00:00
Okay, so that's the antimalarial
agents in a nutshell.
00:04
Let's move on to the amebicides.
00:06
Now amebicides are going to
be divided into two different
groups.
00:14
Those amebicides that act
systemically in the tissues
and those are for people
with systemic infections.
00:20
And those amebicides that acts
exclusively in the bowel wall.
00:24
And those are people who
have more GI limited disease.
00:28
Now you can say that agents
are very similar to
the anti-malarial agents.
00:33
Chloroquine,
metronidazole, tinidazole.
00:36
These are all agents
that you've seen before.
00:38
Luminal amebicides act on
organisms on the bowel wall
itself.
00:44
So these are the agents here
that you can see that we use
for luminal agents.
00:50
And we'll go through
each of them in detail.
00:55
Let's start off
with the emetines.
00:57
So the emetines are a group
of drugs that block ribosomal
movement along
the messengerRNA.
01:03
So this is kind of an
interesting visual idea.
01:06
Imagine that that messengerRNA
is a long railroad track.
01:10
The ribosome is a kind of like
a car on a train that just
travels along the track.
01:16
And as it travels along
the track it reads different
codes in the messengerRNA
and produces a protein.
01:22
The movement of that ribosome
along the railroad track is
blocked by this class of drugs.
01:27
And by that method inhibits
proteins synthesis specially for
organisms like amoeba.
01:33
In terms of toxicity, there's
quite severe toxicity with these
agents and it's actually extremely common.
01:41
GI distress is going to
be the number one type.
01:44
You can also sometimes
get muscle weakness.
01:46
And in terms of cardiac
muscle, you can get arrhythmia,
and congestive heart failure.
01:51
So be very aware of the side
effects of these medications.
01:56
The other agents that we use
to kill, to act as amebicides
are metronidazole
and tinidazole.
02:03
So we have seen before
in our other lectures on
anti-bacterials.
02:08
The mechanism of action we
belief is through bio-activation
by anaerobes to form
cytotoxic products.
02:16
Now there's a nitro group that's
reduced by ferredoxin that can
also be quite toxic too.
02:21
The drug of choice, this is
the drug of choice in severe
intestinal wall disease
and hepatic abscesses,
metronidazole in particular.
02:30
It works very well in extra
intestinal diseases as well.
02:33
So I'm not suggesting that
metronidazole can't be used
in systemic disease.
02:37
I'm just suggesting that in
terms of luminal disease
and hepatic abscesses
it's a very good drug.
02:44
Metronidazole is the drug
of choice in trichomoniasis
and several other types
of amebic infections
or anaerobic infections.
02:55
Tinidazole is effective
against metronidazole-resistant
organisms.
03:00
So it is our backup plan when
metronidazole doesn't work.
03:09
Other agents that we used in
the treatment for amebicide
activity is dyloxanide.
03:16
Now it is a luminal amebicide.
03:18
It is converted within the gut
itself to the freebase form.
03:22
The freebase form is an
amebicide through an unknown
mechanism.
03:27
It is the drug of choice
in asymptomatic amebiasis.
03:31
So it's very, very effective.
03:33
It's used in mild intestinal
disease in combination with
other drugs.
03:38
Toxic effects are really related
and limited to the bowel.
03:42
And we're talking about
abdominal bloating with a lot of
gas production or diarrhea.
03:49
Iodoquinol is another agent that
is considered luminal amebicide.
03:57
It is used in mild to
moderate to severe infections.
04:01
So it's a whole
range of infections.
04:03
Toxic effects once again are
fairly limited to the bowel.
04:07
And they tend to be
common but not a severe.
04:10
And people will complain of some
mild abdominal bloating
or they will complain about diarrhea.
04:14
Overdose symptoms.
04:16
In overdose we have to be
aware of significant problems
including thyroid enlargement.
04:23
Quite severe skin reactions.
04:25
And in some cases neurotoxicity.
04:27
And in terms of the
neurotoxicity, one of the most
feared ones is visual
dysfunction which can also get
a peripheral neuropathy as well.
04:40
Paromomixin,sorry, Paromomycin
is also a luminal amebicide
and it is also an
aminoglycocide antibiotic.
04:48
So we did covered very briefly
in our anti-bacterial lectures
too.
04:53
It may be superior
to other agents
in asymptomatic infection.
04:57
So it maybe something
that starts to take over.
05:00
And it may already have done
so in your local hospital.
05:03
It's used in combination with
tetracyclines like doxycycline
for mild disease.
05:08
In terms of toxicity, headaches,
dizzines, rashes and anthralgia
are very common with this
class of agent and with all
aminoglycocide agents.
05:18
The toxicity risk is going to be proportional to renal function.
05:23
So if a person has stage 3 renal
disease, the toxicity risk is
actually quite high.
05:31
So the next drug that I want to
mention is nitazoxanide which is
quite a good drug.
05:37
It has activity against a whole range of protozoan agents.
05:41
It works quite well against
Entameoba histolytica.
05:44
It works well against the
Helminths class of organisms.
05:48
It works quite well
against Giardia Lambia.
05:52
And if you recall that's
the one we prozactly call it
the "Rocky Mountain Runs."
That's where you get quite
explosive diarrhea
from drinking effected
river water or lake water.
06:04
A bit of a note on that.
06:08
We commonly think of that being
something common to the rocky
mountains because of it's name.
06:13
But in actual fact it's not just
limited to places like Alberta
in Canada or Colorado
in the United States.
06:19
It's also present
in the northeast.
06:22
So it's present in
Ontario in Canada.
06:24
It's present also in places like
rural Pennsylvania or New York
in the northen United States.
06:31
So don't just think of
it as a western disease.
06:34
It's also an east coast
disease as well.
06:37
We also use it against
cryptosporidium.
06:39
We can also use it in other
agents of protozoa too.
06:43
Now we also can use this agent
in those organisms that are
resistant to metronidazole
which is becoming more and more
common as time goes on.
06:53
So I suspect that this drug is
going to become more important
with time.
06:57
Now here's the overview
of the treatment.
07:00
And I'll just go over it again.
07:02
And we also have the final slide
as a downloadable image that you
can look at yourself
on your own time.
07:08
So for asymptomatic intestinal
infection, I have mentioned to
you before that we like
this drug diloxanide.
07:16
It's a very, very active
agent and it works quite well.
07:19
In terms of mild to moderate
intestinal infections, we move
to metronidazole.
07:26
And we also add in luminal
agent like the one
that was listed above
With respect to the severe
intestinal infections,
we have of course are going
to use metronidazole.
07:37
Now if the agent is resistant
to metronidazole, we will
substitute tinidazole.
07:43
We will always add a luminal agent with the metronidazole
in severe infections.
07:48
Alternatives can be
tetracyclines
or one of the emetines as well
plus a luminal agent.
07:55
In terms of patients who have
hepatic abscesses and other
types of extra intestinal
disease, we are going to use
metronidazole.
08:04
Or in resistant cases
we'll use tinidazole.
08:06
Plus we will add a luminal agent.
08:08
So you notice that moderate,
sorry, severe intestinal disease
and hepatic abscesses are
treated essentially the same.
08:16
So there's the entire graphic.
08:18
We'll have that as
a downloadable for you
so that you can look at
it on your own.