Pharmacodynamics: How do drugs act on the
body?
In the Chalk Talk episodes on pharmacokinetics,
we looked at what the body does to a drug;
that is, how it’s absorbed, distributed,
metabolized, and excreted from the body.
In these next two episodes on pharmacodynamics,
we’ll be taking a detailed look at the effect
of a drug at its site of action.
In general, drugs don’t initiate new metabolic
processes in the body but alter biochemical
processes.
To do so, they interact with specific target
structures in the body, for example, receptors
and enzymes.
These interactions can either enhance or inhibit
downstream biochemical processes.
Drugs that activate a receptor or an enzyme
are termed agonists, whereas drugs that have
an inhibiting effect are called antagonists.
So, the effect of an agonist is comparable
to that of a natural enzyme effector or an
endogenous signaling molecule for a receptor.
In contrast, antagonists are analogous to
natural inhibitors of enzymes or receptors.
Besides these drugs, there are other types.
Some interact with DNA whereas others interfere
with osmotic cell balance.
In this Chalk Talk episode, we won't be focusing
on such drugs but on the various mechanisms
of drug-receptor interactions.
Imagine a receptor on the surface of a cell
to which a drug is able to bind.
Under physiological conditions, the extracellular
binding of a signaling molecule to this receptor
activates an intracellular signaling cascade.
For the drug, the presence of this receptor
makes the cell a potential site of action
to which it can bind to.
Let’s assume that the drug is an agonist
that elicits signal transduction at a receptor.
Principally, it can act in one of two ways:
The agonist could bind to the receptor and
produce an effect similar to that of the endogenous
signaling molecule.
Such drugs are termed direct agonists.
Alternatively, instead of causing a signal
itself, the drug could enhance the action
of the endogenous signaling molecule, for
example, by increasing the release of signaling
molecules.
Such drugs are termed indirect agonists.
If the aim is to impair signal transduction
at the receptor, then antagonists are used.
Antagonists can also act in different ways
and are typically classified as competitive
and non-competitive.
A competitive antagonist binds to the same
site as the endogenous signaling molecule,
blocking its binding site at the receptor.
As a result, a lower amount of signaling molecules
bind to the receptor on the cell surface,
reducing their overall effect.
A non-competitive antagonist binds to a site
other than the usual receptor binding site.
But as this binding causes conformational
changes in the structure of the receptor-binding
site, it decreases or even abolishes the physiological
effect of the signaling molecule.
To get a more complete picture, we’d also
like to mention the presence of substances
termed functional antagonists.
Despite their name, their mechanism of action
strongly differs from that of other antagonists.
In fact, functional antagonists act like agonists:
They bind to a receptor and actively promote
a reaction, which then physiologically counteracts
a downstream process.
The induced reaction, therefore, reduces the
effects of the downstream process without
any direct interaction between the functional
antagonist and this process.
In short, the drug doesn’t antagonize the
endogenous signaling molecule, but rather
a physiological function.
This may sound somewhat confusing initially
but you probably already know a drug with
such a mechanism of action: It’s adrenaline,
which is a functional antagonist.
In allergic reactions, adrenaline antagonizes
vasodilation caused by histamine, without
both signaling molecules binding to the same
receptor.
Let’s go back to drugs that directly affect
signal transduction at the receptor.
This process isn’t only regulated by competitive
and non-competitive antagonists but also by
partial agonists.
These drugs bind directly to the receptor,
where they generate a signal that is similar
yet weaker than the endogenous signal.
As a result, drug binding to the receptor
leads to an overall weaker signal.
The physiologic effects of a drug don’t
only depend on its mechanism of action but
especially on its dose.
We’ll be taking a detailed look at the relationship
between dose and response in our next episode
on pharmacodynamics.
