Pharmacodynamics: Agonist, partial agonist and antagonist

Transcript

Pharmacodynamics refers to the mechanisms and effects of medications within the body.

Or more simply, it’s what medications do to the body and how they do it.

Alright, so, in order to have an effect, many medications have to reach their target cells and bind to a receptor.

Receptors are specialized proteins found inside the cell or on its membrane. When they bind to a signal molecule called a “ligand”, they can alter their shape or activity, which ultimately results in some change in the cell’s activity or behavior.

You can imagine the ligand as the key that fits into the lock, which is the receptor, causing it to open or activate.

Now, depending on the effect a medication has on its receptor, they are often divided into two major categories: agonists and antagonists.

An agonist is a medication that mimics the action of the signal ligand by binding to and activating a receptor.

On the other hand, an antagonist is a medication that typically binds to a receptor without activating them, but instead, decreases the receptors ability to be activated by other agonist.

Okay, now the maximal effect or response an agonist can produce, abbreviated as Emax, is determined both by the number of receptors bound to the agonist, which depends mainly on the amount of the agonist given, also known as dose, as well as its intrinsic activity, which is the ability of the agonist to fully or partially activate its receptors.

Let’s plot all this into a nice graph to show the relationship between the dose given, on the x axis, (usually on a logarithmic scale), and the response produced, on the y axis.

So full agonists, upon binding to the receptor at high doses, are capable of producing a maximal response of 100% Emax on the y axis.

This represents the point where all available receptors are bound to an agonist.

In contrast, partial agonists, even at very high doses, result in a smaller response, so their Emax will be lower.

For example, a 70% response would shift the curve downwards.

In other words, a full agonist is like a really well made spare key that’s just as effective as the ligand, while a partial agonist is a poorly made spare key that could open the lock, but it takes longer.

Alright, at the other end of the spectrum, antagonists can be divided into competitive antagonists, and non-competitive antagonists.

So, a competitive antagonist will bind to the exact location where the ligand is suppose to bind, kind of like putting the wrong key into the keyhole, which prevents the right key from being used.

Now competitive antagonists can be reversible, where they can unbind from the receptor after a while, or irreversible where they bind to the receptor permanently.

The inhibition caused by reversible competitive antagonists can be overcome when there are more ligands floating around.

So when it unbinds, it’s more likely for one of the ligands to bind.

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