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Welcome to this short
lecture on pharmacogenetics,
as an illustration of
personalized pharmacotherapy.
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Why do we discuss this topic?
It is because
pharmacogenetics is relevant,
and because people differ.
Pharmacogenetics is
a special area of
biochemical genetics
that deals with
variation in drug responses and
the contribution of
genetics to this variation.
It intends to describe
the genetically
controlled variations
in both drug disposition
(pharmacokinetics)
as well as drug response
(pharmacodynamics).
The key finding here is
the concept of
polymorphisms because
they refer to frequently
occurring monogenetic variants,
commonly with a
frequency above 1%,
and they will display a specific
polymorphic distribution.
0:58
This means that if you look at
the frequency of
different polymorphisms,
these polymorphisms
will always show
something like a
Gaussian distribution
with different curves
following each other.
What you can see on this
slide, for instance,
is that there are very
rare groups of SNPs
while others are
much more common.
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What does this mean?
People differ.
If you consider these
genetic polymorphisms,
you could either
try to assess this
based on the pharmacokinetics,
so that the pharmacokinetics
will differ
based on polymorphisms
between different patients
or related to pharmacodynamics,
so that the effect of a
given concentration will be
different between
different patients
because of different
polymorphisms.
To illustrate this,
related to pharmacokinetics,
you could actually focus on
the differences associated with
different activities of
isoenzymes (drug metabolism)
or transporters
that contribute to
the distribution of
different drugs.
If you subsequently focus
on pharmacodynamics,
you can imagine that
receptors are different.
Let's say that the
sensitivity of receptors to
a given concentration of drug
can be different between
different patients,
and the same is true, for
instance, for ion channels.
Sometimes, it can also be
post-receptor type of enzymes
that function differently
and, therefore, may result
in different outcomes.
It's important to realize
that patients may have
different polymorphisms
related to pharmacokinetics
as well as pharmacodynamics for
a given compound or
clinical indication.
That's what I will try to
explain on the next slide.
We will discuss
polygenetic responses.
