Antagonist and dose-response curves

Question 1

Antagonist

Answer 1

Blocks effect of agonist

Question 2

Do pure antagonists have effects when there is no agonist resent?

Answer 2

No

Question 3

3 classes of antagonist

Answer 3

Chemical, physiological and pharmacological

Question 4

What are chemical antagonist commonly known as?

Mechanism?

Answer 4

Chelating agents

Binding of 2 agents inhibit each other

Question 5

Mechanism of physiological inhibitors

Example

Answer 5

2 agents with opposing effects cancel each other out

Insulin and glycogen

Question 6

Mechanism for pharmacological inhibitors

Answer 6

Bind and block action of agonist receptor response

Question 7

Non-receptor agonists

3 ways they can work?

Answer 7

Don’t bind to same receptor as agonist
Inhibit directly (e.g. antibodies)
Inhibit activation pathways
Activate opposing pathways

Question 8

2 types of non-receptor antagonists?

Answer 8

Chemical and physiological antagonists

Question 9

Agonist that reversibly binds to the orthosteric/active site is known as…

Answer 9

Competitive agonist

Question 10

How does agonist dose response curve change when a competitive agonist is added?
Why?

Answer 10

Shifts to the right
Same form and max

It is reversible so the antagonism can be overcome

Question 11

How is dose ratio calculated?

Answer 11

EC50 of agonist and antagonist/EC50 of agonist only

Question 12

What does dose ratio show?

Answer 12

Increase in agonist concentration needed with antagonist to get the same reaction as without

Question 13

What is the antagonist dissociation constant?

Answer 13

Concentration of antagonist to inhibit agonist by half

Question 14

What type of bond to irreversible non-competitive antagonists form with he orthosteric site?

Answer 14

Covalent

Question 15

How does dose response curve change with irreversible antagonist added?
Why?

Answer 15

Parallel shift to right and decreased E max

Binds irreversible so antagonism cannot be overcome with increased agonist concentration

Question 16

How does addition of irreversible agonist change EC50?

Answer 16

Increase

Question 17

What determines duration of effect of irreversible antagonist?

Answer 17

Rate of receptor turnover

Question 18

Sometimes competitive and non-competitive antgaonist curves can look the same, why?

Answer 18

Receptor reserves or small concentration of antagonist and lots of receptors

Question 19

What do irreversible antagonists act the same as?

Answer 19

Partial agonists

Question 20

How do non-competitive (allosteric) antagonists cause inhibition?

Answer 20

Bind to allosteric site and cause conformational change so agonist cannot bind

Question 21

How does dose response curve change when allosteric antagonist is added?

Answer 21

Shift to right and decrease in Emax

Question 22

Therapeutic window?

Answer 22

Dose range that produces required therapeutic effect without causing toxicity