Sodium valproate (valproic acid) (Epilim) acts by inhibiting GABA transaminase, the enzyme responsible for the breakdown of the inhibitory neurotransmitter, GABA, so increasing its concentration at GABA receptors.
Sodium valproate is extensively metabolised in the liver and has a tV2 of 13 h. It is 90% bound to plasma albumin. Sodium valproate is a nonspecific inhibitor of metabolism, and indeed inhibits its own metabolism, and that of lamotrigine, phenobarbitone, phenytoin and carbamazepine. Sodium valproate does not induce drug metabolising enzymes but its metabolism is enhanced by induction due to other drugs, including antiepileptics.
Sodium valproate is effective for a wide range of seizure disorders, including generalised and partial epilepsy, and the prophylaxis of febrile convulsions and post-traumatic epilepsy.
Adverse effects can be troublesome. The main ones of concern, particularly to women, are weight gain, teratogenicity (see p. 416), polycystic ovary syndrome, and loss of hair which grows back curly.6 Nausea may be a problem. Some patients exhibit a rise in liver enzymes which is usually transient and without sinister import, but they should be closely monitored until the biochemical tests return to normal as, rarely, liver failure occurs (risk maximal at 2-12 weeks); this is often indicated by anorexia, malaise and a recurrence of seizures. Other reactions include pancreatitis, and coagulation disorder due to inhibition of platelet aggregation (coagulation should be assessed before surgery).
Ketone metabolites may cause confusion in uring testing in diabetes.
Metabolic inhibition by valproate prolongs the action of co-administered antiepilepsy drugs (see above). The effect is significant and the dose of lamotrigine, for example, should be halved in patients who are also taking sodium valproate.
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