Drug Receptor Interactions Flashcards
What are the four types of receptor
enzymes
carrier molecules
ion channels
neurtransmiters
Law of Mass Action
The rate of a chemical reaction is proportional to the product of the concentration of the reactants
Equilibrium when rate of associations =
rate of dissociations
The equilibrium dissociation constant (KD) represents what
the concentration of drug required to occupy 50% of the receptors at equilibrium.
what is Kd
a measure of affinity of any one drug for a receptor
Hill Langmuir equation
Fractional occupancy =
[D] / [D] + KD
what is the equilibrium dissociation constant for agonists
pD2 = -log10(KD)
what is efficacy
the amount of receptors that need to be occupied to elicit the maximum response (this does not need to be 100% of receptors|)
effectiveness of the drug
the ability of the drug to eilcicate a response once bound to its receptor
how is the response calculated via occupancy theory
[DR] / [RT]
DR = the number of occupied receptors
RT = total number of receptors
therefore its the percentage of receptors occupied
it Is also equal to the function of the stimulus
how do you calculate occupancy
k2/k1
rate constant of dissociations over the rate constant of associations
what are the left over receptors called if 100% occupancy of receptors is not required
spare receptor(s) (theory)
What kind of relationship do the graphs associated with affinity and efficacy have
sigmoidal relationship
Partial Agonists
these have low efficacy as they never reach the max poetical response, however it does increase the percentage of the response
full agonist
this enhances the reaction causing the response to reach its % max as the concentration of the agonist increases.
occupancy/binding when you add both partial and full agonists
may bind to all the receptors so at full occupancy but some are bound by partial and some full so it will not reach its max % response due to the low efficacy of the partial agonist
competitive antagonism
a drug which interacts/binds reversibly with receptors to form a complex but does NOT ENVOKE RESPONSE
Competes for the active sites so occupies them but does not activate them
MAX RESPONSE OF AGONIST REMAINS THE SAME
what is Ka
equilibrium dissociation constant for an antagonist
- the concentration of antagonist that makes it necessary to add twice as much agonist to produce a response as would be needed in the absence of the antagonist
what happens to a log dose-response curve when a competitive antagonist is added
It is displaced to the right as increasing the concentration of an agonist overcomes the antagonist inhibiting qualities
The linear sections are parallel
what is the schild equation
r = ([A]/KA) + 1 r = the ratio by which [D] must be increased to overcome competition by [A]
what is pA2
pA2 = -log10(KA)
a way of comparing the affinity of an antagonist
irreversible competitive antagonism
binds to the receptor but dissociates slowly, if at all
all others are loosely bound. Therefore these cannot be out competed even after an increase in concentration of the agonist
what effect does irreversible competitive antagonism have on the log dose-receptor curve
the curve is decreased
the maximum response to the agonist Is decreased.
overtime the agonists bind and unbind as they are loosely attached, when they unbind the irreversible competitive antagonist can bind and therefore it continues to go down over time as more and more agonists are replaced with the antagonists which never unbind
allosteric modulators
bind to sites on the receptor other than the agonist binding site and can modify agonist activity
- these are regulatory
- can modify affinity or efficacy
- potentiate (increase the power) or inhibit
conformational change on the active site to just changes function
- a form of uncompetitive antagonist as it blocks by steric hinderance and not direct competition for the active site
inverse agonists
they act to dampen the response - they bind and elicit a RESPONSE and this is the key difference between them being an agonist and an antagonist.
- these can be overcome by increasing the conc of the agonist
what is affinity a measure of
the concentration range over which a drug binds to its receptor (KD OR KA)
examples of drug receptor interactions
direct control of the ion channel - hyperpolarisation
direct control of effector enzyme - protein phosphorylation
