Antagonists And Dose Response Flashcards
Give an example of an antagonist
Terfenedine and the H1 receptors
Why on the 2 state hypothesis for antagonist is there no active state
They don’t cause an action but suppress it
What is the effect of propanolol on BP when bound to B2
Lowered heart rate
What are the 3 classes of antagonists
1- chemical : binding to inactivate drugs
2- physiological : 2 molecules against eachother
3: inactivated a RECEPTOR
Explain the 2 branches of antagonists
Active site binding - they bind to active site
Allosteric binding - bind elsewhere in receptor
What are reversible and irreversible active site antagonists
Reversible = competitive antagonists
Irreversible = non competitive (bind by covalent bond)
What are the allosteric reversible and irreversible
Both are non competitive antagonists
What can’t be measured with antagonist dose response curves
Efficacy of drug (no active state)
How can competitive antagonists (active site) work
Similar shape to the normal agonist
Block the active site
Why are competitive antagonists reversible
Overcome by increasing agonist concentration
What way does the dose response curve go with a competitive antagonist
Right
You need a larger dose of agonist to form the same response due to competition
What happens to EC50 when there is a competitive antagonists
It gets higher in presence of antagonist due to competition
Need higher dose of agonist for response
What happens to the eMAX with reversible competitive antagonists
It stays the same. You can overcome it by adding agonist
What is the dose ratio calculation to measure inhibition of competitive antagonists
Agonist + antagonist EC50 / agonist only EC50
Which plot can compare different competitive antagonists
Schild plot
Plots antagonists conc and the dose ratio - 1 (agonist+ antagonist/ agonist EC50)
What is the schild plot equation
Dose ratio -1 = conc of antagonist / antagonist dissociation constant (kb)
What is kb in terms of competitive antagonist
Antagonist dissociation constant
What is the pa2 value
Antagonist conc needed to reduce agonist response by 50%
How do you work out the pa2
-log kb (dissociation constant)
What does a high dose ratio mean
More agonist needed to produce effect
Antagonist is better inhibitor
Why does the slope on schild plot only work on competitive antagonists (reversible)
Only competitive antagonists line is linear to dose ratio (others aren’t affect by dose)
What are irreversible active site antagonist give example
Antagonists which bind to AS covalently blocking agonist
Eg penecillin b lactam
What happens to the EC50 and eMAX with irreversible AS antagonists
Both get decreased
What does the duration of the irreversible antagonists depend on
Receptor turnover
How would you decide if something is a partial agonist which also decreases eMAX or an irreversible antagonist
Irreversible antagonist won’t work if presence of agonist isn’t there
How does a non competitive allosteric antagonist work
Binds allosterically and stops downstream signalling
Give an example of non competitive antagonist
Nifedipine which stops ca influx downstream
What effect does a non competitive allosteric antagonist have on eMAX
Decreases it because agonist receptor doesn’t have downstream signalling/effect
