Pharmacodynamics: Key Terms

Question 1

What is a ligand?

Answer 1

A ligand is a substance that can interact with a target protein or receptor.
Ligands usually bind to a specific site on the signalling protein.
They can be endogenous signalling molecules eg hormones, neurotransmitters, antacids or ions or then can be exogenous molecules eg drugs.

Question 2

What is an agonist?

Answer 2

An agonist is a substate that binds to a receptor and activates the receptor to then produce a measurable biological response.

Question 3

What is an antagonist?

Answer 3

Antagonists are ligands that have affinity for a receptor or target protein but do not produce a biological response.
Antagonists block the effects of agonists

Question 4

What is affinity?

Answer 4

Affinity is a measure of the strength (or avidity) with which a ligand or drug binds to a receptor
Affinity can also be thought of as the likelihood of how well a ligand will optimally ‘fit’ the receptor or target protein binding site.

Question 5

What is the measurement or parameter used to define affinity?

Answer 5

Affinity is measured by Kd.
Kd is defined as the concentration of a ligand at which 50% of all available receptors are bound.
The lower the Kd, the greater the affinity.

Question 6

Intrinsic efficacy is a term used to describe the ability of a ligand to…

Answer 6

generate the active form of the receptor (R*)

Question 7

What is ligand efficacy?

Answer 7

This is the ability of a ligand to cause a measurable biological response.

Question 8

How do we define agonist potency?

Answer 8

Potency is defined as the concentration of a drug that evokes 50% of its maximal response (Emax). The term EC50 is used to represent this concentration.
The lower the value for EC50, the more potent is the drug or ligand (because a lower conc. of the drug is required to generate 50% of the maximal response)

Question 9

What is a partial agonist?

Answer 9

Partial agonists are ligands that evoke responses that are lower than the maximal response of a full agonist (lower Emax)

Question 10

Compared to a full agonist, a partial agonist has..

Answer 10

…lower intrinsic efficacy

Question 11

Name the three main types of drug antagonism. For each type, indicate both the location of the antagonist binding site and the possible types of binding at the site.

Answer 11

1. Reversible competitive antagonism
   This takes place at the same bidding site as the endogenous ligand (orthosteric site).
   The interaction is relatively weak (non-covalent) bonding.
2. Irreversible competitive antagonism
   Takes place at the same binding site as the endogenous ligand (orthosteric site)
   Irreversibel interaction reflects high affinity with very slow dissociation -may be covalent bonding.

3.Non-Competitve antagonism
Binding occurs at a separate allosteric site -no competitive for otherosteric site access
Interaction can be either low or high affinity and could include non-covalent or covalent bonding.