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Flashcards in Epilepsy Deck (16)
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What is epilepsy

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


What is a partial seizure

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


What are the two types of generalised seizure

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


What are antiepileptic drug targets, thats action is inhibition

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


What is the negative effect of GABA metabolism inhibitors

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


How do metabolic inhibitors increase GABA transmission

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


Examples of benzodiazepines that increase GABA transmission

Clonazepam, diazepam, clobazam


Examples of barbiturates that increase GABA transmission



What are problems associated with GABA metabolite inhibitors

Problems with causing depression


What is the action of valproate

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


What is the target for excitatory inhibitors

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


What is use-dependent blocking shown by Nav channel inhibitors

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


What is the most widely used antiepileptic

Carbamazepine, phenytoin


What are calcium channel regulator mechanisms of action

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


What is GABApentin

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


What is Levetiracetam

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