Benzodiazepine Antagonists: Flumazenil

BENZODIAZEPINE ANTAGONISTS: FLUMAZENIL

Flumazenil is one of several 1,4-benzodiazepine derivatives with a high affinity for the benzodiazepine binding site on the GABA_A receptor that act as competitive antagonists. It blocks many of the actions of benzodiazepines, zolpidem, zaleplon, and eszopiclone, but does not antagonize the central nervous system effects of other sedative-hypnotics, ethanol, opioids, or general anesthetics. Flumazenil is approved for use in reversing the central nervous system depressant effects of benzodiazepine overdose and to has-ten recovery following use of these drugs in anesthetic and diag-nostic procedures. Although the drug reverses the sedative effects of benzodiazepines, antagonism of benzodiazepine-induced respi-ratory depression is less predictable. When given intravenously, flumazenil acts rapidly but has a short half-life (0.7–1.3 hours) due to rapid hepatic clearance. Because all benzodiazepines have a longer duration of action than flumazenil, sedation commonly recurs, requiring repeated administration of the antagonist.

Adverse effects of flumazenil include agitation, confusion, diz-ziness, and nausea. Flumazenil may cause a severe precipitated abstinence syndrome in patients who have developed marked benzodiazepine dependence. In patients who have ingested benzo-diazepines with tricyclic antidepressants, seizures and cardiac arrhythmias may follow flumazenil administration.