Epilepsy

Question 1

What is epilepsy

Answer 1

An unprovoked seizure in the brain characterized by high frequency discharge by a group of neurons

Question 2

What is a partial seizure

Answer 2

A seizure localized to one hemisphere - dependent on the brain region involved
activity in the motor cortex - convulsions in part controlled by that region
Activity in the hypothalamic region - salivation, autonomic discharge
Activity in the reticular formation - loss of consciousness

Question 3

What are the two types of generalised seizure

Answer 3

Tonic-clonic (grand mal) High frequency activity all over the brain followed by rhythmic wave type activity - loss of consciousness

Absence type (petit mal) - synchronised slow oscillatory behaviour - Involves thalamic neurons dependent on T-type calcium channels - manifests in children as a brief absence

Question 4

What are antiepileptic drug targets, thats action is inhibition

Answer 4

1. GABAa receptors - increase activation
2. GABA uptake inhibitors - reduced reuptake back into neurons
3. GABA metabolism - inhibition of enzymes responsible for GABA metabolism

Question 5

What is the negative effect of GABA metabolism inhibitors

Answer 5

Leads to widespread effects - stimulation of GABA receptors gives some specificity

Question 6

How do metabolic inhibitors increase GABA transmission

Answer 6

GABA is produced as a byproduct of Krebs cycle - glutamic acid decarboxylase converts glutamate into GABA
GABA is converted to succinate semialdehyde by GABA transaminase
Vigabatrin covalently binds to GABA transaminase to prevent its metabolism

Question 7

Examples of benzodiazepines that increase GABA transmission

Answer 7

Clonazepam, diazepam, clobazam

Question 8

Examples of barbiturates that increase GABA transmission

Answer 8

Phenobarbitone

Question 9

What are problems associated with GABA metabolite inhibitors

Answer 9

Problems with causing depression

Question 10

What is the action of valproate

Answer 10

Various targets - similar action to vigabatrin, as well as stimulating post synaptic GABA, also inhibits T type Ca channels - so useful against different seizure types

Question 11

What is the target for excitatory inhibitors

Answer 11

Blocking of action potential propogation at the nerve terminal - inhibition of glutamate receptors - targeting of Nav channels - prevents depolarization and AP firing

Question 12

What is use-dependent blocking shown by Nav channel inhibitors

Answer 12

They preferentially block the excitation of cells that are firing repetitively - the higher the frequency of firing - the greater the block
Acts on the inactive state of the sodium channel - causing there to be a greater time difference before it goes back to its closed state and is able to fire again

Question 13

What is the most widely used antiepileptic

Answer 13

Carbamazepine, phenytoin

Question 14

What are calcium channel regulator mechanisms of action

Answer 14

T-type Ca channels can cause rising phase of action potential in specific areas of the brain (thalamus) used to treat absence epilepsy
Ethosuximide is a T-type inhibitor

Question 15

What is GABApentin

Answer 15

Drug - targets accessory subunit that controls trafficking to the membrane of t type channels

Question 16

What is Levetiracetam

Answer 16

Targets protein called synaptic vesicle protein - 2a (SV2A)
Found on the synaptic vesicles containing glutamate
In the presence of the drug the regulated exocytosis of these vesicles and subsequent glutamate release is inhibited