2. Drug - Receptor Interaction (Agonists)

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 mediators?

Answer 2

1. Cell surface receptors as they are too big to pass through the cell surface membrane
2. Intracellular receptors - molecules that are small enough and hydrophobic can pass through the membrane

Question 3

How do receptors work?

Answer 3

They undergo a subtle change in shape which allows for the effect of the chemical mediator to be apparent. The chemical mediator on binding causes a shape change which stabilises the active form of receptor which enhances the interaction with signal transduction.

Question 4

What are the two stages on interaction?

Answer 4

Binding and activation

Question 5

What are Beta-1 adrenoreceptor, (Nor)adrenaline, Dobutamine and atenolol

Answer 5

Beta 1-adrenoreceptor is a receptor, it is what the agonist, antagonist and mediators act on, (Nor)adrenaline is a mediator, Dobutamine is an agonist, and atenolol is an antagonist.

Question 6

What is the difference between, agonist, and antagonists?

Answer 6

Dobutamine - agonist - binds and activates

Atenolol - antagonist - binds but cannot activate

Question 7

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

Answer 7

1. Concentration of drug in vicinity of receptor at a given time - which is influenced by dose, route, distribution
2. Affinity - tendency to bind, i.e. the strength of attraction between receptor and agonist
3. Intrinsic efficacy - ability to activate a shape change leading to a response
4. Nature of receptor-response coupling, signal transduction mechanism
5. Total number of receptors present

Question 8

What is receptor occupancy?

Answer 8

The interaction between the agonist and the receptor, the size of the response will vary with the proportion of receptors occupied by agonist

Question 9

What is the maximum response?

Answer 9

All receptors for that agonist that are present in the tissue are occupied by the agonist

Question 10

What does the proportion of receptors available depend on?

Answer 10

The agonist concentration and the strength of the bonds formed

Question 11

What is the rate of a reversible reaction proportional too?

Answer 11

The product of the concentration of the reactants.

Question 12

What is the equation for occupancy?

Answer 12

Occupancy = [Xa] divided by [Xa] + Ka

Question 13

What is the explanation of a big and small Ka?

Answer 13

When Ka is small the occupancy at a given agonist drug concentration tends towards 100%, a higher Ka means that the proportion of receptor-agonist complexes decreases

Question 14

At 50% occupancy what does Ka equal?

Answer 14

Ka = Xa when half of the receptors are occupied

Question 15

How do you know if the bonds between the receptor and agonist are strong?

Answer 15

Ka is very small i.e pico molar

Question 16

Where will the curve shift when there is a larger Ka

Answer 16

To the right

Question 17

What does occupancy depend on?

Answer 17

Ka and Xa where Xa = the concentration of agonist in vicinity of receptors and Ka is a theoretical measure of affinity of Drug receptors

Question 18

How does actual response vary with agonist concentration

Answer 18

A muscle strip is set up in an organ bath containing suitable physiological medium, the agonist is added and response measured e.g. the force of contraction and a graph plotted

Question 19

What is EC 50 ?

Answer 19

The effective concentration to produce 50% of maximum response.

Question 20

What is the explanation of an increasing EC50?

Answer 20

An increased EC50 results in decreased potency.

Question 21

What is the intrinsic efficacy of an agonist-receptor complex?

Answer 21

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

Question 22

What are full and partial agonists?

Answer 22

Full agonist - Produces the maximum response of which the tissue is capable on activation of all of that population of receptors
Partial agonist - Produces a smaller response even at very high concentrations
They can even have the same potency.

Question 23

What is the intrinsic efficacy of full agonists?

Answer 23

+1 or 100% - they are efficiently coupled to initiation of signal transduction mechanism

Question 24

What is a full agonist of Beta 1 adrenoreceptors?

Answer 24

Dobutamine

Question 25

What is the intrinsic efficacy of partial agonists?

Answer 25

between 0 and +1, they are less efficiently coupled to initiation of a signal transduction mechanism

Question 26

What is a partial agonist of Beta 1 adrenoreceptors?

Answer 26

Pindolol

Question 27

What are inverse agonists?

Answer 27

They cause a negative shape change which stabilises inactive state of receptor and reduces the effect of basal activity

Question 28

What is the intrinsic efficacy of inverse agonists?

Answer 28

Between -1 and 0

Question 29

What is transduction?

Answer 29

Relay of molecules in a signal transduction pathway

Question 30

What are the different types of coupling that can affect the extent of amplification?

Answer 30

1. Chemical gated ion channels
2. Activation of G-proteins linked to ion channels or enzymes
3. Direct activation of enzymes
4. Regulation of gene transcription

Question 31

What is occupancy?

Answer 31

A proportion of the total number of receptors that are in an agonist-receptor complex

Question 32

What is the equation for the size of a response to an agonist?

Answer 32

Look in notes

Question 33

What can explain the reduction in the size of response of chronic exposure to an agonist drug?

Answer 33

1. Increased metabolism
2. Altered characteristics of agonist receptor complex
3. Down-regulation of signal transduction
4. Reduction in the number of receptors
5. Reflex activation of opposing physiological pathways