Metabolism is the chemical
alteration of the drug.
We also call it biotransformation—
that sounds a lot fancier,
but that’s really what’s going on.
It takes the drug and transforms it.
Most of it occurs in the
liver using the P450
and we’ll talk about that in just a minute,
but I want you to have solid, in
your mind, that metabolism
is the chemical alteration or the
biotransformation of the drug.
Most of it happens in the
liver using that P450.
So let’s look at what happens
when a drug is metabolized
because it’s all over the map
what can happen.
You might have faster excretion
of the drug by the kidneys
because the liver takes a
drug that’s lipid soluble
and makes it water soluble so the kidneys
can excrete it in your urine.
It can also inactivate some drugs
so that helps the body get rid of things
or there’s usually a reason we want
that drug to be inactivated.
Now bioactivation of “prodrugs”—
it means it takes an inactive drug
and makes it active—
so right there, we might be able
to change it into a form
that we can get it out of the body quicker—
take it from lipid to water soluble—
it can either inactivate a drug
or activate a drug.
Now the toxicity levels can also
be increased or decreased,
so when I said it’s all over the map,
I wasn’t kidding, right?
It can have all kinds of reaction because
the liver is amazing in what it can do.
So I might have a risk for increased
or decreased toxicity.
If it inactivates the drug,
then I’m going to have
less risk for toxicity.
If it activates the drug, then it might
increase my risk for toxicity.
So when you’re thinking about metabolism—
it happens mostly in the liver.
The biggest concept is it can
take lipid-soluble drugs
and make them water soluble,
it can inactivate drugs or activate drugs.
Now that cytochrome P450 system—
this is really killer—
because it’s a microsomal enzyme system,
but it is a group of 12 closely
related enzyme families.
It is amazing at what it can do.
It metabolizes drugs and
So endogenous just means those are
things that my body makes by itself—
we’re focusing on what the P450
system does to drugs,
but it also has some really cool factors
in the rest of your body.
So, if it takes a “prodrug,”
then it can have bioactivated in the liver
and then it can be distributed out
to the rest of the body
to do what we need it to do.
So the cytochrome P450 system is something
that’s worth noting in your notes.
So pause and just see if you can kind
of recall what the key concepts are.
So the most important things you want
to remember about the P450 system
is that it is 12 closely related
and it is amazing at what it can
do with activating “prodrugs.”