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Old 05-31-2012
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Drug Competitive versus Non-Competitive; Reversible versus Irreversible Antagonism

I was solving pharma questions in Uworld...had one doubt

Is competitive antagonism always reversible and non-competitive antagonism always irreversible????? This was my understanding untill i came across a line in uworld-" non-competitive antagonist or irreversible, competitive antagonist reduces the efficacy of an agonist i.e., it reduces the height of agonist in D-R curves"

I always thought non-competitive antagonists are always irreversible...am i true???? i would be grateful if someone can clarify this confusion....
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Don't get the confusion here. What are you asking exactly?
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Its true that competitive inhibitors are reversible and non -competitive aren't. I think the latter statement is wrong and that it should have been that the competitive inhibitors decrease affinity (increases km) and non- competitive inhibitors decrease efficacy.
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my question is simple- are competitive antagonists always reversible and non-competitive ones irreversible??????

accrdng to the statement i saw in uworld, it clubbed irreversible feature with competitive antagonists- see this -" non-competitive antagonist or irreversible, competitive antagonist reduces the efficacy of an agonist i.e., it reduces the height of agonist in D-R curves"
. Hence got confused....
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Some competetive antagonists bind irreversably. This simply means they bind to the same/related site as the agonist, but once bound to the active site they cannot be removed easily or at all. But if you increase the concentration of the agonist, which competes for the active site, the simple fact that you have way more agonist than antagonist will mean, that the antagonist won't have a chance to bind and irreversibly inhibit the enzyme.

And yes you can have non-competetive reversible inhibition. This simply means they bind to a diff site than the active site and it can be reversible or irreversible. So in this case the active site is free for the agonist/substrate to bind, but binding of the agonist won't mean anything because the enzyme itself has been 'muted'.
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[QUOTE=slowpoke;122763]Some competetive antagonists bind irreversably. This simply means they bind to the same/related site as the agonist, but once bound to the active site they cannot be removed easily or at all. But if you increase the concentration of the agonist, which competes for the active site, the simple fact that you have way more agonist than antagonist will mean, that the antagonist won't have a chance to bind and irreversibly inhibit the enzyme.

"And yes you can have non-competetive reversible inhibition. This simply means they bind to a diff site than the active site and it can be reversible or irreversible. So in this case the active site is free for the agonist/substrate to bind, but binding of the agonist won't mean anything because the enzyme itself has been 'muted'."
non competitive inhibitors are always irreversible and always binds to the regulatory site of substrate and neva on the active site.your above statement is wrong dude.

non competitive Irreversible inhibitors reduce efficacy while competitive reversible Inh reduce potency
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Quote:
non competitive inhibitors are always irreversible and always binds to the regulatory site of substrate and neva on the active site.your above statement is wrong dude.
Common misconception. I remember having the same confusion during my 2nd year of medschool. Turned out competetive doesn't always mean reversible and non-competetive doesn't always mean irreversible.

Even though I don't recall the exact toxin, there was one that my prof used as an example, I think it was an acetylcholine esterase inhibitor that bound to the active site irreversibly, a perfect example of a competetive and irreversible inhibitor.

As for non-competetive and reversible, they bind to a different site other than the active site and mute the activity of the enzyme until they dissociate from the enzyme. Some never dissociate (irreversbile), some do.
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I agree

Quote:
Originally Posted by slowpoke View Post
Common misconception. I remember having the same confusion during my 2nd year of medschool. Turned out competetive doesn't always mean reversible and non-competetive doesn't always mean irreversible.

Even though I don't recall the exact toxin, there was one that my prof used as an example, I think it was an acetylcholine esterase inhibitor that bound to the active site irreversibly, a perfect example of a competetive and irreversible inhibitor.

As for non-competetive and reversible, they bind to a different site other than the active site and mute the activity of the enzyme until they dissociate from the enzyme. Some never dissociate (irreversbile), some do.
I agree. Even I can't remember but there was such an example involving ACh receptors in my 2nd year too.
Phenoxybenzamine is another example Irreversible Competitive alpha antagonist. There are also a lot of examples in Anti retroviral therapy that are exceptions to these so called rules.
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Old 06-01-2012
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Thanks slowpoke and everyone....I was wrong and now my understanding of this concept has changed.... and in a right way..!!!!!!!!!!
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Quote:
Originally Posted by drssbaz View Post
I agree. Even I can't remember but there was such an example involving ACh receptors in my 2nd year too.
Phenoxybenzamine is another example Irreversible Competitive alpha antagonist. There are also a lot of examples in Anti retroviral therapy that are exceptions to these so called rules.
phenoxybenzamine is what???
phenoxybenzamine is an IRREVERSIBLE NONCOMPETITIVE antagonist dude.
you guys should site a valid example.i have neva heard of competitive ireversible Inh before but will be glad to learn
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Irreversible competitive antagonism occurs with most drugs that have reactive groups that form a covalent bond with the receptor, such as aspirin, omeprazole, and MAO inhibitors. Aspirin covalently attaches an acetyl group to the serine residue in the active site.

Last edited by Romaeus; 06-01-2012 at 07:35 AM. Reason: Corrected silly typos
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Quote:
Originally Posted by Romaeus View Post
Irreversible competitive antagonism occurs with most drugs that have reactive groups that form a covalent bond with the receptor, such as aspirin, omeprazole, and MAO inhibitors. Aspirin covalently attaches an acetyl group to the serine residue in the active site.
2010kaplan pharmacolgy pg 229
"aspirin irreversibly inhibits cycloxygenase by forming a covaleny bond via acetylation of a serine OH group NEAR the active site"
it binds NEAR the active site & NOT ON ACTIVE site therefore causing conformational change
thats a typical noncompetitive irreversible Inh
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According to Rang & Dale's Pharmacology those drugs, including aspirin, are considered to be irreversible competitive antagonists.
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Just came across this info in uworld.....

Competitive antagoinsts can be reversible if they bind to the active site by IONIC BOND and irreversible if there is COVALENT BOND.............
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How can there be an irreversible competitive drug if by meaning it wouldn't be able to compete with anything by being irreversible? I know what text books says I just don't find the logic to it... if it is competitive then by definition it has to be reversible right? otherwise how can it compete with anything by being irreversible... that is what I am not getting :S S.O.S. pls someone help
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Competitiveness has nothing to do with reversibility or irreversibility, two are independent attributes.

Competitiveness is site of binding, reversibility is bond.

So, competitive means binds to same site as substrate, ionic bond=reversible, covalent bond=irreversible

non-competitive means binds to different site.

At least this is how i'm keeping it in control from making me go berserk
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