Membranes and receptors - 8

Question 1

Define a ligand

Answer 1

A molecule (or e.g. ion) that binds specifically to a receptor.

Question 2

Define affinity

Answer 2

Is a ligand’s ability to bind to its receptor. The higher a ligand’s affinity for its receptor the stronger the binding in the receptor-ligand complex.

Question 3

Define efficacy

Answer 3

The ability of a ligand to cause a (measurable) response. This is goverened by intrinsic efficacy PLUS cell/tissue-dependent factors.

Question 4

Define agonist

Answer 4

A ligand that binds to a receptor and activates it.

Question 5

Define potency

Answer 5

a

Question 6

Define partial agonist

Answer 6

a

Question 7

Define intrinsic efficacy

Answer 7

How good an agonist is at generating the active state of a receptor.

Question 8

Define antagonist

Answer 8

A ligand that binds to a receptor and stops it from being activated by its agonist.

Question 9

Define functional antagonism

Answer 9

a

Question 10

Define reversible competitive antagonism

Answer 10

a

Question 11

Define non-competitive antagonism

Answer 11

a

Question 12

How do drugs exert effects?

Answer 12

Binding to targets - these are mainly proteins, with the exception being some antimicrobial drugs and anti-tumour drugs which bind DNA.

Question 13

What percentage of the drugs on the market target GPCRs?

Answer 13

~30% (~50 targets)

Question 14

What is a biologic?

Answer 14

any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from chemically synthesized pharmaceuticals, they include vaccines, blood, or blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living cells used in cell therapy

Question 15

What factor is critical in determining a drugs action?

Answer 15

The concentration of drug molecules around their receptor target.

Question 16

What is the molar range that is optimal for drugs to work at?

Answer 16

Nanomolar range.

Question 17

What does 1 mole of a substance mean?

Answer 17

It is Avagadro’s constant: 6 x 10^23 molecules of that substance.

Question 18

Why are drugs calculated using molarities rather than concentration?

Answer 18

Molarity works in number of molecules per volume, rather than grams per volume. This is important for drug action becauses it is the number of molecules around the drug target that effects the action of the drug. Therefore you could have the same concentration of two drugs in grams/L but not have the same number of molecules of each drug.

Question 19

How do most drugs interact with receptors?

Answer 19

Most bind irreversibly.

Question 20

Binding of drugs to targets obeys the law of mass action. What does this mean? What is the consequences of this?

Answer 20

It’s a law that states that, in a solution that is at dynamic equilibrium, the rate of a chemical reaction is proportional to the product of the masses of the reactants. Therefore the action of a drug (ligand) binding a receptor is affected by both the number of ligands and number of receptors.
ligand + receptor ligand-receptor complex

Question 21

Do antagonists have intrinsic efficacy?

Answer 21

No - upon binding they are unable to create the conformational change which activates the receptor.

Question 22

How can you measure how well a drug bind to its receptor (drug-receptor interactions)?

Answer 22

By binding of radioactively labelled ligands to cells or membranes prepared from cells. You can then measure how the proportion of bound receptors changes as drug concentration is increased.

Question 23

What is Bmax a measure of?

Answer 23

The maximum binding capacity (all receptors bound with ligand) - if you know the concentration of drug used to reach the Bmax, you can work out the number of receptors present.

Question 24

What is Kd a measure of?

Answer 24

It is the dissociation constant - a measure of the affinity of a drug for its receptor. It is the concentration of drug required to give 50% occupancy of the AVAILABLE receptors (i.e. half of Bmax).

Question 25

Drug A has a Kd of 10^-9nM and drug b has a Kd of 10^-3mM. Which has the higher affinity?

Answer 25

Drug A - 50% of its receptors are occupied at a significantly lower concentration of the drug. Therefore it has a greater ability to bind to its receptor than drug B (higher affinity).

Question 26

How does K(A) differ from K (d)?

Answer 26

K(A) is a measure of affinity like K(d) but has been determined by pharmocological methods rather than radiactive labelling of ligands.

Question 27

At a 1nM concentration of a drug with a Kd of 1nM, what is the number of receptors bound (there are 100,000 receptors present)?

Answer 27

50,000: half of the available receptors because the concentration of the drug is equal to Kd (the concentration of the drug which gives 50% occupancy of receptors).

Question 28

How is drug concentration normally plotted on a graph of drug concentration against proportion of bound receptors? What is the effect of this on the shape of the graph?

Answer 28

a