Pharmacodynamics definitions Flashcards
metric prefix subdivision in order of siza
molar –> millimolar –>. micromolar –> nanomolar –> picomolar
Log10 of number
power by which 10 has to be raised to get that number
what is the log number of 1000
10 x 10 x 10 = 10^3 log1000= 3
Log10 of 0.000001m
Log10^ -6
A ligand =
a substance that can interact with a target protein or receptor • Binds to specific site on that signalling protein • Ligands can endogenous (hormones, ions or NT) or exogenous
An agonist=
a substance which binds to a receptor and activates the receptor to then produce a measurable biological response
An antagonist=
a substance which binds to a receptor, but does not produce a biological response • block the effects of agonists
Affinity=
is a measure of the strength of which a ligand or drug binds to a receptor
What is the measurement used to define affinity?
Affinity is measured by Kd
Kd=
the concentration of ligand at which 50% of all available receptors are bound • lower the value of Kd the greater affinity
Intrinsic efficacy=
A term used to describe the ability of a ligand to generate the active form of the receptor (R*- active form of receptor)
agonist has
intrinsic efficacy and affinity
antagonist has
affinity but no intrinsic efficacy
Ligand efficacy=
ability to cause a measurable biological response
Clinical efficacy=
relates to response with therapeutic value e.g, does the drug reduce blood pressure
Agonist potency=
the concentration of a drug that evokes 50% of its maximal response (Emax) -The term EC50 is used to represent this concentration
The smaller the EC50
- the higher the potency of the drug
Partial agonist=
ligands that evoke responses that are lower than the maximal response of the full agonist (i.e they have lower Emax values)
Compared to a full agonist, a partial agonist has
lower intrinsic efficacy • Partial agonists have a lesser ability to activate the receptor • Therefore doesnt evoke the maximal biological response
which drug has the highest intrnsic activity?
B
Which drug has the highest potency?
A
measuremnts used in the binding curves
Kd and Bmax
concentration-response curve measurements
EC50 and Emax
Bmax
the maximum amount of drug/luigand which can bind to the receptor
-can be used to measure the density of the receptor site in a particular tissue e.g. fluorescent tagging
How to measure kd on a binding curve?
how to emasure EC50 on a response curve?
antagonism can be achieve by
1) Antagonism of the action of agonist at its receptor using a ligand
2) Antagonism of a cellular tissue event being mediated by one mechanism by another mechanism (functional) antagonism
3 main types of antagonism
Reversible competitive antagonism
Irreversible competitive antagonism
Non competitive antagonism
reversible compeitive antagonsim
◦Takes place at the same binding site as the endogenous ligand (orthosteric site)
◦Interaction is by relatively weak, non covalent bonding
Irreversible competitive antagonism
◦Takes place at the same binding site as the endogenous ligand (orthosteric site)
◦Irreversible interaction reflects high affinity with very slow dissociation- may be covalent binding
Non competitive antagonism
◦Binding occurs at separate allosteric site- no competition for orthosteric site access
◦Interaction can be either lo or high affinity and could include non covalent and covalentbonding
Experiments show that only 10% of M3 receprtors in airway smooth muscle need to bind Ach to achieve maximal contraction, The EC50 for Ach is around 10^-7M compared to a Kd = 10-6M
what pharmacodynamic principele xplains the difference between the EC50 and Kd for ACh at the M3 receptor
Spare muscarinic M3 receptors
a new drug Painex developed rto reduce chronic pain acts on a subset of glutamate receptors int he CNS. With increasing cocnenration, painex increases the Kd for glutamate. At higher cocnenretion it reduces the Emax of glutamate by 50%. What best describes the likely pharmacodynamic action of this drug?
non-competitive antagonist
