Carbamazepine

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Indications for carbamazepine. • Epilepsy - 1st choice Rx for focal seizures with & without secondary generalisation & for primary generalised seizures • Trigeminal neuralgia - 1st choice Rx to control P & reduce frequency & severity of attacks • Bipolar disorder - as an option for prophylaxis in pt's resistant to or intolerant of other medication
MOA of carbamazepine. The MOA of carbamazepine is incompletely understood. It appears to inhibit neuronal sodium channels, stabilising resting membrane potentials & reducing neuronal excitability (see Phenytoin). This may inhibit spread of seizure activity in epilepsy, control neuralgic P by blocking synaptic transmission in the trigeminal nucleus & stabilise mood in bipolar disorder by reducing electrical ‘kindling’ in the temporal lobe & limbic system.
SE's of carbamazepine. • GI upset • Neurological effects - esp dizziness & ataxia • Hypersensitivity - affects about 10% & usually manifests as mild maculopapular rash • Antiepileptic hypersensitivity syndrome affects about 1 in 5000 people taking carbamazepine or phenytoin, usually within 2/12 of starting Rx. Clinical features include severe skin reactions (e.g. Stevens–Johnson syndrome, toxic epidermal necrolysis), fever & lymphadenopathy with systemic (e.g. haematological, hepatic, renal) involvement & mortality of about 10%. • Oedema & hyponatraemia - due to ADH-like effect
CI's, cautions, & important interactions of carbamazepine. CI's: • Antiepileptic hypersensitivity syndrome Cautions: • Carbamazepine exposure in utero is associated with neural tube defects, cardiac & urinary tract abnormalities & cleft palate. Women with epilepsy planning pregnancy should discuss Rx with a specialist & start taking high-dose folic acid supplements before conception. • Hepatic DS (due to ^risk of toxicity) • Renal DS (due to ^risk of toxicity) • Cardiac DS (due to ^risk of toxicity) Important interactions: Carbamazepine induces cytochrome P450 enzymes, reducing plasma concentration & efficacy of drugs that are metabolised by P450 enzymes (e.g. warfarin, oestrogens & progestogens). Carbamazepine is itself metabolised by these enzymes, so its concentration & adverse effects are ^by cytochrome P450 inhibitors (e.g. macrolides). Complex interactions occur with other antiepileptic drugs as most alter drug metabolism. The efficacy of antiepileptic drugs is reduced by drugs that lower the seizure threshold (e.g. SSRIs, tricyclic antidepressants, antipsychotics, tramadol).

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