Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: BrePco Biopharma Ltd., Suite One, The Avenue, Beacon Court, Sandyford, Dublin D18HX31, Ireland
Pharmacotherapeutic group: Cardiac therapy, adrenergic and dopaminergic agents
ATC code: C01CA04
Dopamine hydrochloride stimulates adrenergic receptors of the sympathetic nervous system. Dopamine hydrochloride has principally a direct stimulatory effect on β1-adrenergic receptors, but also appears to have an indirect effect by releasing norepinephrine from its storage sites. Dopamine hydrochloride also appears to act on specific dopaminergic receptors in the renal, mesenteric, coronary, and intracerebral vascular beds to cause vasodilation. Dopamine hydrochloride has little or no effect on β2-adrenergic receptors.
At higher doses (10 to 20 μg/kg/min), dopamine hydrochloride can also stimulate alpha-1 receptors, resulting in vasoconstriction and increased peripheral vascular resistance.
The main effects of dopamine hydrochloride depend on the dose administered.
In IV doses of 0.5-2 μg/kg/min, dopamine hydrochloride acts predominantly on dopaminergic receptors; in IV doses of 2-10 μg/kg/min, dopamine hydrochloride also stimulates β1-adrenergic receptors, resulting in an increase of cardiac output. At higher doses, dopamine hydrochloride also stimulates alpha-1 adrenergic receptors. This results in vasoconstriction, increased peripheral vascular resistance, and an increase in blood pressure. The pressor effect of dopamine hydrochloride can be used to raise blood pressure in cases of hypotension or shock.
Vasoconstriction induced by dopamine hydrochloride, or any other vasoactive agent, can affect both the peripheral vascular system and the pulmonary vascular system. This can lead to changes in peripheral vascular resistance and blood pressure, as well as pulmonary vascular resistance (PVR).
Premature infants often have physiological differences compared to full-term infants and older children. One significant difference is the maturation of adrenergic receptors, including beta-1 receptors and these receptors may not be fully developed and may exhibit a variable response to dopamine hydrochloride, which may have a more or less pronounced effect on cardiac contractility compared to older infants or adults.
Some premature infants may show a robust positive inotropic response, while others may have a more limited response.
These differences in receptor maturation and individual variability require careful monitoring and titration of dopamine hydrochloride to optimise cardiac function while minimizing the risk of adverse effects.
Orally administered dopamine hydrochloride is rapidly metabolised in the gastrointestinal tract. Following IV administration, the onset of action of dopamine hydrochloride occurs within 5 minutes, and dopamine hydrochloride has duration of action of less than 10 minutes.
Dopamine is widely distributed in the body but does not cross the blood-brain barrier to a substantial extent. It is not known if dopamine crosses the placenta.
Dopamine hydrochloride has a plasma half-life of about 2 minutes. Dopamine hydrochloride is metabolised in the liver, kidneys, and plasma by MAO and catechol-O-methyltransferase to the inactive compounds homovanillic acid (HVA) and 3, 4-dihydroxyphenylacetic acid. In patients receiving MAO inhibitors, the duration of action of dopamine hydrochloride may be as long as 1 hour. About 25% of a dose of dopamine hydrochloride is metabolised to norepinephrine within the adrenergic nerve terminals.
Dopamine hydrochloride is excreted in urine principally as HVA and its sulfate and glucuronide conjugates and as 3, 4-dihydroxyphenylacetic acid. A very small fraction of a dose is excreted unchanged. Following administration of radio labelled dopamine hydrochloride, approximately 80 % of the radioactivity reportedly is excreted in urine within 24 hours.
Elimination half-life in neonates is between 5 and 11 minutes. In critically ill infants and children clearance reportedly ranges from 48 to 168 mL/kg/min with the higher values reportedly in younger patients.
Clearance of dopamine hydrochloride is unpredictable in infants, particularly neonates. Clearance may be as much as 2-fold greater in those < 2 years of age.
Substantial interindividual variation was seen in dopamine hydrochloride pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine hydrochloride.
Available data suggest that dopamine hydrochloride and pharmacokinetics are similar to those in adults. Wide interindividual variability has been noted. A consistent relationship between clearance and age has not been demonstrated.
There is no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of this summary of product characteristics.
Standardized reproductive toxicity studies were not performed for dopamine hydrochloride. Studies available show conflicting results.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.