Epilepsy: how seizures occur and how drugs work

Question 1

What are non gated ion channels responsible for

Answer 1

Resting membrane potential

Question 2

What are voltage gated ion channels responsible for

Answer 2

Na+, K+, Ca++, Cl-

Dendrite information
Action potential and depolarisation

Question 3

What does glutamate do to neurones

Answer 3

Excites them

Question 4

What does GABA do to neurones

Answer 4

inhibits them

Question 5

What does burst firing look like

What is burst firing like in some forms of epilepsy

Answer 5

Spikes in quick succession

Burst firing in an abnormal amount is seen in some forms of epilepsy

Question 6

What are Epileptiform discharges due to

Answer 6

Neuronal bursting
Increased synaptic effets (both glutamate and GABA)
Glia effects
Non-synaptic effects

Question 7

what happens in the initiation and early seizure

Answer 7

Excitatory burst overcome inhibition

Question 8

What happens in the synchronisation of the epileptic activity (middle phase of seizure)

Answer 8

Local and long-range synaptic connections make neurons fire together

Question 9

What happens in the Termination of a seizure

Answer 9

Synaptic inhibition

Hyperpolarization due to opening of K channels

Activation of Adenosine, opioids, endocannabinoids and other effects

Question 10

What do generalised seizures often reflect a disturbance of

Answer 10

Normal thalami-cortical circuits

Question 11

What drugs are effective in generalised seizures

Answer 11

Ethosuximide, benzodiazepines

Both target receptors involved in thalamo-cortical circuits

Question 12

What is Epileptogenesis

Answer 12

The process following an injury that leads to the first of a series of spontaneous and recurring seizures

Question 13

What structural changes can occur in epileptogenesis

Answer 13

Cell loss inhibitory - (if there’s less inhibition, then there’s an excess of excitatory circuits)

Axonal sprouting- (extra excitatory circuits)

Neurogenesis

Gliosis (glial reaction)

Neuro- inflammation

BBB breakdown

Question 14

What molecular changes can occur in Epileptogenesis

Answer 14

Neuronal channels: NA, K, Ca, Cl, HCO3

Receptors: GABA, AMPA, NMDA, Ach

Neurotransmitter transporters

Neuro

Question 15

What are the functional changes which occur in Epileptogenesis

Answer 15

gap junctions

Glia (which act to buffer extracellular environment)

Question 16

What do AEDs do to sodium channels

Answer 16

Prolongs inactivated state of channel

• Block increases with repetitive activation
• Reduces burst firing

Question 17

Why is Persistent Sodium current important in epilepsy

What drugs target the Persistent Sodium current

Answer 17

Persistent sodium current means Na+ is let into neurons persistently which means neurone is slightly more depolarised and more likely to fire off an action potential

Some AEDs selectively bind to Na persistent channels—-> Lacosamide

Question 18

How do some sodium channels cause epilepsy

Answer 18

Caused by mutations in sodium channels (outcome of mutation depends on Gain or Loss of channel function and neuron implicated- inhibitory vs excitatory)

Question 19

What can some brain lesions do to Na p channels

Answer 19

Cause change in sodium channel function (acquired channelopathy)

Question 20

What can Loss of function mutations in Sodium channels in interneurons might have epilepsy worsened by

Answer 20

Lamotrigine

Question 21

How do some AEDs promote inhibition

What drugs do this

Answer 21

Enhance Cl- current at GABA receptors

BEnzidiazepines
Barbiturates
Topiramate

Question 22

Mode of action of Vigabatrin

Answer 22

Reduce GABA degradation or uptake (it is a GABA transaminase inhibitor)

Higher GABA levels prevents fading of inhibition

Question 23

Mode of action of Tiagabine

IS it commonly used

Answer 23

reduce GABA degradation or reuptake by acting as a GABA reuptake inhibitor

Higher GABA levels prevent fading of inhibition

Not commonly used because it is not universally effective

Question 24

What is the mode of action of perampanel

Answer 24

AMPA receptor inhibitor

Question 25

Mode of action of Levetiracetam and Brivaracetam

Answer 25

SV2a inhibitor

Question 26

Mode of action of Zonisamide, Topiramate

Answer 26

Na channel, Carbonic anhydrase inhibition

Question 27

What are seizures caused by

Answer 27

Abnormal burst firing and synchronisation in normal/modified neural circuits