Pharmacology receptors Flashcards
define receptor
macromolecule component of the cell which interacts with a drug to produce its characteristic effects
what does Kd measure and what is it
drug affinity for its receptor
an equilibrium dissociation constant
difference between an agonist and antagonist
agonist - cause conformational change to the receptor
antagonist - do not cause conformational changes
how much of the total drug do you assume is bound
a negligible amount
at equilibrium the rate of the reverse reaction is equal to what
the rate of the forward reaction
what is Rt
total number of receptors
what is D, DR and r
D - total drug concentration
DR - concentration of bound drug
r - fractional occupancy of the receptors
how do you calculate r
DR/Rt
how do you calculate Kd
[D][R]/[DR]
what will a plot of r against [D] produce
a rectangular hyperbola curve
what will a plot of r against log[D] produce
a sigmoidal curve
what is occupation theory
Response[E] = number of receptors occupied
what is pD2
negative log of the agonist concentration that gives half the maximal response
what is a limitation of the occupation theory in terms of pD2
overestimates the Kd in some receptor systems
drug appears to bind more tightly than it actually does
what is an antagonists ability to block receptors based on
affinity for the receptor
relative concentration of [A] to [D]
define dose ratio
the ratio of the agonist concentration that elicits the same response either in the absence [D0] or in the presence of an antagonist [Da]
what does it mean if the response is the same in the absence and presence of an antagonist
the occupancy of the agonist is the same irrespective if there are spare receptors
how do you calculate the dose ratio from a dose-response curve
determine the agonist concentration at 50% for each curve
then divide the curves with antagonist present by the one in absence of antagonist
i.e. [D1]/[D0], [D2]/[D0]
what is an assumption made for the dose ratio
based on law of mass action
assumes simple competitive antagonism
what is Gaddum-Schild equation independent of
independent of the agonist used
as long as it competes for the same receptor as the antagonist
there are no assumptions about what in the Gaddum-Schild equation
relationship between response and number of receptors occupied
if the dose ratio is 2 what is the Ka and -logKa
Ka = A2
-logKa = pA2
what is pA2
the negative log of the antagonist concentration that gives a dose ratio of 2
if the slope on a logarithmic graph of log(dose ratio) - 1 (y-axis) and log[A] (x-axis) is equal to one what does this indicate about the type of antagonist
its competitive
the drug-receptor interaction is rapidly reversible is an assumption of what theory
occupancy theory
what are two assumption of the occupancy theory
all agonists for a given receptor can produce the same maximal response
the maximal response occurs when all the receptors are occupied
(these assumptions are low-key dog)
all agonists for a given receptor produce the same maximal response, what is the problem with this assumption
some agonist drugs act on a receptor and produce a weak response - partial agonist
what can partial agonists act as
competitive antagonists to full agonists
what does a (alpha) mean
the ability of a drug to induce an effect - intrinsic activity
what would the a for a partial antagonist be
<1
what is the difference between a full agonist with high and low efficacy
high efficacy - needs to occupy a smaller amount of receptors to induce maximal response
low efficacy - need to occupy a larger amount of receptors to achieve maximal response
what are 2 modification to the occupancy theory to account for partial agonists
effect depends on the affinity of the drug for its receptor
effect depends on the drugs ability to induce a conformational change in the receptor
what is constitutive activity
some receptors have some activity during their resting state
what is an inverse agonist
reverses constitutive activity, decreasing basal activity
