MR 8

Question 1

What is meant by the terms affinity, efficacy and potency when applied to drug molecules?

Answer 1

Affinity - likelihood of a drug binding to its target.

Efficacy is two fold
A) the ability to form an active form of the receptor. This is the Intrinsic Efficacy.

B) cell and tissue dependent factors. Together, these are known as efficacy.

C) potency - the amount of drug required to evoke a response.
- a combination of efficacy and affinity.

Question 2

What is meant by Bmax, Kd and EC50

Answer 2

Bmax is the maximum binding capacity, and it gives us information about the number of receptors.

Kd - the dissociation constant, a measure of affinity

EC50 - the effective concentration giving half of the maximum response

Question 3

What is a partial agonist?

Answer 3

A drug/ligand that cannot give a maximal response, even with 100% receptor occupancy.

Question 4

What is the EC50 of a partial agonist equal to?

Answer 4

It’s Kd.

Question 5

Briefly explain what is meant by the term ‘spare receptors’

Answer 5

This is the notion that some cells can give give a maximal response without all of the receptors being occupied. This means there are some spare receptors present.

Question 6

How do spare receptors confer sensitivity to cells?

Answer 6

They allow a maximal response at a lower dose of drug.
Simply by having more receptors than needed, the number of receptors needed for activation is lower and hence lower dose of drug needed.

Question 7

Explain the changes in Kd for a drug if a receptor with initially 10,000 receptors (all need to be activated for maximal response) changes the number of receptors to:
A)100,000
B)20,000
C)5,000

Answer 7

A) more receptors - less drug needed - Kd decreases. 10% binding for 100% response.
b) more receptors - less drug needed - Kd decreases. 50% binding for 100% response.
C) less than the minimum receptors require for maximal response and so therefore 100% binding but maximal response is not achieved.

Question 8

What does a low Kd mean in terms of affinity?

Answer 8

High affinity.

Question 9

Describe agonists and antagonists in terms of their relative efficacy and affinity.

Answer 9

Agonists bind to receptors and evoke a response.
- they display both affinity and efficacy.

Antagonists bind to receptors and do not evoke a response.

• they display affinity only.
• they do not ‘switch off’ a receptor.
• they simply do not activate it.