NA VALPROATE

1. A carboxylic acid

1. Works by blocking Na+ current and therefore, probably blocking sustained high frequency repetitive firing of neurons.
2. May reduce NMDA receptor excitation
3. May also increase GABA levels.

All the above act to stabilize membrane potential and reduce seizure activity.

1. PO, IV

1. Bioavailability of 80%
2. It is very highly bound to plasma protein and very ionized – the Vd is essentially confined to extracellular water (0.15L/kg). This makes it a dialyzable toxin.

1. Hepatic enzymes.
2. T ½ ~15 hours.

1. Urine

1. GTCS
2. Absence seizures (the drug of choice)
3. Useful in controlling myoclonic seizures
4. Can be used IV to treat status epilepticus
5. Bipolar disorder
6. Migraine prophylaxis

1. Na Valproate is an enzyme inhibitor – in increases the level of phenytoin and carbamazepine, as well as phenobarbital.
2. Because it is highly bound to plasma proteins, it displaces phenytoin from its binding site.

1. Neurological SES – ataxia, fine tremor, coma and cerebral oedema in major OD.

1. Idiosyncratic reaction – severe hepatotoxicity (especially in the very young patients, or if patient already has pre-existing liver disease, and also if there are other hepatotoxins).
2. N/V, GIT upset
3. Thrombocytopaenia
4. Birth defects – spina bifida/CVS, orofacial abnormality