Let's move on to the spasmolytics.
We have two types of spasmolytics and we divide them up
into acute use and chronic use.
Acute use spasmolytics are a single agent here,
cyclobenzaprine. And chronic use are other agents
Let's talk about cyclobenzaprine. The prototypical agent of
cyclobenzaprine. There are other agents that are available,
but I think for your exam,
you can just focus on cyclobenzaprine.
We often use it in acute spasm due to a muscle injury.
It has some sedative activity. It is a muscarinic agent.
It does act at the brainstem, and that will reduce
resting tone of output from the brainstem.
Now, these do not work for patients who have cerebral palsy
or spinal cord injury.
Let's move on to those chronic use agents. These are drugs
that act either through the central nervous system
or act peripherally at the muscle.
Diazepam is a benzodiazepine. And as you know already from
our previous lectures, diazapam acts at the GABA A receptor.
It works in both the brain and in the spinal cord.
Baclofen acts at the GABA B receptor complex
in the brain and spinal cord.
We haven't talk about GABA B yet. And tizanidine
acts at the alpha 2 receptor in the spinal cord.
Now, let's take a look at these beutiful illustrations
put together by our IT team.
You've already seen the first one.
That's the GABA A receptor complex.
And you already know that both barbiturates and
benzodiazepines, as well as the reversal agent flumazenil
bind at the GABA A receptor. This GABA B receptor is a
complex structure. It has two membrane spanning units
that go back and forth across the membrane.
It is coupled to a certain type of a G type protein
and it does a couple of things. It inhibits voltage-gated
calcium channels. It inhibits adenylyl cyclase.
And it activates certain types of potassium channels.
We've already done this before, but once again, diazepam
works at the benzodiazepine site of the GABA A receptor site.
And remember, of course, that it increases the frequency of
open channel and that is an important exam question.
Baclofen, on the other hand,
acts through the GABA B receptor complex.
Now, the GABA B receptor complex in this particular instances,
located both in presynaptic terminals and postsynaptic nerves.
So in presynaptic nerves,
we're talking about calcium channel activity,
and in postsynaptic nerves,
we're talking about chloride channel activity.
This also causes membrane hyperpolarization and inhibition,
just like GABA A. It does result in less muscle contraction,
and it is quite useful in muscle spasm related to muscle injury
or to neurological disease.
So, many of our patients who have severe spasticity from
previous insult are very responsive to baclofen.
Tizanidine is an imidazole. It is related to clonidine in a
sense, and it works on alpha receptors in the spinal cord.
If you remember this particular image from our autonomic
nervous system lecture, I have told you before that
the voluntary nerves are not just in the sacrum as this image
would suggest, but it's throughout the entire spinal cord.
Remember that, at the motor end plate, you have nicotinic
cholinergic receptors that are active upon nerve stimulation.
Let's talk about actions at the muscle.
Dantrolene is our single agent here.
Now, dantrolene is a complex molecule of at least 3 rings.
It acts at something called the ryanodine receptor.
Now, ryanodine interferes with calcium release
from the sarcoplasmic reticulum.
You get reduced excitation-contraction coupling
when you have this drug on board.
Cardiac and smooth muscle are not affected. That's
actually quite a relief because if you think about it,
we don't want to affect cardiac and smooth muscle,
we only want to affect skeletal muscle.
And this therefore has a very specific use
in a disease called malignant hyperthermia,
which is brought about by certain types of anesthetics.
We've already spoken about this.
The other nice thing about this particular agent is that
it does not have an effect on the central nervous system
or on the neuromuscular junction itself.
As I said to you before, the most important use
is going to be in malignant hyperthermia.
And I've said this to you before,
and I'm going to say it again,
malignant hyperthermia, dantrolene,
one minute, must treat quickly.