Session 9.2: Pharmodynamics - receptor theory Flashcards
do most drugs bind reversibly or irreversibly to receptors
mostly reversibly - associate then dissociate
binding obeys what law
law of mass action (binding related to concentration of reactants and products)
ligand + receptor
reversibly to form ligand-receptor complex
what must a ligand to bind to a receptor
affinity for its receptor
higher concentration of ligand = so higher affinity = stronger/higher binding
how is binding measured
measure binding of radioactively labelled ligand (radioligand) to intact cells or cell membranes. incubate and allow to come to equilibrium and measure bound radioligand
a single cell will have about
10000 or 100000 receptors
as concentration of drug increases
amount of drug bound to receptor increases (curve - sigmoidal plot/semi log plot)
what is Bmax
the max binding capacity - receptor number
which is found where curve levels out
what is the dissociation constant, Kd or KD
the concentration of drug that is required to occupy half the available receptors
draw line to curve and down
if Kd is lower
higher affinity
what is affinity
a measure of the strength with which a ligand or drug binds to a receptor
the likelihood of how well a ligand will optimally fit the receptor or target molecular binding site
how many receptors occupied per cell at certain kd
half the number of receptors present
how is the graph made into a log scale
converting the concentration into log units or plotting data on a log scale
log10 1000
= 3
ligand concentrations are usually
much lower than 1M
1mM =
10^-3 M = -3 log10 M
how to calculate log 10 in calculate
press log and input number
what are antagonists
drugs that bind to receptors and simply block the binding of other ligands (exogenous or endogenous)
what are agonists
activate the receptor by binding
binding governed by affinity
when bound the receptor is activated and then response occurs (this is governed by intrinsic efficacy)
what are the difference between agonists and antagonists
agonists - efficacy and affinity
antagonists - only affinity (blocks effects of agonists)
how is a drug classified with pharmacological efficacy
causes a response in tissue - vasodilation
how is a drug classified with clinical efficacy
does the drug cause a measurable change - eg: lower blood pressure - how well a treatments suceeds in achieving its aim
intrinsic efficacy is a term used to describe the ability of a ligand to
generate the active form of the receptor
what is ligand efficacy
causes a measurable biological response
the affinity determines
how much of the drug is required to be taken
if high - binding at low concentrations of hormones, neurotransmitters and drugs
what is used to treat morphine/heroin overdose
morpine/heroin are agonists of u-opioid receptors, naloxone used as is high affinity agonist of u opioid receptors (GPCRs) so outcompetes opioid
fenatnyl
very high affinity agonist
naloxone not able to outcompete fenatnyl at opiod receptors
what responses of agonist binding could occur
changes in signalling pathway
changes in cell or tissue behaviour - contraction
how is response measured
concentration-response curve
what is E max
the effect maximum (curve levels off)
what is EC50
the effective concentration giving 50% of the maximal response = drug POTENCY
how is concentration response curve units in
log10 drug concentration
what is the difference between drug concentration and dose
concentration - known conc of drug at site of action
dose - conc at site of action unknown, dose in mg or mg/kg
lower the EC50
more potent drug or ligand is
what is favourable activation also dependent on
delivery route - direct?
