Antiepileptics Flashcards
Glutamate
- function
- receptors
- mechanism
- excitatory neurotransmitter
- NMDA, AMPA, etc
- AP > Na+ mediated Ca2+ influx > depolarization and vesicle release
GABA
- function
- receptors
- mechanism
- recycling
- inhibitory neurotransmitter
- GABA a receptor
- binds to receptor > Cl- influx > counteract depolarization
- recycling: converted to SSA by GABAT (transaminase)
What are the 3 mechanisms of AEDs?
- Na+ and Ca2+ channel inhibition
- Enhancement of GABA activity
- Inhibition of glutamate activity
Name the Na+ and Ca2+ channel modulators
- carbamazepine
- phenytoin
- lamotrigine
- valproate (also a GABAT inhibitor)
Name the GABA enhancers
- Benzodiazepines
- vigabatrin
- valproate
- Levetiracetam
6 properties of benzodiazepines
- Anxiolytic
- Sedative
- Hypnotic
- Muscle relaxant
- Anti-convulsant
- Amnesic
Mechanism of action of benzos
- 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
Benzos used in epilepsy
- diazepam
- midazolam
- lorazepam
- clobazam
Phenytoin
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
Phenytoin - side effects
- confusion
- gum hyperplasia, acne, hirsutism
- ataxia, nystagmus
- rashes to severe recations
- haematological/ anaemia
What are the drugs that lower seizure threshold (reduce AED efficacy)
- SSRIs
- TCAs
- antipsychotics
- tramadol
Sodium valproate - mechanism
- Both a sodium channel blocker and GABA transaminase inhibitor
Sodium valproate - side effects
- GI upset
- weight gain
- tremor, ataxia, behavioural
- thrombocytopenia and increased LFTs
- hair loss
- teratogenic
- SIADH, hyponatremia
What birth defects can occur in foetal valproate syndrome?
- spina bifida
- Facial and skull malformations (including cleft lip and palate)
- congenital heart defects eg VSD
- gastroschisis
- hypospadias with undescended testes
- limb abnormalities
carbamazepine - mechanism and ADRs
- inhibit neuronal Na+ channels
- ADRs: GI upset, dizziness/ataxia, mild maculopapular rash, SIADH/hyponatremia/oedema