Lecture 5

Question 1

What terminology is different between receptors and enzymes?

Answer 1

Receptors have ligands which can be agonists and antagonists while enzymes have substrates, products and inhibitors

Question 2

What is the difference between a concentration-response curve and a dose-response curve

Answer 2

Concentration-response curve is used when there is an isolated system is immersed while a dose is the amount given to the whole organism

Question 3

What is a saturation effect?

Answer 3

When increasing the concentration of the drug does not result in an increased effect, but does NOT require all agonists to be bound to receptors

Question 4

What is Emax?

Answer 4

The maximum effect possible (saturation effect)

Question 5

What is pD2?

Answer 5

A measure of agonist potency, a higher pD2 means a greater potency

Question 6

What is EC50?

Answer 6

The effective concentration that produces 50% of the maximum effect, a lower EC50 means a greater potency

Question 7

What is ED50?

Answer 7

The effective dose that produces the 50% of the maximum effect

Question 8

What is the relationship between pD2 and EC50?

Answer 8

pD2=-logEC50

Question 9

What shape is characteristic of concentration response curves?

Answer 9

Sigmoidal

Question 10

What is IC50?

Answer 10

The concentration of an antagonist which inhibits half of the agonist response

Question 11

What are the changes to an agonist concentration response curve in the presence of reversible and irreversible antagonists?

Answer 11

with a reversible antagonist the curve is right shifted (but not downwards shifted) with no effect on maximal response
With an irreversible antagonist the curve is left shifted and will plateau out at a lower level

Question 12

What is competitive reversible antagonism?

Answer 12

When the antagonist is reversible and competes directly with the agonist for the same binding site on the receptor resulting in a higher agonist concentration being required to produce the same effect

Question 13

What is pA2?

Answer 13

-log (2*concentration that gives EC50), varies with different receptor and agonists is a measure of the potency of the antagonist

Question 14

What is an example of a competitive reversible antagonist?

Answer 14

Propranolol at beta-2 receptors,

Atropine at M

Question 15

What is competitive irreversible antagonism?

Answer 15

An antagonist competes for the same binding site as the agonist but the antagonist has much greater affinity and can typically not be easily removed from the receptor and therefore not be overcome through increasing the amount of agonist

Question 16

What is the potency measure for competitive irreversible antagonists and non-competitive antagonists?

Answer 16

pD2 DASH

Question 17

What is an example of a competitive irreversible antagonist?

Answer 17

Phenoxybenzamine at H1 receptors

Question 18

What occurs to the concentration response curve in the presence of low and high concentrations of competitive irreversible antagonists?

Answer 18

In low concentrations there would be a right shift in the curve with no change in the maximal response due to the spare receptor theory (this has never been practically proven)
In high concentrations there would be a strong right shift and a large depression in the maximal response,this has been practically proven

Question 19

What is the spare receptor theory?

Answer 19

The theory that there are more receptors than required to create a maximal response in a tissue so some of these receptors can be occupied by competitive irreversible antagonists and there will still be enough free receptors present to induce a maximal response

Question 20

What is non-competitive antagonism?

Answer 20

Don not bind to the same receptor or binding site as the agonist and therefore can not be out competed by changing the concentration of agonists
Its actions occur occur through interfering with the cascade of events initiated by receptor-agonist binding

Question 21

What is the effect of a non-competitive antagonist on the concentration response curve?

Answer 21

A non-parallel rightwards shift with a depression in the max response

Question 22

What is an example of non-competitive antagonist?

Answer 22

Verapamil antagonism of histamine

Question 23

What is physiological antagonism?

Answer 23

Occurs when the actions of two agonists working at two different receptor types have opposing effects

Question 24

What is an example of physiological antagonism?

Answer 24

Histamine acting at H1 receptors to cause bronchoconstriction and adrenaline acting and beta-2 receptors to cause bronchodilation

Question 25

What is a partial agonist?

Answer 25

Agonists which do not elicit a maximal response, despite having full receptor occupancy

Question 26

What is an example of a partial agonist?

Answer 26

Methysergide at 5HT receptors

Question 27

What is the effect of partial agonists on full agonists?

Answer 27

Initially, at low concentrations the partial agonist will aid the agonist while at higher concentrations the partial agonist will act as an antagonist as it will get in the way of the full agonist and therefore reduce the effect that could have been gained

Question 28

What is an inverse agonist?

Answer 28

Some receptors are always on, ligands can bind to this resting state resulting in a change in state resulting in less constitutive activity
Inverse agonists is essentially the same as a competitive reversible antagonist

Question 29

Can a competitive reversible antagonist be distinguished from a competitive irreversible antagonist based only off a concentrations response curve?

Answer 29

No, this is theoretically possible due to the spare receptor theory but is not practically possible