32. Anticonvulsants

Question 1

What are seizures?

Answer 1

Sudden changes in behaviours caused by electrical hypersynchronisation of neuronal networks in the cerebral cortex

Question 2

How is incidence of epilepsy changing?

Answer 2

Increasing

Question 3

How can epilepsy be diagnosed?

Answer 3

• Electroencephalography (EEG)

* MRI

Question 4

What are the different types of epilepsy seizures?

Answer 4

Generalised seizures
• Tonic-clonic
• Absence
• Tonic/atonic
• Myoclonic
• Stutus epilepticus

Partial/focal seizures
• Simple
• Complex

Question 5

What is a tonic-clonic seizure?

Answer 5

• Loss of consciousness
• Muscle stiffening
• Twitching
• Deep sleep
• Wakes up

Most common manifestation of epilepsy

Question 6

What is an absence seizure?

Answer 6

Brief staring episodes with behavioural arrest (trance like)

Question 7

What is a tonic/atonic seizure?

Answer 7

• Tonic - sudden muscle stiffening

* Atonic - sudden loss of muscle control

Question 8

What is a myoclonic seizure?

Answer 8

Sudden, brief muscle contractions - lots of muscle movement

Question 9

What is status epilepticus?

Answer 9

Over 5 minutes of continuous seizure activity

Most dangerous manifestation

Question 10

What happens to awareness in a simple (partial) seizure?

Answer 10

Retained awareness

Question 11

What happens to awareness in a complex (partial) seizure?

Answer 11

Impaired awareness

Question 12

What happens in the brain during a generalised seizure?

Answer 12

Increased synchronisation simultaneously in both hemispheres of the brain

Question 13

What happens in the brain during a partial/focal seizure?

Answer 13

• Begins within a particular area of the brain and may spread out
• Can progress into a generalised seizure
• Symptoms depend on where it occurs

Question 14

Describe neurotransmission at a glutamatergic synapse

Answer 14

• AP arrives at pre-synaptic terminal
• Ca2+ influx through VGCCs
• Vesicle exocytosis
• Synaptic vesicle associated protein (SV2A) allows vesicle to attach to pre-synaptic membrane (docking protein)
• Glutamate is released into the synapse
• Glutamate activates excitatory post-synaptic receptors e.g. NMDA

Question 15

What is carbamazepine and how does it work?

Answer 15

Voltage-gated sodium channel blocker
• VGSCs open and enter an inactive state
• Carbamazepine stabilises the inactive state of the Na+ channel - more likely to stay that way
• Less neuronal depolarisation
• Reduced neuronal activity

Question 16

What is the onset activity and half-life of carbamazepine and lamotrigine?

Answer 16

Fast onset: 1 hour

Long half-life: 16-30 / 24-34 hours respectively

Question 17

When is carbamazepine used?

Answer 17

• Tonic-clonic seizures

* Partial seizures

Question 18

Why should you be careful when using carbamazepine?

Answer 18

• CYP450 inducer
• Reduces the activity of other drugs
• Potential severe skin side effects in individuals with a particular HLA-B allele (more common in oriental people)

Question 19

What is Lamotrigine and how does it work?

Answer 19

Voltage-gated sodium channel blocker
• Directly inactivates Na+ channels
• Reduces glutamate neuronal activity (more selective for glutamatergic neurones)

Question 20

What is Lamotrigine used for?

Answer 20

• Tonic-clonic seizures

* Absence seizures

Question 21

How are the VGCCs found on the heart different to the ones found in the CNS?

Answer 21

• Heart: L-type - targeted by CCBs

* CNS: T-type

Question 22

What is Ethosuximide, how does it work and what is its half-life?

Answer 22

• T-type VGCC antagonist
• Reduces activity in relay thalamic neurones
• Long half-life: 50 hours

Question 23

What is ethosuximide used for?

Answer 23

Absence seizures

Question 24

How does Levetiracetam and Topiramate affect glutamate exocytosis/receptors?

Answer 24

Levetiracetam
• Synaptic vesicle associated protein (SV2A) inhibitor
• Prevents and reduces glutamate exocytosis

Topiramate
• Glutamate receptor antagonist
• Inhibits NMDA and kainate receptors
(• also affects VGSCs and GABA receptors)

Question 25

What is the onset, half-life and use of Levetiracetam and Topiramate?

Answer 25

• Fast onset: 1 hour
• Half-life: 10 and 20 hours respectively
• Used for myoclonic seizures

Question 26

Apart from reducing glutamate activity directly, how else can we indirectly reduce neuronal activity in epilepsy?

Answer 26

Increase GABA transmission

Question 27

Why is GABA the most active neurotransmitter?

Answer 27

Does not necessarily need excitation at the pre-synaptic terminal - can be released by itself
(released continuously/tonically or following neuronal stimulation)

Question 28

What form of diazepam is used for treating seizures and why?

Answer 28

Rectal gel
• Fast onset: within 15min (but a short half-life of 2 hours)
• May not be able to access the veins during a seizure

Question 29

When is diazepam used in epilepsy?

Answer 29

Status epilepticus

Question 30

How does Sodium valproate (and Vigabatrin) work to treat epilepsy (all forms apart from status epilepticus)?

Answer 30

• Inhibits GABA transaminase (GABA => glutamate)

* This increases GABA mediated inhibition and reduces glutamate being formed

Question 31

What is the onset and half-life of Sodium valproate?

Answer 31

Fast onset: 1 hour

Half-life: 12 hours