Anticonvulsants

Question 1

What is the difference between epilepsy and an epileptic seizure?

Answer 1

Epilepsy: A syndrome characterised by a tendency to have recurrent unprovoked seizures.
Epileptic seizure: It is a clinical manifestation of epilepsy, it is a manifestation of irregular/asynchronous firing patterns due to neuronal overactivity

Question 2

What is meant by a general seizure?

Answer 2

Arises simultaneously from both cerebral hemispheres
Divided into; absence, tonic-clonic, myoclonic
Always causes loss of consciousness

Question 3

What is meant by a partial/focal seizure?

Answer 3

Starts in one specific area of one hemisphere
Divided into;
Simple-does not lose consciousness
Complex-results in altered or loss of awareness
Separated by site of onset e.g. temporal lobe

Question 4

What are the possible symptomatic ‘structural/metabolic’ causes of epilepsy?

Answer 4

Tumour
Head injury
Infection
Stroke

Question 5

What is meant by a secondary generalised seizure?

Answer 5

Starts as a partial seizure and spreads as a tonic-clonic generalised seizure.

Question 6

Describe neurotransmission at the glutamatergic synapse

Answer 6

VGSC opens; Na+ influx, depolarisation
VGKC opens; K+ efflux, repolarisation
VGCC opens: vesicle exocytosis
SV2A helps glutamate vesicle to attach to pre-synaptic membrane
Glutamate activates excitatory post-synaptic NMDA, AMPA and Kainate receptors

Question 7

What are the drug targets of glutamate inhibitors?

Answer 7

VGSC blocker, VGKC enhancer, VGCC blocker, SV2A blocker, AMPA-R blocker, Kainate-R blocker

Question 8

Name the Na+ channel blocker of choice for partial and tonic-clonic seizures

Answer 8

Carbamazepine
Stabilises inactive state of Na+ channel
Induces expression of hepatic enzymes
16-30hr half-life

Question 9

Name an anti-epileptic drug used for most forms of epilepsy apart form absence seizures

Answer 9

Phenytoin

[or Phenobarbital]

Question 10

Name a VGKC enhancer

Answer 10

Retigabine

Question 11

Name a Ca channel blocker and what type of epilepsy it is used in

Answer 11

Ethosuximide
T-type Ca2+ channel antagonist
Mainly used for absence seizures
Long half-life (50hrs)

Question 12

Name the drug that targets SV2A and when is it used?

Answer 12

Levetiracetam
Binds to synaptic vesicle protein to stop glutamate release.
Monotherapy for focal seizures

Question 13

Which drug targets the Kainate receptor?

Answer 13

Topiramate
Inhibits GluK5 subunit of kainate receptor
Also affects VGSCs & GABA receptors
Indicated for most types of epilepsy

Question 14

Which drug targets the AMPA receptor?

Answer 14

Perampanel
Selective inhibitor of AMPA receptor
Used as adjunct for partial seizures

Question 15

Describe the neurotransmission of GABA

Answer 15

GABA synthesised from glutamate acts on post-synaptic inhibitory GABAa receptors.
Taken up but GAT on pre-synaptic neurone
GABA metabolised by GABA-transaminase in glial cells

Question 16

Which are the anticonvulsant drugs acting on GABAa receptors?

Answer 16

Clonazepam (BDZ), all types of epilepsy.

Phenobarbital (BARB), all types of epilepsy apart form partial seizures, interacts with many drugs.

Question 17

How does tigabine work?

Answer 17

Selective inhibitor of GAT-1, stops GABA reuptake

Used as adjunct in partial seizures

Question 18

What are the two drugs inhibiting GABA transaminase?

Answer 18

Sodium valproate, used in all types of epilepsy

Vigabatrin, Monotherapy for infantile spasm or as an adjunct for partial seizures