How is it that these two classes of drugs are working. Well
it is all through the GABA A receptor. This beautiful
illustration was made by our IT team, Mandy and Jenny, so
kudos to them because it's a fantastic illustration.
And it really clearly lays out where each of the drugs works
on the GABA A receptor. It's a very complex macromolecule
that spans the membrane. It's made up of 5 subunits and take a
look at each of the points of interaction with different drugs.
So you can see that GABA has two particular acitivity points.
Benzodiazepine has an activity point in between the alpha
and gamma subunit. A drug like zolpidem which is one of those
atypical drugs also acts at a similiar site but just a little
bit further down. And you can see that the barbiturates are
transmembrane and they act almost solely on the alpha subunit.
Now they act differently. And this is going to be a recurring
theme that I'm going to mention several times in several lectures.
And you can guarantee yourself that this is going to be on your
exam. So recognise that the GABA A receptor is important for
your exams and recognise how these drugs interact with the
GABA A receptor is going to be important for your exams.
Once you are out in clinical practice and don't have to
write exams anymore, you can forget what I just told you
until your next set of recertification exams. Let's start off
with the benzodiazepines. So the GABA receptor that responds
to benzodiazepines is present in many regions of the brain.
It's present in the cerebral cortex, and in the cerebral cortex
benzodiazepines can cause confusion and amnesia. It's present
in the thalamus. And this is where you have disinhibtion,
sedation and motor inhibition because that's what the thalamus
does after all. Benzodiazepines also work in the limbic structures
of your brain. Now remember limbic structures are the lizard
part of your brain. It's the oldest part of our brain.
It's where have our core emotion and our most base instincts.
And anxiety is a base emotion. It's a survival technique.
We feel anxious when we know we are in danger. Now, benzodiazepines
will inhibit activity in the limbic structures and that's how
it works to reduce anxiety. It's also partly why we get
sedated with benzodiazepines too. How do benzodiazepines
work with the GABA receptor. How it does this is it causes
increased flow of chloride through the channel. It increases
the frequency of opening by the channel. And by doing this
it helps GABA to inhibit the gamma subunit. It binds between
the alpha and gamma units and it acts through many types of
receptors all over the brain as I mentioned before. So remember
that benzodiazepines increase the frequency of opening.
Benzodiazepines are fantastic for anxiety states. Alprazolam
or Xanax is the most prescribed anti-anxiety medication in the
United States. Other ones include clonazepam, lorazepam
and diazepam. We sometimes do use tricyclic antidepressants
for anti-anxiety and we can refer to lecture number 9
the antidepressant section to understand a little bit more
about how TCAs work. Benzodiazepines are used for muscle
spasticity and diazepam is probably the most commonly used
for this indication. And we also use benzodiazepines for
ethanol or alcohol withdrawal. We use a long acting
benzodiazepine for this. And a good example of a long acting
benzodiazepine is diazepam again and there is another one
called chlordiazepoxide. But if you remember diazepam I think
that's the more important one. Flumazenil is an antagonist to
the benzodiazepines. You can see that it binds to an area
just under where the benzodiazepines bind. It's used as a
reversal agent in overdoses. And it binds at a site
inferior to the benzodiazepines so that the benzodiazepine
cannot bind to the gamma subunit. Flumazenil, antagonist,
antidote to the benzodiazepines. So just remember that. The
trade name is Anexate. I think it's safe for you to remember
the trade name. And the reason why is because when you look
in crash kits, it's going to be labelled Anexate and not