Pharm 101: Carbamazepine

Class

Anticonvulsant
Mood stabiliser

Pharmacodynamics

• Structurally similar to tricyclic antidepressants such as imipramine
• Works by sodium channel blockade in a manner similar to phenytoin:
  • Presynaptic blockade of synaptic transmission
  • Inhibits high frequency repetitive firing of neurons
• Also acts at adenosine receptors and as an anti-cholinergic

Pharmacokinetics

• Bioavailability ~99%
• Peak levels 6-8 hours after administration, food slows absorption
• Volume of distribution 1L/kg
• 70% plasma protein bound
• Liver metabolism to active metabolites (carbamazepine epoxide), only 5% excreted unchanged
• Half life initially 36 hours then shortens over time to 12 hours
• CYP enzyme inducer:
  • Results in increased clearance of anticonvulsant drugs including itself, as well as phenytoin, valproate, lamotrigine, diazepam
  • Can result in breakthrough seizures
  • Increases metabolism of OCP reducing its effectiveness
  • Note valproate and phenytoin may inhibit carbamazepine elimination

Clinical uses

• Anticonvulsant for partial and generalised tonic-clonic seizures
• Bipolar mood disorder
• Trigeminal neuralgia

Adverse effects

• CNS:
  • Nystagmus, diplopia
  • Ataxia
  • Sedation occurs only at high doses
• GI: upset, hepatic dysfunction
• Haematological: benign leukopenia
• Dermatological: erythematous skin rash, rarely Stevens-Johnson Syndrome
• Metabolic: hyponatraemia
• Overdose causes seizures and cardiac toxicity. Activated charcoal may assist in elimination of drug

Further Reading

• Long N. Carbamazepine Toxicity. LITFL
• Burns E. Carbamazepine Cardiotoxicity. ECG Library. LITFL