Diazepam, brand names: Valium, Seduxen, in Europe Apozepam, is a 1,4-benzodiazepine derivative, which possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Diazepam is used to treat anxiety and tension, and is the most effective benzodiazepine for treating muscle spasms. It is also used as a sedative premedication for various medical procedures, and to treat alcohol and opiate withdrawal symptoms.
Mode of action
Diazepam affects mainly the central nervous system. It binds in to specific benzodiazepine-receptors, which are part of the GABA-receptors. When diazepam binds to this receptor, it causes an increase in the inhibitory effects on GABA. The effect of diazepam does not last long, partly because it is fairly quickly redistributed into tissues and fat deposits, and partly because of the adaptation of benzodiazepine receptors.
Pharmacokinetics
Diazepam can be administered orally, as an injection (i.v. and i.m.), or as a suppository. When taken orally, diazepam is rapidly absorbed. Absorption is much slower and more erratic when diazepam is given as an intramuscular injection. Diazepam is highly lipid-soluble and therefore crosses the blood-brain barrier easily.
Diazepam is metabolised in the liver, and it has a biphasic half-life. The first phase half-life (t1/2α) is 24-48 hours, and its main active metabolite, desmethyldiazepam, has a half-life of 2-5 days. Diazepam's other active metabolites include, among others, temazepam and oxazepam. Diazepam and its metabolites are excreted into the urine.
Side effects
Diazepam has few side effects. It increases the sedating effects of alcohol and hypnotics. It can paradoxically cause agitation. As with all benzodiazepines, diazepam can cause physiological tolerance and occasionally psychological addiction when used for a long time, especially when the doses are large. Withdrawal symptoms can be minimized by tapering off the drug slowly.
