Benzodiazepines


Drugs in

Long-acting
  • diazepam
  • chlordiazepoxide
  • nitrazepam
Short-acting
  • lorazepam
  • oxazepam
  • temazepam

Features

  • anxiolytic
  • sleep inducing
  • anticonvulsant
  • muscle relaxants

Indications

  • SHORT TERM USE ONLY
  • insomnia
  • generalised anxiety (not phobic)
  • Panic attacks
  • Anterograde amnesia in procedures such as endoscopy (high dose)
  • Tetanus
  • Reduction muscle spasm due to pain
  • alcohol withdrawal states
  • control of violent behaviour
  • Emergency Tx status epilepticus
  • second-line treatments in refractory epilepsy
  • Febrile convulsions

Mechanism of action

  • potentiation of GABA inhibitory effects

Pharmacokinetics

  • Absorption oral>I.M
  • Produce active metabolites with longerT1/2 e.g (T1/2 20-80hrs, N-desmethyl metabolite T1/2 200hrs)
  • Highly bound to protein in plasma
  • Metabolised in the liver, but weak microsomal enzyme inducers
  • Age influenced elimination (except oxazepam)
  • Slow withdrawal of BDZ needed

Side-effects

  • drowsiness
  • sedation
  • ataxia
  • respiratory depression
  • disinhibition (possibly leading to aggression)
  • tolerance
    • withdrawal syndrome
    • marked anxiety
    • shakiness
    • abdominal cramps
    • perceptual disturbances
    • persecutory delusions
    • fits
  • Sedation - drowsiness & lightheadedness
  • CNS depression - ataxia & confusion
  • Dependence with long-term (>2wk) use
  • Withdrawal syndrome
  • Hangover with continuous administration
  • Hypnotics at high dose

Contra-indications

  • Respiratory depression
  • Muscle weakness
  • Severe hepatic impairment
    • in liver impairment prefer shorter T1/2
  • Not used alone in depression
  • alcohol potentiates effects

Interactions

  • With other centrally acting drugs
  • Inhibition BDZ by cimetidine and omeprazole
  • Opioid analgesics
  • Antibacterials
    • e.g. isoniazid inhibits metabolism diazepam
  • Antiepileptics e.g. phenytoin
 

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