An experiment is conducted to assess the effects of drug A on the hemodynamic actions of epinephrine. Two groups of healthy volunteers are selected. The first group receives only low-dose epinephrine, and its effects on diastolic blood pressure and heart rate are monitored and shown below (epinephrine group). The second group is pretreated with drug A and then infused with low-dose epinephrine to produce a new set of curves (epinephrine + drug A group). Which of the following medications is most likely to be drug A?

Question

An experiment is conducted to assess the effects of drug A on the hemodynamic actions of epinephrine.  Two groups of healthy volunteers are selected.  The first group receives only low-dose epinephrine, and its effects on diastolic blood pressure and heart rate are monitored and shown below (epinephrine group).  The second group is pretreated with drug A and then infused with low-dose epinephrine to produce a new set of curves (epinephrine + drug A group).  Which of the following medications is most likely to be drug A?

Quizplus · Accepted Answer

11ec160b_3b9e_3d26_9249_1b32634beb57_MD0001_00 The hemodynamic actions of epinephrine occur secondary to agonistic effects at α1, β1, and β2 adrenoreceptors (relative strength: β₁ = β₂ > α₁). Stimulation of β1 receptors in the heart increases cardiac rate and contractility, which increases systolic blood pressure due to the rise in cardiac output. Stimulation of β2 receptors in the skeletal muscle vasculature produces vasodilation and decreased diastolic blood pressure, while activation of α1 receptors on vascular smooth muscle in the skin and viscera increases peripheral resistance and raises diastolic blood pressure. At low doses, β2-mediated vasodilation predominates, whereas at high doses α1-induced vasoconstriction becomes more pronounced. In this experiment, low-dose epinephrine by itself caused increased heart rate (β1 response) and decreased diastolic blood pressure (β2 response). However, after pretreatment with drug A, the heart rate fails to increase and there is a marked rise in diastolic blood pressure. These effects are best explained by pretreatment with a nonselective beta antagonist such as propranolol. When administered alone, propranolol produces peripheral vasoconstriction (β2 antagonism) without significantly increasing blood pressure (due to concomitant β1 blockade). However, in combination with epinephrine, propranolol will counteract epinephrine's β2-mediated vasodilation and β1-mediated heart rate increase while leaving the α1 effect (vasoconstriction) intact. This will increase diastolic blood pressure and cause a slight reflexive reduction in heart rate. (Choice A) Atropine is a competitive antagonist of cholinergic muscarinic receptors in the heart (M₂). Atropine increases the heart rate by blocking parasympathetic vagal influence; after pretreatment with atropine, epinephrine-mediated tachycardia would increase. (Choice B) Isoproterenol is a nonselective β-adrenergic agonist that stimulates both β2 receptors on vascular smooth muscle (leading to vasodilatation) and cardiac β1 receptors (leading to increases in cardiac rate and contractility). A combination of isoproterenol and epinephrine would further decrease diastolic blood pressure and exacerbate the tachycardia. (Choice C) Phentolamine is a nonspecific alpha-1 and alpha-2 blocker with no beta-blocking effects that cause a profound fall in diastolic blood pressure and reflex tachycardia. If this were drug A, blood pressure would have decreased further in the pretreatment group and the rise in heart rate would have been exacerbated. (Choice D) Phenylephrine is a selective α-adrenergic agonist. Administration by itself may cause elevated systolic and diastolic blood pressures, which may be associated with reflex bradycardia. However, after pretreatment, epinephrine would still produce an initial rise in heart rate due to unopposed β1 stimulation. Educational objective: Epinephrine increases systolic blood pressure (α₁ + β₁) and heart rate (β1), and either increases or decreases diastolic blood pressure depending on the dose (either α1 or β2 predominates). Pretreatment with propranolol eliminates the β effects of epinephrine (vasodilatation and tachycardia), leaving only the α effect (vasoconstriction).

An Experiment Is Conducted to Assess the Effects of Drug