Posted by Sunnely on July 7, 2000, at 23:30:32
In reply to Re: Effexor-side effects, posted by SLS on July 7, 2000, at 6:46:54
Hi Scott,
You do ask tough questions.
Let me see...
There are many types of CYP inhibition. The following are two of the most common types: 1) "competitive" - 2 drugs compete for the same binding site with only one being metabolized (with enough drug one can overcome the inhibition); and 2) "mechanism-based" - the metabolites of the drugs such as cimetidine (Tagamet) or erythromycin (E-mycin) complex with and tie up the CYP.
Both grapefruit juice and Serzone are marked inhibitors of a specific CYP called CYP3A4. I don't know which one inhibits CYP3A4 the most. (Since both are considered marked inhibitors of this CYP, this is probably immaterial.)
"Competitive inhibition" is one of the 2 most common types of antagonizing the action of CYP. The other one is via "mechanism-based" inhibition. (See explanation above). Yes, it is possible that an inhibitor of a specific CYP is also catalyzed (substrate) by the same CYP. There are drugs that are, at the same time "substrates" and "inhibitors" of a specific CYP. For example, Paxil is a "substrate" of CYP2D6 and at the same time an "inhibitor" of this particular CYP. In effect, Paxil is inhibiting its own metabolism. This phenomenon is called "autoinhibition." On the other hand, there are drugs that are "substrates" of a specific CYP and at the same time "inducers" of the same CYP. For example, Tegretol is a "substrate" of CYP3A4 and an "inducer" of this same CYP. In short, Tegretol is inducing its own metabolism. This phenomenon is called "autoinduction." This is the reason why, after several weeks, the blood level of Tegretol tends to decline even if the dose and all other factors remain the same. There are also drugs that are "substrates" of a specific CYP and "inhibitors" of another CYP. This is exemplified by quinidine, a heart drug. There are also drugs that are "substrates" of several CYPs at the same time. There are also drugs that are "inhibitors" of several CYPs at the same time. There are also drugs that are "inducers" of several CYPs at the same time. This CYP busines is too complex to explain. Remember, there are close to 3 dozen human CYP isoenzymes discovered so far (the number still growing), yet we only know very few of them as to how they work.
Yes, Seldane and Hismanal have been off the market (US) due to serious heart conduction problem. They tend to cause electrocardiogram abnormality called "prolongation of QT" interval which can potentially cause serious heart rhythm irregularity called "torsades" and sudden death. (Fexofenadine, an active metabolite of Seldane, without the heart effect, is now available. It is probably more popularly known as Allegra.)
Yes, same stuff with Propulsid (cisapride), that heart "thingie."
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> Hi Sunnely.
>
> Thanks for the explanation.
>
> This whole grapefruit thing is news to me. I wonder to what degree similar drug interactions with other foods have gone unrecognized. Thanks for the URL.
>
> Regarding the differences between the interactions of GJ and Serzone versus Serzone and Propulsid, are these explained by differences in binding affinity or some other form of competition for enzyme sites?
>
> 1. Does GJ bind more tightly than Serzone bind more tightly than Propulsid to CYP?
>
> 2. Is there a difference between "competition" and "inhibition"? Is an inhibitor catalyzed at the site it is inhibiting?
>
> Are you are involve professionally in the medical field? I'm not, but I guess I like to pretend sometimes.
>
> I didn't know that Seldane was discontinued. Heart conduction stuff?
>
>
> - Scott
poster:Sunnely
thread:1893
URL: http://www.dr-bob.org/babble/20000630/msgs/39754.html