Antagonist Actions - Receptors and Drug Actions

Question 1

What does a competitive antagonist do?

Answer 1

binds to receptor so agonist can not; it inhibits agonist from binding therefore inhibiting a response; they compete with other agents for the binding site

Question 2

Key properties of competitive antagonists:

Answer 2

increase the concentration of agonist required to bind a give fraction of receptors; induce a given level of response, shift agonists dose curve to the right to higher the agonist concentrations

Question 3

What happens to agonist curves when antagonists increase?

Answer 3

shifts to right; agonists can still have full-effect at high enough concentration by “out-competing”

Question 4

Shift = 1 + [B]/Kb

Answer 4

[B] = antagonist concentration, Kb = antagonist Kd.
1xKb = agonit curve shifted by factor of 2
9xKb = shifted by factor of 10
99xKb = shifted by factor of 100x
(more B, more shift to right)

Question 5

By increasing antagonist concentrations, we shift agonist dose response curve to right. What happens to the response to a fixed concentration.

Answer 5

Increasing antagonist concentrations DECREASES the response to a fixed concentration of agonist.

Question 6

IC50 refers to what?

Answer 6

half-maximal inhibitory concentration

Question 7

Increasing antagonist concentrations does what to the response to a fixed concentration of agonist?

Answer 7

DECREASES

Question 8

Explain how agonist/antagonist binding can be reversible.

Answer 8

Which ligand is present at a higher ratio to its own Kd determines who occupies the receptor most.

Question 9

What is a partial agonist?

Answer 9

don’t turn on receptor all the way, but active some of it, but not all (dimmer light)

Question 10

What is efficacy?

Answer 10

how well the drug activates the receptor when it is bound;

ZERO efficacy = antagonists, 100% efficacy = agonists, in between 1%-99% = partial.; lower intrinsic activity

Question 11

Differentiate between X axis and Y axis properties.

Answer 11

X axis: affinity and potency (related to concentration)

Y axis: efficacy (related to magnitude of maximal response when all receptors are bound)

Question 12

Give potency example.

Answer 12

If drug works at low concentration, it has a high potency.

Question 13

Give efficacy example.

Answer 13

If drug generate a large fractional response, it has high efficacy.

Question 14

Define potency.

Answer 14

How much drug you have to give to get half of the maximal response.
(a drug can work at very low concentrations (be potent) but induce only a small response (low efficacy)

Question 15

T/F. Many of the most effective drugs are antagonists with an efficacy of zero.

Answer 15

TRUE

Question 16

A partial agonist has less than 100% response, even with 100% receptor occupancy.

Answer 16

TRUE

Question 17

Explain why partial agonists are also partial antagonists.

Answer 17

Partial agonists reduce the full response of agonists, but won’t bring it all the way down to zero; therefore they have partial antagonists effects, too.

Question 18

Endogenous activation state of receptor’s levels can tell you what?

Answer 18

Low endogenous activation = going to act like agonist (help with low HR, ensure adequate resting heart rate),
High endogenous activation = going to act like an antagonist (help with high HR, prevent over-stimulation of heart with exercise or stress)

Question 19

Define receptor subtypes.

Answer 19

multiple different receptor proteins for the same endogenous ligand

Question 20

Properties of subtypes:

Answer 20

different drug selectivity, couple to different signaling pathways and effects, expressed differently in various tissues and cell types, different regulatory properties

Question 21

Example of subtype-selective drugs.

Answer 21

H1 vs. H2: H1 targeted anti-histamines for allergies, H2 targeted anti-histamines for ulcers

Question 22

Define desensitization.

Answer 22

decrease in sensitivity or maximal response.

Question 23

How can desensitization occur?

Answer 23

covalent modification, endocytosis, internalization, down-regulation.