00:00
Let's take a look at some
other classes of drugs
that are used to treat
fungal infections.
00:06
The polyenes, nystatin being
the prototypical drug
is used for superficial infections.
00:11
You can see where it acts
on the cell wall down here.
00:14
It's used topically to
suppress candida infections.
00:18
And it's used as "swish and
swallow" for oral candidiasis.
00:22
The mechanism of action,
remember that these polyene
antifungal agents bind to
ergosterol and caused artificial
pores in the cell membrane.
00:34
This causes leakage of hydrogen
ion, potassium ion,
chloride ion and even sodium
ion through that pore.
00:41
It also increases free radical
formations within the cell
itself which causes toxic
intermediates inside the cell.
00:50
And causes fungal cell death.
00:54
The next polyene I want to
talk about is amphotericin B.
00:57
And you'll notice that the slide
is almost is exactly the same
as nystatin.
01:02
Now these polyenes binds
to ergosterol and caused
artificial pores.
01:07
And once again as with
the nystatin,
it leaks hydrogen,
potassium, chloride and sodium
ions through this pore.
01:14
And you also have free radical formation within the cell
that causes toxicity inside
the fungal cell and cell death.
01:22
Now amphotericin B is a polyene
and it is related to nystatin.
01:27
But it's usually
intravenously administered.
01:30
Nystatin is usually
what we call topical.
01:33
And so it's gargling kind of
an agent that we use in oral
candidiasis.
01:39
Amphotericin B is an intravenous
drug and it's used for much
more serious infections.
01:44
It's eliminated through the
slow hepatic metabolism of it.
01:48
And it's half life is
therefore quite long, 2 weeks.
01:52
It has minimal renal excretion.
01:54
But we do make small adjustments
to this medication in class 4
or stage 4 renal failure.
01:59
Clinically we use it
for systemic mycoses.
02:03
And usually ones that
are fairly serious.
02:05
It's the widest antifungal
spectra of any antifungal agent
on the market.
02:11
It works against aspergillosis.
02:12
It works against blastomycosis.
02:15
It works against candida,
cryptococcosis, histoplasmosis
and mucor.
02:22
It also used intravenous
or rarely intrathecally.
02:27
I have seen it used
intrathecally once in my career.
02:30
Now mycotic corneal ulcers
and keratitis are one of
the potential treatments of that
we can use amphotericin B for.
02:39
Now in terms of the toxicity
of this medication,
the most interesting thing that I've seen with this agent is,
infusion related chills.
02:49
So patients suddenly start
feeling very cold and -- I don't
really have an explanation
as to why that's occurring.
02:56
Patients will also have nausea,
muscle spasms and vomiting.
02:59
And sometimes patients will have
this shock like fall in blood
pressure.
03:05
So a lot of time we will
premedicate these patients
with antihistamines
or even glucocorticoids.
03:11
You have to be very aware that
ampho B can cause renal tubular
acidosis.
03:16
And can cause magnesium
wasting and potassium wasting.
03:19
Now the magnesium and potassium
wasting are kind of coming hand
in hand.
03:23
Most of the time when you have
magnesium wasting, you're also
going to have potassium wasting.
03:28
The other toxic
effects include anemia.
03:32
That's usually due to decreased
erythropoietin production from
the kidney.
03:37
You can have those
nephrotoxic effects.
03:40
These are usually
dose limited however.
03:42
Now we have a liposomal
version of amphotericin B.
03:47
These amphotericin B liposomes
package the amphotericin B on
the inner surface or on
the inside of these liposomes
or I should say endozomes.
03:59
And the reduce renal toxicity,
we call that
lysosomal amphotericin B
or liposomal amphotericin B.
04:08
The correct term is actually liposomal.
04:10
We do give intrathecally this
medication but it is associated
with seizures in neurologic damage.
04:18
So that is a treatment
that we try to avoid
unless we're really in trouble.