Drugs And Rceptors

Question 1

How can we calculate molarity of a drug?

Answer 1

Molarity = concentration / molecular weight.

Question 2

What property of drug binding means that it is affected by concentrations?

Answer 2

Drug binding is reversible and so it is a balance between association and dissociation.

Question 3

What is the affinity of a drug for a receptor?

Answer 3

This is how strongly the drug binds to the receptor.

Question 4

What is efficacy?

Answer 4

This is the ability of the ligand-receptor complex to mount a cellular response.

Question 5

Do antagonists have efficacy?

Answer 5

No because they are blocking the binding of agonists which would have efficacy.

Question 6

What is Bmax?

Answer 6

This is the maximum binding capacity and indicates receptor number.

Question 7

What is KD?

Answer 7

This is a measure of affinity and is the concentration at which half of the receptors are filled.

Question 8

What is EC50?

Answer 8

This is the effective concentration of drug which gives 50% of maximal response.

Question 9

How does dose differ from concentration?

Answer 9

Dose is the amount of a drug given to a patient, but the actual concentration at the site of action is unknown.

Question 10

What is potency?

Answer 10

This is a property of a drug which takes into account affinity and efficacy.

Question 11

Explain the differences between two drugs of different efficacies but different affinities.

Answer 11

If the two drugs have the same affinity then the same amount will be bound to the receptors presuming that concentrations are the same, however for the more efficacious drug there will be a greater cellular response.

Question 12

Why must our drugs be selective?

Answer 12

This reduces unwanted side effects as it will mean that they only work at particular sites which we select them for.

Question 13

Name three ways in which drugs can be selective.

Answer 13

Efficacy, affinity and route of administration.

Question 14

What are spare receptors?

Answer 14

These are receptors on a cell which do not need to be filled in order for a maximal response to occur.

Question 15

What is the significance graphically of conc against binding and Response of spare receptors?

Answer 15

Spare receptors mean that the response curve is shifted to the left compared to the binding curve.

Question 16

In what type of receptor are spare receptors most commonly seen?

Answer 16

They are most commonly seen in ones that link to other proteins as application of the signal post-receptor is the limiting factor.

Question 17

How do spare receptors increase sensitivity?

Answer 17

They allow responses at low agonist concentrations because when that percentage of sites are full this can be adequate for a maximal response.

Question 18

What affect does changes in receptor number have?

Answer 18

This causes changes in potency and the response which is caused by the same concentration of drug.

Question 19

Define a partial agonist.

Answer 19

This may have Kd~EC50 and so with no spare receptors there is insufficient efficacy for a maximal response to occur.

Question 20

Why are partial agonists useful to us as drugs?

Answer 20

The produce a more controlled response, and work in the absence or low levels of ligand but also act as antagonists when ligand levels are high.

Question 21

What can be said about the efficacies of two drugs which display the same intrinsic efficacies?

Answer 21

They can be different, because on may require more drug to be bound to the receptors in order for a maximal response to occur.

Question 22

What is reversible competitive antagonism?

Answer 22

This is a balance between the ligand and antagonist concentration. If there is more antagonist then there will be less ligand binding and so a minimised response.

Question 23

What is IC50?

Answer 23

This is the concentration of antagonist which is needed for 50% inhibition.

Question 24

What features does irreversible competitive antagonism show?

Answer 24

With increased time or increased antagonist, the inhibition is non-surmountable because more receptors become blocked.

Question 25

What affect does irreversible competitive antagonism have at high agonist concentrations?

Answer 25

It still has the ability to suppress maximal response.

Question 26

On a conc agonist against response curve, what affect will increasing amounts of antagonist have on the curve?

Answer 26

It will cause it to keep shifting to the right.

Question 27

How does non-competitive antagonism work?

Answer 27

This binds to a site on the receptor which is not the ligand binding site. This means that it causes a change in ligand affinity and or efficacy.

Question 28

Other than GPCRs, what type of receptor can non-competitive antagonism happen to?

Answer 28

This can happen to ion channels: e.g. GABA receptors.

Question 29

Give an example of high subtype receptor specificity.

Answer 29

Allosteric regulation of GPCRs is an example of this and leads to non-competitive inhibition.

Question 30

What is the difference between homologous and heterologous desensitisation?

Answer 30

In homologous, only one receptor is affected. This could be due to a decrease in receptor number for example. In heterologous, all receptors that cause that cellular process are desensitised.

Question 31

How can G protein coupled receptors be desensitised?

Answer 31

Phosphorylation of receptor, reversible receptor internalisation and down regulation,

Question 32

What enzymes can phosphorylase receptors?

Answer 32

Protein kinase C, cGMP dependant protein kinase, specific receptor kinases such as B adrenoceptor kinase.

Question 33

What is the difference between reversible receptor internalisation and down regulation?

Answer 33

For a short stimulus, the receptors are internalised by receptor mediated endocytosis, they are then sorted and recycled to the cell surface. For a longer stimulus, the receptors can be targeted to lysosomes and broken down and so the only way for resensitisation is receptor synthesis.