Dopamine

Dopamine is an Inotropic agent belonging to Alpha Adrenergic Agonist.

Dopamine is approved for the treatment of Shock; hemodynamic imbalance, hypotension, and heart failure. It is also used in the treatment of Bradycardia and Solid organ Transplants.

Dopamine is rapidly absorbed from the small intestine and is widely distributed, and gets metabolized in the kidney, liver, and plasma by monoamine oxidase and COMT to inactive metabolites, homovanillic acid, and 3,4-dihydroxyphenylacetic acid and approx. 25% is metabolized to norepinephrine. Dopamine gets excreted via urine with a half-life of approx. 2 minutes.

The common side effects associated with Dopamine include headache, sedation, Gynecomastia, mydriasis, dizziness, asthenia, asthma attacks, dry mouth, vomiting, fatigue and gangrene of extremities, etc.

Dopamine is available in the dosage form of infusion solution D5W, and injectable solution.

Dopamine is available in India, Europe, the USA, and China.

Dopamine, belonging to Alpha Adrenergic agonist, acts as an inotropic agent. Dopamine is a peripheral vasostimulant used to treat low blood pressure, low heart rate, and cardiac arrest. Low infusion rates act on the visceral vasculature to produce vasodilation, including the kidneys, resulting in increased urinary flow.

Dopamine stimulates dopaminergic receptors at lower doses producing renal and mesenteric vasodilation; at higher doses stimulates both dopaminergic and β1-adrenergic receptors producing cardiac stimulation and renal vasodilation; at large doses stimulates α-adrenergic receptors. In the brain, Dopamine acts as an agonist to the five dopamine receptor subtypes (D1, D2, D3, D4, D5).

The onset of action of Dopamine occurs within 5 minutes.

The Duration of Action for Dopamine is within 2-10 minutes.

The Tmax was found within 1 hour and Cmax in blood reached up to 2 µg/L.

• Dopamine is available in the form of infusion solution D5W, and injectable solution.
• To be administered by intravenous infusion only after dilution with the appropriate diluents. Dopamine hydrochloride should be infused into a large vein whenever possible, preferably with an infusion syringe pump system. Special care should be given to the perfusion rate in order to avoid inadvertent boluses.

Dopamine is approved for the treatment of Shock; hemodynamic imbalance; hypotension; heart failure. It is also used in the treatment of Bradycardia and Solid organ Transplant

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.

Dopamine is approved for use in the following clinical indications:

• Shock

Dopamine increases myocardial contractility, selectively redistributes perfusion to essential viscera, and allows a pharmacologic titration of effect, it is a logical first-choice catecholamine for treatment of Shock and refractory heart failure.

• Hemodynamic Imbalance:

In the treatment of hemodynamic imbalance, Dopamine stimulates cardiac muscle contraction and increases the heart rate, which results in improved cardiac output. Its vasodilatory effects improve the blood flow to vital organs such as the kidneys, enhancing their function.

• Hypotension

Dopamine is a peripheral vasostimulant used to treat low blood pressure, low heart rate, and cardiac arrest. Low infusion rates (0.5 to 2 micrograms/kg per minute) act on the visceral vasculature to produce vasodilation, including the kidneys, resulting in increased urinary flow. Intermediate infusion rates (from 2 to 10 micrograms/kg/min) stimulate myocardial contractility and increase electrical conductivity in the heart leading to increased cardiac output.

• Heart failure

Dopamine infusions in the range of 0.5-4 micrograms/kg per minute are beneficial in the acute treatment of congestive heart failure because of the renal effects and the positive inotropic effects of direct beta1 adrenoceptor stimulation.

Dopamine is indicated for the control of ventricular response rate in adult patients with chronic atrial fibrillation.

• Although not approved there have been certain off-label uses documented for Dopamine:

Bradycardia

Solid organ Transplant.

The dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Dopamine is available in various dosage strength : 40 mg/100 ml, 80 mg/100 ml, 160 mg/100 ml, 320 mg/100 ml.

Dopamine is available in the form of infusion solution D5W, and injectable solution.

Dopamine is approved for the treatment of Shock; hemodynamic imbalance; hypotension; heart failure. It is also used in the treatment of Bradycardia and Solid organ Transplant

Heart Failure: Limit sodium to no more than 2,300 mg a day (eating only 1,500 mg a day is an even more effective goal). Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories.

The dietary restriction should be individualized as per the patient's requirements.

Dopamine may be contraindicated in the following

• Dopamine is contraindicated in patients with pheochromocytoma or uncorrected tachyarrhythmias including ventricular fibrillation and ventricular tachycardia.
• Decreased the dopamine dose if an increased number of ectopic beats is observed.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows

• Tissue Ischemia

Administration of Dopamine to patients who are hypotensive from hypovolemia can result in severe peripheral and visceral vasoconstriction, reduced renal perfusion and hypouresis, tissue hypoxia, lactic acidosis, and poor systemic blood flow despite "normal" blood pressure. Address hypovolemia prior to initiating Dopamine in Dextrose Injection.

Gangrene of the extremities has occurred in patients with occlusive vascular disease or who received prolonged or high-dose infusions. Monitor for changes to the skin of the extremities in susceptible patients.

Extravasation of Dopamine HCl in Dextrose Injection may cause necrosis and sloughing of surrounding tissue. To reduce the risk of extravasation, infuse into a large vein, check the infusion site frequently for free flow, and monitor for signs of extravasation.

• Emergency Treatment of Extravasation

To prevent sloughing and necrosis in areas in which extravasation has occurred, infiltrate the ischemic area as soon as possible, using a syringe with a fine hypodermic needle with:

• 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% Sodium Chloride Injection in adults.
• 0.1 to 0.2 mg/kg of phentolamine mesylate up to a maximum of 10 mg per dose in pediatric patients.

Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours

• Cardiac Arrhythmias

Dopamine may cause arrhythmias. Monitor patients with arrhythmias and treat them appropriately.

• Hypotension after Abrupt Discontinuation

Sudden cessation of the infusion rate may result in marked hypotension. Gradually reduce the infusion rate while expanding blood volume with intravenous fluids.

• Severe Hypersensitivity Reactions due to Sodium Metabisulfite Excipient

Dopamine HCl in Dextrose Injection, contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Consumption of alcohol is not recommended while receiving this medicine as it may increase the risk of adverse effects and lowers the blood pressure.

Use has been associated with decreased prolactin levels in non-nursing women and in those with hyperprolactinemia; this drug may affect milk production during lactation.

Pregnancy Category C

Animal studies have revealed no evidence of teratogenic effects due to Dopamine. However, in one study, administration of Dopamine to pregnant rats resulted in a reduced survival rate of the newborn and a potential for cataract formation in the survivors. There are no adequate and well-controlled studies in pregnant women and it is not known if Dopamine crosses the placental barrier. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if, in the judgment of the physician, the potential benefit justifies the potential risk to the fetus.

Limit excessive Caffeine intake (examples: coffee, tea, colas, chocolate, and some herbal supplements) while taking Dopamine and avoid medicines containing additional Caffeine whenever possible.

Taking a high amount of Caffeine with Dopamine can gain the risk of nausea, nervousness, palpitations, problems with sleep, rapid heartbeat, or other side effects.

The adverse reactions related to the molecule Dopamine can be categorized as

• Common Adverse effects:

Hemodynamic compromise, Dizziness, peripheral ischemia, dry mouth, asthenia, and somnolence.

• Less Common adverse effects:

High Blood Pressure, Angina, A Type Of Chest Pain, Slow Heartbeat, Ventricular Arrhythmias, A Type Of Abnormal Heart Rhythm, Low Blood Pressure, Trouble Breathing, and Fast Heartbeat.

• Rare adverse effects:

The clinically relevant drug interactions of Dopamine are briefly summarized here.

• Because Dopamine is metabolized by monoamine oxidase (MAO), inhibition of this enzyme prolongs and potentiates the effect of Dopamine. Patients who have been treated with MAO inhibitors within 2 to 3 weeks prior to the administration of Dopamine should receive initial doses of Dopamine no greater than one-tenth of the usual dose.
  
• Concurrent administration of Dopamine and diuretic agents may produce an additive or potentiating effect on urine flow.
• Tricyclic antidepressants may potentiate the pressor response to adrenergic agents.
• Cardiac effects of Dopamine are antagonized by beta-adrenergic blocking agents, such as propranolol and metoprolol. The peripheral vasoconstriction caused by the high doses of Dopamine is antagonized by alpha-adrenergic blocking agents. Dopamine-induced renal and mesenteric vasodilation is not antagonized by either alpha- or beta-adrenergic blocking agents.
• Haloperidol appears to have strong central antidopaminergic properties. Haloperidol and haloperidol-like drugs suppress the dopaminergic renal and mesenteric vasodilation induced at low rates of dopamine infusion.
• Cyclopropane or halogenated hydrocarbon anesthetics increase cardiac autonomic irritability and may sensitize the myocardium to the action of certain intravenously administered catecholamines, such as Dopamine. This interaction appears to be related both to pressor activity and to beta-adrenergic stimulating properties of these catecholamines and may produce ventricular arrhythmias and hypertension. Therefore, EXTREME CAUTION should be exercised when administering dopamine HCl to patients receiving cyclopropane or halogenated hydrocarbon anesthetics. It has been reported that results of studies in animals indicate that dopamine-induced ventricular arrhythmias during anesthesia can be reversed by propranolol.
• The concomitant use of vasopressors and some oxytocic drugs may result in severe persistent hypertension.
• Administration of phenytoin to patients receiving Dopamine has been reported to lead to hypotension and bradycardia. It is suggested that in patients receiving Dopamine, alternatives to phenytoin should be used if anticonvulsant therapy is needed.

Pediatric Use

Safety and effectiveness in children have not been established. Dopamine has been used in a limited number of pediatric patients, but such use has been inadequate to fully define proper dosage and limitations for use.

Geriatric Use

Clinical studies of Dopamine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should start at the low end of the dosing range, reflecting the frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy

Symptoms: Excessive blood pressure elevation, vasoconstriction.

Management: Reduce dose or discontinue infusion. If these measures fail, may consider administration of phentolamine mesylate.

Pharmacodynamics:

Dopamine’s onset of action occurs within five minutes of intravenous administration and the duration of action is less than about ten minutes. Dopamine effects are dosage-dependent.

• At <5mcg/kg/minute, Dopamine activates dopamine D1 and D2 receptors in the renal, mesenteric, and coronary vasculature causing vasodilation.
• At 5 to 10 mcg/kg/minute, Dopamine activates beta-1 receptors enhancing heart rate and contractility.
• At 10 mcg/kg/minute, dopamine HCl activates alpha-1 receptors causing vasoconstriction and increased blood pressure

Pharmacokinetics :

• Absorption

Dopamine is rapidly absorbed from the small intestine.

• Distribution

Following intravenous administration, Dopamine is widely distributed in the body but does not cross the blood-brain barrier to a significant extent. The half-life of Dopamine in adults is less than 2 minutes.

• Metabolism

About 75% of Dopamine is metabolized by monoamine oxidase (MAO) and catechol O-methyl transferase (COMT) in the liver, kidney, and plasma to the inactive compounds homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid, and about 25% is metabolized to norepinephrine in the adrenergic nerve terminals.

• Excretion

About 80% of Dopamine is renally excreted as inactive metabolites within 24 hours. Dopamine is stored in vesicles or diffused back into the plasma.

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