Antagonists And Dose Response

Question 1

Give an example of an antagonist

Answer 1

Terfenedine and the H1 receptors

Question 2

Why on the 2 state hypothesis for antagonist is there no active state

Answer 2

They don’t cause an action but suppress it

Question 3

What is the effect of propanolol on BP when bound to B2

Answer 3

Lowered heart rate

Question 4

What are the 3 classes of antagonists

Answer 4

1- chemical : binding to inactivate drugs

2- physiological : 2 molecules against eachother

3: inactivated a RECEPTOR

Question 5

Explain the 2 branches of antagonists

Answer 5

Active site binding - they bind to active site

Allosteric binding - bind elsewhere in receptor

Question 6

What are reversible and irreversible active site antagonists

Answer 6

Reversible = competitive antagonists

Irreversible = non competitive (bind by covalent bond)

Question 7

What are the allosteric reversible and irreversible

Answer 7

Both are non competitive antagonists

Question 8

What can’t be measured with antagonist dose response curves

Answer 8

Efficacy of drug (no active state)

Question 9

How can competitive antagonists (active site) work

Answer 9

Similar shape to the normal agonist

Block the active site

Question 10

Why are competitive antagonists reversible

Answer 10

Overcome by increasing agonist concentration

Question 11

What way does the dose response curve go with a competitive antagonist

Answer 11

Right

You need a larger dose of agonist to form the same response due to competition

Question 12

What happens to EC50 when there is a competitive antagonists

Answer 12

It gets higher in presence of antagonist due to competition

Need higher dose of agonist for response

Question 13

What happens to the eMAX with reversible competitive antagonists

Answer 13

It stays the same. You can overcome it by adding agonist

Question 14

What is the dose ratio calculation to measure inhibition of competitive antagonists

Answer 14

Agonist + antagonist EC50 / agonist only EC50

Question 15

Which plot can compare different competitive antagonists

Answer 15

Schild plot

Plots antagonists conc and the dose ratio - 1 (agonist+ antagonist/ agonist EC50)

Question 16

What is the schild plot equation

Answer 16

Dose ratio -1 = conc of antagonist / antagonist dissociation constant (kb)

Question 17

What is kb in terms of competitive antagonist

Answer 17

Antagonist dissociation constant

Question 18

What is the pa2 value

Answer 18

Antagonist conc needed to reduce agonist response by 50%

Question 19

How do you work out the pa2

Answer 19

-log kb (dissociation constant)

Question 20

What does a high dose ratio mean

Answer 20

More agonist needed to produce effect

Antagonist is better inhibitor

Question 21

Why does the slope on schild plot only work on competitive antagonists (reversible)

Answer 21

Only competitive antagonists line is linear to dose ratio (others aren’t affect by dose)

Question 22

What are irreversible active site antagonist give example

Answer 22

Antagonists which bind to AS covalently blocking agonist

Eg penecillin b lactam

Question 23

What happens to the EC50 and eMAX with irreversible AS antagonists

Answer 23

Both get decreased

Question 24

What does the duration of the irreversible antagonists depend on

Answer 24

Receptor turnover

Question 25

How would you decide if something is a partial agonist which also decreases eMAX or an irreversible antagonist

Answer 25

Irreversible antagonist won’t work if presence of agonist isn’t there

Question 26

How does a non competitive allosteric antagonist work

Answer 26

Binds allosterically and stops downstream signalling

Question 27

Give an example of non competitive antagonist

Answer 27

Nifedipine which stops ca influx downstream

Question 28

What effect does a non competitive allosteric antagonist have on eMAX

Answer 28

Decreases it because agonist receptor doesn’t have downstream signalling/effect