11. Dose–Response Curves Flashcards
Draw a dose–response curve for a drug and explain its shape.
Response Y
Drug dose X
Dose–response curve
Slow increase and then platuea
Initially, as the dose of drug increases,
more receptors are stimulated,
increasing the response.
As the dose continues to increase,
proportionally fewer receptors available
for stimulation and, therefore, the
response is proportionally less.
Eventually, all the receptors are occupied
and so an increase in dose does not affect an increase in response and the
graph plateaus.
This produces a rectangular hyperbola curve.
Why do we log the plot and what shape does this produce?
We log the dose to produce a sigmoid-shaped plot.
It is easier and more accurate to extrapolate an
estimated response to a given dose using this
shape
(as it is linear between 20% and 80% response)
, rather than the unlogged, rectangular hyperbola graph.
It also allows us to predict the
‘effective dose’ of the drug,
which will produce 50% and 95% of its maximal
effect, the ED50 and ED95.
> ED50
is the dose of a drug required
to produce 50% of its maximal effect,
or the dose of a drug that will produce
a specified effect in 50% of the sample population.
> EC50
is the serum concentration of a drug
required to produce 50% of its maximal effect,
or the concentration of a drug
that will produce a specified
effect in 50% of the sample population.
> LD50
Is the dose of a drug required to
produce a lethal effect in 50% of
the sample population.
> Therapeutic Ratio
= LD50/ED50.
Define the terms drug potency,
> Potency describes the dose of drug
required to produce a response of
a given magnitude.
A drug with a high potency requires
a smaller dose than one of low potency
to produce the same effect.
Usually, the more lipid soluble a drug, the greater is its potency,
e.g. fentanyl (1 μg/kg) is more potent than alfentanil (10 μg/kg).
ED50 is used to define potency and compare drugs.
affinity
> Affinity describes how avidly a drug binds to its receptor.
This is irrespective of whether the drug–receptor interaction produces a response or not.
> Intrinsic activity
> Intrinsic activity describes
the extent to which the drug activates or
stimulates a receptor once bound.
> Efficacy
> Efficacy describes the ability of a drug
to produce the maximal response
or effect once it is bound to its receptor.
> Full agonist
> Full agonist
• Binds to receptors (has affinity)
and produces a maximal response
(efficacy = 1).
• E.g. morphine acting on MOP receptors.
> Partial agonist
• Binds to receptors (has affinity)
but produces a sub-maximal response
(efficacy <1).
• E.g. buprenorphine acting on MOP receptors
> Antagonist
• Binds to receptors (has affinity) but
exerts no effect of its own (efficacy = 0).
Its presence inhibits the action of agonists of all types at that receptor.
• E.g. atenolol acting on β adrenoceptors
> Competitive antagonist
• Binds to receptors at the same site as the agonist and therefore competes with the agonist for this site.
This antagonism can be overcome by increasing the concentration of the agonist.
• E.g. vecuronium competing with ACh at nAChR.
> Non-competitive antagonist
• Binds to receptors at a
different site from the agonist
and so does not prevent the agonist’s
binding to its receptor site.
However, it alters the conformation of the receptor
complex and prevents the agonist from
eliciting a full response.
Its effects are not overcome by increasing the
agonist concentration.
• E.g. ketamine acting at NMDA receptor.
