Drug Induced Liver Disease
you have learned
a huge list of those drugs
that are Hepato toxic
You've also learned about those drugs that
or stimulate cytochrome P450
5% of all adverse drug reactions
are actually hepatic.
Do you see what that statement says?
5% of all adverse drug reactions
are hepato toxic.
liver function tests becomes extremely
important for you.
accounts for 20 to 30%
of fulminant liver failure.
This is no joke.
And once I get past
the general introduction,
of drug induced liver disease,
I will focus upon
and make sure that you
are absolutely clear
about how severe and dangerous
Reactions can be dose-dependent and/or
And the problem is the fact is, often times,
when the drugs have been taken
The patient might not even present
with symptoms and that is scary
You really need to make sure
that you take a proper history
is absolutely important
or psychiatric evaluation
We will talk about that in a second.
with removal of offending drug
The problem with that is the fact that
when you remove the offending drug,
because it might caused
so much damage to your liver,
What's the repair process called?
The repair process
is called fibrosis.
So you might actually have an increased
amount of fibrosis.
depositing the liver, ugh,
and might actually look rather
for fulminant liver failure.
our focus acetaminophen toxicity
It is often times,
the number one cause
of liver transplantation
in the young.
earlier, when I was talking to you
type of liver disease,
I told you that I would have you
I told you that psychiatric
evaluation is important.
Imagine that you have a patient,
a young patient, under a lot of stress-
a lot the pressure,
maybe perhaps doesn't
quite fit into society.
or feels that she is starting
not to fit in the society,
may be there is
depression kicking in,
all of this means to say
that the patient
wishes to commit suicide.
and how easy is it for the patient
to then have access
to Acetaminophen over the counter,
to absolutely no acetaminophen
and how will this may eventually
cause liver damage.
where are you in the liver biochemically
and by that, you should know,
that of the zones in the liver,
zone two, and three
Of all those zones,
which one of those zones will
be affected first
in acetaminophen toxicity?
And that is a wonderful
That will be zone three, isn't?
The reason for that is because
you have that cytochrome
P450 that you know of
or the "enzyme" that is responsible for metabolizing
acetaminophen in the liver and it is
called (CYP2e) is in it?
It is actually called
CYP2YE. At least know CYP2E.,
and that is cytochrome P450
that is responsible
for metabolizing acetaminophen.
so it is actually acetaminophen
that causes damage to the liver?
Well, it's more of
it's metabolite isn't?
in pharmacology, you discuss NAPQI
it is a multiple choice question.
or answer, so that you will be able
to identify, NAPQI.
with all the metabolism that is taking place
with toxcity, how much?
you must know dosage here.
This is one of those instances,
in which dosages thus become
so important because,
it is often times the most common cause
of liver transplantation.
greater than 4 grams.
That is a lot of "Tylenol".
Most common cause of
drug-induced hepatitis is exactly this:
so we talked about this cytochome p450
and we refer to zone three
if it's zone three we have a lot
of (Cyp) 450
there's a lot of metabolism
of the acetaminophen
and what are you releasing? NAPQI.
Take me one step further now.
Normally the liver
is responsible for detoxification
detoxification at some point
comes at the expense
of what biochemical substrate?
all this rings a bell, I'm hoping.
And that glutathione
is responsible for
properly metabolizing your NAPQI
Now this patient took an entire bottle
greater than 4 grams of acetaminophen
that is too much NAPQI that is being
produced in the liver,
thus, the glutathione will be exhausted,
guess what happens,
death right? there's going to be necrosis
place to your liver.
I told you psychiatric evaluation
Is it possible that you have a patient
who is depressed
and also been drinking alcohol,
So look for a patient that
is heavy heavy alcohol drinker
Now use common sense.
Why is it that alcohol and Tylenol
would accelerate Chronic liver disease?
would that heavy alcoholic consumption,
meaning heavy, what does that "heavy"
What am I getting in?
Well those of you that know
your pharmacology well,
you know exactly what I am referring to.
versus acute alcoholism
and its effect on
that enzyme in the liver called
if you're a heavy drinker,
this will accelerate
all that metabolite that is
being released in the liver,
guess what happens to liver damage,
So, whenever you hear the word heavy,
that means chronic alcoholism.
that is far more worse than acute,
acute remember in pharmacology,
would inhibit, cytochrome 450
But if you know if your patient
is psychiatrically ill,
and they are depressed,
then chances are
that they are a chronic heavy drinker.
So what they're going to find?
You're going to find
really high levels of ALT
and AST, both of them
either resolves without sequelae
or results in death in the liver.
That is really dangerous.
Means to say
that liver is going to die so quickly
And we’ll talk about this upcoming
in which, if you are to go
to end-stage liver disease,
you would expect other signs
and symptoms of your patients
with cirrhosis wouldn’t you?
Such as portal hypertension,
such as increased
estrogen, palmer erythema such as
spider telangiectasia but with a patient with
You may not even see
any of that keep that in mind.
if you and I agree, that
glutathione will be exhausted.
Wouldn't be nice to find
a drug that replenishes
We have N-acetylcysteine mucomyst
you know it is being N-acetylcysteine
may come as action, glutathione.