PBL 2 PHARMACOLOGY - agonsits and antagonists

Question 1

what is an agonist?

Answer 1

an activating molecule

Question 2

what is an antagonist?

Answer 2

an inhibiting molecule

Question 3

what is efficacy?

Answer 3

the tendancy of a drug to activate a receptor

Question 4

what is the name for a drug with maximum efficacy?

Answer 4

full agonist

Question 5

what is the name for a drug with zero efficacy?

Answer 5

antagonist

Question 6

how do antagonists work?

Answer 6

• when they bind they don’t activate the receptor

- they exert their effects by blocking activity of an agonist

Question 7

what happens if no agonist is present?

Answer 7

there is no measurable effect — a functional assay relies on receptor activation to produce a measurable effect

Question 8

what does the functional Gaddum equation describe?

Answer 8

the effect produced by agonist D, in the presence of a competitive antagonist I

Question 9

what is meant by Ki?

Answer 9

the antagonist dissociation constant — the antagonist affinity

Question 10

does binding affinity relate to efficacy?

Answer 10

binding affinity, as measured by Kd, does NOT relate to efficacy

Question 11

what is potency of a drug a measure of?

Answer 11

a measure of the concentration at which the drug can evoke a specified effect

Question 12

competitive antagonist are surmountable. what does this mean?

Answer 12

the antagonism can be overcome by increasing the agonist concentration

Question 13

is there a change in maximum response for an agonist if a competitive antagonist is present?

Answer 13

no

Question 14

what is competitive antagonism characterised by (in terms of concentration response curve and EC50) ?

Answer 14

characterised by a parallel shift to the right of the concentration curve with an increase in EC50

Question 15

what is EC50?

Answer 15

the conc of agonist giving 50% of the max effect

Question 16

what are Kd and Ki?

Answer 16

a measure of drug affinity

Question 17

what is the difference between Ki and Kd?

Answer 17

• essentially the same thing = a measure of drug affinity
• Kd is normally used when the data have come from a saturation assay and the affinity has been measured DIRECTLY
• Ki is used when the measurement of affinity has been made INDIRECTLY (eg. competition binding assay or via calculations from the Gaddum equation)

Question 18

what is pKi? pKi vs Ki?

Answer 18

• a measure of affinity

- Ki values are not normally distributed but pKi values are — we can take the negative log of Ki to generate pKi

Question 19

what is pA2?

Answer 19

• the negative log of the concentration of antagonist required to double the EC50 for the agonist
• measure of potency (as we are defining a “specific effect”)

Question 20

what is pA2 obtained from?

Answer 20

the concentration of antagonist that gives a concentration ratio of 2

CR = 1 + ( [I] / Ki )

Question 21

what is pA2 effectively equivalent to?

Answer 21

pKi

Question 22

what is tone?

Answer 22

the underlying level of activation of a tissue

Question 23

what is a partial agonist?

Answer 23

a drug that cannot fully activate a receptor, even when all the receptors in the system are occupied

Question 24

compare the EC50 values of a full agonist and partial agonist

Answer 24

they are the same

Question 25

list the 4 parameters of competitive antagonist affinity. which one isn’t included and why?

Answer 25

• Kd
• Ki
• pKd
• pKi

(not pA2, this is a measure of potency, because it is a “concentration to produce a defined effect”)

Question 26

what is affinity?

Answer 26

the tightness of binding of a ligand

Question 27

what is efficacy?

Answer 27

the degree to which a ligand can activate a receptor (max effect a ligand can produce)

Question 28

what is acetylcholine?

Answer 28

a full agonist

Question 29

when does a receptor show spontaneous activity?

Answer 29

in the absence of an agonist

Question 30

what are adrenaline and noradrenaline?

Answer 30

full agonists

Question 31

according to the 2 state model, what does a full agonist have a much higher affinity for?

Answer 31

the active state

Question 32

why is the underlying level of spontaneous activity not affected by antagonists?

Answer 32

because these drugs do not select between the inactive and active states of the receptor — bind to both equally with equal affinity

Question 33

what type of ligand reduces spontaneous activity?

Answer 33

partial agonists — bind tighter to active state but doesn’t select between the 2 states as much as a full agonist

Question 34

what state to inverse agonists bind tighter to and what is the effect of this?

Answer 34

bind tighter to the inactive state — reduce spontaneous activity

Question 35

how do inverse agonists differ from competitive antagonists?

Answer 35

inverse agonists will reduce spontaneous activation of the receptor