A 55-year-old man who has taken lorazepam 6 mg daily for two years ingests an unknown quantity of his tablets and is brought comatose. After flumazenil he awakens briefly, then develops generalised seizures and autonomic instability. The most likely explanation is:

• A Flumazenil precipitated acute benzodiazepine withdrawal in a physically dependent patient ✓
• B Flumazenil directly antagonises lorazepam at the chloride channel pore
• C Flumazenil caused a paradoxical excitatory reaction unrelated to dependence
• D Flumazenil displaced lorazepam from tissue binding sites

Explanation

Flumazenil is a competitive antagonist at the benzodiazepine site of the GABA-A receptor. In chronically dependent patients it abruptly unmasks the downregulated receptor state and can precipitate severe withdrawal, including seizures, and it shortens the half-life protection if a proconvulsant co-ingestant such as a tricyclic was taken. It does not act inside the chloride channel pore nor displace bound drug from tissues.

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.