Pharmacodynamics 1

Question 1

Pharmacokinetics

Answer 1

study of what the body does to the drug

Question 2

pharmacodynamics

Answer 2

study of the action of drugs on the body

Question 3

drug nomencleture

Answer 3

• chemical name
• generic name
• trade name

Question 4

drugs often

Answer 4

mimic or block the action of our own signalling molecules

Question 5

examples of natural drug sources

Answer 5

yew, fox glove, penicillium

Question 6

receptor

Answer 6

generally used to describe the target molecules through which double physiological mediators produce their effects

Question 7

protein targets of drugs

Answer 7

enzymes, transporters, ion channels, receptors

Question 8

non protein targets of drugs

Answer 8

DNA, lipids

Question 9

Principles of drug action

Answer 9

binding, agonism/antagonism, receptor classification, second messengers/signal amplification

Question 10

4 receptor families

Answer 10

ligand gated ion channels
G protein coupled receptors
Kinase linked
nuclear receptors

Question 11

ligand gated ion channels

Answer 11

ionotrophic receptors
passageway through membrane
conformational change
fast siganlling

Question 12

example of ligand gated ion channel

Answer 12

nicotinic acetyl choline receptor

Question 13

GPRC

Answer 13

Metabotrophic

protein with multiple subunits

Question 14

example GPRC

Answer 14

post synaptic muscaranic acetylcholine receptor

Question 15

kinase linked

Answer 15

inside the membrane
gene transcription and protein synthesis
response takes hours

Question 16

example kinase linked

Answer 16

cytokine receptor - insulin receptors

“metabolic change”

Question 17

Nuclear receptors

Answer 17

action in the nucleus - may not be specifically located in the nucleus
hours
gene transcription and protein synthesis

Question 18

example of nuclear receptor

Answer 18

hormone - lipophilic eg oestrogeen receptor

Question 19

Is a drug ever 100% specific?

Answer 19

no - only selective for the receptor over another

Question 20

Specificity

Answer 20

the ability to identify the true negatives

eg 100% - correctly identify all the patients without the disease

Question 21

Can therapeutic dose affect specificity?

Answer 21

yes - which receptors are activated

side effects at higher doses

Question 22

binding is …. in 99% of situations

Answer 22

transient - on/off

Question 23

rate of on and off

Answer 23

K↓1 and K↓-1

Question 24

higher affinity

Answer 24

will bind more readily to its receptor

Question 25

endogenous ligand

Answer 25

binds toa receptor - produced in the body

Question 26

what is K↓D

Answer 26

the dissociation constant which is a measure of the tendency of the drug-receptor complex to dissociate

Question 27

[D] [R] [DR]

Answer 27

K↓1 forwards and K↓-1 reverse reaction

Question 28

K↓D =

Answer 28

k-1 = [D] [R] =? | k1 [DR]

Question 29

1/K↓A

Answer 29

K↓D

Question 30

smaller the K↓D

Answer 30

the higher the affinity

Question 31

Fractional occupancy

Answer 31

how may of the receptors are bound out of all the receptors

Question 32

Dissociation constant from conc/occupancy graph

Answer 32

the conc. of the drug required to occupy 50% of the available receptors

Question 33

p↓A (fractional occupancy) =

Answer 33

([D] / K↓D) | [D] / K↓D + 1

Question 34

saturation binding experiments

Answer 34

radiojlabel the drugs - work out the affinity or K↓D of a receptor. or density (Bmax) of receptor for a specific tissue

Question 35

what is Bmax

Answer 35

density of a specific receptor in a tissue

Question 36

saturation binding: TB, SB, NSB

Answer 36

``` TB = Total Binding (some to other receptors) SB = Specific Binding NSB = Non-specific Binding (to other receptor (control used)) ```

Question 37

axis for saturation binding

Answer 37

x - conc | y - %total bound

Question 38

what is a Scatchard Plot?

Answer 38

showing the amount of receptor bound (X) against bound/free (Y)

Question 39

what line should you see in a Scatchard plot?

Answer 39

straight line

Question 40

what is the gradient equal to in a Scatchard plot?

Answer 40

-1/ KD

Question 41

what is the X intercept in a Scatchard plot?

Answer 41

Bmax - the total density (concentration) of receptors in a sample of tissue

Question 42

B (bound) =

Answer 42

Bmax [D] | [D] + KD

Question 43

how would you investigate competitive binding?

Answer 43

competing off the amount of radio labelled drug - compete for the receptors fixed conc of drug A incubated with increasing conc of drug B

Question 44

IC50

Answer 44

concentration of an inhibitor where the binding is reduced by half

Question 45

Cheng prusoff graph

Answer 45

X - log (B) concentration (M) | Y = binding to protein (pmol/mg)

Question 46

what is Ki? (cheng prusoff)

Answer 46

the dissociation constant (KD) of the unlabelled drug

Question 47

what is KA - cheng prusoff

Answer 47

Dissociation constant (KD) of the radiolabelled drug

Question 48

Cheng prusoff equation - Ki =

Answer 48

IC50 / (1 + ( [A] / KA)

Question 49

does binding a drug to a receptor mean there will be a reponse?

Answer 49

no - antagonist (won't have a response)

Question 50

agonist

Answer 50

activates a receptor to cause a response

Question 51

activation of a receptor leads to

Answer 51

a measurable response | contraction, ion flow, change in HR

Question 52

concentration response curves

Answer 52

``` X = concentration (M) Y = response ```

Question 53

drugs effect is proportional to...

Answer 53

drug concentration

Question 54

EC50

Answer 54

concentration of drug required to bring about a response in 50% of the receptors (50% of maximal response)

Question 55

EC50 or Kd bigger?

Answer 55

EC50 is much less than the KD

Question 56

what would influence whether max effect is able to be achieved

Answer 56

whether it is a full or partial agonist

Question 57

reserve / spare receptors - maximal response

Answer 57

Often, not all receptors need to be occupied for max. effect

Question 58

graded agonis effect

Answer 58

full, partial or inverse agonist

Question 59

“Full” agonists

Answer 59

elicit 100% effect of the endogenous agonist

Question 60

Partial” agonists

Answer 60

elicit < 100% effect

Question 61

Inverse” agonist | does what?

Answer 61

reduce basal receptor activity | - moved the equilibrium back towards the resting state (reducing the effect)

Question 62

what must you be careful not to confuse an inverse agonist with?

Answer 62

antagonist - as they have zero efficacy - not exerting a biological effect - where as inverse agonists are exerting an effect

Question 63

Potency

Answer 63

concentration to observe a response - more potent need less to see a response

Question 64

Agonist Drug “Potency” involves:

Answer 64

affinity + efficacy

Question 65

what is a dose?

Answer 65

concentration given of a dog depending on weight

Question 66

how to you establish what dose to give?

Answer 66

quartal dose response curves. looking at serried effect histogram - normal distribution

Question 67

cumulative quantal dose response

Answer 67

ED 50

Question 68

ED50

Answer 68

the effective dose to produce a therapeutic effect