Agonists and Receptors Flashcards
What is the law of mass action?
The rate of a chemical reaction is proportional to the concentrations of the reacting components.
k1 [D][R] = k2 [DR]
k1 A constant that defines the rate of the forward (association reaction).
k2 A constant that defines the rate of the backward (dissociation reaction)
[D] drug concentration
[R] receptor concentration
[DR] drug receptor complex concentration
Define affinity?
A measure of the strength with which a drug binds to a receptor at a given concentration.
Can be described by the Ka (affinity constant).
Ka reflects the strength of the drug-receptor bond.
Ka = K on/K off
What is the dissociation constant?
It is the constant that reflects the tendency the drug-receptor complex to dissociate back to its drug and receptor components
where KD = koff/kon
KD= [D][R]/[DR]
KD is also the molar concentration of a drug when 50% of its receptors are occupied at equilibrium
What is the relationship between the association constant and dissacoiation constant?
KA= 1/KD
What is meant by the term fractional occupancy?
The proportion of drug attached to the
receptors.
r= [DR]/[Rt]
Rt= [DR] + [R]
What is the formula for fractional occupancy in terms of drug concentration and dissociation contant?
r = [D]/Kd+[D]
Draw a graph representing drug affinity?
x axis= drug concentration
y axis= fractional occupancy
Hyperbolic curve.
Note as Kd increases the curve is shifted to the right (i.e a greater drug concentration is needed to occupy more receptors
Draw a graph representing drug affinity and make the x axis logarthmic.
x axis= drug concentration (logarthmic scale)
y axis= fractional occupancy
The shape of the curve will now be sigmoid.
Note: using a log scale on the x axis makes for easier comparisons of different drugs ED50
What is the ED50?
It is the median effective dose. The dose of a drug that produces a response in 50% of the population to whom it is administered.
ED50 also represents the point at which the fractional occupancy = 0.5 (when 50% of the receptors are bound)
Therefore ED50=KD
This is used to compare the different affinity of drugs.
Define the term efficacy?
Efficacy is a measure of the repsonse of a drug binding to its receptor. Emax is the maximum effect that can be expected once a drug has bound to its receptor.
What is the intrinsic activity of a drug?
Intrinsic activity is the drug’s maximal efficacy as a fraction of the maximal efficacy produced by a full agonist acting on the same receptor under the same conditions.
Therefore a full agonist will have an intrinsic activity of 1.0.
What would be the range of intrinsic activity for the following: a full agonist, a partial agonist, an anatagonist and an inverse agonist?
Full agonist =1
Partial agonist between 0 and1
Antagonist = 0
Inverse agonist between -1 and 0
Define the term potency?
Potency refers to the quantity of drug needed to produce a maximal effect. It will take into account both the affinity and the efficacy of the drug.
What is meant by the term EC50?
Median effective concentration: the concentration of a drug that produces a response exactly halfway between baseline and it’s maximum.
There more potent a drug the lower the EC50.
