PED1003/L03 Antagonists

Question 1

Define an antagonist. (2)

Answer 1

A drug which blocks the response to an agonist
Do not by themselves cause any action by binding

Question 2

Describe the action of propanolol. (3)

Answer 2

Binds to B-adrenoceptor
Propanolol-B-adrenoceptor complex
Decreased blood pressure

Question 3

Give the 3 classes of antagonist.

Answer 3

Chemical
Physiological
Pharmacological

Question 4

What is a chemical antagonist? Use an example.

Answer 4

Binding of two agents to render drug inactive
AKA chelating agents
E.g., protamine binds heparin

Question 5

What is a physiological antagonist? Use an example.

Answer 5

Two agents with opposite effects cancel each other out
E.g., glucocorticoids and insulin

Question 6

What is a pharmacological antagonist?

Answer 6

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

Question 7

What 2 classes can active site binding antagonists be put into?

Answer 7

Reversible - competitive
Irreversible - non-competitive active site

Question 8

What are allosteric binding antagonists called?

Answer 8

Non-competitive

Question 9

Describe the agonist-response curve in the presence of a competitive antagonist.

Answer 9

Parallel shift to right
Can be overcome by increasing [agonist]

Question 10

Describe the agonist-response curve in the presence of an irreversible antagonist. (2)

Answer 10

Parallel shift to right
Reduced maximal asymptote

Question 11

Describe the agonist-response curve in the presence of a non-competitive antagonist

Answer 11

Reduced slope and maximum of dose response curve
(signal transduction rather than effector)

Question 12

What is the dose ratio?

Answer 12

Agonist plus increasing concentrations of competitive antagonist
(Agonist + antagonist EC50)/Agonist EC50

Question 13

What is the Schild Equation?

Answer 13

r-1 = [B]/Kb

Question 14

What is plotted on the x and y axis in a competitive antagonist Schild plot?

Answer 14

x = log(antagonist conc)
y = log(r-1)

Question 15

What is a pA2 value? Give the equation.

Answer 15

Describes the activity of a receptor antagonist in simple numbers
pA2 = -log(Kb)

Question 16

What conditions must follow for calculation of a pA2 value? (2)

Answer 16

Must have a linear relationship
Schild plot slope = 1 (competitive antagonist)

Question 17

What does the extent of antagonist inhibition depend on? (2)

Answer 17

Concentration of competing agonist
Concentration of antagonist

Question 18

Why do irreversible antagonists a) do not have the same form and b) have a reduced maximal response on a dose-response curve?

Answer 18

a) bind irreversibly with receptor
b) cannot be overcome with increased concentration of agonist

Question 19

What happens to EC50 in the presence of an irreversible antagonist?

Answer 19

Increases

Question 20

What allows a parallel shift to the right at lower concentrations with an irreversible antagonist?

Answer 20

Receptor reserves

Question 21

Give an example of a competitive antagonist.

Answer 21

Cimetidine at H2 receptor
Tamoxifen at oestrogen receptor

Question 22

Give an example of irreversible antagonism.

Answer 22

Phenoxybenzamine at a1 receptor

Question 23

Give an example of a non-competitive antagonist.

Answer 23

Nifedipine blocks Ca2+ influx

Question 24

What effect does a non-competitive antagonist have on a dose-response curve? (2)

Answer 24

Reduces slope and maximal effect

Question 25

What is the equation for therapeutic window/index?

Answer 25

TD50/EC50 or LD50/ED50