Epilepsy- absence seizures

Question 1

Valproate

Common indications

Answer 1

1. Epilepsy- first choice drug for the control of generalised or absence seizures and as a treatment option for focal seizures
2. Bipolar disorders- For the acute treatment of manic episodes and prophylaxis against recurrence

Question 2

Valproate

MOA

Answer 2

• The mechanism of action of valproate is incompletely understood, it appears to be a weak inhibitor of neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability
• It also increases the brian content of y-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, which regulates neuronal excitability

Question 3

Valproate

Important adverse effects

Answer 3

• The most common is GI upset
• Neurological and psychiatric effects (tremor, ataxia, behavioural disturbances)
• Thrombocytopenia
• Increase in liver enzymes
• Hypersensitivity- Hair loss
• Life- threatening idiosyncratic adverse effects- liver injury, bone marrow failure

Question 4

Valproate

Warnings

Answer 4

• Women of child bearing age- conception and first tri-mester of pregnancy- Fetal abnormalities (neural tube, cardiac, limb and developmental abnormalities)
• Avoid in hepatic impairment
• Reduce in severe renal impairemnt

Question 7

Valproate

Important Interaction

Answer 7

• Valproate inhibits hepatic CYP enzymes, increasing plasma concentrations and toxicity of drugs metabolised by CYP enzymes
  
  • Warfarin, AEDs
• CYP inducers (phenytoin, CBZ) and drugs that displace it from protein binding sites (e.g. aspirin). The efficacy of anti-epileptic drugs is reduced by DRUGs that lower seizure threshold ( SSRI, TCA, Anti-psychotics, tramadol)

Question 8

Valproate

Communication

Answer 8

• Explain that the aim of treatment is to reduce frequency of seizures
• Warn patients that they may have some indegestion when starting valproate- this can be reduced by taking with food
• Seek urgent medical advise- Lethargy, loss of appetite, vomiting or abdo pain (liver poisoning) or bruising, high temp or mouth ulcers (blood discaries)
• Do NOT drive if you have had a seizure in the last year
• MUST counselling patients of child bearing age