Let's move on to the motility disorders.
So the motility disorders can be treated by several agents.
You have the dopamine antagonists, the motilin agonists,
the laxatives, and the anti-diarrheal agents.
Let's start off with the cholinomimetics. So cholinomimetics
lower the sphincter tone of the lower esophageal sphincter.
Now, in the past, we used drugs like bethanechol
but not any more
because bethanechol tends to be a toxic agent and
doesn't really work as well as we had hoped.
Neostigmine which is an acetylcholinesterase inhibitor
is often used in the hospital for acute bowel distention.
Now for further information on this particular agent, I encourage you
to take a look at our autonomic nervous system pharmacology lectures,
you'll have a much better discussion about
this particular drug in that lecture.
Other agents include the dopamine receptor antagonists,
specifically the D2 receptors.
So, metoclopramide is your prototypical example of this.
It causes D2 blockade, and this causes increased bowel transit
so things move a little bit quicker. They may also cause
parkinsonian symptoms so you have to be fairly careful
with these agents. They work also in the area postrema
which is part of the emetic centre of the brain.
And for that reason, it's a very effective antiemetic
in surgery and in cancer patients.
Domperidone is another example of this type of agents.
It does not cross the blood brain barrier
so it makes it a little bit different from metoclopramide.
And it's therefore less likely to cause CNS effects.
Not surprisingly, the anti-emetic effects of domperidone
are really not that significant.
Now, motilin receptor agonists are an interesting group because
the prototypical agent is actually an antibiotic, erythromycin.
It directly stimulates motilin receptors and
has benefits in patients with gastroparesis.
Now, this also explains the common side effect of diarrhoea.
Erythromycin is hard on the system.
And most patients who take erythromycin for an infection complain of
diarrhoea, and that's because of direct motilin receptor agonists activity.
Let's take a look at the laxatives.
Now, laxatives can work in several different ways.
They can be bulk forming. So the classic example of that is psyllium.
Now, psyllium is a seed and in order for it to work properly,
it has to be chewed, and not just chewed but what we call masticated.
And what we mean by that is that it has to be chewed and mixed with saliva
because the salivary amylase will mixed with the psyllium
and activate it.
Now, there are over-the-counter agents that are
groud up psyllium. They come as an orange kind of a powder
that you can spread on your eggs or mix with your orange juice.
Those are actually quite effective.
Over-the-counter agents such as metamucil
contain psyllium that has been activated.
Now, your herbalist naturapathic people like to give
psyllium seeds directly, and that's fine, works really well
as long as they chew it and masticate it,
mix it with their saliva before they swallow.
It's gross. So I don't know why you'd ever want to
choose to do that instead of just take metamucil.
There are stool-softening agents. Docusate sodium is a very commonly
used agent. I use it in probably 60 % of my patients over the age of 80.
Glycerin tablets and glycerin suppositories and mineral oil
is also another way of softening stool.
Now, osmotic cathartics work by actually causing
more water to be present in the stool.
So, it's kind of like creating a gel matrix
within the stool itself so that water stays in the stool,
and that the stool is softer. Magnesium oxide
and all of these other ones are examples of that.
Now, stimulants act by actually irritating the bowel.
The prototypical and very old example of that is castor oil.
I'm sure you saw that on Bugs Bunny when you know they gave the coyote
some stimulants and he had to go to the bathroom really quickly
At least that's how I remember castor oil.
It's not used anymore.
We now use things like aloe and senna which are probably
more gentle and easier on the system.
Chloride channel activators are less used at this point in time.
How they work is by increasing fluid bulk within the stool itself.
And finally, the opioid receptor antagonists are
an interesting way of treating patients.
What happens is is that we know that opioids are constipating.
By blocking the opioid receptor, we believe that this will reduce
constipation, particularly in those patients who are on opioids.
So, there you have the list of the laxatives. Have a look at this.
We're going to present this slide to you as a downloadable slide
so that you can have this in your own slide library.
Let's take a look at some of these other agents now.
I spoke to you before about opioids being constipating,
we can actually use opioids as anti-diarrheal agents as well.
And that seems logical because opioids are
constipating in and out themselves.
However, we don't want to use strong opioids and we actually have
an agent that is a weak opioid, it's commonly sold as Imodium,
it's a analogue of meperidine. It has minimal
central nervous system effects and maximum GI effects.
Originally, when this agent was released on the market,
we thought we would be using it for pain control,
and the GI effects were so bad that people complain about it.
But some enterprising scientist of the drug company said
"Well why don't we use it for diarrhoea?"
And actually it works really well.
So Imodium is probably the number 1 selling
over-the-counter agent for the use in anti-diarrheal treatment.
Other anti-diarrheal agents include kaolin.
So kaolin is a naturally found magnesium aluminum silicate.
And it's hydrated. So it works quite well.
Pectin is an indigestable carbohydrate that comes from apples.
Now the interesting thing about pectin is that
it actually absorbs bacterial toxins and some fluids.
So when you combine kaolin and pectin, you come up with
an agent called Kaopectate which is sold commercially.
Now, this agent can of course cause constipation but when you
giving your patient with diarrhea this agent, it works quite nicely.
Now the problem with Kaopectate is because
it's one of these binders that binds toxin,
if you think about it, it'll also interfere
with the absorption of a whole host of medications.
So patients on Kaopectate, be aware that
your other medications are probably being bound.
It's really important, I'm just going to stop here,
and I'm going to say,
do not use anti-diarrheal agents in patients who have
bloody diarrhea or infectious diarrhea
because the diarrhea in those cases are actually cathartic,
in the truest sense of the word meaning
that you're getting rid of the infectious agent and
diarrhea in this case is a protective mechanism from the disease.
So, if you inhibit the protective mechanism,
you may make the person much sicker.
We're going to cover this in more detail
in your GI system's lecture by Lecturio later
but I just want to put that out there now.