ELM 4.2

Question 1

What is saturation binding?

Answer 1

When an assay is set up with increasing concentrations of a radioligand, with the aim of working out the Kd and the Bmax for that radioligand

Question 2

What is the term F?

Answer 2

the percentage of control binding that we see when we add the competing ligand to the system.

Question 3

What is IC50?

Answer 3

IC50 is a bit like EC50 in that it represents a midpoint on the curve: the concentration of inhibitor (in other words, the competing ligand I) that reduces binding to 50% of the initial value. It’s important to realise though, that IC50 depends on radioligand concentration ([D]) and affinity (Kd). It’s therefore NOT a constant! IC50 is a potency measurement, by the way, rather than an affinity measurement.

Question 4

Mirtazapine

Answer 4

Mirtazapine is an antidepressant. It blocks alpha 2 adrenoceptors in the brain and increases the release of noradrenaline.

Question 5

Atenolol

Answer 5

Atenolol is a beta blocker. It is used to treat angina and is a third line treatment for hypertension

Question 6

Risperidone

Answer 6

Risperidone is an “atypical” antipsychotic. It is primarily used to treat schizophrenia

Question 7

Pancuronium

Answer 7

This drug is part of a class known as the non-depolarizing blockers. It blocks nicotinic receptors at the skeletal neuromusclar junction and produces paralysis. This can be useful in surgery. Pancuronium has a long duration of action and is sometimes used as part of a lethal injection cocktail.

Question 8

Losartan

Answer 8

Angiotensin receptor blockers (ARBs) are first line antihypertensive drugs. They avoid the troublesome cough associated with ACE inhibitors

Question 9

Atropine

Answer 9

Can be used to treat bradycardia. Also useful for reducing secretions during surgery

Question 10

Ondansetron

Answer 10

Can be used to treat bradycardia. Also useful for reducing secretions during surgery

Question 11

Define efficacy

Answer 11

the tendency of a drug to activate a receptor

Question 12

What are full agonists?

Answer 12

Drugs with the maximum possible efficacy

Question 13

How much efficacy do antagonists have?

Answer 13

Zero

Question 14

What are the consequences of antagonists having zero efficacy?

Answer 14

a functional assay relies on receptor activation to produce a measurable effect. Unless there is an agonist present, there is no measurable effect. This means that experiments to investigate antagonists are going to require us to apply antagonist and agonist simultaneously

Question 15

With a competitive agonist, is there a change in the maximum response?

Answer 15

No

Question 16

Surmountable antagonism

Answer 16

When you can overcome the effects of the antagonist by increasing the concentration of the agonist

Question 17

How do you quantify how far the curve has moved?

Answer 17

You take the EC50 that you get with the antagonist, and then you divide by the control EC50 = Concentration Ratio

Question 18

How is competitive antagonism characterized?

Answer 18

by a parallel shift to the right of the concentration response curve with an increase in EC50

Question 19

What is the difference between Kd and Ki?

Answer 19

a measure of drug affinity. Kd is normally used when the data have come from a saturation assay and the affinity has been measured directly. KI is used when the measurement of affinity has been made indirectly, such as in a competition binding assay or via calculations from the Gaddum Equation.

Question 20

How do you generate pKi?

Answer 20

take the negative log of Ki - because ki values are not normally distributed but pKi values are

Question 21

What is the difference between pKi and pA2?

Answer 21

pKI is a measure of affinity. pA2 on the other hand, is defined as the “negative log of the concentration of antagonist required to double the EC50 for the agonist”. Because we are defining “a specific effect” this means that pA2 is a measure of potency.

but looking at formula for pA2 = pKi

Question 22

What is the formula for CR for a competitive antagonist?

Answer 22

CR = 1 + [i]/Ki

Question 23

What is the consequence of tone, and what has to be considered?

Answer 23

The consequence of tone is that when you apply an antagonist to an organism, tissue or sometimes even a cell, you may see a change in that system. This is NOT because the antagonist is acting in the absence of agonist but rather, because tone means that an agonist is already present.

Question 24

In this type of question, two statements are given (X and Y). You must decide if each of these statements is true and, if both are true, whether X is the reason for Y.

Statement X: Competitive antagonists decrease the apparent efficacy of agonists

Statement Y: Competitive antagonists increase the apparent EC50 of agonists

Answer 24

Statement X is true, statement Y is false:
Efficacy refers to the maximum effect a ligand can produce. The classic definition of competitive antagonism includes the fact that the maximum effect of the agonist is NOT reduced. Thus X is false. The other classic characteristic of competitive antagonism is that there is a parallel rightward shift of the agonist concentration response curve. This results in an apparent increase in the agonist EC50. Thus Y is true.