L6: Drug Receptor Interactions

Question 1

Law of Mass Action

Answer 1

D + R <—> DR = response

k1 = rate constant (M-1sec-1) - on rate (association)
k-1= rate constant (sec-1) - off rate (dissociation)

• D and R associate at rate proportional to both [D] and [R] - association
• DR dissociates at rate proportional to [DR] only - dissociation
• Reversible

Question 2

At steady state…

Answer 2

rate of association = rate of dissociation

Question 3

EC50

Answer 3

Drug concentration at which drug effect (response) is half-maximal

*Can only be determined from a graph of response (or fractional response) vs dose/concentration

Question 4

Kd

Answer 4

Drug concentration at which receptor-bound drug (receptor occupancy) is half-maximal

*can only read Kd off of graph if it’s receptor-bound drug (fractional receptor occupancy) vs. drug concentration!!

Question 5

Fractional Saturation

Answer 5

Receptor occupancy = fraction of total receptors (RT) occupied by drug (aka fractional saturation) = [DR] / [RT]

= [DR] / [R] + [DR]

Question 6

When [R] = [DR]…

Answer 6

[D] = Kd and [DR]/[RT] = 0.5

Question 7

Agonists

Answer 7

-Full agonist: Maximal Response
-Partial agonist: Partial Response
-Inverse agonist: Decreases Basal Response

Question 8

Antagonists (inhibitors)

Answer 8

Bind to receptor but do not promote response

I + R <—> IR (no response)

Question 9

Competitive vs Noncompetitive Antagonist

Answer 9

Competitive: compete for same binding site

Noncompetitive: bind to distal (different) site to where drug binds

Question 10

Receptor Desensitization

Answer 10

Response decreases with time and/or repetitive stimulation

Question 11

Potency

Answer 11

Refers to the dose that causes a given effect
-most potent = lowest EC50
-least potent = highest EC50

Question 12

Efficacy

Answer 12

Refers to the maximum response (effect)
-most efficacious = largest response
-least efficacious = smallest response

*Can only be read off graph of response (or fractional response) vs. dose or concentration

Question 13

Therapeutic Index

Answer 13

Therapeutic index = LD50/ED50

Question 14

ED50

Answer 14

= Median effective dose: produces specified effect in 50% of patients

*Can only can be determined from a graph of cumulative fraction of individuals with the response (or more simply, fraction of individuals responding) vs. dose

Question 15

LD50

Answer 15

= Median lethal dose