Dose-Response Relationships Flashcards
(1) What relationship is describe in a dose-response curve?
magnitude of drug effect as a function of the drug concentration (or dose)
(1) Contrast graded and quantal responses.
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)
(2) Compare and contrast EC50 and ED50
effective concentration v. dose for 50% response
(3) Explain how there can be spare receptors given a full response?
- due to magnification of response by cascades and other factors, a fractional occupation of the receptors can generate a full response
- 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]
(3) How are receptor reserves demonstrated?
by washing with an irreversible antagonist, the percent receptors bound for full response can be found in comparison to normal receptor
(3) In the situation of spare receptors, which is greater Kd or EC50?
Kd will be greater than EC50 because the drug is binding at higher concentrations than are required for a dose response
(3) When in irreversible antagonist is used in combination with an agonist, what happens with the dose response curve?
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
(1) How is a quantal dose response curve converted into a sigmoidal curve?
the cumulative precent exhibiting therapeutic effect is plotted against dose
(4) Graphically explain how efficacy and potency are demonstrated on a dose response curve.
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)
(4) Contrast efficacy and potency.
efficacy is whether a drug can demonstrate the desired response, potency is what is the does required for a given response
(5) Define therapeutic index.
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)
(5) Define the certain safety factor
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)
(6) What are the characteristics of an agonist?
activates receptor to initiate a biological response
agonists are intrinsically efficacious
(6) Contrast a full and partial agonist
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
(6) Why does a partial agonist appear to be an antagonist in the presence of a full agonist
it occupies active sites without producing the maximal response while preventing full agonist from achieving maximal response
(6) Describe the efficacy and the biological activity of an antagonist.
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
(7) Contrast competitive and noncompetitive antagonists
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
(7) What is the mechanism of a physiological antagonist?
a drug that produces opposing response by action a different systems (drug has intrinsic activity)
(7) What is the mechanism of chemical antagonists?
the antagonist acts directly on agonist to chemically alter it (ie. effecting how it is absorbed)
(7) When do positive and negative modulators act?
the act in the presence of receptor activation and help to regulate the activity of agonists (+/-)
(7) When and where do inverse agonists work?
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
(8) What is the effect of a competitive antagonist on the dose-response curve and ED50?
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)
(8) Describe 3 possible ways to produce noncompetitive antagonism.
allosteric antagonist
antagonist blocks step beyond receptor activation
two agonist produce opposite responses
(8) How does noncompetitive antagonist effect the ED50 and the maximal effect of the agonist?
ED50 remains unchanged, although the agonists maximum effect is decreased
