Compare and contrast the pharmacodynamics of dopamine and dobutamine.
Pharmacodynamics imply what the drug does to the body. Consideration should be given to mechanism of action, effects on various organs, relationship of dose to effect. indications for use, and type of adverse effects. These drugs are essential parts of the intensivist's armamentarium, and a good level of understanding should have been displayed.
Dopamine:
• Immediate precursor of noradrenaline, and also serves as a neurotransmitter in central and peripheral nervous systems,
• Doses of Q.5 to 2 meg/kg/min (via stimulation of DA-1 and DA-2 receptors) increase renal blood flow, urine flow and sodium excretion (inhibit sodium resorption in proximal tubules)
• Haemodynamic effects are due to noradrenaline release (up to 500/o) and direct stimulation of alpha, beta and noradrenergic receptors. Can lose effect with time (due to depletion of noradrenaline stores in periphery and heart).
• Doses of 2-5 meg/kg/min increase cardiac contractility and cardiac output with minimal change in heart rate/BP/SVR. Increasing dose up to 10 meg/kg/min increase CO/HR. and BP.
• Doses above 10 meg/kg/min result in increasing alpha adrenergic mediated vasoconstriction.
• Can increase intrapulmonary shunt (increase CO), but pulmonary vasoconstriction can occur.
• Dopamine also stimulates receptors in the zona glomerulosa of the adrenal cortex to decrease aldosterone secretion.
• A selective increase in renal and splanchnic blood flow occurs, and low doses have been thought to prevent the vasoconstrictive effects of other agents. The clinical significance of these effects are controversial (?harm to GIT via shunting from mucosa).
• Dopamine inhibits TSH and prolactin release as well as other potential negative effects on anterior pituitary function.
• Other side effects include nausea/emesis, tachyarrhythm.ias (particularly AF), anginal pain, profound vasoconstriction (including if local extravasation (treat with phentolamine]), and impairment of hypoxic ventilatory drive.
• Used to increase cardiac output and as a mild vasopressor (cardiogenic or septic shock), and as a diuretic (no evidence to support renal protective role).
Dobutamine:
• Racemic mixture of + and - isomers. + isomer stimulates both beta-adrenergic receptors. - isomer is potent selective alpha-1-ad.renergic agonist No indirect stimulation of receptors. Metabolite (3-0-methlydobutamine) is potent inhibitor of alpha receptors. Net effect is balance between various receptor effects.
• At commonly used dose ranges (2-15 meg/kg/min) increases contractility, with little effect on HR at doses < I0 meg/kg/min. Usually little effect on SVR and PVR as balance between alpha- 1 and beta-2 effects (CVP and PAWP usually decrease). Some tolerance with time but less than with dopamine.
• Enhances urine output by increasing cardiac output. No other significant metabolic or endocrine effects.
• Side effects include dysrhythmias (less than dopamine), tachycardia, headaches, anxiety, tremors, changes in BP. •
• Used to increase cardiac output without need to effect peripheral resistance (cardiogenic or septic shock) or desire to have metabolic/endocrine effects of dopamine. Also used to assess for myocardial ischaemia (stress test).
Though it may be tempting to unload a massive amount of pharmacological knowledge onto such a question, the candidate is reminded that these days we only have 10 minutes per question.
Features |
Dobutamine |
Dopamine |
Class |
Synthetic catecholamine |
Endogenous catecholamine |
Pharmacokinetics |
IV infusion 5-15mcg/kg/min Rapidly metabolised by COMT; |
Half-life 2-3minutes |
Receptor activity |
Predominantly a beta-1 receptor agonist; other isomer is a partial alpha-1 agonist |
Predominantly beta-1 receptor agonist at low doses, with more alpha-effects as dose escalates |
Mechanism |
increases heart rate and contractility by increasing the intracellular levels of cAMP, thus increasing the availablility of intracellular calcium. |
increases heart rate and contractility by increasing the intracellular levels of cAMP, thus increasing the availablility of intracellular calcium. |
Adverse effects |
Increased inotoropy |
Arrhythmogenic at the high doses required for treatment of severe sepsis Increased cardiac oxygen demand due to increased contractility and heart rate may cause ischaemic phenomena No evidence for any renal protective effects |