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Enzyme inhibition and other fun stuff » Cam W.

Posted by Jane D on September 24, 2001, at 12:13:03

In reply to Re: Experiences w/ switching from SSRI to tricyclic? » Jane D, posted by Cam W. on September 20, 2001, at 21:37:14

> There may have been some problem (mostly theoretical) in switching from Prozac (fluoxetine) to Ethipramine, as Prozac > Having said that, even this interaction probably would not be significant, in the real world. The CYP-2D6-enzyme system is usually in a state of overabundance in the liver and, even after a short term inihibition by Prozac, there should be enough of the enzyme around to metabolize the Ethipramine.
>
> Unless of course, you were a "poor metabolizer" (ie. had lower than normal levels of the CYP-2D6 enzyme; like 5% of the caucasian population).

I had been wondering about the real life significance of these interactions. Does this mean, for example, that unless you were already a poor metabolizer you would not need to worry about your Prozac disabling your Codeine? And is the inhibition dose dependant?

> Hopefully, I answered your second question, as well. The reason quick metabolizers would use Prozac to wean from Effexor (or Zoloft or Paxil or Luvox) is because of it's very long half-life. When you inhibit an enzyme system, there is less enzyme around to metabolize the drug. Quick metabolizers would have an overabundance of enzyme around.

So. Let's see if I understand this. The withdrawal symptoms are caused by the rapid reduction of serotonin levels. The serotonin levels fall more rapidly in quick metabolizers causing worse symptoms. Replacing a drug like Effexor with Prozac could work in 2 ways. Directly by its SSRI properties - fully replacing the SSRI properties of the Effexor at first, and then, because of its long half life, allowing the serotonin levels to fall slowly. Or, theoretically, by inhibiting the 2D6 enzyme and thereby slowing down the metabolism of the Effexor so that its own SSRI properties are withdrawn more slowly. And, if this were true, then taking Effexor with, or switching, to a drug that induced 2D6 would make the withdrawal that much worse. Except that in actual practice this would not happen because the inhibition /induction of the enzyme is not significant when compared to the total amount of the enzyme present?

>
> I really hope that you can make something out of this mess. I really did try to be clear. - Cam

You were clear. Of course I had to read it a couple of times :-) I also tried to be clear. Oh well!

Jane


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poster:Jane D thread:79138
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