Lecture 3 - Drug-receptor Theory II - Affinity --> Agonist

Question 1

What is efficacy?

Answer 1

How good a drug is at generating the response

Question 2

What is EC50 compared to KD?

Answer 2

EC50 - where 50% of maximimum response is given
KD - where 50% of receptors are occupied

Question 3

Describe where EC50 would be on a graph compared to KD

Answer 3

EC50 (effective concentration) shifted to the left compared to binding curve.

This is because less agonist is needed to reach 50% binding. This is because there is a receptor reserve i.e. not 100% receptors occupied to give maximal (100%) response - amplification of signal

Question 4

Why is it an advantage to have a receptor reserve?

Answer 4

smaller concentrations are needed

More receptors = further shift to the left

Question 5

Describe the cascade that follows the binding of a muscarinic agonist (e.g. Ach) to receptor

Answer 5

1. activation of G-proteins
2. second messenger systems
3. Rise in intracellular calcium
4. Activation of contractile machinery
5. Contraction

Question 6

What may lead to amplification of response?

Answer 6

Signaling through 2nd messengers may amplify response

Question 7

What is the equation for response?

Answer 7

Response = Maximum conc. of agonist ^slope factor(how many agonists needed to elicit a response from receptor) /////// conc. of agonist^slope factor + EC50^slope factor

Question 8

What does EC50 allow us to predict?

Answer 8

Size of responses as well as potency

Question 9

Why does the curve shift left due to an increase in potency?

Answer 9

Higher potency = less needed to elicit a response

Question 10

What does potency of an agonist depend on?

Answer 10

Affinity, efficacy & space receptors

Question 11

What is the difference between a full agonist and a partial agonist?

Answer 11

Full agonist - 100% response
Partial agonist - e.g. 70% response

Question 12

In what case would KD = EC50, meaning a bioassay can be used?

Answer 12

If a drug is a partial agonist - as 100% of receptors would have to be filled to get the max response

Question 13

Why might a partial agonist with a high affinity be useful?

Answer 13

to avoid overdose

Question 14

What can a partial agonist behave like in the presence of a full agonist?

Answer 14

an antagonist - as they are not able to produce the same maximum, causing a shift to the right in the concentration response curve

Question 15

What is efficacy a measure of?

Answer 15

a measure of a single agonist-receptor complex’s ability to generate a response

Question 16

What 3 properties determine the effect of a drug in a living system?

Answer 16

Specificity - interact with a structurally defined site/receptor (chemical properties/molecular structure)

Affinity - agonist and antagonists’ ability to bind to receptor (KD)

Efficacy - agonist (not antagonists) ability to activate receptor 0 <= E => 1 a full agonist has an efficacy of 1, antagonists have an efficacy of 0.

Question 17

How do you find relative potencies?

Answer 17

Comparison of equieffective doses of standard and unknown gives a valid measure of their relative potencies, whereas measuring the size of response t given concentration doesn’t tell you anything about potency

Question 18

What can occur in an opioid overdose?

Answer 18

Respiratory depression - overactivation of receptors can lead to complete arrest of breathing