Epilepsy

Question 1

What are focal seizures thought to be due to?

Answer 1

Imbalance between inhibitory and excitatory input within certain brain regions

Question 2

Where do focal/partial seizures commonly occur?

Answer 2

Temporal lobe

Question 3

What are the motor symptoms of focal seizures?

Answer 3

Clonic movement - jerking, twitching
Speech arrest

Question 4

What are the sensory symptoms?

Answer 4

Visual disturbances
Tingling and numbness
Rising epigastric sensation

Question 5

What is hyperexcitability?

Answer 5

When there is excessive glutamate and ACh (excitatory NTs) and insufficient GABA and dopamine (inhibitory NTs)

Question 6

What is hypersynchronisation?

Answer 6

Abnormal excessive and synchronised neuronal activity → spreading wave of depolarisation

Question 7

What is the target of Diazepam?

Answer 7

GABAₐ receptors → alpha subunit
On post synaptic neurones in temporal lobe

Question 8

What effect does it have on the target?

Answer 8

1. BZD (benzodiazepine/diazepam) binds to GABAₐ receptors
2. Potentiates (i.e. increases) Cl- influx, by increasing effectiveness of GABA activation
3. Hyperpolarisation of temporal lobe neurones
4. Decreases excitability of neuronal cell

Question 9

What did diazepam treat (in this case)?

Answer 9

Febrile seizures - convulsions in children caused by elevated body temperatures

Question 10

Examples of anti-epileptic drugs

Answer 10

Lamotrigine
Pregabalin
Levetiracetam

Question 11

What is lamotrigine’s drug target?

Answer 11

VG Na+ channels on glutamatergic neurons in the temporal lobe

Question 12

What is the effect of lamotrigine on its target?

Answer 12

Inhibits the VG Na+ channel
→ Reduced depolarisation
→ Inhibits release of excitatory NT glutamate
→ Less excitatory stimulatation of post synaptic membrane

Question 13

What is pregabalin’s target?

Answer 13

VG Ca 2+ channels on glutamatergic neurons in the temporal lobe

Question 14

What is the effect of pregabalin on its target?

Answer 14

Inhibition of VG Ca 2+ channels
→ No Ca 2+ influx
→ Reduced vesicle exocytosis and release of glutamate
→ Less excitatory stimulation of post synaptic membrane

Question 15

What is levetiracetam’s drug target?

Answer 15

Synaptic vesicle protein SV2A in glutamatergic neurones in temporal lobe

Question 16

What is the effect of levetiracetam on its target?

Answer 16

Inhibition of synaptic vesicle protein SV2A
→ Interferes with vesicle fusion
→ Reduced release of glutamate-containing vesicles

Question 17

How does the anti-epileptic drug sodium valproate work?

Answer 17

Inhibition of GABA transaminase (primary effect)

Question 18

Why does sodium valproate have low selectivity?

Answer 18

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

Question 19

Why is sodium valproate not given to women of child-bearing potential?

Answer 19

Teratogenicity → neural tube defects, foetal valproate syndrome FVS
Mechanism: unknown, could be to do with inhibition of folate receptors