L16 - receptor antagonists: inducing a response

Question 1

define ligand

Answer 1

something that binds to a receptor, drives the response

Question 2

define agonist

Answer 2

ligand that binds and activates a receptor

Question 3

define affinity

Answer 3

how well a drug binds to a receptor

Question 4

efficacy

Answer 4

how well a drug activates a receptor

Question 5

affinity + efficacy leads to?

Answer 5

response

Question 6

agonist + receptor =

Answer 6

agonist bound receptor

Question 7

if an agonist bound receptor is active what happens?

Answer 7

a response

Question 8

what is used to measure a response?

Answer 8

concentration response curve

Question 9

as concentration of agonist A (drug) increases in biological system what happens to the response?

Answer 9

• at first the response increase
• after a while the maximum response is reached to the graph levels off

Question 10

describe the first part of a concentration response curve in depth

Answer 10

• the initial low concentrations cause a small/limited response
• due to low receptor occupancy

Question 11

describe the second part of a concentration response curve in depth

Answer 11

• as drug increases a response is evoked in a linear fashion
• as more receptors are taken up

Question 12

describe the third part of a concentration response curve in depth

Answer 12

• response is maxed out
• full receptor occupancy
• max biological response

Question 13

what is Emax on a concentration response curve?

Answer 13

• maximum effect produced by an agonist
• not max response of biological system
• shows how effective the agonist is at producing response

Question 14

what is EC50?

Answer 14

• concentration of agonist needed to cause 50% of the Emax (so if max response is 100%, EC50 will be the conc at 50%)
• used to compare different agonists in same system

Question 15

if higher concentrations of agonist B are needed to produce the same response as agonist A, what does this suggest?

Answer 15

agonist B is less potent.

• A + B had the same Emax
• however, A has a lower EC50

Question 16

if agonist A + B have the same Emax what does this mean?

Answer 16

have same efficacy (activate receptor as well as each other)

Question 17

different EC50 values suggest?

Answer 17

different potencies

Question 18

describe partial agonists

Answer 18

• don’t produce full response in biological system
• limited receptor occupancy (poor affinity)
• or can’t produce full response (poor efficacy)

Question 19

agonists that produce full response

Answer 19

• full agonists
• good efficacy

Question 20

so if an agonist produces a Emax of less that 100% what does this mean?

Answer 20

• partial agonist
• reduced efficacy
  (make sure u remember that calculating EC50 is always 50% of the Emax)

Question 21

what are inverse agonists?

Answer 21

• when biological systems and receptors have a basal level of activity when NO agonists are present
• e.g heart muscle contraction
• this is called constitutive activity
• can be reduced by certain drugs
  (reduce response below basal levels)

Question 22

what is biased agonism?

Answer 22

• diff agonists produce diff responses through same receptor
• as they promote different activation states of receptor
• so diff second messengers
• leading to diff responses

Question 23

what can G protein coupled receptors do in terms of biased agonism?

Answer 23

• single G proteins or arrestin
• diff agonists will activate each signalling pathway