Antagonists Flashcards
What is antagonism?
Drug/ligand that reduces/blocks the agonist response
- Receptor antagonism
- ^ heart rate
- ^ cardiac muscle’s force of contraction
- adrenergic receptor ‘beta’ (B-1) : Block the (β-1); decreases heart rate
e.g. adrenaline, propanolol (anti-hypertensive)
do antagonists have efficacy?
no, only affinity
Competitive or Non-competitive
means
Reversible or Irreversible reactions
4 combos possible
Competitive antagonism - same binding site
of the endogenous hormone
Block adrenaline binding by occupying the adrenaline binding site in β-1; decreases heart rate (Antagonist)
Both adrenaline and propranolol competing for the same binding sites in β-1
Non-competitive antagonism
[ Glutamate NMDA receptor (Ligand-gated ion channel0 ]
Non-competitive antagonist blocks agonist response by binding different binding site from the agonist
does not need to have identical chemical signatures
Allosteric modulators
Allo- Different
Steric- Binding site
not effect receptors directly
SAQ example:
Practice writing task (SAQ)
Do allosteric modulators benefit designing clinical safe drugs? (no more than 100 words)
Find answers for the questions in text books or articles or authentic resources.
Use paper and pen to write an answer that reflect your understanding of your reading.
Exchange among your peers to gather critiques.
Reversible competitive antagonists
100% response - antagonists present
reaction can be reversed
agonist binds + can leave receptor
(agonist more likely to bind if you increase conc AGONIST MAXIMAL response can be achieved = inc physical response)
Reversible antagonists can dissociate from the receptor
+ antagonist (higher than agonist)
Dissociation of a reversible competitive antagonist from the receptor enables either agonist or antagonist molecules to re-occupy the binding site
surmountable antagonism
By adding more agonists, the agonist maximal response can still be achieved, if the antagonist drug/ligand is reversible and competitive,
Irreversible competitive antagonists
60 % occupancy for max agonist response.
if reaction IRREVERSIBLE
more antagonist added; permanently covenantly bonded and agonist cannot bind = cannot achieve maximal response
Irreversible competitive antagonists
60% occupancy for ____ agonist response:
MAX
What kind of bond forms between antagonists (irreversible) and receptor?
covalent
What is Rmax?
he maximum growth rate of a population under ideal conditions
What is the effect of irreversible binding of antagonist on the agonist binding site (competitive)?
it reduces the number of receptors for the agonist to stimulate the response - agonist concentration does not effect
non-surmountable antagonism
when agonist potency first declines as receptor reserve decreases - the agonist maximum response drops
what are the types of drug antagonisms?
1) Chemical
2) Pharmacokinetic
3) Physiological
1) CHEMICAL ANTAGONISM
Base neutralise the acid, to relief acid reflex, heart burn
[only chemical interactions, no drug targets involved]
2) PHARMACOKINETIC ANTAGONISM
Decreased absorption / altered distribution
-anti-diarrhoeal drugs inhibit gut absorption of other drugs
-vasoconstriction by adrenaline restricts distribution of local anaesthetics
Increased metabolism
-phenobarbital increases liver enzyme activity and stimulates metabolism of many drugs, including warfarin
Increased renal excretion
buffering = anti-coagulant
3) PHYSIOLOGICAL ANTAGONISM
Different physiological mechanism
-blood pressure regulation by DIURETICS - diuretics increases the urine output and by which it reduces the sympathetic control of blood pressure (by adrenaline)
