A patient on long-term prazosin therapy for benign prostatic hyperplasia develops symptomatic hypotension after taking his first dose of tamsulosin prescribed by a new physician. The mechanism underlying this exaggerated hypotensive response is:

• A Additive alpha-1 adrenoceptor blockade at vascular smooth muscle ✓
• B Pharmacokinetic interaction reducing tamsulosin metabolism
• C Increased norepinephrine release due to prazosin-induced baroreceptor sensitization
• D Tamsulosin-induced beta-1 blockade augmenting prazosin's vagotonic effect

Explanation

Both prazosin and tamsulosin are selective alpha-1 adrenoceptor antagonists; combining them produces additive blockade at vascular alpha-1 receptors, greatly enhancing the hypotensive effect. Tamsulosin's relative uroselectivity (alpha-1A preference) does not preclude vascular alpha-1 blockade at therapeutic doses, particularly on a background of prazosin therapy. This synergistic hypotension is a clinically important drug interaction.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.