Dose-Response Relationships

Question 1

(1) What relationship is describe in a dose-response curve?

Answer 1

magnitude of drug effect as a function of the drug concentration (or dose)

Question 2

(1) Contrast graded and quantal responses.

Answer 2

graded responses occur on a continuum, while quantal occur at desecrate values (graded is plotted against response dose, quantal is plotted by percent responding per group against dose)

Question 3

(2) Compare and contrast EC50 and ED50

Answer 3

effective concentration v. dose for 50% response

Question 4

(3) Explain how there can be spare receptors given a full response?

Answer 4

1. due to magnification of response by cascades and other factors, a fractional occupation of the receptors can generate a full response
2. the duration of drug response can exceed drug binding leading to temporally spare receptors

[one unit of binding does not equal one unit of response]

Question 5

(3) How are receptor reserves demonstrated?

Answer 5

by washing with an irreversible antagonist, the percent receptors bound for full response can be found in comparison to normal receptor

Question 6

(3) In the situation of spare receptors, which is greater Kd or EC50?

Answer 6

Kd will be greater than EC50 because the drug is binding at higher concentrations than are required for a dose response

Question 7

(3) When in irreversible antagonist is used in combination with an agonist, what happens with the dose response curve?

Answer 7

shifts curve to the right, you must occupy a greater percentage of available receptors, accomplished by increasing the drug concentration to attain the same response

Question 8

(1) How is a quantal dose response curve converted into a sigmoidal curve?

Answer 8

the cumulative precent exhibiting therapeutic effect is plotted against dose

Question 9

(4) Graphically explain how efficacy and potency are demonstrated on a dose response curve.

Answer 9

the height of the sigmoidal curve measures efficacy, while the further left the curve is the more potent it is (remember at a given concentration a drug maybe more potent than another without being overall more efficient)

Question 10

(4) Contrast efficacy and potency.

Answer 10

efficacy is whether a drug can demonstrate the desired response, potency is what is the does required for a given response

Question 11

(5) Define therapeutic index.

Answer 11

TI is the ratio of dose required to produce toxic effect in 50% patients over the dose required to be efficacious in 50% of patients (not always the best safety measure, only when dose response curves are not shallow)

Question 12

(5) Define the certain safety factor

Answer 12

CSF is the the ratio of the dose required for toxic effects in 1 patient over the dose required for efficacy in 99 patients (bigger ratio is best)

Question 13

(6) What are the characteristics of an agonist?

Answer 13

activates receptor to initiate a biological response

agonists are intrinsically efficacious

Question 14

(6) Contrast a full and partial agonist

Answer 14

a full agonist can produce the maximal response, a partial agonist is less effective at activating receptor and therefore less efficacy than a full agonist

Question 15

(6) Why does a partial agonist appear to be an antagonist in the presence of a full agonist

Answer 15

it occupies active sites without producing the maximal response while preventing full agonist from achieving maximal response

Question 16

(6) Describe the efficacy and the biological activity of an antagonist.

Answer 16

an antagonist is an agent which does not activate receptor upon binding; it has no intrinsic efficacy although it may still have a biological effect by blocking constitutive action at the binding site

Question 17

(7) Contrast competitive and noncompetitive antagonists

Answer 17

competitive competes for agonist binding site and can be out competed. noncompetitive has binds but has no action or has a post receptor site of action and cannot be out competed by agonist

Question 18

(7) What is the mechanism of a physiological antagonist?

Answer 18

a drug that produces opposing response by action a different systems (drug has intrinsic activity)

Question 19

(7) What is the mechanism of chemical antagonists?

Answer 19

the antagonist acts directly on agonist to chemically alter it (ie. effecting how it is absorbed)

Question 20

(7) When do positive and negative modulators act?

Answer 20

the act in the presence of receptor activation and help to regulate the activity of agonists (+/-)

Question 21

(7) When and where do inverse agonists work?

Answer 21

inverse agonists inhibit receptor activity both when the agonist is bond and when it is not bound (has the ability to effect constitutive levels of receptor activity); binding of inverse agonist causes activity of receptor to be below constitutive activity

Question 22

(8) What is the effect of a competitive antagonist on the dose-response curve and ED50?

Answer 22

shifts dose-response curve to the right (higher agonist concentrations need to compete for receptors to effect response, the ED50 increases (notice, agonist max effect is left unchanged)

Question 23

(8) Describe 3 possible ways to produce noncompetitive antagonism.

Answer 23

allosteric antagonist
antagonist blocks step beyond receptor activation
two agonist produce opposite responses

Question 24

(8) How does noncompetitive antagonist effect the ED50 and the maximal effect of the agonist?

Answer 24

ED50 remains unchanged, although the agonists maximum effect is decreased