14: Dose Response 1

Question 1

Define a dose.

Answer 1

amount of drug necessary to yield an desired concentration of drug at the active site (receptor)

Question 2

What is a response?

Answer 2

A response is a clinical or biological effect caused by the presence of a drug

Question 3

Explain what an endpoint is. What are some examples?

Answer 3

Endpoints are the result that are going to be analyzed after the drug is present to evaluate effectiveness.
(physiological, biochemical, etc)

Can be:
- measured parameter of a defined effect (change in blood pressure)
- measurements of percent of population affected (death)

Question 4

What happens to the drug in vivo? What are its effects?

Answer 4

There is genetic variability from patient-to-patient because of the individual’s genes.
- affects drug-metabolism and transport to target cells

Question 5

What is affinity?

Answer 5

The strength with which a drug binds to its target (receptor)
- drug + receptor –> drug-receptor complex

Question 6

What is efficacy?

Answer 6

The degree to which a drug can elicit a desired biological response after interaction with receptor.
- drug-receptor complex –> effect

Question 7

Explain occupancy theory.

Answer 7

The intensity of the drug effect is proportional to the number of occupied receptors.

Question 8

What are some key points of occupancy theory? When is it not true?

Answer 8

• Response is typically nonlinear with respect to the dose. (doubling dose does not mean doubled response)
• half-max response does not correspond to 50% occupancy.

Question 9

How do you calculate Kd? How do you interpret it?

Answer 9

Kd = [L][R]/[LR]
- lower Kd = higher affinity

Question 10

Explain the meaning of EC50.

Answer 10

EC50 is the concentration of a drug required for 50% of the maximal biological response.

Question 11

What is the benefit of using a log scale versus a linear scale when looking for EC50?

Answer 11

A semilog scale will seperate out the curve and EC50 will be easier to identify.

Question 12

Describe the 4 parameter of a dose-response curve.

Answer 12

1. Threshold response - first drug concentration where there is a reponse.
2. Maximal reponse (Emax; efficacy) - adding more drug will not cause a greater effect.
3. Slope - indicates the efficacy of a specific drug concentration
4. EC50 (potency) - drug concentration that gives 50% max response.

Question 13

Explain the difference between STEEP vs SHALLOW slope.

Answer 13

STEEP - there is a SMALL change in drug CONCENTRATION and has MAJOR change in drug EFFECT.

SHALLOW - there is a LARGE change in CONCENTRATION and SUBTLE impact on drug EFFECT.

Question 14

What is the relation of EC50 and potency?

Answer 14

higher potency –> lower EC50
lower potency –> higher EC50

Question 15

What change do you see on the graph of a drug that is less efficacious?

Answer 15

more efficacious –> 100% max response; lower EC50
less efficacious –> lowered max response; higher EC50

Question 16

What effect does potency have on devising dose?

Answer 16

• gives info on how to devise the dose
• has little significance for therapeutic effect
• low potency has a disadvantage only if the dose is large and yields side effects/difficult to administer

Question 17

For drug therapeutics, is efficacy or potency more important?

Answer 17

Efficacy because drugs can have the same potency but different levels of max response.

Question 18

What is an agonist?

Answer 18

Triggers normal mediated by receptors upon their binding.

Question 19

What is a partial agonist?

Answer 19

Weakly triggers normal response by receptor upon their binding.

Question 20

What is a antagonist?

Answer 20

Competes with agonists, reducing agonist’s abilities to trigger responses.
- can bring Emax to 0

Question 21

What is an inverse agonist?

Answer 21

Triggers the opposite response of an agonist after binding to a receptor.
- efficacy drops below zero