Posted by Larry Hoover on January 21, 2007, at 9:05:45
In reply to Re: Emsam Interaction With Vicodin? » Quintal, posted by laima on January 19, 2007, at 12:54:02
>
> Whoa- are you serious? Codeine, as vicodine, had very, very little effect for my post-gum surgery pain-even when I doubled up on it- and I was using zoloft (monotherapy) at the time!For clarification.....
Vicodin is dihydrocodeinone, not codeine. However, it undergoes a similar desmethylation reaction via 2D6, producing dihydromorphinone (hydromorphone, a.k.a. Dilaudid), which is certainly a dominant reason for its narcotic effects.
The 2D6 enzyme has over 100 known genetic variants. In a functional sense, variation in reaction rates exhibited by those genotypes can be over 100-fold. Not 100% difference, 100 times.
People with low 2D6 activity are called slow metabolizers. In Caucasians, that's roughly 10% of the population. For those people, codeine does sweet f all, except for its side effects. I would expect Vicodin to be similarly ineffective.
At the other end of the spectrum are the rapid metabolizers. An oral dose of codeine almost instantaneously converts to morphine, and narcotic intoxication results. Again, perhaps 10% of the population get this reaction.
In between are all the rest, showing still substantial inter-individual variability in reaction rates. As codeine (and dihydrocodeinone) are really pro-drugs (i.e. they are metabolized into more active forms), they serve as something like slow-release versions of morphine and hydromorphone, respectively.
What messes up this already messed up system are all those other drugs which inhibit enzyme 2D6, including virtually all of the SSRIs (speaking from memory). They will turn normal or rapid metabolizers into poor metabolizers.
Myself, I'm a poor metabolizer to begin with. IMHO, it is 2D6 poor metabolizers who are most vulnerable to liver toxicity from nefazodone (Serzone), an effect which led to its withdrawal from most markets.
> I wonder if that's why?
It's pretty good circumstantial evidence.
> Quintal, you might have just solved a mystery or two which have bugged me for several years. Do you know if it goes the other way, too- ie, could codeine render an ssri ineffective, or at least mess around with its actions?
The interaction could be significant, but the results are complex. It depends on the genetic activity of other P450 enzyme systems, and the relative potencies of metabolites. But, the answer is yes.
> I sunk into a really horrific depression immediately after that surgery, and ssris conked out for me for good around that time, too.
Opiates can induce very black depression, particularly immediately following cessation. Antidepressants can indeed be overwhelmed by the opioid-receptor mediated depression.
Lar
poster:Larry Hoover
thread:723652
URL: http://www.dr-bob.org/babble/20070119/msgs/724729.html