Lecture 3 - Pharmacodynamics (Ligands)

Question 1

what is a ligand?

Answer 1

a substance/drug that binds to a receptor and influences its activity

Question 2

ligands can be ____ or ____ to a receptor

Answer 2

agonists or antagonists

Question 3

substances that the body makes which has a physiological effect (typically agonists)

Answer 3

endogenous ligand

Question 4

a substance/drug that binds to and activates a receptor to produce a biological response

Answer 4

an agonist

Question 5

an agonistic response is usually depicted as a:

Answer 5

concentration response curve (or dose-response curve)

Question 6

refers to the concentration of drug that yields a 50% maximal effect

Answer 6

EC50 (effective concentration 50)

Question 7

the maximal biological effect observed with the dose response

Answer 7

Emax

Question 8

how do you calculate the effect for a given concentration of a drug?

Answer 8

E = ((Emax)[drug]) / ([drug] + EC50)

Question 9

the formula used to calculate the effect of a drug is identical to the formula for:

Answer 9

the law of mass action

Question 10

what is the implication when [drug] = EC50?

Answer 10

a half-maximal effect of the drug is observed (Emax/2)

Question 11

a term that refers to the concentration dependence (Emax)

Answer 11

efficacy

Question 12

a term that refers to the concentration dependence (EC50)

Answer 12

potency

Question 13

a drug with strong potency has a low:

Answer 13

EC50 (only a small concentration is required to generate a large effect)

Question 14

a drug with weak potency has a high:

Answer 14

EC50

Question 15

a _____ can generate the maximal observed effect

Answer 15

full agonist

Question 16

a _____ can generates a sub maximal effect, regardless of dose

Answer 16

partial agonist

Question 17

an _____ causes suppression of basal activity

Answer 17

inverse agonist

Question 18

can endogenous ligands be inverse agonists?

Answer 18

no

Question 19

true or false: agonists can vary in both efficacy and potency

Answer 19

true

Question 20

drugs with different _____ exhibit different concentrations required for a particular effect

Answer 20

potency

Question 21

drugs with different _____ exhibit a difference in the maximal effect that can be achieved

Answer 21

efficacy

Question 22

a type of receptor ligand that blocks a biological response by binding to and blocking receptors rather than activating them

Answer 22

antagonist

Question 23

antagonists can be either _____ or _____

Answer 23

competitive, non-competitive

Question 24

a compound that occupies the same binding site as the agonist, but does not exhibit a biological response

Answer 24

competitive antagonist

Question 25

what is a surmountable antagonist?

Answer 25

at high enough concentrations, the antagonist is displaced, and maximal efficacy can be achieved

Question 26

what is the "dose ratio" of a schild plot?

Answer 26

the ratio of agonist EC50 in the presence vs. absence of antagonist

Question 27

what is the formula for the dose ratio?

Answer 27

dose ratio = (agonist EC50 (with antagonist)) / (agonist EC50 (no antagonist))

Question 28

what is the x-intercept of the schild plot?

Answer 28

called the pki and it reflects the potency of the antagonist

Question 29

the highest concentration of antagonist which has no effect on agonist activity

Answer 29

pki

Question 30

the higher the pki, the more:

Answer 30

potent the drug

Question 31

increasing the concentration of a partial agonist while keeping the full agonist at a constant concentration will lead to:

Answer 31

a reduced response as the concentration of the partial agonist increases

Question 32

like competitive antagonists, partial agonists will lead to a _____ shift in the full agonist _____, but will not affect _____

Answer 32

rightward, potency (larger EC50), efficacy (same Emax)

Question 33

what is irreversible competitive antagonism?

Answer 33

the antagonist binds irreversibly to the drug binding site and cannot be displaced by increasing agonist concentration

Question 34

what effects does irreversible non-competitive antagonism have on efficacy and potency?

Answer 34

reduced agonist efficacy, but no effect on potency

Question 35

activate or inhibit a receptor by binding to a site distinct from the primary (orthosteric) site

Answer 35

allosteric ligands

Question 36

what is non-competitive inhibition?

Answer 36

antagonist binding at a distinct site from the agonist (an allosteric site) which prevents activation of the receptor

Question 37

drugs that have an allosteric effect that acts to potentiate/enhance the effects of an agonist

Answer 37

positive allosteric modulators

Question 38

what effects do positive allosteric modulators have on efficacy?

Answer 38

increased efficacy or potency, or both

Question 39

alcohol is a positive allosteric modulator at which receptor?

Answer 39

the GABAa receptor

Question 40

what is the effect of alcohol on the GABAa receptor?

Answer 40

it enhances the effect of the inhibitory neurotransmitter GABA (you need less GABA to bind to the GABAa receptor)

Question 41

drug receptor interaction is determined by:

Answer 41

1) binding of the ligand to the receptor 2) generation of a biological response

Question 42

in most cases, ligand binding is reversible, so receptors continuiously switch between:

Answer 42

occupied and unoccupied states

Question 43

how well and how long a ligand occupies a receptor is dictated by its:

Answer 43

affinity

Question 44

drug affinity is represented by the:

Answer 44

equilibrium dissociation constant (Kd)

Question 45

affinity is governed by:

Answer 45

electrochemical properties of the receptor and ligand

Question 46

a measure of drug-receptor affinity and efficacy

Answer 46

potency

Question 47

a measure of how well a drug activates a receptor

Answer 47

drug efficacy

Question 48

unlike potency, efficacy is independent from

Answer 48

drug affinity

Question 49

true or false: there is not always a direct relationship between drug effect and drug binding

Answer 49

true

Question 50

why can there be this mismatch between drug binding and drug effect?

Answer 50

one reason is that there may be more receptors present than are required for activation of a full biological effect

Question 51

having more receptors than is needed to produce a maximal biological effect

Answer 51

receptor reserve

Question 52

when receptor reserve is observed, application of small concentrations of an irreversible antagonist does not:

Answer 52

reduce the maximum biological effect (need lots of antagonist to reduce the effect)

Question 53

when receptor reserve is observed, it indicates there is a:

Answer 53

surplus of receptors

Question 54

true or false: receptor reserve is always observed

Answer 54

false

Question 55

receptor binding (affinity) and effect (Emax) are related, but not always:

Answer 55

equal