Test 4 definitions Flashcards
Kon
the rate of association or binding of the ligand to the receptor to form the drug receptor complex
Koff
the rate of dissociation or unbinding of ligand from the receptor
ligand
refers to a drug or endogenous substance that binds to a receptor eliciting a cellular or systemic response
receptor
refers to the cellular macromolecule or macromolecular complex with which the drug or ligand interacts to elicit a response
acceptors
things drug interact with that do not directly cause any change in biochemical or physiological response but can alter the pharmacokinetics of a drug’s actions
kd
the equilibrium dissociation constant is equal to the ligand concentration at which 50% of total receptors are bound
fractional occupancy
fraction of total receptors that are occupied by a ligand, equal to [LR]/[R0]
Kd is ___ related to affinity
inversely
if you know the ligand concentration and the kd, you can
determine the percentage bound even though we do no know the number of receptors
receptor occupancy curve
x axis: log [drug]
y axis: receptor occupancy / percent bound
info it can yield:
Kd; Bmax; comparison of affinity
Response/effect curve (graded response curve)
x axis: log [drug] y axis: percent response info it can yield: EC50 Emax comparison of potencies
potency
inversely related to the drug concentration required to produce a defined effect or response; the lower the concentration needed to produce the effect, the more potent the drug
most potent drug
smallest x value
efficacy
ability of a drug to produce a response and is related to the number of drug receptor complexes formed
to compare efficacy of drugs, compare their
Emax values
a graded dose response curve
is achieved by repeatedly exposing a single subject to a progressively increasing doses of drug and measuring the effect
quantal dose response curve
plots the fraction of the population that responds to a given dose of a drug against the drug dose
therapeutic index
equal to the ratio of TD50 to ED50; the larger the ratio, the safer the drug
inverse agonists
selectively bind to the inactivated form of a receptor and shift the conformational equilibrium toward the inactive state; in systems that are non constitutiutively active, inverse agonists will behave like competitive antagonists
a prerequisite for an inverse agonist response is that
the receptor must have a constitutive (aka intrinsic or basal) level of activity in the absence of any ligand
an agonist
increase the activity of a receptor above its basal level whereas an inverse agonist decreases the activity below the basal level
the efficacy of a full agonist
by definition is 100%
neutral antagonist
0%
inverse agonist
less than 0%
intrinsic activity
the ability of a ligand to activate a receptor upon binding; described with a value between 0-1
intrinsic activity
used interchangeably with efficacy; the drug with the highest percent response (on graded dose response curve) would have the highest intrinsic activity
up-regulation of a receptor
the result of increasing the number of receptors and total binding that occurs due to prolonged exposure to an antagonist
___ should be employed when discontinuing use of an antagonist to avoid adverse effects
tapering
downregulation of receptors is
the decrease in the number of receptors and total binding that occurs due to prolonged exposure to an agonist
gives rise to “tolerance”
tapering should be employed to mitigate withdrawal symptoms
when calculating the ligand concentration you must consider
enationmers and plasma protein binding
agonist + reversible antagonist
shifts the dose response curve to the right
agonist + irreversible antagonist
shifts the dose response curve to the right and lowers the height
dose ratio
normal dose multiplied by the dose ratio to reach the same therapeutic effect as the agonist alone
dose ratio (equation)
( [antagonist] / kd of antagonist ) + 1
partial agonists in the presence of a full agonist act as
partial antagonists
ROA affecting therapeutic effect of a drug
first pass; most drugs are inactivated by metabolism thus reducing their therapeutic effect (except prodrugs)
