Benzodiazepines

GENERAL PRINCIPLES

• Benzodiazepines are widely used as sedatives, anxiolytics, hypnotics, and antiepileptics.

• Unfortunately, benzodiazepines are also widely misused and diverted.

Pathophysiology

• Benzodiazepines are positive allosteric modulators of the GABA-A chloride-channel linked receptor. Upon binding, they render the channel more likely to open in response to endogenous GABA binding. Benzodiazepines do not directly open the GABA-A chloride channel and are ineffective in the absence of GABA.

• Benzodiazepines generally have anxiolytic, sedative, hypnotic, and anticonvulsant properties.

DIAGNOSIS

Clinical Presentation

Acute overdose of oral benzodiazepines without co-ingestants produces sedation with normal vital signs and preserved respiration.

• Iatrogenic parenteral benzodiazepine overdose may produce respiratory depression.

• Mixed overdoses of benzodiazepines and other sedatives (especially opioids and ethanol) may produce respiratory depression.

TREATMENT

• Isolated benzodiazepine overdoses rarely require treatment beyond time and careful monitoring. Mixed overdoses involving benzodiazepines may produce respiratory depression requiring intubation and mechanical ventilation.

• Flumazenil, a benzodiazepine receptor antagonist, effectively reverses the effects of benzodiazepines, but is rarely indicated due to the relative safety of benzodiazepines in overdose.

î Avoid flumazenil in patients with known or suspected benzodiazepine dependence, as it may precipitate withdrawal and seizures.

î Avoid flumazenil in patients who have co-ingested agents that cause seizures.

î Consider flumazenil for reversal of iatrogenic oversedation with benzodiazepines in benzodiazepine-naive patients, or for treatment of patients with mixed ingestions including benzodiazepines with respiratory failure.

î Flumazenil should be given at a low dose (typically 0.1 mg IV by slow push which may be repeated if necessary for titration to effect).