carbamazepine

Use

Carbamazepine (Tegretol) has been used for the treatment of trigeminal neuralgias since 1960. Since carbamazepine received approval for use as an antiepileptic agent in the United States in 1974, it became widely used for the management of partial or tonic-clonic epilepsy.

Carbamazepine is also used as a treatment for patients with manic-depressive illness, postherpetic neuralgia, and phantom limb pain. Some of the available dosage forms for carbamazepine include 100-mg and 200-mg oral tablets and a 100-mg/5-mL oral suspension.

Toxicity

 Medscape

Pathophysiology

Carbamazepine is a complex drug that has both anticonvulsant properties in therapeutic doses and a proconvulsant property in overdose situations with supratherapeutic serum levels.

Carbamazepine is chemically and stereospatially related to the tricyclic antidepressant (TCA) imipramine; it is spatially similar to phenytoin.

The therapeutic anticonvulsant mechanism of carbamazepine is similar to phenytoin and is believed to be primarily related to the blockade of presynaptic voltage-gated sodium channels.

Blockage of sodium channels is believed to inhibit the release of synaptic glutamate and possibly other neurotransmitters. It also inhibits N -methyl-D-aspartate (NMDA) receptors and CNS adenosine receptors.

Carbamazepine also has powerful anticholinergic properties through inhibition of the muscarinic and nicotinic acetylcholine receptors. The seizures that occur with carbamazepine toxicity are largely secondary to a central anticholinergic syndrome. The coma and respiratory depression associated with overdose may be related to sodium channel suppression of neurotransmission.

Carbamazepine causes antagonism at the adenosine subtype A1 receptor and agonism at the adenosine subtype A2 receptor. In lower therapeutic doses, this may be partially responsible for the anticonvulsant effect, whereas, in overdose situations, it may increase sedation or precipitate coma.

Cardiac arrhythmias due to carbamazepine are related to its sodium channel and anticholinergic effects. In therapeutic doses, the cardiovascular sodium channels are only minimally affected, and carbamazepine does not appear to be proarrhythmic. However, in overdose situations, carbamazepine produces sodium channel blockade effects similar to those of TCAs.