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Welcome to Pharmacology
by Lecturio.
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I'm Dr. Pravin Shukle.
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We're going to be covering
GI pharmacology today.
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The drugs used for gastrointestinal
order spend a huge range of medications.
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We have drugs for peptic acid
disease, drugs for pro-motility,
drugs for irritable
bowel disease,
drugs for inflammatory bowel
disease, and anti-emetics.
00:27
We have a whole host of other
agents as well for various ailments.
00:32
Let's look at
peptic acid disease.
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We have the antacids,
the H2 blockers, the PPIs,
the mucosal protective
agents, and the antibiotics.
00:45
Let's start off
with the antacids.
00:48
Now, antacids are weak
bases that neutralize
the low pH environment
of the stomach.
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These can include many agents
such as magnesium hydroxide
which is better known
as Milk of Magnesia.
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Milk of Magnesia is a
mainstay of antacid therapy
and it's probably the first line
agent that we use in most cases.
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It has a strong laxative effects
so it's very good for patients
who are also constipated.
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Another agent that we use
is aluminum hydroxide,
commonly known as Maalox.
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It has a strong constipating effects so
it's better for people who have diarrhoea.
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And calcium carbonate and sodium
bicarbonate are just plain antacids.
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They are absorbed by the
gut unlike the other agents.
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The first two agents that I
mentioned tend to stay in the gut,
these agents are
actually get absorbed.
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Let's move on to the H2
receptor antagonists.
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These agents block histamine at the
H2 receptor inside the gastric mucosa,
specifically the parietal cells.
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You can see that they inhibit
stomach acid production directly,
especially at night, so this is a
particularly good agent for people
who have night
time GERD symptoms.
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They are relatively
nontoxic agents,
they are actually sold over the counter now, we don’t even prescribe them.
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Cimetidine was the original and
prototypical drug in this drug class.
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But we actually don't use it because
there are multitude of drug interactions
that we get from this
particular medication.
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Interestingly enough, some of these
agents, in particular cimetidine,
do have an antiandrogen
effect as well at high doses.
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These are the agents
that are commonly sold.
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These agents are sold over the counter, they’re extensively used all around the world.
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Let's move on to the PPIs or
the proton pump inhibitors.
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These are lipophilic weak bases.
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So the agents themselves
are not antacids.
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What they do is they
become protonated,
and they work inside
the parietal cells
and they get concentrated in
these areas up to 1,000 times.
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They irreversibly inactivate the
hydrogen-potassium-ATPase pump.
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What this does is that it ends up causing
less acid secretion, substantially less.
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Now they are
rapidly metabolized.
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They may take 3 to 4 days to actually
have an effect because of this reason.
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They are far more effective than the H2
antagonists that I spoke about earlier
but they last, and they work well, and they
are the mainstay of anti-ulcer therapy.
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There are some toxicity issues
associated with the PPIs.
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You can get diarrhoea,
abdominal pain and headache.
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And you can get hypergastrinemia
if you use them for a long time.
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They may also decrease
the ability of drugs
that require higher acid levels.
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So for example, ketoconazole
requires a high acid environment
within the stomach to become
particularly activated and absorbed,
if you give a PPI the same
time as you give ketoconazole,
you're going to reduce the availability
of ketoconazole to the body
for it to do its job.
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The same thing will happen
with drugs like digoxin.
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Now, a small increase in
respiratory and enteric infections
are associated with PPI use.
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We have many brands out
on the market today,
prototypical drug is omeprazole,
but you have a whole list of other
ones that I've given you here.
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Let's move on to the
mucosal protective agents.
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Now the prototypical example
of this is sucralfate.
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It's a very poorly
soluble molecule.
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It polymerizes
inside the stomach.
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And when I say polymerize what I mean
is is that it forms chains of molecules.
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This polymer will bind to the injured
tissue inside the patient stomach.
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And it forms a protective
coating over those ulcers
and prevents further
damage from occuring.
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The down side of this medication is
it has to be taken 4 times a day.
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And that's really the main reason why
we don't use it as much as we used to,
simply because of
the inconvenience.
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It's a very low toxicity agent.
04:55
It has a very low solubility.
04:57
It's quite effective,
unfortunately it's inconvenient.
05:01
These medications are
great for patients
who are very adherent
to their schedule
and so if you know these patients are
going to follow their instructions,
it's a great choice.
05:14
Let's move on to other agents.
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Misoprostol is an analogue
of prostaglandin E.
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It works at almost the same
point in the system as the PPIs.
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You get increased
mucosal protection
because it directly
inhibits acid secretion.
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And it reduces ulcers
in NSAID users as well.
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The adverse event rate is quite
high because it's poorly tolerated.
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There's lots of GI upset and
diarrhoea associated with this agent.
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And for this particular reason,
it's not used much anymore.
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It is an agent however
that you should be aware of
because it is going to be on
pharmacology portion of your exam.
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Let's move on to agents
like colloidal bismuth.
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So, bismuth subsalicylate,
also called Pepto-Bismol,
gives a protecting coating on
ulcerated tissue much like sucralfate.
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It stimulates mucosal
protective systems as well,
so it goes a little bit further
than sucralfate in that sense.
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It actually has direct
antimicrobial effects.
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And you actually have some
sequestration of enterotoxins.
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So if there are
toxins within the gut,
it actually binds those toxins and
renders them biologically unavailable.
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It reduces stool frequency
in infectious diarrhoea.
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And unfortunately, there is a cosmetic
side effect of this medication,
it causes a black tongue.
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Now the other important issue that you have
to remember is it also causes black stools.
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And many times, people who have
melena type stools from Pepto-Bismol
are misdiagnosed as
having GI bleeds.
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That is not the case.
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So be aware that if you have a patient
who presents with melena type stools
ask first if they were
taking this agent.