Relationship between amount of drug in body and effect of the drug (Owen) 1/26 Flashcards
The [drug] which causes 1/2 maximal response
is called the
EC50 (corresponds
to the KD if there is a linear
relationship between
[D-R] and response)
When the assumption of linearity between [D-R] and response does not hold
the EC50 no longer
approximates the KD.
ex: the EC50 will be
much smaller than the KD when “spare receptors” are present.
when only a small fraction
of the receptor population must be occupied by drug to
give a maximal response
A tissue is said to express “spare receptors”
potency
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.
efficacy
maximal response of a drug
The greater
the maximal response the _______ the efficacy
greater
The “Best in Class” is called a
“full agonist”
any drug that generates a maximal response equal to the “Best in Class” is also referred to as a “full agonist.”
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
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.
Any drug that generates a maximal response less than that elicited
by the “Best in Class” is referred to as a
partial agonist
the dose of drug that generates an EC50
ED50
Although the ED50 is affected by the KD and EC50 it is greatly influenced by the
apparent volume in which
the drug is distributed
ED50 is never equal to
EC50 or KD
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
MOST COMMON MECHANISM OF SURMOUNTABLE
ANTAGONISM:
Competitive interaction between agonist (potency and efficacy) and antagonist (potency but little/no efficacy) at binding site on receptor
that the net effect of a competitive
antagonist is to increase the
apparent KD, or said differently to decrease the apparent potency of the agonist.
WHAT IS THE EFFECT OF BLOCKING
DRUGS ON CONCENTRATION-RESPONSE CURVES?
SURMOUNTABLE
ANTAGONIST
INSURMOUNTABLE
ANTAGONIST
SURMOUNTABLE
ANTAGONIST
same maximum, right shift in EC50==> require higher concentration of agonist to reach the same response ( not apparent shift in EC50 for the agonist)
INSURMOUNTABLE
ANTAGONIST
MAXIMUM DECREASED, EC50 REMAINS THE SAME
CHARACTERISTICS OF INSURMOUNTABLE ANTAGONIST
Produces non-parallel shift in concentration-response curve of agonist
Full effect of agonist cannot be restored by increasing
concentration of agonist
MOST COMMON MECHANISMS 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
effect of drug in an individual
concentration or dose response curve in which GRADED effects of the drugs are related to the concentrations or doses of the drug
effect of a drug in a POPULATION
concentration or dose response curve in which the QUANTAL effect of the drug is related to the concentrations of the drug (all or nothing)
quantal effect
all or noting, present or absent (alive v. dead, awake v. asleep)
A quantal concentration or dose response cure is a plot of:
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)
GRADED Relationships:
ED50s and EC50s indicate
doses and concentrations that
cause 1/2 maximal response in a given INDIVIDUAL
QUANTAL Relationships:
ED50s and EC50s indicate
doses and concentrations that
cause 1/2 of the POPULATION to respond
Since the log dose-response curve is sigmoidal, increasing
the dose of a drug when the response is submaximal
will
enhance the therapeutic effect
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.
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
saftey
The more separation between the therapeutic log dose response curves and the toxic log dose response curves the _______ the drug
safer (ex: penicillin==> said to have a “large therapeutic window”
A drug with low potency and high efficacy may be better than
a drug with low efficacy and high potency.
