W19&21 Agonists and Antagonists Flashcards
(34 cards)
What is an agonist?
A substance which initiates a physiological response when combined with a receptor.
How is Propanalol an antagonist?
- Is a beta blocker
- Binds to beta 1 receptor so adrenaline cannot bind
Drug affinity:
Receptor (inactive) = Free, inactive
Receptor (active) = Bound, inactive
Receptor (active) = Bound, active
What do agonists need to have? (2)
Affinity and Efficacy to produce a physiological response
What do antagonists have?
ONLY affinity (not efficacy)
Can only bind to receptor but will not conformationally change it from inactive to active
Does not produce a response, will block the ability of an agonist’s response
- Efficacy= capacity to bind to a receptor to produce an effect.
What is the Law of mass action?
Association= Disassociation
D + R = DR
What is the definition of
Affinity?
Efficacy?
Affinity- The ability of drug binding to receptor
Efficacy- The ability of a drug to activate the receptor
What is kD?
(Dissociation constant)
The concentration required to occupy 50% of receptor
= Measure of drug affinity
What is EC50/Potency?
EC50 - Effective Concentration of agonist for 50 % of a response
It is an empirical measure of agonist potency
A lower kD value means..
A higher affinity as the drug is associated to the receptor
- inversely proportional
Plotting drug concentration and receptor occupancy:
Better to plot a log concentration/dose vs Receptor occupancy/affinity
- as a sigmoid curve is produced and is easier to read
What is meant by ‘Efficacy’ of drug?
Where do you find the Efficacy of a drug?
Once drug bound to receptor complex, how well it can covert drug from inactive to active
By looking at RMax (at top of curve)
What is meant by Full Agonist/ Receptor reserves?
Produces 100 % response with 50% occupation (Full Agonist); Receptor reserves
e.g. only 2/4 receptors bound but leads to an 100% receptors
What is a Partial agonist?
Produces less than 100 % max response with maximal receptor occupation
e.g. all receptors filled but only a 40% response
Acts as an antagonist in the presence of a full agonist.
e.g Tolazoline effect on Phenylephrine
What does potency mean?
Response
Examples of full agonists (for info)
Morphine, Heroin, Oxycodone
Examples of partial agonists (for info)
Codeine, Acebutolol
What is an antagonist?
A substance which interferes with or inhibits the physiological action of another.
What is antagonism?
Drug/ligand that reduces/blocks the agonist response
Types of antagonism?
- Receptor antagonism
- Pharmacokinetic
- Reversible/Irreversible competitive
- Chemical
Define:
Orthosteric (Competitive binding)
Allosteric (Non-competitive)
- Same binding site of the endogenous hormone
- Different binding site of the endogenous hormone
Non-competitive antagonism?
- Non-competitive antagonist blocks agonist response by binding different binding site from the agonist
- Non-competitive antagonists doesn’t need to have identical chemical signatures (look at the structure of glutamic acid and memantine)
What are Reversible antagonists?
Can bind and then dissociate from the receptor
Dissociation of a reversible competitive antagonist from the receptor enables either agonist or antagonist molecules to re-occupy the binding site
Reversible competitive antagonists
Most common
- Competition between antagonist and agonist about which will bind to the receptor. If agonist conc increases it will replace the agonist. e.g. Naloxone
By adding more agonists, the agonist maximal response can still be achieved, if the antagonist drug/ligand is reversible and competitive,
(surmountable antagonism)
Increasing agonist concentration could reverse and regain agonist maximal response (surmountable antagonism)
