Posted by Quintal on August 22, 2007, at 23:46:40
In reply to Re: Nardil - rash 20 mn later » Quintal, posted by girlnterrupted78 on August 22, 2007, at 21:56:32
>Did you find 2 different articles on this?
No.
>First you say it's a sign of overdose, and then that it's an interaction with Clonazepam. Are there two different theories on flushing?
I said flushing is listed as a sign of overdose (in patient/physician information leaflets) *and* I found one study on PubMed where Nardil was associated with flushing. There are probably multiple mechanisms involved with flushing. As I said earlier GABA may be one of the most important factors, and that would seem to correlate with the clonazepam interaction, i.e. excess GABA or something along those lines. A Google search of Nardil + flushing reveals many results, mostly patient/physician information leaflets and drug monographs. In all I examined, flushing was listed as a sign of overdose. A search of phenelzine + flushing on PubMed revealed only one result - the study I posted above.
>First of all, it began around 4 days after I increased the dose (enough for too much Nardil to accumulate in my body).
Yeah, that's what I thought too.
>Both reactions disappeared immediately when I cut the dose down to 60mgs. I actually purposely missed 2 doses to bring the amount of Nardil down in my body, and then started clean the next day on 60mgs.
Well that's sounding like a very strong case for the overdose theory. Clonazepam probably exacerbated the problem, most likely through some GABAergic mechanism? I think you were put on a very rapid titration of Nardil too?
Dr. Ken Gillman says that Nardil may inhibit the enzymes that metabolize it, and this is dose-dependent, so the higher the dose, less Nardil is excreted, increasing the risk of overdose in the higher dosage range I would imagine.
__________________________________________________Phenelzine may be metabolised by acetylation which shows great genetic variation. The possible implication (research is still equivocal) of this is the dose may have to be greatly varied between patients depending on their genetic acetylater status. The data established for the structurally similar drug, isoniazid, is probably a model, particularly for their shared properties of neuropathy and hepatotoxicity (8-12).
A further difference and potential complication is that phenelzine has non-linear pharmacokinetics because it both blocks, and is metabolised by, monoamine oxidase (13-15).
Isoniazid is an inhibitor both CYP2C19 and CYP3A isoforms, this is the likely mechanism by which it slows the elimination of e.g. phenytoin, carbamazepine, diazepam, triazolam, and primidone. Slow acetylators may be at increased risk for adverse drug interactions, as the degree of inhibition is concentration dependent (16).
http://www.psychotropical.com/maois_full.shtml
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