Antagonist and dose-response curves Flashcards
Antagonist
Blocks effect of agonist
Do pure antagonists have effects when there is no agonist resent?
No
3 classes of antagonist
Chemical, physiological and pharmacological
What are chemical antagonist commonly known as?
Mechanism?
Chelating agents
Binding of 2 agents inhibit each other
Mechanism of physiological inhibitors
Example
2 agents with opposing effects cancel each other out
Insulin and glycogen
Mechanism for pharmacological inhibitors
Bind and block action of agonist receptor response
Non-receptor agonists
3 ways they can work?
Don’t bind to same receptor as agonist
Inhibit directly (e.g. antibodies)
Inhibit activation pathways
Activate opposing pathways
2 types of non-receptor antagonists?
Chemical and physiological antagonists
Agonist that reversibly binds to the orthosteric/active site is known as…
Competitive agonist
How does agonist dose response curve change when a competitive agonist is added?
Why?
Shifts to the right
Same form and max
It is reversible so the antagonism can be overcome
How is dose ratio calculated?
EC50 of agonist and antagonist/EC50 of agonist only
What does dose ratio show?
Increase in agonist concentration needed with antagonist to get the same reaction as without
What is the antagonist dissociation constant?
Concentration of antagonist to inhibit agonist by half
What type of bond to irreversible non-competitive antagonists form with he orthosteric site?
Covalent
How does dose response curve change with irreversible antagonist added?
Why?
Parallel shift to right and decreased E max
Binds irreversible so antagonism cannot be overcome with increased agonist concentration
How does addition of irreversible agonist change EC50?
Increase
What determines duration of effect of irreversible antagonist?
Rate of receptor turnover
Sometimes competitive and non-competitive antgaonist curves can look the same, why?
Receptor reserves or small concentration of antagonist and lots of receptors
What do irreversible antagonists act the same as?
Partial agonists
How do non-competitive (allosteric) antagonists cause inhibition?
Bind to allosteric site and cause conformational change so agonist cannot bind
How does dose response curve change when allosteric antagonist is added?
Shift to right and decrease in Emax
Therapeutic window?
Dose range that produces required therapeutic effect without causing toxicity
