Valproate

Question 1

What are indications for valproate use?

Answer 1

• Epilepsy
• Bipolar Disorder

Question 2

What type of epilepsy is valproate used in?

Answer 2

• First line - generalised
• First line - Abscence

Question 3

What is the mechanism of action of valproate?

Answer 3

Appears to be a weak inhibitor of neuronal sodium channels, stabilising resting memebrane potentials and reducing neuronal excitability. It also increases the brain content of GABA

Question 4

What are important adverse effects of valproate?

Answer 4

• GI upset
• Neurological and psychiatric effects - tremor, ataxia, behavioural disturbances
• Thrombocytopenia
• Transient increase in LFTs
• Pancreastitis
• Bone marrow failure
• Antiepileptic hypersensitivity syndrome

Question 5

When should valproate use be avoided?

Answer 5

• Women of child-bearing age
• First trimester pregnancy

Question 6

What are the effects of valproate use on a foetus?

Answer 6

• Neural tube defects
• Craniofacial defects
• Cardiac defects
• Limb abnormalities

Question 7

Is valproate a cytochrome P450 inhibitor or inducer?

Answer 7

P450 inhibitor

Question 8

What would happen to the valproate concentration if another drug which was a P450 inducer was given?

Answer 8

Concentration would be reduced - increased risk of seizure

Question 9

What advice would you give patients on valproate?

Answer 9

• Take tablets with food
• Seek medical advice for adverse symptoms
• Discuss contraception and pregnancy

Question 10

What might you want to monitor if someone was on valproate?

Answer 10

LFTs - before and 6 months after initiation