(4A) Pharmacodynamics: Drug response – Partial and full agonists

Agonist

• a drug (or ligand) that binds to a receptor, receptor changes shape and activates it.

• → signaling occurs

  → biological response

Full agonist

• agonist capable of producing the full/maximal response.

• Full agonists can mimic natural/endogenous ligands.

Full Agonist - example

• epinephrine/isoproterenol/norepinephrine

• albuterol

• morphine/endogenous opioid example

Heart-Rate / Agonist Example

Substances acting at the same receptor can produce different responses depending on how they interact with that receptor.

Professor told the class to focus on the heart-rate portion of the figure.

The figure/example compared:

• norepinephrine

• epinephrine

• isoproterenol

In the professor's example, isoproterenol was presented as producing the strongest heart-rate effect.

Efficacy

maximum effect a drug can produce.

Efficacy aka

ceiling effect

Emax = maximum effect

Efficacy - graph

On a graph:

↑ drug concentration (x-axis)

→ ↑ response (y-axis)

→ eventually response stops increasing

→ plateau = Emax

The curve is S-shaped when concentration is shown on a log scale.

Intrinsic activity

• how well the drug-receptor complex activates the receptor and produces a response.

• This helps explain the difference between full and partial agonists.

Agonist Competition

• A natural ligand and a drug agonist can compete for the same receptor site.

• Which substance occupies more receptors depends partly on affinity.

Affinity

strength of binding between a ligand/drug and receptor.

Higher affinity →

more likely to occupy the receptor

Affinity

The natural ligand does not automatically…

The natural ligand does not automatically have the higher affinity.

It depends on the specific chemical interaction between the drug and receptor.

Receptor Occupancy

More receptors being activated → greater combined biological response

Partial agonist =

binds and activates the same receptor as a full agonist, but cannot produce the full maximal response.

Full vs Partial Agonist

	Full Agonist	Partial Agonist
Binds receptor?	Yes	Yes
Activates receptor?	Yes	Yes
Reaches full maximum?	Yes	No
Emax	Full/higher	Lower
Intrinsic activity	Higher	Lower