NAPLEX Question of the Week: Ordered Response

A sometimes overlooked question type is the subject of our question of the week.
NAPLEX Question of the Week: Ordered Response

Rank the following vasopressors from most specific to least specific alpha-1 agonist activity.

A. Dopamine

B. Norepinephrine

C. Phenylephrine

D. Vasopressin



Answer with rationale:

The correct answer is C) phenylephrine, B) norepinephrine, A) dopamine, and D) vasopressin.

Knowledge of adrenergic receptor physiology is important to understand the effects of medications that target these receptors. Alpha-1 receptors are largely found in the vasculature, and their activation results in vasoconstriction. The heart contains many beta-1 receptors, the activation of which causes an increase in heart rate and contractility. Many beta-2 receptors are located in the airway, and stimulation leads to bronchodilation. In contrast to these first three receptors, alpha-2 receptors are located on the pre-synaptic side of neurons. Alpha-2 agonists (such as clonidine) work by negative feedback to decrease sympathetic activity and blood pressure.

Norepinephrine is an agonist at alpha-1, alpha-2, beta-1, and beta-2 receptors, but its alpha-1 activity is greater than its beta activity. In other words, it has more effects on the vasculature than on the heart. Due to its vasoconstrictive efficacy and its relatively low risk of tachyarrhythmias, norepinephrine is the first-line vasopressor for most patients who have septic shock.

Dopamine is an agonist at dopamine, alpha-1, alpha-2, beta-1, and beta-2 receptors. Compared to norepinephrine, it is less specific for alpha-1 receptors and has more activity at beta-1 receptors. Dopamine is used as a vasopressor far less often than norepinephrine due to the increased risk of tachyarrhythmias associated with dopamine’s beta-1 stimulation. However, this beta-1 activity may be useful in patients who are bradycardic and require vasopressors.

Phenylephrine is an agonist at alpha receptors only. The activity at alpha-1 receptors leads to vasoconstriction, but because this is unopposed by any beta-1 activity, the body may respond to the increase in blood pressure with reflex bradycardia. Phenylephrine is not often used as a vasopressor and would not be an ideal choice in patients with decreased cardiac output.

Vasopressin, also known as antidiuretic hormone, has no activity at alpha and beta receptors. Instead, it is an agonist at V1 receptors in the vasculature and V2 receptors in the renal tubule. Stimulation of V1 receptors results in vasoconstriction while stimulation of V2 receptors causes reabsorption of water from the renal tubule. Vasopressin is often added as the second vasopressor when norepinephrine alone does not sufficiently increase blood pressure in septic shock.

December is here! We will have some tips in the coming weeks to get your prepared for the exam at the turn of the calendar. Have a great week!

Dr. B

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