Relationship btw amount of drug and effect Flashcards Preview

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Flashcards in Relationship btw amount of drug and effect Deck (53):
0

Dose response causal chain

dose of drug -> drug at target site -> drug-receptor complex -> response

1

what relationships are linear?

dose of drug and [drug] at target site
[drug-receptor complex] and response

2

what relationships are non linear?

[drug] at target site -> [drug receptor complex]

3

what is the dominant non linear relationship in the causal chain?

formation of the drug-receptor complex

4

what does the drug-receptor complex determine?

the shape of the dose-effect and the concentration-effect relationships

5

A plot of [D]free versus [R-D] is

hyperbolic

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A plot of log [D]free versus [R-D] is

sigmodial

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A plot of [D]free versus response is

hyperbolic

8

A plot of log [D]free versus response is

sigmoidal

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The [drug] which causes 1/2 maximal response is called

EC50 and corresponds to the Kd if there is a linear relationship between [D-R] and response

10

Potency refers to

EC50 of a drug

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when the assumption of linearity does not hold, the EC50

no longer approximates the Kd

12

Spare receptors

when present, the EC50 will be much smaller than the Kd

13

Tissue express "spare receptors" when

only a small fraction of the receptor population must be occupied by drug to give a maximal response

14

The lower the Ec50, the

greater the potency

15

A low Kd and high number of spare receptors increases

the potency of the drug

16

Efficacy

refers to the maximal response of a drug

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the greater the maximal response,

the greater the efficacy

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The more effectively a drug engages signal-transduction systems in a cell per unit receptor occupied, the

greater is the efficacy of that drug

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best in class

Full agonist and any drug that generates a maximal response equal to the "best in class" is also referred to as "full agonist"

20

Partial agonist

any drug that generates a maximal response less than that elicited by the "best in class"

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Even if Drug A is a full agonist and Drug B is a partial agonist, they can still the same what?

Potency

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Shape of dose versus Response

Hyperbolic

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shape of Log dose vs. Response

sigmoidal

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ED50

dose which causes 1/2 maximal response
affected by Kd and EC50 it is greatly influenced by apparent volume in which drug is distributed

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ED50 is never equal to

EC50 or Kd

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characteristics of surmountable antagonist

produces parallel shift in concentration-response curve of agonist
Full effect of agonist can be restored by increasing concentration of agonist

27

Common mechanism of surmountable antagonism

competitive interaction between agonist (potency and efficacy) and antagonist (potent but no or little efficacy) at binding site on receptor

28

The net effect of a competitive antagonist is to increase the apparent

Kd, or said differently to decrease the apparent potency of the agonist

29

Addition of competitive antagonist causes

apparent shift in EC50 for the agonist
because takes higher concentration for a response

30

Characteristics of insurmountable antagonist

produce non-parallel shift in concentration-response curve of agonist
full effect of agonist cannot be restored by increasing concentration of agonist

31

Common mechanism of insurmountable antagonism

competitive but irreversible binding of antagonist to binding site on receptor
allosteric modulation of receptor by antagonist so as to attenuate coupling of receptor to signal transduction
blockade of signal transduction "downstream" of receptor

32

Quantal effect

is an effect that is either present or absent

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Quantal concentration

or dose response curve is a plot of concentration or dose versus % patients in the population who exhibit the quantal response at the given concentration or dose

34

we represent the effect of a drug in an Individual as a concentration or

dose response curve in which the graded effects of the drug are related to concentrations or doses of the drug

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we represent the effect of a drug in a Population as a concentration or

dose response curve in which the Quantal effect of the drug is related to concentrations or doses of the drug

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If quantal response happens to be death then ED50 is called

LD50

37

Although both graded and quantal relationships have ED50s and EC50s, the parameter are

NOT the same for graded and Quantal relationships

38

Graded relationships

Ed50s and EC50s indicate doses and concentrations that cause 1/2 maximal response in a given individual

39

Quantal relationships

ED50s and Ec50s indicate doses and concentrations that cause 1/2 of the population to respond

40

Since the log dose-response curve is sigmoidal, increasing

the dose of a drug when the response is submaximal will enhance the therapeutic effect

41

Since the log dose-response curve is sigmoidal, increasing

the dose of a drug when the response is maximal will not improve the therapeutic effect but may subject the patient to toxicity

42

The log dose-response curve is sigmoidal, regardless of whether the

"response" is therapeutic or toxic

43

The safety of a drug can be assessed by examining the log dose-response curves for

therapeutic versus toxic effects

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The more separation between the therapeutic log dose-response curves and the toxic log dose-response curves, the

safer the drug

45

A drug with low potency and high efficacy may be better than a drug with

low efficacy and high potency

46

Potency is a determinant of

how much of the drug must be given to obtain a "ceiling" effect

47

Efficacy refers to the magnitude of

the "ceiling" effect

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In an antagonist is being employed to block the effect of an agnoist, it is important to know whether the antagonist is of

surmountable or insurmountable type

49

Dose of insurmountable antagonist usually does not need upward adjustment as amount of

agonist in body increases

50

Dose of surmountable antagonist must be increased if amount of agonist (endogenous or exogenous) in the patient

increases

51

Graded dose/concentration relationships help to understand

how changing dose of drug will effect the degree of response of an individual patient

52

Quantal dose/concentration relationships help to understand

how changing dose of drug will effect the % of your patients who will experience a defined response