Pharmacology of flumazenil.
Flumazenil, an imidazobenzodiazepine, is the first benzodiazepine antagonist available for clinical use. It is a specific competitive antagonist at benzodiazepine receptors, which are associated with receptors for gamma-aminobutyric acid, the most important inhibitory neurotransmitter in the central nervous system. Administered orally, it has a low bioavailability and the preferred route is intravenous. Its usual clinical role is to reverse the effects of benzodiazepine sedation; however, administered before, or with, other benzodiazepines, it modifies their effects, the extent of such modification depending on the dose, duration of effect and relative receptor affinity of the agonist. Flumazenil also reverses adverse physiological effects of benzodiazepines. Its indications include reversal of benzodiazepine-induced sedation, termination of benzodiazepine-induced anaesthesia, return of spontaneous respiration and consciousness in intensive care patients and the treatment of paradoxical reactions to benzodiazepines. Other potential indications include its use in hepatic encephalopathy, alcohol intoxication and coma; however, these claims still require substantiation. Following sedation reversed with flumazenil, minimal residual effects of the agonist can sometimes be detected using psychomotor tests and are due to the relatively short half-life of flumazenil, but are of no clinical consequence. There is concern that flumazenil could precipitate an acute withdrawal syndrome following long-term benzodiazepine administration; however, the available evidence suggests otherwise and that it could be useful in the treatment of benzodiazepine tolerance. The existence of flumazenil is important, with implications for future research and the development of minimally invasive therapy and day-case surgery. With increasing pressures on non-anaesthetically trained practitioners to perform sedation, flumazenil has important implications for safety.
Whitwam
J G
JG
Royal Postgraduate Medical School, London, UK.
Amrein
R
R
D000284:Administration, Oral; D000556:Ambulatory Surgical Procedures; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D001682:Biological Availability; D005442:Flumazenil / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D058787:GABA-A Receptor Antagonists; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors; D007275:Injections, Intravenous; D019060:Minimally Invasive Surgical Procedures; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control
D018756:GABA Antagonists; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D005442:Flumazenil