2. Drug-Receptor Interaction - Antagonists (1)

Question 1

What is a receptor?

Answer 1

Protein target with which a naturally occurring chemical mediator binds specifically to initiate a cellular response

Question 2

What are the two classes of chemical mediator?

Answer 2

Molecules that are too big to pass membrane and rely on CSM receptors
Molecules that are small enough to pass through and directly activated by intracellular receptor proteins

Question 3

What will the binding of a chemical mediator result in?

Answer 3

Causes a shape change which stabilises active form of receptor, enhances interaction with signal transduction mechanisms

Question 4

What are the two stages of interaction for drug action?

Answer 4

Binding

Activation

Question 5

What are the two stages of interaction for drug action?

Answer 5

Binding

Activation

Question 6

What are the two categories of drug interaction?

Answer 6

Category 1
agonist 
bind and activate
mimics action of chemical mediator
will be a response 

Category 2
receptor antagonist- binding of chemical mediator or agonist drug blocked
bind but do not activate
no response

Question 7

What are the 5 factors that affect size of response to a receptor agonist?

Answer 7

1. Concentration of drug in vicinity of receptor at a given time
2. Affinity - tendency to bind, strength of attraction between agonist and receptor
3. Intrinsic efficacy- ability to activiate a shape change leading to repsonse
4. Nature of receptor-response coupling “signal transduction mechansm”
5. Total number of receptors present

Question 8

How does the size of response from the agonist-receptor complex?

Answer 8

Proportion of receptors occupied by agonist

Question 9

How does the size of response from the agonist-receptor complex?

Answer 9

Proportion of receptors occupied by agonist

Question 10

When does the maximum response to agonist occur?

Answer 10

When all receptors for that agonist that are present in that tissue are occupied by agonist

Question 11

What does the proportion of the total receptors available which are occupied depend on?

Answer 11

Agonist conc

Strength of bonds formed

Question 12

What is Ka?

Answer 12

Equibibrium constant- sometimes called the dissociation constant - for agonist drug A

Characteristic of the drug-receptor complex and has dimensions of conc

Question 13

What is the eqn of occupancy?

Answer 13

[Xa]/[Xa] + Ka

Question 14

What happens when Ka is a very small value?

Answer 14

The occupancy at a given agonist drug conc tends towards 100%

Question 15

What happens as the numerical value of Ka increases?

Answer 15

Proportion of occupied receptors at a given agonist conc decreases

Question 16

What is meant when Ka=Xa?

and why?

Answer 16

Ka is numerically equal to the conc of agonist when half od the total receptors present are occupied

increase in Ka means a decrease in affinity of agonist for receptor

Question 17

How does actual response vary with agonist conc?

Answer 17

Biological response to agonist is usually measured downstream in a cell or tissue

muscle set up under controlled conditions in a bath and agonist is added and response is recorded on a computer screen

Question 18

What is EC50?

Answer 18

a practical, indirect, measure
of Drug A’s potency, measured downstream
of receptor – relates agonist drug A’s
concentration to biological effect produced
as a consequence of occupancy

The effective conc to produce 50% maximum response

Question 19

What is the effect of an increase in EC50?

Answer 19

A decrease in potency

Question 20

What are the properties of agonist receptor complex?

Answer 20

The ability of an agonist when binding to a receptor to activate a change in shape to the receptor

conformational changes reuired to couple to occupied signal transduction mechanism

Question 21

Why do full agonists have an intrinsic efficacy of 1 (100%)

Answer 21

They are efficiently coupled to initiation of signal transduction mechanism

They evoke the maximum shape change response with which the receptor protein is capable.

Question 22

Why do partial agonists have an intrinsic efficacy value between 0 and 1?

Answer 22

Less efficiently coupled to initiation of signal transduction mechanism

evoke less than the max shape change response of which the receptor is capable

Question 23

What are inverse agonists?

Answer 23

Can

Question 24

What are inverse agonists?

Answer 24

Can couple to and casue some activation of signal transduction even when not occupied by agonist

Question 25

How is a conventional agonist different to an inverse agonist?

Answer 25

Cause a -ve shape change which stabilises inactive state of receptor and attenuates coupling/basal activity

Question 26

What are the three stages of cell signalling?

Answer 26

Reception
Transduction
Response

Question 27

What are the four categories of receptor in order of increasing amplification?

Answer 27

Chemical gating of ion channels
Activation of G-proteins linked to ion channels or enzymes
Direct activation of enzymes
Regulation of gene transcription

Question 28

What happens during desensitisation of response on chronic exposure to an agonist drug.

Answer 28

Increase in removal/ metabolism of drug
Altered characteristics of agonist receptor complex
Exhaustion, down-regulation of signal transduction mechanism downstream from receptor
Decrease in the number of receptors