BB Lecture 12-13: Pharmacodynamics I and II

Question 1

What is the difference between pharmacodynamics and pharmacokinetics?

Answer 1

what the drug does to the body
vs
what the body does to the drug

Question 2

What kinds of plots are used for analyzing drug effects in pharmacology?

Answer 2

semilog transformation

effect (or fraction of receptor bound by drug) against log dose or concentration

Question 3

What are agonists?

Answer 3

produce a response by changing the rate of a biological process from its basal rate (most always increasing it above basal activity- inverse agonists do the opposite)

Question 4

What is a direct agonist?

Answer 4

a drug that binds to and directly activates a receptor

its binding to the receptor evokes the response

Question 5

What is an indirect agonist?

Answer 5

drug that increases the level of an endogenous agonist

has no effect if endogenous agonist is not present

Question 6

What is a full agonist?

Answer 6

can stimulate a signaling pathway to the maximum extent possible in that tissue

Question 7

What is intrinsic efficacy?

Answer 7

the effect produced by the drug binding to a single receptor

Question 8

How can you tell the intrinsic efficacy of an agonist?

Answer 8

if there are spare receptors for a drug, the response curve lies to the L of the binding curve
the fewer spare receptors an agonist has, the lower the intrinsic efficacy

Question 9

How is affinity related to the dissociation constant (kd) for a drug-receptor interaction?

Answer 9

drugs with small dissociation constants have high affinity for the receptor
high affinity means less [drug] is needed to occupy the same number of receptors

Question 10

What does the potency of a full agonist tell you?

Answer 10

the potency is inversely related to the concentration needed to produce a response
the lower the required concentration, the higher the potency

Question 11

What factors determine the potency of a full agonist?

Answer 11

affinity
intrinsic efficacy
the most potent full agonists have high affinity and high intrinsic efficacy

Question 12

What is a partial agonist?

Answer 12

an agonist that is incapable of producing the full response of a system (even when its concentration is sufficient to bind all of the receptors)
has low intrinsic efficacy

Question 13

What do the binding curves and the concentration response curves look like for partial agonists?

Answer 13

they are superimposed

because every additional receptor that is bound by a drug leads to a larger response

Question 14

What are inverse agonists?

Answer 14

produce a response in the opposite direction to that of a full or partial agonist

Question 15

Describe the equilibrium between active and inactive conformations for the different kinds of agonists.

Answer 15

full agonist: I<a>A</a>

inverse agonist= I only</a>

Question 16

How do you calculate the number of receptors bound to a drug?

Answer 16

B= ( Bmax x [D] ) / ( KD + [D] )
where:
Bmax= total # of receptors
KD= dissociation constant for the drug
[D] = concentration of the drug

Question 17

How do you calculate the effect of a drug if you can assume it is linearly related to binding?

Answer 17

E = ( Emax x [D] ) / ( EC50 + [D] )
where:
Emax = drug’s max effect (response)

Question 18

What are antagonists?

Answer 18

bind receptors and do not change activity but prevent an agonist from producing a response

Question 19

What are competitive antagonists?

Answer 19

antagonists that compete with agonists for a binding site

Question 20

What are non-competitive antagonists?

Answer 20

antagonists that bind somewhere other than the location an agonist binds (may even be a different protein) and blocks response to the agonist

Question 21

What are irreversible antagonists?

Answer 21

covalently modify the receptor, rendering it permanently inactive

Question 22

How does a reversible competitive agonist impact a concentration-response curve?

Answer 22

shifts the curve for the agonist to the R

can be overcome by increasing agonist concentration (surmountable)

Question 23

How can you calculate the response of an agonist to a competitive reversible antagonist?

Answer 23

E= (Emax x [D] ) / { EC50 (1 + [A]/Ka) + [D] }

Question 24

How can you calculate the amount of agonist bound to a receptor in the presence of a competitive reversible antagonist?

Answer 24

B = ( Bmax x [D] ) / { Kd ( 1 + [A]/Ka ) + [D] }

where:
[A] is the concentration of the antagonist
Ka is the dissociation constant of the antagonist

Question 25

What is the pA2?

Answer 25

parameter that is used to compare the abilities of different competitive antagonists to inhibit agonist-induced responses
specific for a drug to a specific receptor (can change for the same drug interacting with a different receptor)

Question 26

How do you calculate pA2?

Answer 26

pA2= -log(Ka)

Question 27

What does a high pA2 indicate?

Answer 27

a relatively low concentration of antagonist is sufficient to effectively block the response to an agonist

Question 28

What is the potency of an antagonist?

Answer 28

antagonists have NO potency because they have no intrinsic activity
if you hear they have “low potency” they mean they have a low pA2 (and the opposite for “high potency”)

Question 29

What are irreversible and noncompetitive (allosteric) antagonists?

Answer 29

produce a non-surmountable effect (increasing the maximal effect of an agonist does not restore its maximal response)

Question 30

What impacts the extent of the inhibition by an irreversible antagonist?

Answer 30

1. duration of treatment

2. concentration

Question 31

How does an irreversible/noncompetitive antagonist effect a full agonist’s concentration-response curve?

Answer 31

the curve becomes increasingly flatter (shorter) as the concentration of antagonist increases
this can be blunted if the intrinsic efficacy of the agonist is higher (allows for more spare receptors)

Question 32

How does an irreversible/noncompetitive antagonist effect a partial agonist’s concentration curve?

Answer 32

by definition partial agonists do not allow for spare receptors, so the curve will be dramatically flattened from the beginning as any of the available receptors will be lost