Relationship between amount of drug in body and effect of the drug (Owen) 1/26

Question 1

The [drug] which causes 1/2 maximal response

is called the

Answer 1

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

Question 2

When the assumption of linearity between [D-R] and response does not hold

Answer 2

the EC50 no longer
approximates the KD.

ex: the EC50 will be
much smaller than the KD when “spare receptors” are present.

Question 3

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

Answer 3

A tissue is said to express “spare receptors”

Question 4

potency

Answer 4

refers to the EC50 of a drug. lower the EC50 = greater the potency.
A low KD and a high number of spare receptors increases the potency of a drug.

Question 5

efficacy

Answer 5

maximal response of a drug

Question 6

The greater

the maximal response the _______ the efficacy

Answer 6

greater

Question 7

The “Best in Class” is called a

Answer 7

“full agonist”

any drug that generates a maximal response equal to the “Best in Class” is also referred to as a “full agonist.”

Question 8

agonists A & B produce the same maximal response so these drugs are both ________. However if agonist A has a lower EC50 than agonist B, agonist A is said to be

Answer 8

a more potent agonist than agonist B

( image on slide 28) two sigmoidal curves with same max response, but different EC50s.

agonist A lying further to the left, i.e. having a lower EC50(requires a lower concentration to produce the half maximal response.

Question 9

Any drug that generates a maximal response less than that elicited
by the “Best in Class” is referred to as a

Answer 9

partial agonist

Question 10

the dose of drug that generates an EC50

Answer 10

ED50

Question 11

Although the ED50 is affected by the KD and EC50 it is greatly influenced by the

Answer 11

apparent volume in which

the drug is distributed

Question 12

ED50 is never equal to

Answer 12

EC50 or KD

Question 13

CHARACTERISTICS OF SURMOUNTABLE ANTAGONIST:

Answer 13

Produces parallel shift in concentration-response curve of agonist

Full effect of agonist can be restored by increasing
concentration of agonist

Question 14

MOST COMMON MECHANISM OF SURMOUNTABLE

ANTAGONISM:

Answer 14

Competitive interaction between agonist (potency and efficacy) and antagonist (potency but little/no efficacy) at binding site on receptor

Question 15

that the net effect of a competitive

antagonist is to increase the

Answer 15

apparent KD, or said differently to decrease the apparent potency of the agonist.

Question 16

WHAT IS THE EFFECT OF BLOCKING

DRUGS ON CONCENTRATION-RESPONSE CURVES?

Answer 16

SURMOUNTABLE
ANTAGONIST

INSURMOUNTABLE
ANTAGONIST

Question 17

SURMOUNTABLE

ANTAGONIST

Answer 17

same maximum, right shift in EC50==> require higher concentration of agonist to reach the same response ( not apparent shift in EC50 for the agonist)

Question 18

INSURMOUNTABLE

ANTAGONIST

Answer 18

MAXIMUM DECREASED, EC50 REMAINS THE SAME

Question 19

CHARACTERISTICS OF INSURMOUNTABLE ANTAGONIST

Answer 19

Produces non-parallel shift in concentration-response curve of agonist

Full effect of agonist cannot be restored by increasing
concentration of agonist

Question 20

MOST COMMON MECHANISMS OF INSURMOUNTABLE

ANTAGONISM

Answer 20

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

Question 21

effect of drug in an individual

Answer 21

concentration or dose response curve in which GRADED effects of the drugs are related to the concentrations or doses of the drug

Question 22

effect of a drug in a POPULATION

Answer 22

concentration or dose response curve in which the QUANTAL effect of the drug is related to the concentrations of the drug (all or nothing)

Question 23

quantal effect

Answer 23

all or noting, present or absent (alive v. dead, awake v. asleep)

Question 24

A quantal concentration or dose response cure is a plot of:

Answer 24

concentration or dose versus % of patients in the population who exhibit the quantal response at
the given concentration or dose (% of individuals responding at or below indicated dose or concentration)

Question 25

GRADED Relationships:

ED50s and EC50s indicate

Answer 25

doses and concentrations that

cause 1/2 maximal response in a given INDIVIDUAL

Question 26

QUANTAL Relationships:

ED50s and EC50s indicate

Answer 26

doses and concentrations that

cause 1/2 of the POPULATION to respond

Question 27

Since the log dose-response curve is sigmoidal, increasing
the dose of a drug when the response is submaximal
will

Answer 27

enhance the therapeutic effect

Question 28

Since the log dose-response curve is sigmoidal, increasing
the dose of a drug when the response is maximal
will

Answer 28

not improve the therapeutic effect

but may subject the patient to toxicity.

Question 29

since the log dose-response curve is sigmoidal, regardless of whether the “response” is therapeutic or toxic the ______ of a drug can be assessed by examining the log-dose response curves for therapeutic versus toxic effects

Answer 29

saftey

Question 30

The more separation between the therapeutic log dose response curves and the toxic log dose response curves the _______ the drug

Answer 30

safer (ex: penicillin==> said to have a “large therapeutic window”

Question 31

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

Answer 31

a drug with low efficacy and high potency.