LC 39

Question 1

PK (pharmacokinetics)

Answer 1

absorption, distribution, metabolism, elimination. What the body does to the drug - how is it absorbed, how does it metabolize and how is it secreted?

Question 2

PD (pharmacodynamics)

Answer 2

Binding, activation, systemic response. What does it do to target, what is our target?

Question 3

Binding Studies

Answer 3

Measure of a drug’s affinity for a receptor

Question 4

General idea about receptor to drug ratio in a cell free system

Answer 4

Drug amount can vary but receptors for that drug stay pretty constant

Question 5

K1

Answer 5

drug is bound to the receptor, Kon, how fast the drug binds the receptor

Question 6

K-1

Answer 6

drug is not bound to its receptor, Koff, how fast a drug leaves the receptor

Question 7

KD

Answer 7

dissociation constant, signifies receptor binding. Equal to k-1/k1. drug concentration at which half the receptors are occupied

Question 8

EC 50

Answer 8

at which the drug is having 50% of max effect

Question 9

Low KD

Answer 9

high affinity, k-1 is low and k1 is high

Question 10

High KD

Answer 10

low affinity, k-1 is high and k1 is low

Question 11

Concentration response study

Answer 11

A study to determine the magnitude of the effect of a drug in vitro, described by EC50 and EMAX

Question 12

M

Answer 12

drug concentration

Question 13

Dose response study

Answer 13

Combination of pharmacodynamic and pharmacokinetics. Study used to determine the effectiveness of a drug in vivo - Described by ED 50

Question 14

ED 50

Answer 14

measured in ug/m2, drug dose at which 50% of the population shows a therapeutic effect

Question 15

TD 50

Answer 15

Amount of drug at which 50% of population experiences toxic effects

Question 16

LD 50

Answer 16

Amount drug at which 50% of the population experiences lethal effects

Question 17

Therapeutic index

Answer 17

comparing effectiveness and toxicity - LD50/ED50

Question 18

Dose Response and ED 50

Answer 18

How much effect does the drug have in the body: ED 50

Question 19

LD 50 and TD 50

Answer 19

How bad is the drug for the body: TD 50, LD 50

Question 20

Concentration

Answer 20

mass/volume - must be able to be practically measured. The absolute concentration must be close to approximately the concentration of the drug at its receptor.

Question 21

Dose

Answer 21

mass/weight - better for studies where measuring the concentration in the body is impractical

Question 22

What is a dose response study dependent on?

Answer 22

• binding
• signaling
• PK effects

Question 23

How are drug doses plotted?

Answer 23

drug dose against the percent population with therapeutic effects

Question 24

Dose response studies is done in vivo - true or false?

Answer 24

true

Question 25

% population with toxic effects plotted against drug dose is described by what?

Answer 25

TD 50

Question 26

%population with lethal effects plotted against drug dose is described as what?

Answer 26

LD 50

Question 27

Determining effective dose requires balancing _____ effects with _____ effects

Answer 27

therapeutic, toxic

Question 28

What is therapeutic index of a drug defined as?

Answer 28

LD50/ED50

Question 29

generally safer drugs have larger/smaller therapeutic indexes

Answer 29

Larger, this means there is a greater range between your therapeutic benchmark and toxic benchmark

Question 30

Two examples of relatively safe drugs

Answer 30

amoxicillin and penicillin which are at a >100:1 ratio

Question 31

Two examples of midrange drugs

Answer 31

morphine and diazepam which are around 70:1 to 100:1 ratio

Question 32

Dangerous drug examples (15:1 and less)

Answer 32

cocaine, chemotherapy, etc

Question 33

Applying PD: spare receptors

Answer 33

Describe how comparing Kd and EC50 can reveal spare receptors and their relevance

Question 34

Spare receptors

Answer 34

What are spare receptors and what are their practical effects?

Question 35

When EC50=Kd…

Answer 35

50% effect=50% binding, the potency of the response is equal to the binding affinity. 1:1 binding ratio of receptors to signal pathway

Question 36

What is the limiting step when EC50=Kd?

Answer 36

Receptor binding is the limiting step in the signal pathway

Question 37

When EC50 < Kd….

Answer 37

the potency of response is greater than the binding affinity. More of an effect than expected which means binding is not the limiting step and there are more receptors than we thought

Question 38

What does it suggest when the response magnitude is greater than the % receptors bound?

Answer 38

this suggests there are spare receptors

Question 39

If there are spare receptors in a situation where there are 8 receptors and 50% are bound how many signal pathways are active?

Answer 39

4 signal pathways are active, 2:1 ratio of receptors to pathways

Question 40

What is the limiting step when EC50

Answer 40

the signaling effect is the limiting step in the signaling pathway

Question 41

Spare receptors create _______ as they have a receptor reserve ready to use if the receptors are ______ .

Answer 41

redundancy, deactivated

Question 42

Purpose of spare receptors when dealing with irreversible inhibitor

Answer 42

to make sure the pathways can still run at full capacity even if some pathways are inhibited

Question 43

Without spare receptors what happens to the Emax during irreversible inhibitor binding?

Answer 43

Emax is lowered

Question 44

How do spare receptors make non-competitive antagonists look like competitive antagonists?

Answer 44

They require more drug but can get to the same intensity of effect as opposed to a situation with no spare receptors where non-competitive inhibitors prevent drugs from ever reaching optimal effectiveness. Non-competitive typically lowers Emax whereas competitive raises EC50