Pharmacodynamics Flashcards
occupancy definition
the proportion of receptors occupied by the drug
saturability
once the receptors are fully bound (saturated) more drug makes no difference to occupancy
dissociation constant Kd
the concentration of drug at which 50% of receptors are occupied
what does the graph show
selectivity
what does the graph show
saturability
the effect is limited as the receptor occupancy is finite
what is dissociation constant a measure of?
drug activity
change in concentration relationship to binding
gives the same level of binding
however the affinity affects the level of binding
comparing affinities
different drugs have different affinities for the same receptor because they have different structures
specificity
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
how to calculate therapeutic index
toxic dose/therapeutic dose
high TI
1000 approx
easy to avoid toxic effects
wide therapeutic window
low TI
10 approx
difficult to avoid toxic effects
narrow therapeutic window
why do more drug effects look like this
all drugs do more than their headline activity
agonist
affinity= binds to receptor
efficacy= causes an effect
antagonist
affinity= binds to receptor
no efficacy= causes no effect
what is potency
an expression of the activity of a drug
in terms of the concentration needed to produce a defined effect
EC50
concentration of an agonist that produces 50% of the maximal possible effect of that agonist
what are spare receptors
the proportion of receptors that need not be occupied to elicit a maximal response
what is EC50 a measure of
potency
what is Kd a measure of
affinity
what is a full agonist
elicits a maximal response without binding all receptors
there are spare receptors
what is a partial agonist
can’t elicit a maximal response
despite 100% occupancy
competitive antagonist
has no efficacy and elicits no response
what do steroids end in
one
may have something else after e.g. pancuronium rather than pan curium
competitive antagonism
mutually exclusive binding
both agonist A and B bind to the same site
non-competitive antagonism
agonist and antagonist can bind to different sites on receptor
such as the orthosteric and the allosteric sites
orthosteric site
where the endogenous ligand binds
allosteric site
any other site on a receptor
channel blockers
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
reversible drugs
equilibrium between binding and unbinding
can be to orthosteric/allosteric sites
irreversible drugs
covalent modification of target
very high affinity
can be to orthosteric/allosteric sites
pattern of effect changes with irreversible drugs
receptor/ ion channels
reversible: ticagrelor
irreversible: clopidogrel
target: P2Y receptor (GPCR)
transporters
reversible: citalopram
irreversible: omeprazole
target: SERT proton pump
enzymes
reversible: ibuprofen
irreversible: aspirin
target: COX= cyclo-oxygenase
