Dopamine

IONOTROPES, VASOPESSOR

1. DOPAMINE DR ZIKRULLAH

2. 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- d ihydr o xy p henyl a lanine . 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. HISTORY

3. 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. INTRODUCTION

4. Each ampoule contains 200 mg /5ml

5. STRUCTURE

6. SYNTHESIS

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

8. 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 MECHANISM OF ACTION

9. 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 ….

10. 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 is by virtue of increasing ventricular afterload Contd …

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

12. 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 Dopamine increase cardiac index by 18% Microcirculatory flow did not change significantly It is used only intravenously . PHARMACOKINETICS

13. Dopamine is often used in situation where both cardiac stimulation and peripheral vasoconstriction is desired such as cardiogenic shock Also used to correct the hypotension in the septic shock . But norepinephrine has become the preferred vassopressor in this condition Low dose is often used in an attempt to prevent or reverse acute renal failure CLINICAL USES

14. 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 Contd …

15. The sympathomimetic amines dopamine is potent ionotropic agents Used in pulmonary edema Forcefully contracts the heart and thus decreases the pulmonary load DOPAMINE IN PULMONARY OEDEMA

16. Like dobutamine, dopamine is inactivated by higher PH So ,alkaline fluids should not be infused along with dopamine D-5-- Yes RL -- No NS -- yes DNS-- No HAEMACCEL -- No DOPAMINE INFUSION IN WHICH FLUID ?

17. Maintaining adequate MAP ,hepatic blood flow and oxygen exchange with dopamine required a consequent increased cardiac output. Which was responsible for increase global oxygen demand Dopamine also impaired hepatic energy balance In vasoplegic septic pt preferrential treatment with dopamine compared with norepinephrine had no advantage DOPAMINE vrs NORADRENALINE

18. 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. DOPAMINE AND DOBUTAMINE COMBINED INFUSION

19. Low dose simultaneously increases: Glomerular filtration rate Renal blood flow Urine output Conti-

20. Use 5 ml 2 ampoule / vials containing 40 mg /ml dopamine HCL add to 500 ml isotonic saline [Final concentration= 40mic /drop ] INFUSATE

21. No of drops= Body weight ( in Kg)× µ/kg/min 40 2 amp of dopamine i.e 400 mg in 500 ml of NS 40kg X 10 =10 drop/ min 40 60kg x 10 = 600 = 15 drops/min 40 40 80kg x 10 = 800 = 20 drops/min 40 40 DOSE CALCULATION

22. 2 amp (200 x 2) in 500 ml NS No. of drops = no of µ/ min is valid only for 40 kg body weight If body Wt changes  no. of drops will change Contd ---

23. 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 in isotonic saline to prepare the infusate Always delivered into , large central veins DOSE AND ADMINISTRATION

24. 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 DOSING REGIMEN

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

26. Tachyarrhythmia's are the most common adverse effects of dopamine Malignant tachyarrhythmia [ Multifocal ventricular ectopic , ventricular tachycardia ] The most feared complication of dopamine infusion is limb (Fingers /toes ) necrosis Extravasations of drug through a peripheral vein can be treated with local injection of phentolamine [5 to 10 mg in 15 ml saline ] ADVERSE EFFECTS

27. 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 dysarrythmogenic than epinephrine Contd …

28. 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 …

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

30. Cyclopropane Bromocriptine Dyhydroergotamine Entacapone Halothane Linezolide (antibiotic ) Phenytoin DRUGS MAY INTERACT WITH DOPAMINE

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

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

33. Thank you…