DRUG- RECEPTOR INTERACTIONS AND ELICITED DRUG RESPONSES

Question 1

The higher the equilibrium dissociation constant, the …… the affinity

Answer 1

smaller

Question 2

What is the equilibrium dissociation constant?

Answer 2

Equilibrium dissociation constant is the concentration of drug that binds 50% of the receptors in the system.

Question 3

What is spare receptor?

Answer 3

Spare receptors are receptors that exist in excess of those required to produce a full effect

Question 4

Describe the graded dose response curve.

Answer 4

• It relates to the dose with the intensity of effect.
• It is administered to one individual or isolated tissue.
• Curve is hyperbolic if it is a graded dose response curve.
• However, the curve is sigmoid if it is a graded log dose-response curve.

Question 5

What is quantal DRC?

Answer 5

• Quantal DRC relates the dose with the number of individuals showing a particular effect (one effect only).
• It was administered to a group of individuals.
• The response is prefixed, either yes or no only.
• From this graph, we can obtained ED50, EC50, TD50, LD50 as well as therapeutical index.

Question 6

What is potency?

Answer 6

Potency is the amount of drug need to produce effect

Question 7

What is efficacy?

Answer 7

Efficacy is the ability to activate the receptor

Question 8

List 2 types of antagonist.

Answer 8

• competitive antagonist
• non competitive antagonist

Question 9

Describe competitive antagonism.

Answer 9

• Competitive antagonism are structurally similar to agonist.
• Competitive antagonism will compete with agonist for binding with the same receptor.
• It is a reversible reaction and the effect only last for a short time.
• If the dose of agonist is increased, it can overcome the competitive antagonist and occupy the receptor again.
• Maximum efficacy still can achieve but it is going to shift to right in parallel.

Question 10

Describe non competitive antagonism.

Answer 10

• Non competitive antagonism often structurally different from agonist and bind at a site other than agonist binding site.
• It is irreversible.
• Agonist fails to bind with the receptor.
• The effects are going to last longer than a competitive antagonism.
• The efficacy can never achieved and the graph will shift to right and smaller height.

Question 11

What will happen if prolonged exposure to agonist?

Answer 11

• Desensitization or down regulation will occur where the sensitivity of tissue to agonist will be reduced.
• This is due to the reduction in the total number of receptor in the tissue and reduced the signal transduction.
• This will causes the therapeutic effect to be reduced after prolonged exposure which is also known as pharmacodynamic tolerance.

Question 12

What will happen if prolonged exposure to antagonist?

Answer 12

• This will causes upregulation or sensitisation to occur which means the sensitivity of tissues to the agonist will be increasing.
• This is due to the increased number of new receptors in the tissue and activation of signal transduction.
• This will result in excessive response upon sudden withdrawal of antagonist after prolonged exposure which also known as withdrawal syndrome.

Question 13

What information you can get from graded DRC?

Answer 13

1. Compare potency
2. Compare efficacy
3. To predict the nature of the drug- receptor interaction
   - full agonist
   - partial agonist
   - antagonist