Antiepileptics

Question 1

Glutamate

• function
• receptors
• mechanism

Answer 1

• excitatory neurotransmitter
• NMDA, AMPA, etc
• AP > Na+ mediated Ca2+ influx > depolarization and vesicle release

Question 2

GABA

• function
• receptors
• mechanism
• recycling

Answer 2

• inhibitory neurotransmitter
• GABA a receptor
• binds to receptor > Cl- influx > counteract depolarization
• recycling: converted to SSA by GABAT (transaminase)

Question 3

What are the 3 mechanisms of AEDs?

Answer 3

• Na+ and Ca2+ channel inhibition
• Enhancement of GABA activity
• Inhibition of glutamate activity

Question 4

Name the Na+ and Ca2+ channel modulators

Answer 4

• carbamazepine
• phenytoin
• lamotrigine
• valproate (also a GABAT inhibitor)

Question 5

Name the GABA enhancers

Answer 5

• Benzodiazepines
• vigabatrin
• valproate
• Levetiracetam

Question 6

6 properties of benzodiazepines

Answer 6

1. Anxiolytic
2. Sedative
3. Hypnotic
4. Muscle relaxant
5. Anti-convulsant
6. Amnesic

Question 7

Mechanism of action of benzos

Answer 7

• increase the frequency of Cl- channel opening in the GABA receptor when the GABA is present (increased affinity)
• Increased Cl- within the cell increases
  its resistance to depolarization

Question 8

Benzos used in epilepsy

Answer 8

• diazepam
• midazolam
• lorazepam
• clobazam

Question 9

Phenytoin

Answer 9

Phenytoin
• Causes hyperpolarization via sodium channels (blocks inactive sodium channels)
• Displays zero-order kinetics (metabolised at constant rate irrespective of plasma concentrations)
• Narrow therapeutic index
• CYP450 Enzyme inducer
• teratogenic

Question 10

Phenytoin - side effects

Answer 10

• confusion
• gum hyperplasia, acne, hirsutism
• ataxia, nystagmus
• rashes to severe recations
• haematological/ anaemia

Question 11

What are the drugs that lower seizure threshold (reduce AED efficacy)

Answer 11

• SSRIs
• TCAs
• antipsychotics
• tramadol

Question 12

Sodium valproate - mechanism

Answer 12

• Both a sodium channel blocker and GABA transaminase inhibitor

Question 13

Sodium valproate - side effects

Answer 13

• GI upset
• weight gain
• tremor, ataxia, behavioural
• thrombocytopenia and increased LFTs
• hair loss
• teratogenic
• SIADH, hyponatremia

Question 14

What birth defects can occur in foetal valproate syndrome?

Answer 14

• spina bifida
• Facial and skull malformations (including cleft lip and palate)
• congenital heart defects eg VSD
• gastroschisis
• hypospadias with undescended testes
• limb abnormalities

Question 15

carbamazepine - mechanism and ADRs

Answer 15

• inhibit neuronal Na+ channels

- ADRs: GI upset, dizziness/ataxia, mild maculopapular rash, SIADH/hyponatremia/oedema

Question 16

Levetiracetam

Answer 16

• Binds synaptic vesicle glycoprotein 2A and inhibits presynaptic calcium channels
• ADRs behavioural (suicidal ideation risk doubling)

Question 17

Vigabatrin

Answer 17

• inhibitor of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme responsible for the catabolism of GABA. So increases GABA levels
• can cause visual field defects
• common ADRs: Abdominal pain; anaemia; anxiety; arthralgia; behaviour abnormal

Question 18

Which AEDs are not safe in pregnancy

Answer 18

Least safe to safest:

• valproate
• phenytoin
• lamotrigine