1.4 Antagonists

Question 1

What are the 2 types of dose repsonse relationships?

Answer 1

• GRADED - individual

* QUANTAL - population

Question 2

A higher potency will mean a _____ EC50?

Answer 2

lower

Question 3

Compare efficacy of full and partial agonists.

Answer 3

• Full agonists have high efficacy

* Partial agonists have lower efficacy

Question 4

What is an antagonist?

Answer 4

• An antagonist is a drug which blocks the response to an agonist.

Question 5

True or false

• Pure antagonists do not by themselves cause any action by binding to the receptor.

Answer 5

true

Question 6

What are the 3 classes of antagonist?

Answer 6

1. chemical
2. physiological
3. Pharmacological

Question 7

How does a chemical antagonist work (e.g. not needed):

Answer 7

 Binding of two agents to render active drug, inactive
 Commonly called chelating agents
 Example - protamine binds (sequesters) heparin

Question 8

How does a physiological antagonist work (e.g. not needed):

Answer 8

 Two agents with opposite effects cancel each other out.
 Example – glucocorticoids and insulin, insulin is used to cancel out catabolic effect of glucocorticoids so blood sugar levels aren’t increased, to cancel out any hyperglycaemic effect of giving a patient a glucocorticoud

Question 9

How does a pharmacological antagonist work :

Answer 9

 Binds to receptor and blocks the normal action of an agonist on receptor responses

Question 10

What is the action of these 2:

1) non-competitive active site antagonist
2) non-competitive antagonist
3) competitive antagonists
b) effect on agonist response curve?

Answer 10

1) Non-competitive active site antagonist
Look the same as the agonist, cannot be removed. ( as forms covalent bonds)
b)  Causes parallel shift to right of the agonist-response curve and reduced maximal asymptote.

2) Non-competitive antagonist
Binds to allosteric site, effects signal transduction rather than receptor effects so blocks downstream responses
b)  Reduces slope and maximum of dose response curve
3)  Binds and prevents agonist action but can be overcome with increased agonist concentration.
 Causes parallel shift to right of the agonist-response curve

Question 11

What type of antagonist causes curve to shift to right?

2) Whats happening to EC50 as more antagonist is added?

Answer 11

competitive active site antagonist

2) its increasing

Question 12

What causes dose-response curve to shift to right and maximal asymptope to decrease?

Answer 12

all non-competitive antagonists i.e. orthosteric and allosteric

Question 13

!) what is the schild plot?

2) what is it used to find?
3) Can it be used for all antagonists?

Answer 13

1) Takes the information from the dose ratio of each antagonist concentration to get a numeric value of amount of antagonist required to reduce effect of agonist.
2) gives you the antagonist dissociation constant
3) no , only works for competitive antagonist

Question 14

What is the pA2 value?

2) How do you calculate dose ration?
3) What are the parameters of pA2?

Answer 14

the negative logarithm of the molar concentration of antagonist required to produce an agonist dose ratio equal to 2

2) (agonist+antagonist EC50) divided by (agonist E50)
3) only works if slope is liner are m=1 in schild plot

Question 15

True or false

1) The extent of antagonist inhibition is independent of the concentration of the competing agonist
2) The extent of inhibition depends on the antagonist’s concentration.

Answer 15

1) false

2) true

Question 16

what clinical consideration of this:

1) The extent of antagonist inhibition is dependent on the concentration of the competing agonist
2) The extent of inhibition depends on the antagonist’s concentration.

Answer 16

1) – Varies in response to normal physical activity as well as disease states.
2) Inter individual differences in metabolism or clearance influence plasma concentrations.

Question 17

Why is that irreversible antagonists reduce maximal response of agonists?
2) Why do they not at low concentrations? and this is also the reason why curves shift to the right:

Answer 17

1) the irreversible antagonist
binds irreversibly with the receptor
gives rise to antagonism which cannot be overcome by an increased concentration of agonist
2) receptor reserve, not all receptors need to be bound to have maximal effect.,

Question 18

What is the therapeutic ratio:

2) do you want a big or small one?

Answer 18

– The ratio of the TD50 (toxic dose in 50% of the population) to ED50 (effective dose in 50% of the population)
2) big