Antiepileptics

Question 1

Describe the pathophysiology of seizures.

Answer 1

Excessive synchronous depolarisation, usually starting from defined regions and spreading to other regions. This is due to unbalanced excitatory and inhibitory receptor/ion channel function which favour depolarisation.

Question 2

How are seizures classfied?

Answer 2

1. Generalised: tonic clonic (grand mal), absence (petit mal), myoclonic, atonic
2. Partial: simple or complex
3. Status epilepticus

Question 3

Which antiepileptics are not suitable for absence seizures?

Answer 3

Phenytoin and carbamazepine

Question 4

How do phenytoin and carbamazepine work?

Answer 4

Block voltage-gated Na+ channels

Question 5

Which antiepileptic is contraindicated in pregnancy?

Answer 5

Phenytoin - teratogenic

Question 6

What is the MOA of valproate?

Answer 6

Blocks voltage-gated Na+ and Ca2+ channels AND inhibits GABA transaminase, increasing GABA

Question 7

Which antiepileptics have significant DDIs?

Answer 7

Carbamazepine and phenytoin - potent CYP450 inducers.

Question 8

General adverse effects of antiepileptics?

Answer 8

Dose related: drowsiness, confusion, nausea, mental changes, coma, nystagmus, ataxia, slurred speech, unusual behaviour

Non-dose related: hirsutism, acne, osteomalacia, gingival hyperplasia, folate deficiency, hypersensitivity reactions e.g. SJS

Question 9

Which antiepileptic drug should be chosen initially?

Answer 9

All patients should be commenced on monotherapy initially. All antiepileptic drugs licensed for monotherapy have similar efficacy in newly diagnosed epilepsy.

Carbamazepine, phenytoin and sodium valproate can be considered 1st line treatments. If develop ADR/initial monotherapy unsuccessful, switch to another drug (monotherapy).

Question 10

When should anti-epileptic drug levels be monitored?

Answer 10

1. Assess compliance for pts with refractory epilepsy
2. Assess symptoms due to possible anti-epileptic drug toxicity
3. Titration of phenytoin dose (due to saturation kinetics + interindividual variations)

*Routine checking w/o clear indication is NOT required & not cost effective.

Question 11

What are some risk factors for breakthrough seizures?

Answer 11

• Non compliance to meds
• DDIs that lower blood levels of anti-epileptics
• Alcohol abuse
• Sleep deprivation
• Concurrent illness