Pharmacodynamics

Question 1

occupancy definition

Answer 1

the proportion of receptors occupied by the drug

Question 2

saturability

Answer 2

once the receptors are fully bound (saturated) more drug makes no difference to occupancy

Question 3

dissociation constant Kd

Answer 3

the concentration of drug at which 50% of receptors are occupied

Question 4

what does the graph show

Answer 4

selectivity

Question 5

what does the graph show

Answer 5

saturability
the effect is limited as the receptor occupancy is finite

Question 6

what is dissociation constant a measure of?

Answer 6

drug activity

Question 7

change in concentration relationship to binding

Answer 7

gives the same level of binding
however the affinity affects the level of binding

Question 8

comparing affinities

Answer 8

different drugs have different affinities for the same receptor because they have different structures

Question 9

specificity

Answer 9

refers to the nature of the interactions
specific vs non-specific
example salbutamol binds specifically to both beta1 and beta2
but it is selective for beta2

Question 10

how to calculate therapeutic index

Answer 10

toxic dose/therapeutic dose

Question 11

high TI

Answer 11

1000 approx
easy to avoid toxic effects
wide therapeutic window

Question 12

low TI

Answer 12

10 approx
difficult to avoid toxic effects
narrow therapeutic window

Question 13

why do more drug effects look like this

Answer 13

all drugs do more than their headline activity

Question 14

agonist

Answer 14

affinity= binds to receptor
efficacy= causes an effect

Question 15

antagonist

Answer 15

affinity= binds to receptor
no efficacy= causes no effect

Question 16

what is potency

Answer 16

an expression of the activity of a drug
in terms of the concentration needed to produce a defined effect

Question 17

EC50

Answer 17

concentration of an agonist that produces 50% of the maximal possible effect of that agonist

Question 18

what are spare receptors

Answer 18

the proportion of receptors that need not be occupied to elicit a maximal response

Question 19

what is EC50 a measure of

Answer 19

potency

Question 20

what is Kd a measure of

Answer 20

affinity

Question 21

what is a full agonist

Answer 21

elicits a maximal response without binding all receptors
there are spare receptors

Question 22

what is a partial agonist

Answer 22

can’t elicit a maximal response
despite 100% occupancy

Question 23

competitive antagonist

Answer 23

has no efficacy and elicits no response

Question 24

what do steroids end in

Answer 24

one
may have something else after e.g. pancuronium rather than pan curium

Question 25

competitive antagonism

Answer 25

mutually exclusive binding both agonist A and B bind to the same site

Question 26

non-competitive antagonism

Answer 26

agonist and antagonist can bind to different sites on receptor such as the orthosteric and the allosteric sites

Question 27

orthosteric site

Answer 27

where the endogenous ligand binds

Question 28

allosteric site

Answer 28

any other site on a receptor

Question 29

channel blockers

Answer 29

particular example of non-competitive antagonism blocker may bind when the channel is open and/or closed some channels have no agonist e.g. voltage-gated sodium channels

Question 30

reversible drugs

Answer 30

equilibrium between binding and unbinding can be to orthosteric/allosteric sites

Question 31

irreversible drugs

Answer 31

covalent modification of target very high affinity can be to orthosteric/allosteric sites pattern of effect changes with irreversible drugs

Question 32

receptor/ ion channels

Answer 32

reversible: ticagrelor irreversible: clopidogrel target: P2Y receptor (GPCR)

Question 33

transporters

Answer 33

reversible: citalopram irreversible: omeprazole target: SERT proton pump

Question 34

enzymes

Answer 34

reversible: ibuprofen irreversible: aspirin target: COX= cyclo-oxygenase