s2-L17-Principles of pharmacology-part 2 Flashcards
(16 cards)
Describe reversible competitive
antagonists function
-competes with the agonist for the same binding site, or binds to an adjacent site that overlaps and prevent the agonist from binding.
-both agonist and antagonist bind reversibly.
-binding is mutually exclusive.
-both produce a parallel shift to the right of the agonist log dose-response curve
What is the effect/response if binding is competitive and reversible?
the agonist maximal effect still possible.
- we can outcompete antagonist by increasing [agonist].
Why is the agonist maximal effect still possible even if the binding is competitive and reversible?
Bc competitive antagonism is SURMOUNTABLE meaning its able to overcome managable.
Describe irreversible competitive
antagonists’ function
-compete with agonist for same binding site BUT binds irreversibly.
-spare receptors are useful here.
- presence of antagonist 👇ses number of available receptors.
- hence 👇ses maximal response.
Describe a non-competitive antagonist and what is its effect?
-A non-competitive antagonist binds at a DIFFERENT binding site.
-prevents the effect of agonist, without preventing its binding
-no competition>no effect on agonist.
-effect of non-competitive antagonist is INSURMOUNTABLE. it cannot be overcome by 👆se in [agonist].
what does partial agonists can also behave as? and why ?
as competitive antagonists bc they both provide low efficacy
Define concentration ratio, hint:-remember the equation
the ratio of the conc. of an agonist that produces a specified response(EC50) in the presence of an antagonist, with the agonist conc. that produces the same response in the absence of antagonist.
EC50 Agonist with antagonist/ EC50 agonist alone
Describe allosteric modulators and their effects.
-ligands that bind to a distinct(allosteric) site on the receptor- different to agonist binding site.
Effect:-
Ligand binding either 👆ses or 👇ses the action produced by agonist.
Describe -ve allosteric modulators(NAM)
- curve higher- agonist alone
- curve below - agonist + NAM - decreased functional response
Describe +ve allosteric modulators (PAM)
-curve higher - agonist + PAM - increase in functional response, increased agonist binding to receptor
-curve below - agonist alone
Describe the allosteric effects on different receptors
-antagonist (allosteric receptor) can bind to ion channels to allows Cl- come through transmembrane protein(ligand gated channels).
- the benzodiazepine receptor( or binding site)
-BZ agonists 👆se the affinity of the GABA site for GABA and thereby 👆se channel opening.
What does the allosteric antagonist( -ve modulator) can do?
-betacarbolines at the GABAa receptor
-binds (reversibly) at a distinct site from the agonist and 👇se affinity of agonist binding site for agonist.
-reduce likelihood of agonist binding
Name types of Benzodiazepine ‘receptor’ ligands
-Agonists - Diazepam
-Antagonist - flumazenil
-Inverse agonist - betacarbolines
Give examples of channel blockers and what they do ?
-ie: phencyclidine(PCP) at the NMDA receptor
-bind inside the channel and prevent the passage of ions
-binding of channel blockers tends to be enhanced by receptor activation
- use dependence!!!-channel need to be open.
what are physiological antagonists and what do they do?
-ie: acetylcholine and adrenaline in the heart
- produce opposite effects on tissue
-produce a non-selective suppression of the response. (work by activating opposing pathways).
Define Desensitization and use Heroin as an example of what happens in the body
-when receptors become less responsive due to prolonged or repeated exposure to an agonist reduces the response to that drug
ie:-opiate drugs of abuse like heroin(u opioid receptor agonists).
-effects through inhibition of 2nd messenger (adenylyl cyclase)
👇
prolonged agonist exposure
👇
upregulation of 2nd messenger
👇
increased [agonist]required to produce same level of inhibition. > by temporarily overcoming receptor inactivation and saturating available receptors.
ie:- inactivation of nicotinic receptors
-receptor driven into an ‘inactivated’ state
NMJs ???
