Alcohol withdrawal

Mechanism

• chronic alcohol consumption enhances GABA mediated inhibition in the CNS (similar to benzodiazepines) and inhibits NMDA-type glutamate receptors
• alcohol withdrawal is thought to be lead to the opposite (decreased inhibitory GABA and increased NMDA glutamate transmission)

Features

• symptoms start at 6-12 hours: tremor, sweating, tachycardia, anxiety
• peak incidence of seizures at 36 hours
• peak incidence of delirium tremens is at 48-72 hours: coarse tremor, confusion, delusions, auditory and visual hallucinations, fever, tachycardia

Management

• patients with a history of complex withdrawals from alcohol (i.e. delirium tremens, seizures, blackouts) should be admitted to hospital for monitoring until withdrawals stabilised
• first-line: long-acting benzodiazepines e.g. chlordiazepoxide or diazepam. Lorazepam may be preferable in patients with hepatic failure. Typically given as part of a reducing dose protocol
  • lorazepam is often preferred in patients with liver cirrhosis. Lorazepam is metabolised through glucuronidation, which is less affected by liver function. Even in patients with significant liver impairment, glucuronidation tends to remain intact, making lorazepam a safer choice
  • chlordiazepoxide, on the other hand, undergoes hepatic oxidation via the cytochrome P450 system, which is significantly impaired in cirrhosis. This can lead to prolonged drug accumulation and an increased risk of toxicity, including sedation and hepatic encephalopathy.
• carbamazepine also effective in treatment of alcohol withdrawal
• phenytoin is said not to be as effective in the treatment of alcohol withdrawal seizures