An unresponsive young woman is brought to the emergency department. She is known to take alprazolam regularly and also takes imipramine. After intravenous flumazenil she awakens briefly and then develops generalised seizures. The most likely explanation is:

• A Flumazenil displaced imipramine from plasma proteins, raising free tricyclic levels
• B Flumazenil directly activated NMDA receptors causing excitation
• C Flumazenil precipitated withdrawal seizures in a benzodiazepine-dependent patient ✓
• D Flumazenil inhibited hepatic metabolism of alprazolam, causing acute toxicity

Explanation

Flumazenil antagonises benzodiazepines at the GABA-C receptor and reverses sedation, but in chronically dependent patients it precipitates an acute abstinence syndrome including seizures. It is also risky when a proconvulsant such as a tricyclic antidepressant has been co-ingested, since it removes benzodiazepine protection. Flumazenil has no intrinsic agonist activity and no protein-binding interaction with imipramine, excluding B and A.

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.