Agonists and dose response curves

Question 1

Is salbutamol

a) Alpha 2 - adrenoreceptor antagonist
b) beta 2 - adrenoreceptor agonist
c) alpha 1 - adrenoreceptor agonist
d) beta 1 - adrenoreceptor antagonist

Answer 1

b

B2 adrenoreceptor agonist

Question 2

What is the effect of salbutamol?

Answer 2

Activates B2 adrenoreceptor = G2 = bronchodilation

Question 3

Why are concentration response curves semi log?

Answer 3

Linear concentration range is too large so x axis is log

Question 4

0.0001 in log form

Answer 4

-4

Question 5

What is the dose-response relationship when looking at an isolated system?

Answer 5

Graded

Question 6

What is the dose-response relationship when looking at the response of a popualtion?

Answer 6

Quantal

Question 7

Describe the shape of quantal relationship on graph?

Answer 7

Upside down U

Question 8

What 2 values and corresponding characteristics can be determined from % response and log concentration graph?

Answer 8

EC50 = potency
Emax = Efficacy

Question 9

Drug A has EC50 of 10
Drug B has EC50 of 5
Which has a higher potency?

Answer 9

B

Question 10

Why can affinity not be calculated from % response concentration curve?

Answer 10

Affinity needs values for receptor occupancy - y axis would need to be % receptor occupancy

Question 11

What are the 2 stages of the 2 state hypothesis?

Answer 11

Affinity and efficacy

Question 12

How are affinity and efficacy measured?

Answer 12

Affinity = occupancy
Efficacy = activation

Question 13

Define affinity

Answer 13

Strength a drug binds to receptor

Question 14

How is affinity calculates?

Answer 14

Rate of association/rate of dissociation (k1/K-1)

Question 15

When a drug has a high affinity how do K1 and K-1 compare?

Answer 15

K1 is higher

Question 16

What is Kd?

Answer 16

Equilibrium dissociation constant

Question 17

When does Kd apply?

Answer 17

For any given receptor and drug in any tissue as long as the receptor is the same

Question 18

Uses of Kd?

Answer 18

Identify unknown receptors, compare affinity fo different drugs on same receptor

Question 19

Assuming there is a linear relationship between receptor occupation and effect how can Kd be calculated?

Answer 19

Kd = EC50

Question 20

Kd has an inverse relationship with affinity

How can Kd be calculated?

Answer 20

K-1/K1

Rate of dissociation/rate of association

Question 21

Lower Kd has what affect on affinity (and hence probably potency)?

Answer 21

Higher

Question 22

What is potency dependent on?

Answer 22

Affinity
Efficacy
receptor density
Efficiency of stimulus response mechanism

Question 23

EC50

Answer 23

The concentration of drug needed for 50% of maximum response

Question 24

Relationship between EC50 and potency?

Answer 24

Lower EC50 = higher potency

Question 25

What does it mean if a system has spare receptors?

Answer 25

Receptors can amplify signal so the maximum response is achieved with small receptor occupancy

Question 26

Efficacy definition

Answer 26

Ability of agonist to activate receptor

Question 27

What value on dose response curve does efficacy correspond to?

Answer 27

Emax

Question 28

Do full or partial agonist have higher efficacy?

Answer 28

Full

Question 29

What is full agonist? | What is partial agonist?

Answer 29

Max response corresponds to max response a tissue can give | Max response it elicits is lower than max response a tissue can give

Question 30

Why are partial side effects used?

Answer 30

Alleviate side effects

Question 31

What are inverse agonists?

Answer 31

Agonists that bind receptor and move equilibrium t left to decrease signalling pathways They have a higher affinity for the inactive complex

Question 32

What are allosteric modulators?

Answer 32

Ligands that bind and effect binding of endogenous agonist

Question 33

Difference between positive allosteric modulator (PAM) and negative allosteric modulator (NAM)

Answer 33

``` PAM = increase affinity/efficacy of endogenous agonist NAM = decrease affinity/efficacy of endogenous agonist ```

Question 34

Tachyphylaxis?

Answer 34

Desensitisation of receptor due to continued/repeated use

Question 35

What causes desensitisation?

Answer 35

Conformational change, internalisation of receptor, altered drug metabolism

Question 36

After tachyphylaxis, if the drug is stopped and started again at another date how does sensitivity change?

Answer 36

Increased