Contraindications
One of the main contraindications is severe hepatic dysfunction or failure. Liver function should be checked prior to valproate commencing and be monitored in the first 6 months. Full blood counts should also be taken due to anaemia, leucopenia, pancytopenia.
Caution
- Renal failure (may need to reduce dose based on valproate level)
- Pancreatitis
- Coagulation disorders
- Systemic lupus erythematosus
Sodium Valproate is thought to work by three separate methods:
- Increasing the amount of GABA in the brain
- Blocking Sodium Channels
- Blocking Calcium Channels
Valproate increases the amount of GABA in the brain by inhibiting the enzyme GABA Transaminase, which normally breaks down GABA. This means there is an increase in the amount of the inhibitory neurotransmitter, which obviously helps to prevent neurones from "firing."
By blocking both sodium and calcium channels, Valproate prevents the depolarisation of neurones, which also prevents the "firing" of the neurone.
Can be given either orally or IV.
The most serious side effects from Sodium Valproate are sudden onset of liver failure, acute pancreatitis and severe thrombocytopenia.
Other, less severe side effects include:
- Nausea and vomiting
- Diarrhoea
- Weight gain
- Oedema
- Hallucinations
Unfortunately, Sodium Valproate interacts with a number of the other drugs. It is a recognised inhibitor of metabolism through the cytochrome P450 system. This can be problematic with other anti-epileptic drugs, namely Carbamazepine and Lamotrigine. Valproate inhibits one of the enzymes responsible for breaking down Carbamazepine to its metabolites, and therefore it may well be necessary to adjust the dose of Carbamazepine in a patient who takes both drugs, to avoid a toxic build up of the drug.
Whilst it is not quite so clear how Valproate inhibits the clearance of Lamotrigine, it is still necessary to reduce the dose of the latter when both drugs are prescribed.
Drugs which lower the seizure threshold (making seizures more likely in all patients) such as anti-depressants and anti-psychotics can produce an antagonistic effect to valproate.
See Anti-Epileptic Therapy.
Sodium Valproate is metabolised almost exclusively by the liver.
