Domina

Composition:

Each 1 ml solution contains 40mg Dopamine Hydrochloride.

Excipients:

Hydrochloric Acid, Sodium Metabisulphite, Sodium Hydroxide, Water for injection.

Mechanism of Action:

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.

Pharmacodynamic:

The predominant effects of dopamine are dose-related.

-At low rates of infusion (0.5 - 2mcg/kg/min) dopamine cause vasodilation that is presumed to be due to a specific agonist action on dopamine receptors in the renal, mesenteric, coronary, and intracerebral vascular beds. 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 not associated with a decrease in osmolality of the urine.

-At intermediate rates of infusion (2 - 10mcg/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. Total peripheral resistance (alpha effects) at low and intermediate doses is usually unchanged.

-At higher rates of infusion (10 – 20mcg/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 alpha adrenoceptors predominates and vasoconstriction may compromise the circulation of the limbs and override the dopaminergic effects of dopamine, reversing renal dilation and naturesis.

Pharmacokinetic:

Absorption: Following IV administration, the onset of action of dopamine occurs within 5 minutes, and the drug has duration of action of less than 10 minutes.

Distribution: The drug 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.

Excretion: Dopamine has a plasma half-life of about 2 minutes. Dopamine is metabolized in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-0-methyltransferase to the following inactive compounds: homovanillic acid (HVA) and 3, 4-dihydroxyphenylacetic acid.

In patients receiving MAO inhibitors, the duration of action of dopamine may be as long as 1hour. About 25% of a dose of dopamine is metabolized to norepinephrine within the adrenergic nerve terminals.

Dopamine 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.

Indications:

Anapam is indicated for the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarction, trauma, endotoxic septicemia, open-heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure.

Poor Perfusion of Vital Organs - In a number of oliguric or anuric patients, administration of Dopamine HCl has resulted in an increase in urine flow, which in some cases reached normal levels. Dopamine HCl may also increase urine flow in patients whose output is within normal limits and thus may be of value in reducing the degree of pre-existing fluid accumulation.

Low Cardiac Output - Increased cardiac output is related to dopamine’s direct inotropic effect 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).

Hypotension - Hypotension due to inadequate cardiac output can be managed by administration of low to moderate doses of dopamine HCl which have little effect on SVR. At high therapeutic doses, dopamine’s alpha-adrenergic activity becomes more prominent and thus may correct hypotension due to diminished SVR.

Contraindications:

Hypersensitivity to the active substance or to any of the excipients.
Patients with phaeochromocytoma or hyperthyroidism.
The presence of uncorrected atrial or ventricular tachyarrhythmia or ventricular fibrillation.

Dosage And Administration:

Anapam is administered by intravenous infusion only after dilution with the appropriate diluents.

Adults:

Begin infusion of dopamine hydrochloride solution at doses of 2.5microgram/kg/min in patients who are likely to respond to modest increments of heart force and renal perfusion.

In more severe cases, administration may be initiated at a rate of 5mcg/kg/min and increased gradually in 5 to 10mcg/kg/min increments up to 20 to 50mcg/kg/min as needed. If doses in excess of 50mcg/kg/min are required, it is advisable to check urine output frequently.

In patients who do not respond to these doses, additional increments of dopamine may be given in an effort to achieve adequate blood pressure, urine flow and perfusion generally.

Dosage of dopamine should be adjusted according to the patient’s response, with particular attention to diminution of established urine flow rate, increasing tachycardia or development of new dysrhythmias as indications for decreasing or temporarily suspending the dosage.

Pediatric Population:

The safety and efficacy of dopamine in pediatric patients has not been established.

Elderly Population:

No variation in dosage is suggested for geriatric patients. However, close monitoring is suggested for blood pressure, urine flow and peripheral tissue perfusion.

Warnings And Precautions:

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.
Patients who have been receiving MAO inhibitors prior to the administration of dopamine HCl will require substantially reduced dosage.
Careful monitoring of the following indices is necessary during dopamine HCl infusion, as with any adrenergic agent: blood pressure, urine flow, and, when possible, cardiac output and pulmonary wedge pressure.
Prior to treatment with dopamine HCl, hypovolemia should be fully corrected, if possible, with either whole blood or plasma as indicated. Monitoring of central venous pressure or left ventricular filling pressure may be helpful in detecting and treating hypovolemia.
If a disproportionate increase in diastolic blood pressure and a marked decrease in pulse pressure are observed in patients receiving dopamine HCl, the rate of infusion should be decreased and the patient observed carefully for further evidence of predominant vasoconstrictor activity, unless such effect is desired.
If an increased number of ectopic beats are observed, the dose should be reduced if possible.
At lower infusion rates, if hypotension occurs, the infusion rate should be rapidly increased until adequate blood pressure is obtained. If hypotension persists, dopamine HCl should be discontinued and a more potent vasoconstrictor agent such as norepinephrine should be administered.
Dopamine HCl should be infused into a large vein whenever possible to prevent the possibility of extravasation into tissue adjacent to the infusion site. Extravasation may cause necrosis and sloughing of surrounding tissue. Large veins of the antecubital fossa are preferred to veins in the dorsum of the hand or ankle. Less suitable infusion sites should be used only if the patient’s condition requires immediate attention. The physician should switch to more suitable sites as rapidly as possible. The infusion site should be continuously monitored for free flow.
Patients with a history of occlusive vascular disease (for example, atherosclerosis, arterial embolism, Raynaud’s disease, cold injury, diabetic endarteritis, and Buerger’s disease) should be closely monitored for any changes in color or temperature of the skin in the extremities. If a change in skin color or temperature occurs and is thought to be the result of compromised circulation in the extremities, the benefits of continued dopamine HCl infusion should be weighed against the risk of possible necrosis. This condition may be reversed by either decreasing the rate or discontinuing the infusion.
When discontinuing the infusion, it may be necessary to gradually decrease the dose of dopamine HCl while expanding blood volume with intravenous fluids, since sudden cessation may result in marked hypotension.

Side Effects:

Adverse reactions to Dopamine are related to its pharmacological action.

System organ class	frequency	Side effect
Blood and lymphatic system disorders	uncommon	azotemia
Nervous system disorders	common	headache
Nervous system disorders	uncommon	piloerection
Eye disorders	uncommon	mydriasis
Cardiac disorders	common	Ectopic heart beats, tachycardia, anginal pain, palpitation, hypotension, vasoconstriction
Cardiac disorders	uncommon	Aberrant conduction, bradycardia, widened QRS complex, hypertension, gangrene, fatal ventricular arrhythmias have been reported on rare occasions
Respiratory, thoracic and mediastinal disorders	common	dyspnea
Gastrointestinal disorders	common	Nausea, vomiting

Gangrene of the extremities has occurred when high doses were administered for prolonged periods or inpatients with occlusive vascular disease receiving low doses of dopamine HCl.

Drug Interactions:

Anesthetics:

The myocardium is sensitized by the effect of Dopamine, Cyclopropane or halogenated hydrocarbon anesthetics, and these should be avoided. This interaction applies both to pressor activity and cardiac beta-adrenergic stimulation

Alpha and Beta Blockers:

The cardiac effects of Dopamine are antagonized byβadrenergic blocking agents such as Propranolol and Metoprolol, and the peripheral vasoconstriction caused by high doses of dopamine is antagonized byαadrenergic blocking agents. Dopamine-induced renal and mesenteric vasodilation is not antagonized by eitherαorβadrenergic blocking agents

Monoamine Oxidase (MAO) Inhibitors:

MAO inhibitors potentiate the effect of Dopamine and its duration of action. Patients who have been treated with MAO inhibitors prior to administration of Dopamine will therefore require a substantially reduced dosage

Phenytoin:

Administration of IV Phenytoin to patients receiving dopamine has resulted in hypotension and bradycardia, some clinicians recommend that Phenytoin be used with extreme caution, in patients receiving dopamine

Dopamine may increase the effect of diuretic agents.
The ergot alkaloids should be avoided because of the possibility of excessive vasoconstriction.
Tricyclic anti-depressants and guanethidine may potentiate the pressor response to dopamine.
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.
The concomitant use of vasopressors and some oxytocic drugs may result in severe persistent hypertension.

Incompatibilities:

Dopamine should not be added to any alkaline intravenous solutions.
Admixtures containing Gentamicin Sulfate, Cephalothin Sodium, Cephalothin Sodium Neutral or Oxacillin Sodium should be avoided.
Admixtures of Ampicillin and Dopamine in 5% glucose solution are alkaline and incompatible and result in decomposition of both drugs.
Admixtures of Dopamine, Amphotericin B in 5% glucose solution are incompatible as a precipitate form immediately on mixing.

Overdose:

In the case of accidental overdosage, as evidenced by excessive elevation of blood pressure, reduce rate of administration or temporarily discontinue Dopamine HCl until patient’s condition stabilizes. Since dopamine’s duration of action is quite short, no additional remedial measures are usually necessary. If these measures fail to stabilize the patient’s condition, use of the short-acting alpha-adrenergic blocking agent phentolamine should be considered.

Pregnancy:

Animal studies have shown no evidence of teratogenicity effects with dopamine. However, the effect of dopamine on the human fetus is unknown. Therefore, the drug should be used in pregnant women only when the expected benefits outweigh the potential risk to the fetus.

Lactation:

It is not known if dopamine is excreted in breast milk, nor is the effect on the infant known.