Drug receptor interactions

Question 1

What is affinity?

Answer 1

The strength of the attraction between a drug and its receptor
(agonists & antagonists both have affinity)

Question 2

What does efficacy involve?

Answer 2

agonists only

Question 3

What is the dissociation constant (KD)?

Answer 3

The K𝙳 is the concentration of the drug that occupies 50% of the receptors

Question 4

What is the receptor occupancy equation?

Answer 4

p=[D]/[D]+KD

Question 5

What is RT?

Answer 5

• [R𝖳] = [DR] + [R]
• The total number of receptors.

Question 6

The ability of an agonist to produce a pharmacological effect in a cell/tissue depends on what 2 parameters?

Answer 6

• binding of drug to receptor (determined by AFFINITY)
• activation of receptors and production of response (determined by EFFICACY)

Question 7

What is the EC50 value?

Answer 7

• measures response
• concentration of the drug that gives 50% of the maximum response

Question 8

In terms of EC50, what do agonists display?

Answer 8

they have efficacy and produce a response

Question 9

In terms of EC50, what do antagonists display?

Answer 9

• no efficacy and bind to receptor
• but do NOT produce a response

Question 10

What is the receptor reserve?

Answer 10

High efficacy drugs dont need to occupy all receptors to have a response

Question 11

What ratio of KD to EC50 do strong agonists show?

Answer 11

• EC50 ««< KD
• as to get 50% maximum response only a small proportion of receptors need to be occupied
• therefore drug doesn’t need to be at KD concentration

Question 12

What shows a higher efficacy of a drug in terms of the response and occupancy (p) curves?

Answer 12

the bigger the gap between the occupancy and the response curve, the higher the efficacy of the drug

Question 13

What is potency?

Answer 13

how much drug is needed to produce a particular response

Question 14

What is partial agonism?

Answer 14

how much drug is needed to produce a particular response

Question 15

What are the 4 types of drug antagonism?

Answer 15

• Competitive
• Non-competitive
• Uncompetitive
• Physiological

Question 16

Describe the concentration-effect curves of an agonist and increasing concentrations of antagonist B (if binding reversibly)

Answer 16

• parallel shift in concentration-effect curve to the right
• no reduction in maximum response
• (basically just shows that an increase in [agonist] needed to produce same maximum response)

Question 17

Describe the concentration-effect curves of an agonist and increasing concentrations of antagonist B (if binding IRreversibly)

Answer 17

• Increasing the [agonist] will be insufficient past a certain [antagonist] as due to the irreversible binding
• there will be no free receptors left and so the response curve will not reach 100% response from the agonist

Question 18

Give an example of physiological antagonism

Answer 18

• One drug may antagonise the actions of another via an action on an independent molecular target
• Eg noradrenaline increases HR but acetylcholine decreases HR
• Therefore if given simultaneously they antagonise each other

Question 19

What is meant by constitutive activity of G-proteins?

Answer 19

• G proteins have a resting rate of activity which is above 0
• antagonists will stop rate
• agonists will increase the rate
• inverse agonists will decrease the rate to 0

Question 20

What are inverse agonists

Answer 20

• Negative efficacy
• Ability to switch receptors completely off
• Actions are blocked by COMPETITIVE antagonists

Question 21

What is tolerance

Answer 21

repeated drug administration may lead to adaptive down-regulation of receptors