Pharmacodynamics - Dose-response curves

Efficacy?

The maximum effect a drug can produce, regardless of dose. Read at the plateau of the dose-response curve (E_max)

Potency?

How much drug is needed to produce a given effect. Measured by EC₅₀ (drug concentration that gives 50% of the maximum effect), where a lower EC₅₀ = higher potency = curve further to the left.

Affinity?

How tightly a drug binds to its receptor. Read through binding assays (% bound vs conc.), not dose-response curves.

• Left-shifted curved = higher affinity

Agonist types

• Full agonist: achieves Emax

• Partial agonist: only produces sub-maximal response, even if all receptors are occupied

• Inverse agonist: reduces receptor activity by inducing inactive conformation of receptor (only works on inherently active receptors, e.g., leaky channels)

What is the difference between an inverse agonist and an antagonist?

Inverse agonists inhibit the activity of receptors that are inherently active in the absence of a ligand, resulting in negative efficacy.

• Baseline decreases

Antagonists have no effect on their own, only producing an effect is added together with agonist.

• Baseline stays unaffected

Antagonist?

Molecules that bind to receptors and blocks a/the receptor’s activation by agonists; does not induce a response on their own

• 0 efficacy as it doesn’t trigger a response

• IC₅₀ = antagonist concentration at which the receptor response is reduced by 50%

Competitive antagonist

• Binds to the same site as agonist, competing with it

• Shifts the curve to the right, in parallel

• No change in E_max as it can still be reached by adding more agonist

• Most drugs are competitive antagonists due to their reversible action

Non-competitive antagonists

• Binds either (i) irreversibly to receptor, or (ii) to allosteric site

• Can therefore not be countered by adding more agonist

• Curve flattens, reducing E_max