Pharmacodynamics

Question 1

What does is pharmacodynamics the study of?

Answer 1

Drug-receptor interactions and their biological response

Question 2

What are the general properties of receptors?

Answer 2

Low concentration, high affinity, selective, reversible reaction, complementary binding site

Question 3

How is the affinity of a drug for its receptor quantified?

Answer 3

Equilibrium dissociation constant Kd

Question 4

What unit is Kd measured in?

Answer 4

M

Question 5

Which out of antagonists and agonists cause a conformational change in the receptor?

Answer 5

Agonists

Question 6

What is the law of mass action?

Answer 6

D + R <–> DR

Question 7

How is the rate of forward reaction mesured?

Answer 7

k1 [D][R]

1 as subscript

Question 8

ow is the rate of backward reaction measured?

Answer 8

K-1 [DR]

-1 as subscript

Question 9

What is Kd at equilibrium?

Answer 9

[D][R] / [DR]

Question 10

What is the Langmuir equation?

Answer 10

r = [D] / [D]+Kd

Question 11

What is represented by r in the Langmuir equation?

Answer 11

Fractional occupancy of receptors

Question 12

What shape will the curve of r against [D] be?

Answer 12

Rectangular hyperbola

Question 13

What shape will the curve of r against log [D] be?

Answer 13

Sigmoidal, approximately linear between 20-80% fractional occupancy

Question 14

In what situation is [D] equal to Kd?

Answer 14

When r (fractional occupancy) = 1/2

Question 15

For what interactions can the Langmuir equation / r-log[D] plots be used?

Answer 15

Simple bimolecular interactions

Question 16

How can the Langmuir equation be modified to account for complex interactions?

Answer 16

r = [D]n / [D]n + Kd

Question 17

How can the Hill coefficient n be found?

Answer 17

Gradient of log r/1-r against log[D]

Question 18

What does a Hill coefficient of > 1 represent?

Answer 18

Positive cooperativity

Question 19

What does a Hill coefficient of < 1 represent?

Answer 19

Negative cooperativity

Question 20

What does a Hill coefficient of 1 represent?

Answer 20

Simple interaction

Question 21

What is the occupancy theory?

Answer 21

Response [E] is directly proportional to number of receptors occupied

Question 22

What is the rate theory?

Answer 22

Response [E] is directly proportional to rate of receptor occupation

Question 23

What does R equal in occupancy theory?

Answer 23

E / Emax and D / D + Kd

Question 24

What is R in occupancy theory?

Answer 24

Fractional response

Question 25

What is pD2?

Answer 25

-log of [D] that gives 1/2 maximal response, always positive

Question 26

At half maximal response, what can be said about [D]?

Answer 26

It is equal to Kd

Question 27

What is quantified by pD2?

Answer 27

Affinity of agonist for its receptor

Question 28

What does a high pD2 indicate?

Answer 28

Drug acts at low concentrations

Question 29

What is competitive antagonism?

Answer 29

Agonist and antagonist bind to the same site

Question 30

How can competitive antagonists be overcome?

Answer 30

Increasing drug concentration

Question 31

What is non-competitive antagonism?

Answer 31

Antagonist binds to different site to agonist, or acts irreversibly

Question 32

What is a common example of competitive antagonism?

Answer 32

Acetylcholine (agonist) against atropine (antagonist)

Question 33

What happens to an E/Emax against log[D] curve when more competitive antagonist is added?

Answer 33

Shifts in parallel to the right

Question 34

What happens to an E/Emax against log[D] curve when more non-competitive antagonist is added?

Answer 34

Flattens downwards

Question 35

Which type of antagonism decreases Emax?

Answer 35

Non-competitive

Question 36

What is Ka[D] / (KdKa + Kd[A] + Ka[D])?

Answer 36

[DR] / Rt (total receptors)

Question 37

What is the dose ratio?

Answer 37

Ratio of agonist concentration that elicits the same response in absence or presence of antagonist

Question 38

What is the simplified Gaddum-Schild equation?

Answer 38

[A] / Ka = [Da]/[D0] - 1

Question 39

How is dose ratio calculated?

Answer 39

[Da] / [D0]

Question 40

What is pA2?

Answer 40

-log of antagonist concentration that gives dose ratio of 2

Question 41

How can pA2 be calculated?

Answer 41

-log[Ka]

Question 42

What is pAx?

Answer 42

-log of antagonist concentration that gives dose ratio of x

Question 43

What is specificity assumption of the occupancy theory (assumption 1)?

Answer 43

There are specific receptors for specific agonists

Question 44

What is the response assumption of the occupancy theory (assumption 2)?

Answer 44

All agonists for a given receptor can produce the same maximal response

Question 45

What is the reversibility assumption of the occupancy theory (assumption 3)?

Answer 45

The drug-receptor interaction is rapidly reversible

Question 46

What is the accessibility assumption of the occupancy theory (assumption 4)?

Answer 46

All receptors are equally accessible to the drug

Question 47

What is the interaction assumption of the occupancy theory (assumption 5)?

Answer 47

The receptors do not interact with each other

Question 48

What is the occupation assumption of the occupancy theory (assumption 6)?

Answer 48

The maximum response occurs when all receptors are occupied

Question 49

What is the phenomenon of partial agonists?

Answer 49

Some agonists produce only a weak response

Question 50

How can a partial agonists interact with a full agonist?

Answer 50

Acting as a competitive antagonist

Question 51

What is intrinsic activity (alpha) a measure of?

Answer 51

Ability for a drug to produce an effect

Question 52

What is the intrinsic activity of a full agonist?

Answer 52

1

Question 53

What is the intrinsic activity of a partial agonist?

Answer 53

< 1

Question 54

What is the intrinsic activity of an antagonist?

Answer 54

0

Question 55

What is the phenomenon of spare receptors?

Answer 55

Maximum response can be reached without every receptor being occupied

Question 56

At low concentrations, what does a high efficacy antagonist appear to be?

Answer 56

Competitive

Question 57

At high concentrations, what does a high efficacy antagonist appear to be?

Answer 57

Non-competitive

Question 58

What modifications are made to the occupancy theory to account for partial agonists and spare receptors?

Answer 58

The effect will depend on the affinity of the drug for receptor, and the ability of the drug to induce a conformational change

Question 59

What is stabilised by a high efficacy agonists?

Answer 59

Active receptor conformation

Question 60

What is meant by a receptor's constitutive activity?

Answer 60

Basal activity in resting state

Question 61

What do inverse agonists do?

Answer 61

Decrease constitutive activity of a receptor