Pharmacodynamics: Receptor Theory Flashcards
what is pharmacodynamics
what a drug does to the body
what is critical in determining drug actions
concentration of drug molecules
what is Bmax
maximum binding capacity- information about receptor number
what is kD
dissociation constant
- index of affinity lower value = higher affinity
- reciprocal of affinity
what is the log of a number
the power which 10 has to be raised to to get that number
what are ligand concentrations usually
less than a mole
antagonists
bind to the receptor and simply block the binding of other ligands and do not cause the receptor to activate
they have affinity but no efficacy
agonists
they have affinity and intrinsic efficacy as they can generate or stabilise an active form of the receptor
what is efficacy
intrinsic efficacy and a response
what is clinical efficacy
an indication of how well a treatment succeeds in achieving its aim
what is a response
change in signalling pathway
change in cell or tissue behaviour
what is EC 50
effective concentration giving 50% pf the maximal response
AKA potency
what is concentration- drugs
known concentration of drug at site of action
dose
concentration at site of action generally unknown
where is the therapeutic target in asthma?
beta 2 adrenoceptors in the airways- they provide functional antagonism of contraction which causes relaxation of smoth muscle to relieve bronchospasm
How do we achieve selectivity/ specificity?
drugs like salbutamol have different affinities at different beta adrenoceptors for example its affinity at the beta 2 adrenoceptor is higher than at the beta 1 adrenoceptor in the heart. There is a higher efficacy at the beta 2 adrenoceptor
what determins ec50
affinity and efficacy
which is variable and what is fixed
affinity and intrinsic efficacy- fixed
potency- varies e.g. no of receptors
what are spare receptors
when an agonist induces a full respose without occuping all receptors the receptors that are left are spare receptors
when <100% occupancy = 100% response
what is the purpose of spare receptors?
they increase sensitivity/ potency- allow responses at low concentrations of agonist
what affects receptor number
tend to increase with low activity (up-regulation)
tend to decrease with high activity (down-regulation)
physiological, pathological or drug-induced changes
What are partial agonists?
ligands or chemicals that evoke responses that lower the maximal response of a full agonist (i.e. they have a lower Emax values therefore lower intrinsic efficacy)
they have lower intrinsic activity and lower efficacy
how are partial agonists relevant as drugs
can allow a more controlled response
work in the absence or low levels of endogenous ligands- but ca act as an antagonist if high levels of full agonist
what is functional antagonism
antagonism of a cellular/tissue event being mediated by one mechanism by another mechanism
what is an antagonist
antagonism of the action of an agonist at its receptor using a ligand
reversible competitive antagonism
relies on a dynamic equilibrium between ligands and receptors- ligands can associate and dissociate
they outcompete the agonist and bind reversibly
cause a parallel shift to the right of agonist concentration-response curve
can be overcome
what is IC50
gives an indication of antagonist affinity but influenced by [antagonist] and strength of stimulus
irreversible competitive antagonism
when the antagonist dissociates slowly or not at all
with increased [antagonist] or increased time more receptors are blocked by antagonist- NON-SURMOUNTABLE
Causes a parallel shift to the right pf the agonist response curve and at higher concentrations supress the maximal response so Emax decreases
non-competetive antagonism
bind at any site other than where the natural ligand binds
reduce orthosteric ligand affinity and/or efficacy
