L7 Pharmacodynamics Flashcards
what is the y-axis of Drug Receptor binding curves?
of receptors that are bound
what does the Kd tell us in Drug Receptor binding curves?
the affinity of ligand for receptor - the concentration of drug needed to get 50% of receptor population bound to the drug
In a Drug Receptor binding curve, as the Kd decreases, what happens to affinity?
increases
what is the x axis of Drug Receptor binding curves?
ligand/drug concentration
what will go to 100% binding?
true agonists - can still have different affinities
what type of affinity do we want in drugs?
high affinity - low dose = not as many side effects
what is the x axis in Dose-response curves?
the LOG of the concentration of ligand/drug
what does E stand for in Dose-response curves?
effect - the max effect you can get
what is the y axis in Dose-response curves?
effect
what is EC 50 in Dose-response curves?
concentration at which we are at a 50% max effect
what do Dose-response curves tell us about the drug besides effect?
potency of the drug
drug-receptor binding curves have ___
dose -response curves have ___
affinity
potencies
define spare receptors
when EC 50 is less than Kd
“50% response/effect before we occupy 50% of the receptors” - may only need 10%
what does the spare receptor tell us?
we don’t need to bind all receptors to get max cellular response
what does ED stand for?
effective dose
what is an agonist
binds to receptor and produces an effect in the cell
what is an antagonist?
inhibits the action of an agonist, but has no effect in the absence of the agonist
just occupies receptor and prevent effect
don’t want the effects of an endogenous ligand that is produced by the body
“blocker”
the drug-receptor complex is directly related to ?
[drug] - extent of receptor activation is proportional to [Drug]
what is physiological antagonism
causes a physiological effect that is opposite to that induced by agonist
occurs when drug response mediated by activation of a receptor is antagonized by an opposite response produced by another drug acting on a DIFFERENT RECEPTOR
i.e. histamine (bronchocon) and NE (bronchodil)
what is a chemical antagonist?
antagonist inactivates the agonist chemically before it can act - chemical neutralization
i.e. magnesium hydroxide - combines with acids = neutralizing it = prevents the effects of acid on stomach.
in a dose-response curve, a competitve antagonist binds ____ to the _____ of the receptor
reversibly
active site
in a dose-response curve, antagonists displace the relationship between [drug] and effect to the ____
right
in a dose-response curve, antagonists do not effect
efficacy
in a dose-response curve, antagonists cause a
loss of potency
in a dose-response curve, a noncompetitive receptor antagonist binds to the active site ____
irreversibly - covalently or very high affinity
receptor cannot be activated!
a high concentration of the drug in a dose-response curve would not do what
displace the antagonist from the receptor
in a dose-response curve, with a noncompetitive receptor antagonist what do you find?
fall in efficacy
in a dose-response curve, with a noncompetitive receptor antagonist what do you NOT find a change in
EC 50
the ___ antagonist, the ____ decrease in Emax
larger concentration
bigger
when are there no spare receptors?
when EC50 and Kd are equal
when EC 50 and Kd are equal what do you find
fall in efficacy - not enough receptors unoccupries by antagonist to give full effect response
how can you tell if it is a noncompetitive or competitive antagonist?
first see right shift in EC 50 then a drop in Emax EC 50 change - competitive antagonist EC 50 no change - noncompetitive antagonist Emax change - noncompetitive antagonist Emax no change- competitive antagonist
what is a partial agonist?
agonist that never gives us enough receptor activation to give a 100% biological effect even at max concentration
what is the formula for therapeutic window and index?
TI = TD50/ED50
measure the difference between TD and ED
the wider the gap the safer the drug!
