Lecture 31 - Drugs Acting Through Receptors 1 Flashcards
What are the elements of drug - receptor interactions?
Ligand
Receptor
Biochemistry
Response
Drugs won’t work without …
binding
What is the ‘magic bullet’ concept?
This is an aspiration in pharmacology that is never reached, whereby a drug is specific for a single receptor
What determines binding of a drug to a receptor?
Shape
Forces
Describe the strength and range of ion-ion forces
Strong
Act over large distances
Describe the strength and range of hydrophobic forces
Weak
Act over short distances
However, there are usually many of these bonds, which can summate to form strong interactions.
What happens to binding when the concentration of the ligand changes?
Higher ligand conc.: more binding
What is drug affinity?
A measure of how stable the drug-receptor complex is
What is ‘mass action’
The rate of chemical reaction is proportional to the concentration of the reactants
What do ‘A’ and ‘R’ represent?
A: agonist
R: receptor
What is the forward rate of reaction?
(A) x (R) x forward rate constant
How is the forward rate constant represented?
k+1
How is the backward rate constant represented?
k-1
What is the backward rate of reaction?
(AR) x backward rate of reaction
What happens to the rates of reaction at equilibrium?
Forward rate = backward rate
What is the equilibrium dissociation constant?
Ka
When are half of the ligands bound to the receptor?
Ka = (A)
What is the measure of affinity?
Ka
pKa
At t=0, why is the forward rate of reaction really high?
Because there are no drug-receptor complexes, all the drug is binding to the receptors at this time
Which parameters affect that rate at which the receptor is occupied?
- (A)
- k-1
- Affinity
A … drug will form complexes at lower concentrations
Higher affinity
High pKa represents …
Explain
low affinity
Low affinity drugs require more of the drug to have half of the receptors occupied
Why do we need to get real?
Because occupancy does not always mean response
What is a way that we can measure drug response?
What is this?
EC50
This is the concentration of the drug required to give 50% of the maximal effect on the tissue
Describe the features of steroid hormones binding to their receptors.
Very strong binding via hydrophobic forces
Though these bonds are weak on their own, there are many of the bonds, so they summate to have a great effect.
Why are high affinity drugs favourable?
Increased specificity
–> fewer off target effects
Required dose is lowered
What does a low EC50 mean?
A potent drug
What does a low pEC50 mean?
High potency drug
