L6- Agonists and antagonists Flashcards
What is the equation for the Effect of a drug?
E= (Emax.[D]) / (EC50 + [D])
Emax= max effect Ec50= conc giving 50% max effect
What relationship witll the shape of concentration-effect curves follow?
Hill-Lagmuir like relationship
So rectangular hyperbola on linear scale
Sigmoidal on a log scale.
Are Kd and EC50 the same?
No. Almost always different.
Often EC50 is lower than Kd bevause often receptors activate many enzymes
What does Kd describe?
Affinity
What does EC50 describe?
potency
What is pEC50?
-logEC50
What does EC90 mean?
The concentration required to give 90% max response
What is a receptor?
Binds a ligand and transduces information. (enzyme is not a receptor!)
Whats an agonist?
ligand that binds to a receptor AND actiavtes it
What are the 4 types of antagonism?
- Orthosteric (competitive)
- Allosteric (non-competitive?)
- Functional
- Indirect
Whats the most common form of antagonism?
Competitive/orthosteric
Agonist binds reverisbly but cannot activate recepotr. Competes for binding site with agonist
Describe affects of policarpine and atropine on saliva production?
Policarpine=agonist at muscarinic receptors so increases saliva production
Atropine= antagonist at muscarinic receptors so decreases saliva production
What happens when both policoarpine and atropine are added to saliva production?
production goes back to nomal. Because the baseline of saliva is due to a constant, low level PNS releasing ACh. There’s a lot of agonist around with ACh and pilocarpine, if there’s enough agonist it overcomes the anatagonism of atropine
What happens to concentration response curve when you add anatgonist?
Curve shifts to right
Max response doesnt change
EC50 increase
How can we quantify how much effect th antagonist has on the agonist?
Measure the concentration ratio (CR)
CR= amount we have to increase the agonist conc. to recover control response
What’s the Gaddum equation?
E=(emax.[D]) / ([D]+EC50(1+([B]/kb))
Kb= dissociation constant of anatgonist [B]= antagonist conc.
This equation takes into account the concentration ratio, so shows the effect with the competitive antagonist
What is IC50?
The concentration of antagonist needed to give 50% inhibition. This is dependent on the conc of agonist so is not as useful.
What is pA2?
the -log[Antagonist] that gives a CR of 2.
Conc of anatgonist that means you have to double conc of agonist to get same effect.
pA2=-logKb if perfect
What is selectivity?
Relative potency of a drug in eliciting one effect compared with another.
If it is more potent at one receptor then it is selective for it
What is the equation for [RD]/[Rt]?
RD= drug bound
Rt= Bmax
[RD]/[Rt] = [D]/([D] + Kd)
