Welcome to pharmacology by Lecturio. I'm Dr. Pravin Shukle.
Today, we're going to talk about some anti-seizure
and anti-epileptic medications.
The principal behind anti-epileptic treatment is to ensure that
we're going to be blocking the transmission of neurotransmitters
into the synaptic cleft within the central nervous system.
We have many ways of doing that.
The first way to do that is by blocking sodium channels. Now,
you can see sodium channels are present in the terminal button
at the top of that diagram there.
Sodium channel blockade is a rate dependant process
and doing so gives us a prolonged refractory period. We have
many medications that can cause a blockade of the sodium channel.
The most commonly used is phenytoin, also called Dilantin.
Now, other medications include carbamazepine,
and we also have drugs like lamotrigine
which can block the sodium channel.
Newer drugs have come out onto the markets as well
and you can see them listed there.
Those aren't as important for your exams, but certainly they
are now going to be I think the standard of care going forward.
The second way that we can affect epileptic activity
in the brain is by acting on the GABA channel.
Remember that benzodiazepines increase the frequency of opening
of the GABA channel, allowing chloride to enter into the cell.
Barbiturates also act on the GABA channel by increasing
the duration of opening of that channel.
Now, here is the GABA receptor. This illustration clearly
shows that benzodiazepines and barbiturates both act
on this channel to help move chloride across the membrane.
GABA potentiation can increase the activity of GABA as well.
This isn't acting directly on the channel
but actually acting on the molecules. Topiramate and valproic
acid are two of these agents that can help potentiate
the activity of GABA. There are other ways that
we can affect how GABA acts in the synaptic cleft.
So, we can inhibit the reuptake of GABA from
the synaptic cleft back into the terminal button.
Tiagabine is a drug that inhibits GAT-1,
which is the reuptake molecule.
It prolongs the action of GABA by leaving it in the synaptic
cleft. This results in less activity in the affected neuron
by increasing chloride movement and so
the affected neuron is now unable to depolarize.
Another way that we can affect the post-synaptic neuron
is through calcium channel blockade.
This is a rate dependant phenomenon so the more often that particular
channel is firing, the more effective the treatment will be.
This prolongs the refractory period of the target nerve.
Ethosuximide is a T-channel or a T calcium channel effector.
Valproic acid also works on a similar channel. And gabapentin acts
on the alpha subunit of a reuptake molecule that picks up calcium.
Pregabalin or lyrica is an alpha subunit active agent.
And although it's not used as much in epilepsy,
we do see it a lot in pain management.
Another way that we can affect how effective the
synaptic cleft is is by potassium channel activation.
You can see potassium channels up at the top of that slide.
By activating the potassium channel,
you cause membrane hyperpolarization.
And once again, you're prolonging the
refractory period of that particular nerve.
So this particular drug or this set of drugs
will therefore cause membrane depolarization
or prevent further repolarization of that membrane.
Valproic acid may also be acting on potassium channels too
as well as its activity on calcium.