Agonism

Question 1

What is a competitive antagonist?

Answer 1

a drug which binds to the same site on the receptor to block agonist action → produces NO response = ZERO EFFICACY

Question 2

What effect does a competitive antagonist have on DRC?

Answer 2

• eqm shifts right
• in presence of comp antagonist, ↑ [agonist] required to induce maximal effect on target protein
• however, ↑ [agonist] will outcompete the effect of the competitive antagonist - REVERSIBLE
• net result on DRC: ↓ agonist potency with no effect on efficacy

Question 3

What effect does a competitive antagonist have on EC50?

Answer 3

if you ↑ comp antagonist, then EC50 ↑ will increase as you will need ↑ [agonist] to overcome the antagonist

Question 4

What is a non-competitive antagonist?

Answer 4

• agonist that binds to an allosteric site on receptor to block agonist action

Question 5

What effect does a non-competitive antagonist have on DRC?

Answer 5

• non-comp antagonist binds v strongly to allosteric site HOWEVER NOT COVALENT
• this means ↑ [agonist] will not overcome non-comp antagonist effect - low dissociation rate
• net result on DRC: ↓ agonist efficacy with no effect on potency

Question 6

What does high potency of a drug mean?

Answer 6

A drug substance with a high potency induces a high effect at low dose.

Question 7

What is drug efficacy?

Answer 7

Efficacy is the ability of the drug to produce a response by the activation of the receptor

Question 8

What does a low dissociation constant mean?

Answer 8

The smaller the dissociation constant, the more tightly bound the ligand is, or the higher the affinity between ligand and protein

Question 9

What does a high dissociation constant mean?

Answer 9

The higher the dissociation constant, the less tightly bound the ligand is, or the lower the affinity between ligand and protein

Question 10

What is an agonist?

Answer 10

drug which activates receptor to produce a full response with low receptor occupancy

Question 11

What is a partial agonist?

Answer 11

drug which produces sub-maximal response despite 100% receptor occupancy

Question 12

Describe what is meant by receptor reserve.

Answer 12

where agonist produces max response by only occupying fraction of receptors

Question 13

What is drug selectivity?

Answer 13

the degree to which a drug acts on a given site relative to another site (ie a drug targets several target sites but has a preference to one)

Question 14

What is a biased agonist?

Answer 14

agonist which evokes a better response in one receptor as opposed to another

Question 15

What is a reversible antagonist?

Answer 15

(competitive)

• binds non-covalently to receptor, can be washed out

Question 16

What is an irreversible antagonist?

Answer 16

• binds covalently to receptor, cannot be wash out

Question 17

What is drug potency?

Answer 17

measure of drug conc at which it is effective

Question 18

What is EC50?

Answer 18

conc of agonist required to reach 50% of maximal response

Question 19

What is IC50?

Answer 19

conc of inhibitor required to reach 50% of maximal response

Question 20

What is Emax?

Answer 20

max efficacy of agonist which remains unchanged despite presence of non-competitive antagonist