A hypertensive patient using transdermal nicotine patches reports that the patch controls cravings well on day 1 of each weekly supply, but by day 3 the same patch seems much less effective. The most likely pharmacodynamic explanation is:

• A Tachyphylaxis due to desensitization of nicotinic receptors after sustained exposure ✓
• B Accumulation of nicotine to toxic levels causing receptor blockade
• C Induction of hepatic CYP2A6 increasing nicotine clearance within days
• D Saturation of nicotinic receptors leading to zero-order absorption

Explanation

Continuous agonist exposure causes rapid loss of responsiveness, called tachyphylaxis or desensitization. Nicotinic acetylcholine receptors enter a desensitized conformational state within minutes to hours of sustained agonist occupancy, so the same concentration produces diminishing effect. This is a pharmacodynamic phenomenon at the receptor, not a kinetic one. Enzyme induction (option C) takes days to weeks and does not explain receptor-level unresponsiveness, and options B and D misapply kinetic concepts to a receptor adaptation.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.