Test 4 definitions

Question 1

Kon

Answer 1

the rate of association or binding of the ligand to the receptor to form the drug receptor complex

Question 2

Koff

Answer 2

the rate of dissociation or unbinding of ligand from the receptor

Question 3

ligand

Answer 3

refers to a drug or endogenous substance that binds to a receptor eliciting a cellular or systemic response

Question 4

receptor

Answer 4

refers to the cellular macromolecule or macromolecular complex with which the drug or ligand interacts to elicit a response

Question 5

acceptors

Answer 5

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

Question 6

kd

Answer 6

the equilibrium dissociation constant is equal to the ligand concentration at which 50% of total receptors are bound

Question 7

fractional occupancy

Answer 7

fraction of total receptors that are occupied by a ligand, equal to [LR]/[R0]

Question 8

Kd is ___ related to affinity

Answer 8

inversely

Question 9

if you know the ligand concentration and the kd, you can

Answer 9

determine the percentage bound even though we do no know the number of receptors

Question 10

receptor occupancy curve

Answer 10

x axis: log [drug]
y axis: receptor occupancy / percent bound
info it can yield:
Kd; Bmax; comparison of affinity

Question 11

Response/effect curve (graded response curve)

Answer 11

x axis: log [drug]
y axis: percent response
info it can yield:
EC50
Emax
comparison of potencies

Question 12

potency

Answer 12

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

Question 13

most potent drug

Answer 13

smallest x value

Question 14

efficacy

Answer 14

ability of a drug to produce a response and is related to the number of drug receptor complexes formed

Question 15

to compare efficacy of drugs, compare their

Answer 15

Emax values

Question 16

a graded dose response curve

Answer 16

is achieved by repeatedly exposing a single subject to a progressively increasing doses of drug and measuring the effect

Question 17

quantal dose response curve

Answer 17

plots the fraction of the population that responds to a given dose of a drug against the drug dose

Question 18

therapeutic index

Answer 18

equal to the ratio of TD50 to ED50; the larger the ratio, the safer the drug

Question 19

inverse agonists

Answer 19

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

Question 20

a prerequisite for an inverse agonist response is that

Answer 20

the receptor must have a constitutive (aka intrinsic or basal) level of activity in the absence of any ligand

Question 21

an agonist

Answer 21

increase the activity of a receptor above its basal level whereas an inverse agonist decreases the activity below the basal level

Question 22

the efficacy of a full agonist

Answer 22

by definition is 100%

Question 23

neutral antagonist

Answer 23

0%

Question 24

inverse agonist

Answer 24

less than 0%

Question 25

intrinsic activity

Answer 25

the ability of a ligand to activate a receptor upon binding; described with a value between 0-1

Question 26

intrinsic activity

Answer 26

used interchangeably with efficacy; the drug with the highest percent response (on graded dose response curve) would have the highest intrinsic activity

Question 27

up-regulation of a receptor

Answer 27

the result of increasing the number of receptors and total binding that occurs due to prolonged exposure to an antagonist

Question 28

___ should be employed when discontinuing use of an antagonist to avoid adverse effects

Answer 28

tapering

Question 29

downregulation of receptors is

Answer 29

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

Question 30

when calculating the ligand concentration you must consider

Answer 30

enationmers and plasma protein binding

Question 31

agonist + reversible antagonist

Answer 31

shifts the dose response curve to the right

Question 32

agonist + irreversible antagonist

Answer 32

shifts the dose response curve to the right and lowers the height

Question 33

dose ratio

Answer 33

normal dose multiplied by the dose ratio to reach the same therapeutic effect as the agonist alone

Question 34

dose ratio (equation)

Answer 34

( [antagonist] / kd of antagonist ) + 1

Question 35

partial agonists in the presence of a full agonist act as

Answer 35

partial antagonists

Question 36

ROA affecting therapeutic effect of a drug

Answer 36

first pass; most drugs are inactivated by metabolism thus reducing their therapeutic effect (except prodrugs)