Principles of Pharmacology 2

Question 1

What is the name of the curve/relationship which quantifies drug effects?

Answer 1

The concentration-response curve/relationship.

Question 2

If the concentration-response curve is plotted as the LOG of the drug concentration, what shape will the curve be?

Answer 2

Sigmoidal.

Question 3

What is the shape of the concentration-response curve?

Answer 3

Rectangular hyperbola.

Question 4

What is the name benefit of the log method of plotting the concentration-response curve?

Answer 4

Is graphically represents a minimum and maximum concentration concentration of a drug.

Below the minimum concentration the drug has no effect. This is called the threshold concentration.

Question 5

What is the name of the concentration below which a drug has no effect?

Answer 5

The threshold concentration .

Question 6

Between what X2 percentage concentrations is the (log)concentration-response curve linear?

Answer 6

Between 20-80%.

Question 7

What is the Ec50 value, and where is it taken from a lot concentration-response curve?

Answer 7

Ec50 = the concentration of drug needed to elicit 50% of the maximum response for that drug. (It contains a ‘c’ for concentration, whereas Emax does not, meaning Emax related to response and NOT concentration).

It is found by finding the Emax, where the curve plateaus on the response axis (y-axis), then calculating half of this value. Follow this point vertically to the curve then downwards when it intersects it to find the LOG Ec50 value on the x-axis (log drug concentration axis). REMEMBER THIS IS A LOG VALUE SO MUST BE ‘UNDONE’ BEFORE FINDING THE TRUE EC50 VALUE!! (10^value on axis = true answer).

Question 8

What is the Emax value, and how is it found on the log concentration-response curve.

Answer 8

It is the maximum response a drug can elicit.

It is calculated by finding the plateau of the curve and following this point across vertically to the y-axis (drug response axis).

Question 9

Which axis is response and which is concentration in the concentration-response curve graph?

Answer 9

Y-axis = response

X-axis = concentration

Question 10

What does the Ec50 value tell us?

Answer 10

The potency of a drug. A lower concentration needed to produce half its maximum effect indicates the drug is more potent.

Question 11

Why would you have X2 concentration-response curves on the same graph and what would you hope to see?

Answer 11

One would be for the good effects of a drug and one for the bad (side) effects. You would ideally see these graphs as far apart as possible so that good effects are elicited at low concentrations and bad ones at high concentrations.

Question 12

What shape is the curve of drug concentration against % of drug receptors occupied? What about if it is (log) drug concentration.

Answer 12

A rectangular hyperbola normally, sigmoidal if logged.

Question 13

How is drug concentration written on the x-axis?

Answer 13

[D]

Question 14

What is Kd?

Answer 14

The concentration of the drug required to occupy 50% of the receptors (@ equilibrium).

Question 15

Which value tells us the affinity of a drug to its receptors?

Answer 15

The Kd value, the lower the Kd the higher the affinity of the drug to its receptor.

Question 16

Do both agonists and antagonists have efficacy?

Answer 16

No, only agonist have efficacy as this is the ability to produce a conformational change in the receptor which brings about the response.

Question 17

What are the X2 types of agonist?

Answer 17

Partial agonists

Full agonists

Question 18

What are the characteristics of partial agonists in terms of efficacy and effectiveness?

Answer 18

Efficacy = low

Effectiveness = low

Question 19

What are the characteristics of full agonists in terms of efficacy and effectiveness?

Answer 19

Efficacy = high

Effectiveness = high

Question 20

What is the meaning of partial agonist in regards to % of receptors occupied?

Answer 20

It fails to produce a maximal effect despite filling all of the receptors.

Question 21

What is the meaning of full agonist in regards to % of receptors occupied?

Answer 21

Will produce a maximal response after only filling a small % of the receptors.

Question 22

What will the differences between full and partial agonists look like in their log concentration-response curves?

Answer 22

The partial one will not reach maximal response and will also be shifted to the right, as the same level of response will take a larger concentration of the drug to achieve.

Question 23

What are the X2 types of antagonists and what is the difference between them?

Answer 23

Competitive antagonists
- Directly compete with agonists for the same receptor binding site, but do not activate it (therefore have affinity but not efficacy).

Non-competitive antagonists
- Bind to a different site (allosteric site) on the receptor and cause a conformational change in structure which stops the agonist binding to its own receptor binding site.

Question 24

Competitive antagonists can be reversible or irreversible. In reversible competitive antagonists how can the blockade can be surmountable? And what would this look like on a log concentration-response curve?

Answer 24

The blockade is surmountable by increasing the concentration of agonist, and the curve will be shifted to the right but still reach maximal response as it will simply take a higher agonist concentration to produce the same response.

Question 25

Why is it not possible to comment on AGONIST affinity from a log concentration-response curve alone, but it is for an antagonist?

Answer 25

AGONIST response is a combination of affinity AND efficacy, however antagonist response is purely affinity as they have NO efficacy.

Question 26

A measurement of antagonist affinity is the “dose-ratio”. What is this?

Answer 26

The ratio to which you have to increase the agonist to attain the same response from the agonist as you would have pre-antagonist.

Question 27

What is the pA2 value in relation to antagonist affinity?

Answer 27

pA2 = -log [antagonist which requires the agonist concentration to be doubled to produce the same response] (I.e. the dose ratio = 2.0)

Question 28

What does a greater pA2 indicate?

Answer 28

Greater pA2 = Greater antagonist affinity

Question 29

What do the concentration-response curves for partial agonists, irreversible competitive antagonists and non-competitive antagonists all have in common?

Answer 29

They all shift right and down (do not reach maximal response).