A medical student is conducting a pharmacology experiment to determine the effects of a certain drug. She infuses this drug intravenously over different dose ranges and measures several important hemodynamic parameters. Graphs plotting the observed changes in renal blood flow and cardiac output are shown below.
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Which of the following drugs was most likely used in this experiment?
Hemodynamic effects of adrenergic agonists | ||||
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Agonist | Receptor | SVR | Cardiac | Renal |
Dobutamine | β1 > β2 | ↓ | ↑ | – |
Dopamine | D1 > β1 > α1 | –/↓ | ↑ | ↑ |
α1 > β1 > D1 | ↑ | –/↓ | ↓ | |
Epinephrine | β1 > β2 > α1 | –/↓ | ↑ | – |
α1 > β1 > β2 | ↑ | –/↓ | ↓ | |
Isoproterenol | β1 = β2 | ↓ | ↑ | – |
Norepinephrine | α1 = β1 > β2 | ↑ | – | ↓ |
Phenylephrine | α1 | ↑ | ↓ | ↓ |
SVR = systemic vascular resistance. | ||||
Dopamine is an adrenergic agonist that has varying effects based on the dose. At low doses, dopamine stimulates D1 receptors in the renal vasculature and tubules, inducing an increase in renal blood flow, glomerular filtration rate, and sodium excretion. Vasodilation of the mesenteric, cerebral, and coronary vascular beds is also prominent at low doses.
As the dosage increases, dopamine begins to stimulate β1adrenergic receptors in the heart, increasing cardiac contractility, heart rate, and systolic blood pressure. At the high end of the dose range, stimulation of α1receptors in the systemic vasculature leads to generalized vasoconstriction, which can result in decreased cardiac output due to the increased afterload.
(Choice B) Edrophonium is a short-acting acetylcholinesterase inhibitor used in the diagnosis of myasthenia gravis (ie, Tensilon test). Through its cholinergic effects, edrophonium reduces heart rate, cardiac conduction, and cardiac contractility.
(Choice C) Epinephrine increases heart rate, myocardial contractility, and cardiac output by stimulating β1 receptors. At low doses, stimulation of β2 receptors in the skeletal muscle vasculature produces vasodilation that can cause decreased blood pressure. At high doses, α1-induced vasoconstriction in the skin and viscera becomes more pronounced. Epinephrine does not significantly increase renal blood flow (even at lower doses) due to the lack of D1 receptor stimulation.
(Choice D) Esmolol is a cardioselective β1 blocker with a short duration of action. Esmolol decreases heart rate, myocardial contractility, and cardiac conduction without affecting renal blood flow.
(Choice E) Phenylephrine is a selective α1-adrenergic receptor agonist that causes a generalized increase in peripheral vascular resistance and blood pressure. Its use results in significant renal, splanchnic, and mesenteric vasoconstriction.
Educational objective:
Low-dose dopamine infusion stimulates D1 receptors in the renal and mesenteric vasculature, resulting in vasodilation and increased blood flow to these sites. Increasing doses of dopamine stimulate β1 and α1 receptors, resulting in increased cardiac output and elevated systemic vascular resistance. At the high end of the dose range, the increase in afterload can result in decreased cardiac output.