FRCA Notes


Carbamazepine


  • Used as an anti-epileptic drug, in the management of trigeminal neuralgia and as a mood stabiliser in psychiatric disease
  • Similar mechanism of action to phenytoin i.e. binding and stabilising inactive Na+ channels, reducing generation of action potentials

Absorption

  • Almost 100% oral bioavailability

Distribution

  • 75% protein bound
  • VD 1L/kg

Metabolism

  • Extensive hepatic metabolism to the active metabolite carbamazepine 10,11-epoxide (retains 30% anticonvulsant activity)
  • Induces its own metabolism

Excretion

  • Long half-life: 25 - 65hrs
  • Excretion almost exclusively renal as unconjugated metabolites

Drug interactions

  • Is a powerful CYP450 enzyme inducer
  • Levels of carbamazepine may be increased by erythromycin
  • Increases risk of SLE in woman by 90%

Neurological

  • Mild neurotoxic effects are common and limit its use
  • Other effects include headache, diplopia, ataxia, vomiting and drowsiness
  • With chronic use can cause resistance to aminosteroid NMBA

Renal

  • Anti-diuretic effect leading to SIADH/water retention

Gastrointestinal

  • Drug-induced hepatitis

Teratogenicity

  • Dose-dependent teratogenicity affecting 1 in 300 - 2,000 live births
  • Foetal Hydantoin Syndrome
  • Facial abnormalities and microcephaly
  • IUGR and mental retardation

Haematological

  • Agranulocytosis (rare)

Other

  • Rashes (5-10%)