Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

Carbamazepine

Carbamazepine is also used in the treatment of trigeminal neuralgia. Its mode of

action is similar to that of phenytoin. It may be given orally or rectally.

Effects


Central nervous system – mild neurotoxic effects including headache, diplopia,

ataxia, vomiting and drowsiness are common and often limit its use.


Metabolic – it may produce an antidiuretic effect leading to water retention.


Miscellaneous – drug-induced hepatitis, rashes in 5–10% and rarely agranulocyto-

sis.


Teratogenicity – it causes facial abnormalities, intrauterine growth retardation,

microcephaly and mental retardation. The incidence increases with dose. Overall

incidence is about 1/300–2000 live births.


Drug interactions – as carbamazepine induces hepatic enzymes, it demonstrates

many of the interactions seen with phenytoin. Levels of concurrently administered

phenytoin may be elevated or reduced. Erythromycin can increase serum levels of

carbamazepine.

Kinetics

Carbamazepine is well absorbed from the gut with a high oral bioavailability.

Itis approximately 75% plasma protein bound and undergoes extensive hepatic

metabolism to carbamazepine 10,11-epoxide, which retains about 30% of carba-

mazepine’s anticonvulsant properties. It powerfully induces hepatic enzymes and

induces its own metabolism. Its excretion is almost entirely in the urine as unconju-

gated metabolites.

Sodium valproate

Uses

Sodium valproate is used in the treatment of various forms of epilepsy including

absence (petit mal) seizures and in the treatment of trigeminal neuralgia.

Mechanism of action

Sodium valproate appears to act by stabilizing inactive Na+channels and also by

stimulating central GABA-ergic inhibitory pathways. It is generally well tolerated.

Effects


Abdominal – it may cause nausea and gastric irritation. Pancreatitis and potentially

fatal hepatotoxicity are recognized following its use.


Haematological – thrombocytopenia and reduced platelet aggregation.


Miscellaneous – transient hair loss.


Teratogenicity – it causes neural tube defects.