DIAZEPAM

In 1957 the first #benzodiazepine (BZD) chlordiazepoxide was discovered by accident (chance modification of tricyclic-like compounds) as having sedative and anti-convulsant properties. It was marketed as Librium in 1960. #Diazepam (Valium) followed in 1963 #prescribing

Viewed as an improvement on barbiturates, by the 1970s, the BZDs became the most prescribed drugs in the world, mainly for neuroses #prescribing

BZDs are effective and relatively safe for appropriate short-term use (great care is needed in the elderly). But long-term use can lead to major issues, including toxicity, dependency and addiction. There are currently 13 BZDs on the UK formulary: 4 for anxiety, 4 for epilepsy and 5 for insomnia #prescribing

Another indication for chlordiazepoxide and #diazepam includes alcohol withdrawal, as long-acting and active metabolites allow smoother withdrawal with lower seizure risk. #Diazepam is useful for muscle spasm/dystonia; diazepam, temazepam, midazolam are used for conscious sedation and for premed; lorazepam is used for panic attack #prescribing

GABA is a powerful inhibitory neurotransmitter acting in brain. #Diazepam/BZDs bind in the GABA ‘A’ receptor pocket, increasing chloride influx. This causes hyperpolarisation, which enhances the effects of GABA. Hence there is greater inhibition of nerve signaling, reducing spasm and causing sedation. Alcohol is also an indirect GABA agonist #prescribing