Drug Receptor Interactions Flashcards
(35 cards)
What is meant by the drug-receptor theory?
Interactions between the drug and the receptor are reversible as the binding is loose and doesn’t involve strong chemical bonds.
There is a systematic relationship between the drug concentration and the magnitude of the response obtained.
What allows competitive antagonists to fulfil their function?
The binding between the receptor and the drug is loose and reversible so when they unbind, this allows the competitive antagonists to bind.
What are the four regulatory protein families which are commonly drug targets and covered by the term ‘receptor’?
- enzymes
- ion channels
- carrier molecules
- neurotransmitters
What is an agonist?
Will bind to the active site of a receptor and cause a biological response.
What is an antagonist?
Will binds to the active site of a receptor and block a biological response. An antagonist has no intrinsic efficacy.
How chemically similar are antagonists and agonists?
Must have similar chemical properties as they are both able to bind to the same active site.
However their chemical properties must still be slightly different as when they bind to the same active site, they induce different biological responses.
What is the relationship between the equilibrium dissociation constant and affinity?
High Kd = low affinity of binding
Low Kd = high affinity of binding
What are the extra receptors called if less than 100% of receptors are needed to evoke a maximum response?
Spare receptors
What does the Law of Mass state?
The rate of a chemical reaction is proportional to the product of the concentration of the reactants
What does Kd represent?
The concentration of drug required to occupy 50% of receptors at equilibrium. Kd is different for every drug and is the measure of affinity of any one drug for a receptor.
What is meant by affinity?
Measure of binding of the drug to the receptor.
‘How easy it is to break the complex once it has formed’
How can we calculate the affinity of a drug?
We can use ratio-ligand binding.
What is pD2?
log of Kd [pD2 = -log10(Kd)
What is meant by efficacy?
Measure of the drugs ability to cause a biological response once bound to a receptor.
Max. response can be obtained by occupying <100% of receptors.
If a low number of receptors is needed to evoke a maximum response then the drug is said to be efficacious.
When is a maximum response generated?
When a particular stimulus is generated by receptor occupation.
What is the occupancy theory?
Response = [DR]/[RT]
How is efficacy measured?
Once the receptor is occupied, how many units of drug receptor complexes are needed to elicit a response? There must be a conformational change which causes the receptor to give a biological response. This is a measure of efficacy.
What is a competitive antagonist?
A drug that binds with receptors to form a complex but this complex doesn’t evoke a response.
What effect do competitive antagonists have on the log-dose response curve?
Shifts it to the right as more drug is needed to outcompete the antagonist.
How can we calculate the drug ratio?
Using the Schild equation.
What is pA2?
A way of comparing the affinity of an antagonist. Similar to pD2 of an agonist. pA2 = -log10(Ka)
What is an irreversible antagonist?
It binds to the receptor but dissociates very slowly if at all. If the concentration of agonist increases, this will have no effect on the efficacy of the drug as the antagonist as not unbinding.
What effect do irreversible antagonists have on the log-dose response curve?
slope of log-dose response curve is decreased as maximum response to agonist decreases.
Why does the response gradually dampen with time in the presence of irreversible antagonists?
Agonist binds to the receptor but binding isn’t tight so agonist can come on and off the receptor providing a window of opportunity for the irreversible antagonist to bind. Once bound, this doesn’t unbind and so there are less receptors available for the agonists so over time, the response dampens.
