A woman using ephedrine nasal drops for decongestion finds that the drug stops working after several days of frequent use. The most likely mechanism for this rapid loss of response is:

• A Downregulation of alpha-adrenergic receptors in nasal mucosa
• B Formation of neutralising antibodies against ephedrine
• C Induction of hepatic CYP enzymes accelerating ephedrine metabolism
• D Depletion of norepinephrine stores from sympathetic nerve endings ✓

Explanation

Ephedrine is an indirectly acting sympathomimetic that displaces norepinephrine from storage vesicles in adrenergic nerve terminals. Repeated dosing exhausts these stores, so successive doses release progressively less transmitter and the effect fades within hours to days. This is tachyphylaxis, and it is characteristic of indirect-acting agents such as ephedrine and tyramine. Receptor downregulation takes longer to develop, ephedrine is largely excreted unchanged rather than extensively metabolised, and antibodies do not form against small synthetic molecules.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.