LHD - Antagonists

Question 1

What is Physiological antagonism?

Answer 1

The behaviour of a substance that produces effects counteracting those of another substance

Question 2

What are 2 features of competitive antagonists?

Answer 2

1. The agonist and antagonist bind to the same site
2. The block can be overcome by increasing the concentration of the agonist

Question 3

What are 3 features of the Dose-response curve for a competitive antagonist? (Increasing antagonist)

Answer 3

1. Dose-response curves shift to the right in a parallel fashion
2. The apparent pD2 decreases in the presence of the competitive antagonist
3. The is no change in Emax

Question 4

What are 2 features of Non-competitive antagonists?

Answer 4

1. The antagonist binds to a different site on the receptor or acts irreversibly
2. The block CANNOT be overcome by increasing the concentration of the agonist

Question 5

What are 3 features of the dose-response curve for non-competitive antagonists?

Answer 5

1. The pD2 is not changed
2. Emax decreases
3. Dose-response curves are NOT parallel

Question 6

What is an example of a ganglion blocker?

Answer 6

Hexamethonium

Question 7

Agonist vs Antagonist (2)

Answer 7

1. Antagonist molecules are much larger
2. Antagonist molecules contain accessory binding sites

Question 8

What does an antagonist’s ability to block a response depend on? (2)

Answer 8

1. The relative affinity of the agonist (KD) and antagonist (KA) for the receptor
2. The relative concentrations of the agonist [D] and antagonist [A]

Question 9

What is DOSE RATIO?

Answer 9

The ratio of the agonist concentration in the presence of the antagonist [D1] against the agonist concentration in the absence of the antagonist [D0]

Question 10

When is the occupancy by the agonist assumed the same?

Answer 10

If the response in the presence and absence of the antagonist is the same

Question 11

What is the GADDUM-SCHILD EQUATION?

Answer 11

[DA]/[D0] -1 = [A]/KA

Question 12

What are 3 assumptions about the DOSE RATIO?

Answer 12

1. This analysis is based on the law of mass action and assumes simple competitive antagonism
2. No assumptions are made about the relationship between response and the number of receptors occupied
3. It is INDEPENDENT of the AGONIST used – so long as it competes with the antagonist for the SAME receptor

Question 13

What is pA2?

Answer 13

The negative log of the antagonist concentration that gives a dose ratio of 2