Dopamine

DOPAMINE — dopamine hydrochloride injection, solution
General Injectables & Vaccines, Inc

Description

Dopamine Hydrochloride Injection, USP is a clear, practically colorless, aqueous, additive solution for intravenous infusion after dilution. Each mL contains either 40 mg, 80 mg, or 160 mg dopamine HCl, USP (equivalent to 32.3 mg, 64.6 mg and 129.2 mg dopamine base respectively) in Water for Injection, USP, containing 9 mg sodium metabisulfite as an antioxidant. The pH range (2.5 to 5.0) may be adjusted with citric acid and/or sodium citrate. The solution is sterile and nonpyrogenic. Dopamine HCl, a naturally occurring catecholamine, is an inotropic vasopressor agent. Its chemical name is 3,4 dihydroxyphenethylamine hydrochloride and its chemical structure is:

Formula1
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Dopamine HCl is sensitive to alkalis, iron salts and oxidizing agents. DOPAMINE must be diluted in an appropriate, sterile parenteral solution (see DOSAGE AND ADMINISTRATION section) before intravenous administration.

Clinical Pharmacology

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. Dopamine’s onset of action occurs within five minutes of intravenous administration, and with dopamine’s plasma half-life of about two minutes, the duration of action is less than ten minutes. If monoamine oxidase (MAO) inhibitors are present, however, the duration may increase to one hour. The drug is widely distributed in the body but does not cross the blood-brain barrier to a significant extent. Dopamine is metabolized in the liver, kidney, and plasma by MAO and catechol-O-methyltransferase to the inactive compounds homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid. About 25% of the dose is taken up into specialized neurosecretory vesicles (the adrenergic nerve terminals), where it is hydroxylated to form norepinephrine. It has been reported that about 80% of the drug is excreted in the urine within 24 hours, primarily as HVA and its sulfate and glucuronide conjugates and as 3,4-dihydroxyphenylacetic acid. A very small portion is excreted unchanged. The predominant effects of dopamine are dose-related, although actual response of an individual patient will largely depend on the clinical status of the patient at the time the drug is administered. At low rates of infusion (0.5-2 mcg/kg/min) dopamine causes vasodilation that is presumed to be due to a specific agonist action on dopamine receptors (distinct from alpha and beta adrenoceptors) in the renal, mesenteric, coronary, and intracerebral vascular beds. At these dopamine receptors, haloperidol is an antagonist. The vasodilation in these vascular beds is accompanied by increased glomerular filtration rate, renal blood flow, sodium excretion, and urine flow. Hypotension sometimes occurs. An increase in urinary output produced by dopamine is usually not associated with a decrease in osmolarity of the urine. At intermediate rates of infusion (2-10 mcg/kg/min) dopamine acts to stimulate the beta1-adrenoceptors, resulting in improved
myocardial contractility, increased SA rate and enhanced impulse conduction in the heart. There is little, if any, stimulation of the beta2-adrenoceptors (peripheral vasodilation). Dopamine causes less increase in myocardial oxygen consumption than isoproterenol, and its use is not usually associated with a tachyarrhythmia. Clinical studies indicate that it usually increases systolic and pulse pressure with either no effect or a slight increase in diastolic pressure. Blood flow to the peripheral vascular beds may decrease while mesenteric flow increases due to increased cardiac output. At low and intermediate doses, total peripheral resistance (which would be raised by alpha activity) is usually unchanged. At higher rates of infusion (10-20 mcg/kg/min) there is some effect on alpha-adrenoceptors, with consequent vasoconstrictor effects and a rise in blood pressure. The vasoconstrictor effects are first seen in the skeletal muscle vascular beds, but with increasing doses they are also evident in the renal and mesenteric vessels. At very high rates of infusion (above 20 mcg/kg/min), stimulation of alphaadrenoceptors predominates and vasoconstriction may compromise the circulation of the limbs and override the dopaminergic effects of dopamine, reversing renal dilation and natriuresis.

Indications

DOPAMINE is indicated for the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarctions, trauma, endotoxic septicemia, open heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure. Where appropriate, restoration of blood volume with a suitable plasma expander or whole blood should be instituted or completed prior to administration of DOPAMINE. Patients most likely to respond adequately to DOPAMINE are those in whom physiological parameters, such as urine flow,
myocardial function, and blood pressure, have not undergone profound deterioration. Multiclinic trials indicate that the shorter the time interval between onset of signs and symptoms and initiation of therapy with volume correction and DOPAMINE, the better the prognosis.
Poor Perfusion of Vital Organs: Urine flow appears to be one of the better diagnostic signs by which adequacy of vital organ perfusion can be monitored. Nevertheless, the physician should also observe the patient for signs of reversal of confusion of comatose condition. Loss of pallor, increase in toe temperature, and/or adequacy of nail bed capillary filling may also be used as indices of adequate dosage. Clinical studies have shown that when DOPAMINE is administered before urine flow has diminished to levels approximating 0.3 mL/minute, prognosis is more favorable. Nevertheless, in a number of oliguric or anuric patients, administration of DOPAMINE has resulted in an increase in urine flow which in some cases reached normal levels. DOPAMINE may also increase urine flow in patients whose output is within normal limits and thus may be of value in reducing the degree of preexisting fluid accumulation. It should be noted that at doses above those optimal for the individual patient urine flow may decrease, necessitating reduction of dosage. Concurrent administration of DOPAMINE and diuretic agents may produce an additive or potentiating effect.
Low Cardiac Output: Increased cardiac output is related to the direct inotropic effect of DOPAMINE on the myocardium. Increased cardiac output at low or moderate doses appears to be related to a favorable prognosis. Increase in cardiac output has been associated with either static or decreased systemic vascular resistance (SVR). Static or decreased SVR associated with low or moderate increments in cardiac output is believed to be a reflection of differential effects on specific vascular beds with increased resistance in peripheral beds (e.g., femoral) and concomitant decreases in mesenteric and renal vascular beds. Redistribution of blood flow parallels these changes so that an increase in cardiac output is accompanied by an increase in mesenteric and renal blood flow. In many instances the renal fraction of the total cardiac output has been found to increase. The increase in cardiac output produced by DOPAMINE is not associated with substantial decreases in systemic vascular resistance as may occur with isoproterenol.
Hypotension: Hypotension due to inadequate cardiac output can be managed by administration of low to moderate doses of DOPAMINE, which have little effect on SVR. At high therapeutic doses, the alpha adrenergic activity of DOPAMINE becomes more prominent and thus may correct hypotension due to diminished SVR. As in the case of other circulatory decompensation states, prognosis is better in patients whose blood pressure and urine flow have not undergone profound deterioration. Therefore, it is suggested that the physician administer DOPAMINE as soon as a definite trend toward decreased systolic and diastolic pressure becomes evident.

Contraindications

DOPAMINE should not be used in patients with pheochromocytoma.
DOPAMINE should not be administered in the presence of uncorrected tachyarrhythmias or ventricular fibrillation.

Warnings

Do NOT add DOPAMINE to any alkaline diluent solution, since the drug is inactivated in alkaline solution. Patients who have been treated with monoamine oxidase (MAO) inhibitors prior to the administration of DOPAMINE will require substantially reduced dosage. See Drug Interactions, below. 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 nonasthmatic people.

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