Pharmacodynamics - receptors

Question 1

What are drug concentrations calculated in? Why?

Answer 1

Molarity

Because it looks at the number of molecules per L

Question 2

How is molarity calculated?

Answer 2

g/L
___
Mr

Question 3

What are the different units of molarity?

Answer 3

molar, M

millimolar, mM

micromolar, muM

nanomolar, nM

picomolar, pM

Question 4

How do you get from molar to millimolar?

Answer 4

Multiply by 1000

Question 5

How do you get from millimolar to molar?

Answer 5

Divide by 1000

Question 6

What is a ligand?

Answer 6

A molecule or ion that binds specifically to a receptor

Question 7

How do ligands interact with receptors?

Answer 7

Bind to receptors

and then dissociate from the receptor

Question 8

What is the proportion of ligands that bind to receptors?

Answer 8

Enough to reach equilibrium in the reversible reaction

ligand + receptor ligand-receptor complex

Question 9

What are the effects that a ligand can have on a receptor once it’s bound to it?

Answer 9

Can activate it

Can just bind to it with no other effect

Question 10

What are the types of ligands based on the effect they have on the receptor?

Answer 10

Agonists - activate the receptor

Antagonists - bind to the receptor, block it from agonists

Question 11

What must a ligand have in order to bind to its receptor?

Answer 11

It must have affinity for the receptor

Question 12

What is affinity?

Answer 12

The ability of the ligand to bind to its receptor

Question 13

What must a ligand have in order to activate its receptor

Answer 13

Intrinsic efficacy

Question 14

What is intrinsic efficacy?

Answer 14

The ability of the ligand to activate its receptor

Question 15

What must a ligand have in order to bring about a cell response?

Answer 15

Efficacy

Question 16

What is efficacy?

Answer 16

The ability of the ligand to bring about a larger cell response

Question 17

What are the factors of efficacy?

Answer 17

Intrinsic efficacy

Other factors inside the cell, tissue etc.

Question 18

Do agonists and antagonists have affinity?

Answer 18

Yes

because both bind to their receptor

Question 19

Do agonists and antagonists have intrinsic efficacy?

Answer 19

Only agonists do, because only agonists activate the receptor
not antagonists

Question 20

Do agonists and antagonists have efficacy?

Answer 20

Only agonists do, because only agonists activate the receptor to start off the process of bringing about the cell response
not antagonists

Question 21

Why do antagonists not have efficacy?

Answer 21

Because they cannot activate the receptor
so it can’t interact with effector proteins
no cell response

Question 22

What shape does a graph of x axis-drug concentration against y axis-receptor saturation look like?

Answer 22

Rectangular hyperbola

Question 23

What is Bmax?

Answer 23

Maximum binding of receptors

Question 24

What is Kd?

Answer 24

Drug concentration that gives half of Bmax

Question 25

What does Kd measure? How?

Answer 25

Measures affinitiy of drug The lower the Kd, means lower concentration of drug required to bind to half of the receptors, so drug has higher affinity for receptor and oppositely too

Question 26

What shape does a logarithmic graph of x axis-drug concentration against y axis-receptor saturation look like?

Answer 26

Sigmoidal curve

Question 27

What is the difference between concentration and dose?

Answer 27

Dose - drug concentration given to patient, at site of action is unknwon Concentration - known drug concentration at site of action

Question 28

What shape does a graph of x axis-drug concentration against y axis-size of response look like?

Answer 28

Rectangula hyperbola

Question 29

What is Emax?

Answer 29

Maximum size of response

Question 30

What is EC50?

Answer 30

Drug concentration that gives half of Emax

Question 31

What is EC50 a measure of?

Answer 31

Potency

Question 32

What is potency?

Answer 32

The ability of a ligand to bind to its receptor, activate its receptor and bring about a cell response of a certain size

Question 33

What are the factors of potency?

Answer 33

Affinity Intrinsic efficacy Efficacy Number of receptors

Question 34

What would a logarithmic graph of x axis-drug concentration against y axis-size of response look like?

Answer 34

Sigmoidal curve

Question 35

For a ligand-receptor complex, which of the following are fixed and which are variable: - affinity - intrinsic efficacy - efficacy - potency

Answer 35

Affinity - fixed Intrinsic efficacy - fixed Efficacy - variable Potency - variable

Question 36

Do all of the receptors have to be bound by ligand in order to get the maximum response? Why?

Answer 36

No | because of spare receptors

Question 37

What are spare receptors?

Answer 37

Receptors that don't need to be bound to | to get the maximum response

Question 38

Why is it possible for spare receptors to exist?

Answer 38

Because of signal amplification few ligands binding to their receptors can generate a relatively massively response Responses are limited can't continuously increase all the time

Question 39

How does receptor number affect potency?

Answer 39

If have a higher number of spare receptors lower concentration of drug needed to give bigger response means higher drug potency

Question 40

How does receptor number affect the maximum response?

Answer 40

Need to have enough receptors to give maximum response | if have fewer receptors, get smaller response than maximum

Question 41

Can receptor number change?

Answer 41

Yes, not fixed

Question 42

How can receptor number change? Why?

Answer 42

Can increase in number, with low activity Can decrease in number, with high activity

Question 43

How does drug tolerance develop?

Answer 43

Cells decrease their receptor number | need higher concentration of drug to bring about same-size response next time

Question 44

How do the graphs for x axis-drug concentration against y axis-receptor saturation and y axis-size of response compare if there are no spare receptors?

Answer 44

They are the same | same percentage of receptor saturation gives same percentage of size of response

Question 45

How do the graphs for x axis-drug concentration against y axis-receptor saturation and y axis-size of response compare if there are spare receptors present?

Answer 45

The size of response curve is to the left of the receptor saturation curve means smaller percentage of receptor saturation gives bigger percentage of cell response

Question 46

What is intrinsic activity?

Answer 46

The ability of the ligand to produce the maximum sized response

Question 47

What are the types of agonists?

Answer 47

Full agonists Partial agonists

Question 48

What are full agonists?

Answer 48

Agonists that can bring about maximum response

Question 49

What are partial agonists?

Answer 49

Agonists that can only bring about part of the maximum response

Question 50

What are the intrinsic activities of full and partial agonists?

Answer 50

Full agonists have high intrinsic activity Partial agonists have low intrinsic activity

Question 51

What are the efficacies of full partial and agonists?

Answer 51

Full agonists have high efficacy Partial agonists have low efficacy

Question 52

How do spare receptors relate to full and partial agonists?

Answer 52

May or may not be spare receptors with full agonists No spare receptors with partial agonists but still don't give maximum response

Question 53

Are partial agonists fixed?

Answer 53

No | can be converted into full agonists

Question 54

How is a partial agonist converted into a full agonist?

Answer 54

By increasing receptor number | still low efficacy at each receptor but enough receptors to add up and give maximum response

Question 55

What are the types of antagonism?

Answer 55

Competitive - reversible - irreversible Non-competitive

Question 56

What is the most common type of antagonism?

Answer 56

Reversible competitive antagonism

Question 57

What is reversible competitive antagonism?

Answer 57

Antagonist binds to ligand-binding site on receptor | prevents agonist binding

Question 58

What shape does a graph of x axis-antagonist concentration against y axis-size of response look like?

Answer 58

Vertically reflected sigmoidal curve

Question 59

What is IC50?

Answer 59

Concentration of antagonist that gives inhibition of 50% of the maximum response

Question 60

What is IC50 a measure of?

Answer 60

Antagonist potency

Question 61

How are the effects of reversible competitive antagonism overcome?

Answer 61

By increasing the concentration of agonist | so it outcompetes the antagonist and binds to the ligand-binding site on its receptor

Question 62

How do reversible competitive antagonists affect the drug concentration-size of response curve?

Answer 62

Cause it to shift to the right | meaning a higher drug concentration is required to give the same-size response

Question 63

What is irreversible competitive antagonism?

Answer 63

Antagonist binds to ligand-binding site on receptor does not dissociate prevents agonist binding

Question 64

How are the effects of irreversible competitive antagonism overcome?

Answer 64

They can't be

Question 65

How do irreversible competitive antagonists affect the drug concentration-size of response curve?

Answer 65

Shift the curve to the right as higher drug concentrations are required to bind to the spare receptors Suppress the curve as there are not enough available receptors to produce the full response

Question 66

What is non-competitive antagonism?

Answer 66

Antagonist binds to allosteric site | reduces effects of affinity or efficacy of agonist at orthosteric site

Question 67

What is the orthosteric site?

Answer 67

Site where endogenous ligand binds

Question 68

What is pharmacodynamics?

Answer 68

Study of what a drug does to the body