Anticonvulsants

Question 1

What is an epileptic seizure?

Answer 1

Sudden change in behaviour resulting from electrical hyper-synchronisation of cortical neuronal networks

Question 2

What is epilepsy?

Answer 2

Neurological condition causing frequent seizures

(Effects between 2-7% of population, this has increased over last 40 years) Diagnosis can be achieved via brain activity measurements – EEG or MRI.

Question 3

What are the two main types of epilepsy?

Answer 3

Partial/Focal – the excess discharge is localised to one area of the brain

Generalised – the synchronised discharge affects all brain areas

Question 4

What are the main mechanisms of anti-epileptic drugs?

Answer 4

Enhancing GABA-mediated inhibition
Inhibiting glutamate-mediated excitation
Na+ channel blockade (blocking nerve conduction)
Calcium channel blockade

Question 5

Give an example of a group of drugs that enhance GABA-mediated inhibition.

Answer 5

Benzodiazepines - E.g Diazepam

These act as positive allosteric modulators

Question 6

Name two drugs that inhibit glutamate-mediated excitation.

Answer 6

Presynaptic = levatiracetam (SV2A inhibitor, stops vesicle docking)

Postsynpatic = Topiramate – Inhibits NMDA and Kainate receptors/ VGSC & GABA receptor effects (used in myoclonic seizure)

Question 7

Name three drugs that exert their effect as AEDs by blocking action potentials (Na+ channel blockade).

Answer 7

Carbamazepine

Phenytoin

Lamotrigine

Question 8

What does Levatiracetam bind to in order to inhibit glutamate release?

Answer 8

SV2A

This is a protein found on the synaptic vesicle membrane

Question 9

What are the two main excitatory receptors?

Answer 9

AMPA and Kainate (Na+/Ca2+ channel)

NMDA

Question 10

Name important drugs that block the presynaptic calcium channel, hence preventing neurotransmitter exocytosis.

Answer 10

Ethosuximide – T-type channel antagonists – reduces thalamic relay activity, used in absence seizures.

Gabapentin
Pregabalin

Question 11

What are the two most severe forms of allergic reaction to AEDs?

Answer 11

Stevens-Johnsons Syndrome

Toxic Epidermal Necrosis

Question 12

What polymorphism confers increased risk of getting severe AED allergic reactions?

Answer 12

HLA-B*1502

Question 13

What AED is almost universally indicated for clinical use?

Answer 13

Sodium Valproate

Question 14

What is the mechanism of action of Sodium Valproate?

Answer 14

Inhibits GABA transaminase, increase concentration of GABA. Indicated for all forms of epilepsy first line.