Drug Receptor Interactions

Question 1

What is meant by the drug-receptor theory?

Answer 1

Interactions between the drug and the receptor are reversible as the binding is loose and doesn’t involve strong chemical bonds.

There is a systematic relationship between the drug concentration and the magnitude of the response obtained.

Question 2

What allows competitive antagonists to fulfil their function?

Answer 2

The binding between the receptor and the drug is loose and reversible so when they unbind, this allows the competitive antagonists to bind.

Question 3

What are the four regulatory protein families which are commonly drug targets and covered by the term ‘receptor’?

Answer 3

• enzymes
• ion channels
• carrier molecules
• neurotransmitters

Question 4

What is an agonist?

Answer 4

Will bind to the active site of a receptor and cause a biological response.

Question 5

What is an antagonist?

Answer 5

Will binds to the active site of a receptor and block a biological response. An antagonist has no intrinsic efficacy.

Question 6

How chemically similar are antagonists and agonists?

Answer 6

Must have similar chemical properties as they are both able to bind to the same active site.
However their chemical properties must still be slightly different as when they bind to the same active site, they induce different biological responses.

Question 7

What is the relationship between the equilibrium dissociation constant and affinity?

Answer 7

High Kd = low affinity of binding

Low Kd = high affinity of binding

Question 8

What are the extra receptors called if less than 100% of receptors are needed to evoke a maximum response?

Answer 8

Spare receptors

Question 9

What does the Law of Mass state?

Answer 9

The rate of a chemical reaction is proportional to the product of the concentration of the reactants

Question 10

What does Kd represent?

Answer 10

The concentration of drug required to occupy 50% of receptors at equilibrium. Kd is different for every drug and is the measure of affinity of any one drug for a receptor.

Question 11

What is meant by affinity?

Answer 11

Measure of binding of the drug to the receptor.

‘How easy it is to break the complex once it has formed’

Question 12

How can we calculate the affinity of a drug?

Answer 12

We can use ratio-ligand binding.

Question 13

What is pD2?

Answer 13

log of Kd [pD2 = -log10(Kd)

Question 14

What is meant by efficacy?

Answer 14

Measure of the drugs ability to cause a biological response once bound to a receptor.

Max. response can be obtained by occupying <100% of receptors.

If a low number of receptors is needed to evoke a maximum response then the drug is said to be efficacious.

Question 15

When is a maximum response generated?

Answer 15

When a particular stimulus is generated by receptor occupation.

Question 16

What is the occupancy theory?

Answer 16

Response = [DR]/[RT]

Question 17

How is efficacy measured?

Answer 17

Once the receptor is occupied, how many units of drug receptor complexes are needed to elicit a response? There must be a conformational change which causes the receptor to give a biological response. This is a measure of efficacy.

Question 18

What is a competitive antagonist?

Answer 18

A drug that binds with receptors to form a complex but this complex doesn’t evoke a response.

Question 19

What effect do competitive antagonists have on the log-dose response curve?

Answer 19

Shifts it to the right as more drug is needed to outcompete the antagonist.

Question 20

How can we calculate the drug ratio?

Answer 20

Using the Schild equation.

Question 21

What is pA2?

Answer 21

A way of comparing the affinity of an antagonist. Similar to pD2 of an agonist. pA2 = -log10(Ka)

Question 22

What is an irreversible antagonist?

Answer 22

It binds to the receptor but dissociates very slowly if at all. If the concentration of agonist increases, this will have no effect on the efficacy of the drug as the antagonist as not unbinding.

Question 23

What effect do irreversible antagonists have on the log-dose response curve?

Answer 23

slope of log-dose response curve is decreased as maximum response to agonist decreases.

Question 24

Why does the response gradually dampen with time in the presence of irreversible antagonists?

Answer 24

Agonist binds to the receptor but binding isn’t tight so agonist can come on and off the receptor providing a window of opportunity for the irreversible antagonist to bind. Once bound, this doesn’t unbind and so there are less receptors available for the agonists so over time, the response dampens.

Question 25

What are allosteric modulators?

Answer 25

They bind to sites on the receptor other than the agonist binding side and can modify activity due to modification of the active site.

Question 26

What are allosteric sites?

Answer 26

They are regulatory and not active binding sites. When a drug binds, a response isn’t initiated but it can potentiate/inhibit efficacy of the drug that binds to the active site.

Question 27

What type of antagonist are allosteric modulators?

Answer 27

Non-competitive antagonists.

Question 28

What effect do partial agonists have?

Answer 28

They dampen the response to a full agonist as some receptors are occupied by partial agonists which gives a smaller response than the full agonist. Therefore the overall response is lower than if the full agonist was occupying 100% of receptors.

Question 29

What effect do partial agonists have on the log-dose response curve?

Answer 29

Curve shifts to the right.

Question 30

How do non-competitive antagonists work?

Answer 30

Antagonist blocks access to the active site through steric hindrance. They block signal transduction events so lower the maximum effect.

Question 31

How do inverse agonists work?

Answer 31

Bind to receptors but dampen the overall response.

Question 32

What is the difference between an inverse agonist and an antagonist?

Answer 32

An antagonist binds to a receptor and blocks a biological response. An inverse agonist binds to a receptor and gives a biological response which is to dampen the overall response.

Question 33

What receptor is an example of an ion channel having direct control over an ion?

Answer 33

Nicotinic acetylcholine receptors

Question 34

What receptor is an example of an ion channel having control over an ion through binding to G-protein coupled receptors?

Answer 34

Muscarinic acetylcholine receptors

Question 35

Relate the concept of drug-receptor interactions to signal transduction mechanisms.

Answer 35

Coupled to regulation of ion channel but also coupled to the regulation of an effector molecule so the drug may increase or decrease the activity of the ion channel through the regulation of the G-protein coupled receptor. Equally, it may increase of decrease the activity of the effector molecule through modulation of the G-protein coupled receptor.