Which blood pressure response would you expect in a patient taking guanethidine when given indirect-acting sympathomimetics compared to direct-acting sympathomimetics?

Which blood pressure response would you expect in a patient taking guanethidine when given indirect-acting sympathomimetics compared to direct-acting sympathomimetics?

• A. Normal response to indirect-acting agents; exaggerated response to direct-acting agents
• B. Reduced response to indirect-acting agents; exaggerated response to direct-acting agents
• C. Exaggerated response to both direct- and indirect-acting agents
• D. Reduced response to both direct- and indirect-acting agents

Answer: (B)

Guanethidine depletes norepinephrine from sympathetic nerve terminals, effectively dampening sympathetic outflow. Indirect-acting sympathomimetics rely on releasing the stored norepinephrine to raise blood pressure, so with depleted NE their effect is muted. Direct-acting sympathomimetics stimulate vascular receptors directly, independent of NE release, and the reduced sympathetic tone can lead to receptor upregulation (a form of denervation supersensitivity). That makes the vessels more responsive to direct-acting agents, producing an exaggerated blood pressure rise. So you’d expect a reduced response to indirect-acting drugs and an exaggerated response to direct-acting drugs.

Guanethidine depletes norepinephrine from sympathetic nerve terminals, effectively dampening sympathetic outflow. Indirect-acting sympathomimetics rely on releasing the stored norepinephrine to raise blood pressure, so with depleted NE their effect is muted. Direct-acting sympathomimetics stimulate vascular receptors directly, independent of NE release, and the reduced sympathetic tone can lead to receptor upregulation (a form of denervation supersensitivity). That makes the vessels more responsive to direct-acting agents, producing an exaggerated blood pressure rise. So you’d expect a reduced response to indirect-acting drugs and an exaggerated response to direct-acting drugs.