cardiovascular effects of dopamine are mediated by several distinct types of receptors that vary in their affinity for dopamine. At low concentrations, the primary interaction of dopamine is with vascular D1 receptors, especially in the renal, mesenteric, and coronary beds. By activating adenylyl cyclase and raising intracellular concentrations of cyclic AMP, D1 receptor stimulation leads to vasodilation. Infusion of low doses of dopamine causes an increase in glomerular filtration rate, renal blood flow, and Na+ excretion. Activation of D1 receptors on renal tubular cells decreases sodium transport by cAMP-dependent and cAMP-independent mechanisms. Increasing cAMP production in the proximal tubular cells and the medullary part of the thick ascending limb of the loop of Henle inhibits the Na+-H+ exchanger and the Na+,K+-ATPase pump. The renal tubular actions of dopamine that cause natriuresis may be augmented by the increase in renal blood flow and the small increase in the glomerular filtration rate that follow its administration. The resulting increase in hydrostatic pressure in the peritubular capillaries and reduction in oncotic pressure may contribute to diminished reabsorption of sodium by the proximal tubular cells. At somewhat higher concentrations, dopamine exerts a positive inotropic effect on the myocardium, acting on beta1 adrenergic receptors. Dopamine also causes the release of norepinephrine from nerve terminals, which contributes to its effects on the heart. Tachycardia is less prominent during infusion of dopamine than of isoproterenol. Dopamine usually increases systolic blood pressure and pulse pressure and either has no effect on diastolic blood pressure or increases it slightly. Total peripheral resistance usually is unchanged when low or intermediate doses of dopamine are given, probably because of the ability of dopamine to reduce regional arterial resistance in some vascular beds, such as mesenteric and renal, while causing only minor increases in others. At high concentrations, dopamine activates vascular alpha1 receptors, leading to more general vasoconstriction. For more Mechanism of Action (Complete) data for DOPAMINE (9 total), please visit the HSDB record page.

Pharmacodynamics

Dopamine is a natural catecholamine formed by the decarboxylation of 3,4-dihydroxyphenylalanine (DOPA). It is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings.