The actions of benzodiazepines are due to the potentiation of the neural 
inhibition that is mediated by gamma-aminobutyric acid (GABA). Practically all 
effects of the benzodiazepines result from their actions on the ionotropic 
GABA(A) receptors in the central nervous system. Benzodiazepines do not activate 
GABA(A) receptors directly but they require GABA. The main effects of 
benzodiazepines are sedation, hypnosis, decreased anxiety, anterograde amnesia, 
centrally mediated muscle relaxation and anti-convulsant activity. In addition 
to their action on the central nervous system, benzodiazepines have a 
dose-dependent ventilatory depressant effect and they also cause a modest 
reduction in arterial blood pressure and an increase in heart rate as a result 
of a decrease of systemic vascular resistance. The four benzodiazepines, widely 
used in clinical anaesthesia, are the agonists midazolam, diazepam and lorazepam 
and the antagonist flumazenil. Midazolam, diazepam and flumazenil are 
metabolized by cytochrome P450 (CYP) enzymes and by glucuronide conjugation 
whereas lorazepam directly undergoes glucuronide conjugation. CYP3A4 is 
important in the biotransformation of both midazolam and diazepam. CYP2C19 is 
important in the biotransformation of diazepam. Liver and renal dysfunction have 
only a minor effect on the pharmacokinetics of lorazepam but they slow down the 
elimination of the other benzodiazepines used in clinical anaesthesia. The 
duration of action of all benzodiazepines is strongly dependent on the duration 
of their administration. Based on clinical studies and computer simulations, 
midazolam has the shortest recovery profile followed by lorazepam and diazepam. 
Being metabolized by CYP enzymes, midazolam and diazepam have many clinically 
significant interactions with inhibitors and inducers of CYP3A4 and 2C19. In 
addition to pharmacokinetic interactions, benzodiazepines have synergistic 
interactions with other hypnotics and opioids. Midazolam, diazepam and lorazepam 
are widely used for sedation and to some extent also for induction and 
maintenance of anaesthesia. Flumazenil is very useful in reversing 
benzodiazepine-induced sedation as well as to diagnose or treat benzodiazepine 
overdose.