Epilepsy Flashcards
What are focal seizures thought to be due to?
Imbalance between inhibitory and excitatory input within certain brain regions
Where do focal/partial seizures commonly occur?
Temporal lobe
What are the motor symptoms of focal seizures?
Clonic movement - jerking, twitching
Speech arrest
What are the sensory symptoms?
Visual disturbances
Tingling and numbness
Rising epigastric sensation
What is hyperexcitability?
When there is excessive glutamate and ACh (excitatory NTs) and insufficient GABA and dopamine (inhibitory NTs)
What is hypersynchronisation?
Abnormal excessive and synchronised neuronal activity → spreading wave of depolarisation
What is the target of Diazepam?
GABAₐ receptors → alpha subunit
On post synaptic neurones in temporal lobe
What effect does it have on the target?
- BZD (benzodiazepine/diazepam) binds to GABAₐ receptors
- Potentiates (i.e. increases) Cl- influx, by increasing effectiveness of GABA activation
- Hyperpolarisation of temporal lobe neurones
- Decreases excitability of neuronal cell
What did diazepam treat (in this case)?
Febrile seizures - convulsions in children caused by elevated body temperatures
Examples of anti-epileptic drugs
Lamotrigine
Pregabalin
Levetiracetam
What is lamotrigine’s drug target?
VG Na+ channels on glutamatergic neurons in the temporal lobe
What is the effect of lamotrigine on its target?
Inhibits the VG Na+ channel
→ Reduced depolarisation
→ Inhibits release of excitatory NT glutamate
→ Less excitatory stimulatation of post synaptic membrane
What is pregabalin’s target?
VG Ca 2+ channels on glutamatergic neurons in the temporal lobe
What is the effect of pregabalin on its target?
Inhibition of VG Ca 2+ channels
→ No Ca 2+ influx
→ Reduced vesicle exocytosis and release of glutamate
→ Less excitatory stimulation of post synaptic membrane
What is levetiracetam’s drug target?
Synaptic vesicle protein SV2A in glutamatergic neurones in temporal lobe
What is the effect of levetiracetam on its target?
Inhibition of synaptic vesicle protein SV2A
→ Interferes with vesicle fusion
→ Reduced release of glutamate-containing vesicles
How does the anti-epileptic drug sodium valproate work?
Inhibition of GABA transaminase (primary effect)
Why does sodium valproate have low selectivity?
Valproate acts on multiple receptors including:
- Inhibition of GABA transaminase (primary effect)
- Inhibition of voltage-gated Na channels
- Inhibition of voltage-gated Ca channels
- NMDA receptor blockade
Consequence: huge no of side effects due to lots of targets
Why is sodium valproate not given to women of child-bearing potential?
Teratogenicity → neural tube defects, foetal valproate syndrome FVS
Mechanism: unknown, could be to do with inhibition of folate receptors
