Describe the physiological basis for the mechanism of action of three commonly used anticonvulsant groups. Give an example of a drug for each mechanism of action.
The three main anticonvulsant mechanisms required were:
1. Sodium channel blockers. These promote the inactive state of voltage activated Na
channels. Sodium channels are unable to open for a period of time making the neuron
more refractory to action potential generation. Rapid repetitive firing is diminished and
spread of electrical activity to adjacent brain areas is suppressed.
Examples: phenytoin, carbamazepine, lamotrgine, Na valproate
2. Drugs that enhance GABA mediated synaptic inhibition. This increases the influx of
chloride ions into the cell and hyperpolarizes the neuron. 3 mechanisms:
a. Act on GABA receptor. Example: benzodiazepines, barbiturates
b. Inhibit GABA transporter and reduce neuronal GABA reuptake. Example: tiagabine.
c. Promote GABA release. Example: gabapentin.
3. Drugs that inhibit Calcium channels. Limit activation of voltage activated Ca channel
known as the T current. Example.: Na valproate
Other mechanisms of action with examples if described earned extra marks. These included
glutamate /NMDA receptor inhibition. Example: magnesium.
It is impossible to guess how much detail they wanted for "extra marks", but hopefully something like this would be enough:
| Mechanism/class | Drug target | Examples |
|
Ion channel modulators: reduce neuronal excitability by altering the resting membrane potential, stabilising the channels involved in the conduction of action potentials, or inhibiting the intracellular calcium flux which triggers excitatory neurotransmitter release. |
K+ channels |
|
| Ca2+ channels |
|
|
| Na+ channels |
|
|
| GABA potentiators: Increased inhibitory neurotransmission by either directly affecting the GABA ligand-gated chloride channel, decreasing the reuptake of GABA from the synapse, or decreasing the breakdown of GABA. | GABAA |
|
| GABA reuptake transporter |
|
|
| GABA catabolism |
|
|
| Presynaptic neurotransmitter release modulators: decrease the release of neurotransmitters | SV2A |
|
| Postsynaptic inhibitors of neurotransmission: decrease the effect of released neurotransmitter ligands on their receptors | AMPA |
|
| NMDA |
|
|
| God only knows what effect |
|
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