It’s Professor Dave, I wanna tell you about
pharmacokinetics.
In the previous tutorial, we learned about
all of the different ways that drugs can be
administered, or basically the ways that drugs
can enter the body, whether in the mouth,
through the skin, directly into the bloodstream,
or otherwise.
Now we want to talk about what happens next.
Once drugs are inside your body, how do they
move around, and get to where they need to go?
Do they stay in the body indefinitely, or
are they eventually removed from the body
somehow?
The study of pharmacokinetics deals with precisely
these issues, and in learning about this,
we can highlight four main processes.
Those are absorption, distribution, metabolism,
and excretion.
Absorption generally describes the way the
drug moves from its site of administration
across one or more membranes, often into the
bloodstream, if it was not administered there directly.
Distribution describes its journey through
the bloodstream to target cells and specific
target molecules within.
Metabolism describes the ways that it eventually
gets modified by enzymes and rendered ineffective,
and excretion describes the way it then exits
the body, typically either through urine or feces.
We want to understand each of these processes,
as well as the ways that interactions with
food, drink, other drugs, and additional factors
can have an influence on them, so let’s
get a closer look at these now.
As we said, the first step is absorption.
If a drug is administered topically, this
could mean moving through the skin or a mucous
membrane, and subsequently through the walls
of nearby blood vessels.
If administered orally, this would mean being
absorbed through the lining of the stomach
or intestines, a process which would be slowed
by the presence of food.
Some drugs will pass through the cells that
comprise these membranes by passive transport,
others by active transport, but one way or
another they will make it through on the way
to their destination.
In describing this process, it will be appropriate
to review the term “bioavailability”.
This term describes the proportion of a drug
that is successfully absorbed into systemic
circulation.
Next, we mentioned distribution.
This is the way that drugs move through the
bloodstream, after being absorbed into it,
or injected into it.
There are many factors that influence this,
like the way that the drug interacts with
the components of blood, such as plasma proteins.
If the drug binds too tightly to these proteins,
it will not be able to reach its target cells.
Sometimes, a second drug is administered in
conjunction with the first that has a higher
affinity for these proteins than the first
one does, thus serving the sole purpose of
displacing the primary drug once bound to
the protein, allowing it to be delivered to
its destination.
Beyond these blood elements, there are other
factors that may hinder the movement of a drug.
These are anatomical barriers found in certain organs.
We have already discussed the blood-brain
barrier in the biopsychology series.
This prevents certain substances from passing
out of the bloodstream into brain tissue.
Some drugs will not be able to surpass this
barrier, while others will, such as psychotropic
drugs, or those affecting the mind.
There is also the blood-placental barrier,
that regulates which substances can pass from
the bloodstream of a pregnant woman into the fetus.
There are, however, a number of substances
that are able to pass through this barrier
that can still do harm to the fetus, such
as alcohol and certain medications.
And then there is the blood-testicular barrier,
which prevents many substances from reaching
the male testes, therefore making disorders
of the testes difficult to treat.
After distribution, there is metabolism.
This describes any chemical reactions that
the drug may participate in, often aimed at
inactivating it and targeting it for excretion.
If a drug is traveling through the bloodstream,
it is highly likely to be metabolized to some degree.
For example, if a drug is taken orally, it
will be absorbed through the intestinal wall,
and for this reason, the part of the circulatory
system it enters is a collection of blood
vessels called the hepatic portal system.
These carry blood directly to the liver, where
they will be metabolized in some manner.
This is called the first-pass effect, referring
to the first pass of a drug through the liver,
and this will typically greatly reduce the
bioavailability of a drug.
In certain cases, metabolism in the liver
actually activates a drug, but this is less
common, and the first pass effect can inactivate
over 90 percent of an orally administered
drug before it is able to reach general circulation.
This must be taken into account when determining
appropriate dosage.
Of course, drugs eventually reach their target
cells, but even then, after enough time elapses,
they will be metabolized.
There are many different enzymes in the body
that perform these metabolic functions, which
are very important, because the immune system
is only good at dealing with large biological
particles like viruses or bacteria.
It has no defense against small molecules,
so this detoxification mechanism aimed specifically
at small molecules had to evolve for life
to exist in a chemical world.
Finally, after metabolization there is excretion,
where the drug or its remnants exit the body.
This is typically done via exhalation, sweating,
urination, or defecation.
The kidneys are heavily involved in this process,
as they must remove harmful substances from
the bloodstream.
Some drugs are metabolized into gaseous form,
and are thus easily exhaled.
Some drugs are excreted through bile, a substance
secreted by the liver to aid in digestion,
as bile is recirculated back to the liver
via enterohepatic recirculation, whereby most
of the drug can then be excreted by the kidneys,
and the rest will exit in the form of feces.
And as we said, glands that produce fluids
such as saliva and sweat can also promote
excretion, though this method tends to be
less effective.
And with that, we have traced the journey
of a drug into the body, around the body,
and out of the body, which gives us a basic
understanding of pharmacokinetics.
