Lecture 3 Drug Affinity

Question 1

what is affinity?

Answer 1

how attracted the agonist drug is to the receptor forming a complex

Question 2

Forward rate constant

Answer 2

where the agonist and receptor form a complex

Question 3

what is efficacy?

Answer 3

how good a molecule is at causing signalling after binding with receptor

Question 4

Efficacy of an anatgonist

Answer 4

has an efficacy of 0 because they cause no response

Question 5

Efficacy of full agonists

Answer 5

these have an efficacy of 1

Question 6

number of receptors occupied

Answer 6

this is governed by the affinity of the drug to the receptor

Question 7

what is a partial agonist?

Answer 7

this is an agonist that cannot produce a full response even at full occupancy, so have an intermediate efficacy of 0-1

Question 8

KD

Answer 8

this is a dissociation constant and is equal to the reverse reaction divided by forward reaction

Question 9

KD at a high affinity

Answer 9

KD is a smaller number because the binding is successful so chances of coming apart is lower

Question 10

Occupancy

Answer 10

occupancy of a receptor may or may not result in activation of the receptor

Question 11

Occupancy with high affinity

Answer 11

with high affinity, occupancy will be high even at low concentrations

Question 12

how to measure occupancy

Answer 12

using a radioligand binding assay involving a radioactive ligand to make drug radioactive

Question 13

measuring receptor affinity - tissue and incubation conditions

Answer 13

• tissue contains protein receptors so they do not degrade
• adding antioxidants for reaction to oxygen in air

Question 14

measuring receptor affinity - radioligand

Answer 14

• ligand is biologically active
• cannot change molecule structure of drug
• radioactivity needs to be 100%

Question 15

hydrogen as a radioactive ligand

Answer 15

does not cause structural change and has a long half-life. however, is expensive and specialist labs required

Question 16

iodine as a radioactive ligand

Answer 16

has a similar aromatic hydroxy group compared to hydrogen but has a short half-life

Question 17

measuring receptor affinity - separation

Answer 17

if low affinity the bound radioactivity falls off and washes away so becomes difficult to measure.

Question 18

measuring receptor affinity - non-specific binding

Answer 18

• ligand may bind to other substance in the test tube and other proteins
• the affinity is low but can still happen