Week 1- Epilepsy tutorial

Question 1

In a GABA synapse, identify one of each of the 4 main drug target sites

Answer 1

Enzyme: GABA transaminase
Ion channel: VGSC/VGCC
Transport protein: GABA reuptake transporter
Receptor: GABA receptor

Question 2

What is the drug target site for diazepam and how may this reduce seizures?

Answer 2

Diazepam binds to GABA alpha receptors, increasing the amount of stimulation from GABA. GABA has an inhibitory effect, helping reduce seizures

Question 3

What is the method of action of lamotrigine and why would this help reduce seizures?

Answer 3

It targets VGSC, preventing sodium influx and therefore depolarisation at the presynaptic membrane.

Question 4

What is the method of action of pregabalin and why would this help reduce seizures?

Answer 4

It targets VGCC, preventing calcium ion influx, stopping the eventual exocytotic release of glutamate vesicles from the presynaptic membrane

Question 5

What is the method of action of levitiracetam and why would this help reduce seizures?

Answer 5

It targets SV2A, a vesicle protein with a key role in exocytosis, preventing the release of glutamate into the synapse, preventing glutamate related over stimulation

Question 6

What is the method of action of tiagabine and why would this help reduce seizures?

Answer 6

It targets GABA reuptake transporter, preventing the fast removal of GABA from the synapse and allowing GABA to have a higher inhibitory effect

Question 7

What is the method of action of vigabatrin and why would this help reduce seizures?

Answer 7

It targets GABA transaminase, preventing the conversion of GABA to succinyl semi-aldehyde, allowing it to have a greater inhibitory effect

Question 8

Describe what low selectivity means and give an example of an anti epileptic drug that has this characteristic

Answer 8

This is when a drug doesn’t have localised effects and can effect receptors in parts of the body that are not intended to be targets e.g. reproductive organs. An example is sodium valproate