Antagonists and dose-response curves

Question 1

What is an antagonist?

Answer 1

A drug that blocks the response to an agonist

Question 2

Antagonist examples

Answer 2

Terfenadine at the H1 receptor.

Question 3

What are pure antagonists?

Answer 3

Do not by themselves cause any action by binding to the receptor

Question 4

General classes of antagonists

Answer 4

Chemical
Physiological
Pharmacological

Question 5

Chemical antagonists

Answer 5

Binding of 2 agents to render active drug, inactive.

Commonly called chelating agents

Question 6

Example of a chemical antagonist

Answer 6

Protamine binds (sequesters) heparin

Question 7

Physiological antagonists

Answer 7

Two agents with opposite effects cancel each other out

Question 8

Example of physiological antagonist

Answer 8

Glucocorticoids and insulin

Question 9

Pharmacological antagonists

Answer 9

Binds to a receptor and blocks the normal action of the agonist on receptor responses.

Question 10

Types of active binding site receptor antagonists

Answer 10

Reversible (Competitive antagonist)

Irreversible (Non-competitive active site antagonist)

Question 11

Type of allosteric site receptor antagonists

Answer 11

Reversible and irreversible (Non-competitive antagonists)

Question 12

Efficacy and antagonists

Answer 12

Pure antagonists do not by themselves cause any ‘action’ by binding to the receptor.
Antagonists (no efficacy) - AR* doesn’t exist.

Question 13

Competitive pharmacological antagonism

Answer 13

Binds and prevents agonist action but can be overcome with increased agonist concentration
Causes parallel shift to the right of the agonist response curve.

Question 14

The dose ratio

Answer 14

Agonist plus increasing concentrations of competitive antagonist
(Agonist + antagonist EC50 (x) / Agonist EC50 (y) )

Question 15

Schild plot for competitive antagonists

Answer 15

r - 1 = [B] / Kb
r = Dose ratio
[B] = Antagonist concentration
Kb = Antagonism dissociation constant

Question 16

What do pA2 values describe?

Answer 16

The activity of a receptor antagonist in simple numbers

Question 17

pA2 =

Answer 17

• Log Kb

Question 18

Irreversible (Non-competitive active site) pharmacological antagonism

Answer 18

Bind and forms irreversible covalent bonds with receptors.

Causes parallel shift to the right of the agonist-response curve and reduced maximal asymptote.

Question 19

Partial agonist or irreversible antagonist?

Answer 19

An antagonism on its own will do nothing, has to have an agonist as well. Agonists will work on their own.

Question 20

Non-competitive (allosteric site) pharmacological antagonism.

Answer 20

Signal transduction rather than receptor effects.
Downstream responses are blocked (EG Nifedipine blocks Ca2+ influx)
Reduces slope and maximum dose-response curve

Question 21

Therapeutic window/index

Answer 21

Risk:benefit ratio
TD50 / ED50
or
LD50 / ED50