Posted by Sunnely on July 31, 2002, at 20:28:54
In reply to Prozac, Codeine, cyp2d6..CamW or anyone ?, posted by janejj on July 31, 2002, at 14:04:39
Yes, fluoxetine (Prozac) will prevent the pain-killing effects of codeine via inhibition of the CYP2D6 action.
Codeine is a "pro-drug." It is the parent compound but an inactive one. It needs to be converted into an active metabolite which possesses the pain-killing properties. This is achieved by breaking down codeine through the action of the enzyme called CYP2D6. If you combine codeine with Prozac, the conversion process is prevented because Prozac potently inhibits the action of CYP2D6, hence loss of pain-killing effects. BTW, the active metabolite which posseses the pain-killing properties that codeine is converted into is called morphine. An exactly similar event will occur if you combine codeine with paroxetine (Paxil) since Paxil is also a potent inhibitor of CYP2D6.
On a related note, tramadol (Ultram) will lose its pain-killing properties if combined with drugs that are inhibitors of CYP2D6 (e.g., Prozac, Paxil). Ultram is also a "pro-drug," i.e., it needs to be converted into an active metabolite to be an effective pain-killer. The active metabolite is called "M1." Another potential risks of hindering the conversion of tramadol to M1 by Prozac or Paxil is the possiblity of serotonin syndrome and seizure episode, although the latter appears to occur at higher dose of tramadol. It appears that the parent compound, tramadol, has serotonergic effect.
On another related note, some "pro-drugs" have been removed from the U.S. market because of deadly interactions with other drugs or beverages. Example of these drugs are terfenadine (Seldane) and astemizole (Hismanal). Both are nonsedating antihistamines (for hay fever). For example, terfenadine (inactive parent compound) needs to be converted to an active metabolite (fexofenadine) in order to be effective for hay fever. Terfenadine is metabolized via CYP3A4 and converted to the active metabolite, fexofenadine. Unfortunately, if terfenadine is combined with a drug or agent that inhibits the action of CYP3A4 (e.g., grapefruit juice), terfenadine accumulates in the system. In excess, terfenadine is harmful to the heart. Several sudden deaths were reported to the FDA because of these interactions. Subsequently, Seldane and Hismanal (and Propulsid) were removed from the U.S. market. As an offshoot, a safer version of Seldane, consisting mainly of the active metabolite (not harmful to the heart) was developed. It is better known as Allegra.
> Hey
>
> I need to know if taking Prozac is going to Prevent the pain killing properties of Codiene ?
>
> Something to do with cytochrome 2d6, especially cyp2d6 which is inhibited whilst taking an SSRI.
>
> Thanks Janejj
poster:Sunnely
thread:114651
URL: http://www.dr-bob.org/babble/20020731/msgs/114702.html