DOPAMINE

JAHANGIR AHMAD

HISTORY

The function of dopamine as a neurotransmitter was discovered in 1958 by Arvid Carlsson and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden. It was named dopamine because it was a monoamine, and its synthetic precursor was 3,4-dihydroxyphenylalanine . Arvid Carlsson was awarded the 2000 Nobel prize for physiology or medicine for showing that dopamine is not just a precursor of norepinephrine (noradrenaline) and epinephrine (adrenaline) but a neurotransmitter, as well.

INTRODUCTION

Dopamine is an endogenous catecholamine that serve as both a neurotransmitter and a precursor of nor epinephrine synthesis.

When given as an exogenous drug dopamine activates a variety of receptors in dose dependent manner.

Regulates cardiac, vascular and endocrine function.

Each ampoule contains 200 mg /5ml

STRUCTURE

SYNTHESIS

RECEPTORS

o Dopamine acts through D1 , D2 as well as adrenergic alpha and B1 receptors ( But not B2)

o D1 and D2 receptors are the most abundant and widespread in areas receiving a dopaminergic innervation ( namely the striatum ,limbic system, thalamus and hypothalamus) as are D2 receptors, which also occur in the pituitry gland

MECHANISM OF ACTION

At low dose (0.5 to 3 mic /kg /min ):- Selectively activates dopamine

specific receptors in the renal and splanchnic circulation.

Increase blood flow in these region.

Low dose dopamine also directly affects renal tubular epithelial cells.

It causes an increase in urinary Na excretion

Contd…. Intermediate dose (3 to 10 mic /kg /min ):-

It stimulates B1 receptors in the heart and peripheral circulation.

Increases myocardial contractility, increases heart rate and peripheral vasodilatation

It increases myocardial oxygen demand, so when ever dopamine is to be used oxygen must be supplemented

Over all increase in cardiac output Contractile response to dopamine is modest

when compared to dobutamine

Contd…

At high dose (> 10 mic /kg / min ):- Dopamine produces a

progressive activation of alpha receptors in the systemic and pulmonary circulation resulting in progressive pulmonary and systemic vasoconstriction

This vassopressor effect by virtue of increasing ventricular afterload

Contd..

Dopamine not effective orally and does not cross blood brain barrier in sufficient amounts to cause CNS effects.

PHARMACOKINETICS

Rapid metabolism of dopamine mandates its use as a continuous infusion. A portion of the positive inotropic effect of dopamine is due to stimulation of release of endogenous norpinephrine which may predispose to development of cardiac disarrythmias never theless, dopamine is less disarrythmogenic than epinephrine

It is used only intravenously .

CLINICAL USES

Dopamine is often used in situation where both cardiac stimulation and peripheral vasoconstriction desired such as cardiogenic shock

Also used to correct the hypotension in the septic shock .But norepinephrine become the preferred vassopressor in this condition

Low dose is often used in an attempt to prevent or reverse acute renal failure

Contd…

Drug initially administered at a rate of 2 to 5 mic / kg /min . During infusion ,pt require clinical assessments of myocardial function perfusion of vitals organs such as the brain , and the production of urine

Most pts should receive intensive care with monitoring of arterial and venous pressures and ECG

Reduction in urine flow ,tachycardia or the development of arrhythmias may be indications to slow or terminate the infusion

DOPAMINE IN PULMONARY OEDEMA

The sympathomimetic amines dopamine is potent ionotropic agents

Used in pulmonary edema Forcefully contracts the heart and

thus decreases the pulmonary load

DOPAMINE INFUSION IN WHICH FLUID ?

D-5-- No RL -- No NS -- yes DNS-- No HEMACCIL -- No

DOPAMINE AND ADRENALINE/NORADRENALINE COMBINED INFUSION

DOPAMINE AND DOBUTAMINE COMBINED INFUSION

The divergent pharmacologic effects of dopamine and dobutamine make their use in combination potentially useful.Infusion of the combination of dopamine and dobutamine have been noted to produce a greater improvement in cardiac output, at lower doses, than can be achieved by either drug alone.

Conti-

Low dose simultaneously increases:

Glomerular filtration rate

Renal blood flow Urine output

DOSE AND ADMINISTRATION

Commercial preparation of dopamine are concentrated drug solution [Containing 40 mg /80 mg dopamine HCL /ml]

Provided in small volume vial / ampoule in 5 ml /10 ml

THE Preparation must be diluted to prevent intense vasoconstriction during drug infusion

Dopamine solution diluted 100-fold in isotonic saline to prepare the infusate

Always delivered into , large central veins

DOSING REGIMEN

Weight based There are two recommended doses:- 3 to 10 mic /kg /min is for

augmenting cardiac output thereby increasing BP

More than 10 mic /kg /min is recommended to increase the blood pressure directly

INCOMPABILITIES

Like dobutamine, dopamine is inactivated by higher PH So ,alkaline fluids should not be infused along with dopamine

INFUSATE:- Use 5 ml 2 vials containing

40 mg /ml dopamine HCL add to 500 ml isotonic saline [Final concentration= 40mic /drop ]

PRECAUTIONS

Before dopamine is administered to pt in shock ,hypovolemia should be corrected by transfusion of whole blood , plasma or other appropriate fluid

ADVERSE EFFECTS

o Tachyarrhythmia's are the most common adverse effects of dopamine

o Malignant tachyarrhythmia [ Multifocal ventricular ectopic , ventricular tachycardia ]

o The most feared complication of dopamine infusion is limb necrosis

o Extravasations of drug through a peripheral vein can be treated with local injection of phentolamine [5 to 10 mg in 15 ml saline ]

Contd…

Allergic reactions Delays gastric emptying which

could predispose to nosocomial pneumonia

If pt is on dopamine infusion and is to be anaesthetized , he / she will be treated as a full stomach pt

Less dysarrytmogenic than epinephrine

Contd…

Continuous infusion of dopamine increase intraocular pressure

Ventilation effects :- Infusion of dopamine interferes with

the ventilatory response to arterial hypoxemia

They results in unexpected depression of ventilation

ABG have been observed to deteriote during infusion of dopamine

Contd…

Hyperglycemia that is commonly present in pts receiving a continuous infusion of dopamine is likely to reflect drug induced inhibition of insulin secretion

DRUGS MAY INTERACTS WITH DOPAMINE

Cyclopropane Bromocriptine Dyhydroergotamine Entacapone Halothane Linezolide Phenytoine

CONTRAINDICATION

Pt receiving MAO inhibitors Tricyclic antidepressants agents Pheochromocytoma Uncorrected tachyarrhythmia Ventricular fibrillation

If dopamine liquid falls on floor /cloth it gives permanent staining if allowed to dry and was not mopped off wet

Thank you…