Flumazenil is considered for a patient brought comatose after suspected benzodiazepine overdose. In which patient is flumazenil most likely to precipitate acute seizures?

• A A chronic benzodiazepine user with co-ingestion of a tricyclic antidepressant ✓
• B A healthy adult who ingested a single large dose of alprazolam
• C A patient with pure midazolam sedation given endoscopically 1 hour ago
• D A patient with isolated lorazepam overdose and no history of epilepsy

Explanation

Flumazenil competitively antagonises the benzodiazepine site on the GABA-B receptor. In chronically benzodiazepine-exposed patients it precipitates withdrawal, and when a proconvulsant such as a tricyclic antidepressant has been co-ingested, reversal of protective benzodiazepine activity unmasks seizures that are difficult to treat. It is safe in uncomplicated single-drug iatrogenic or accidental benzodiazepine overdose without dependence.

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

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Written and medically reviewed by the StethoPrep medical team.