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What if you take both an inducer and an inhibitor of an enzyme?

Naggers

Naggers

Bluelighter
Joined
Feb 4, 2010
Messages
344
Location
Manchester, UK
I took a one off dose of fluoxetine on Monday, and took some codeine this morning but I seem to still be experiencing inhibition of CYP2D6 due to fluoxetine's ridiculously long half life.

So my question is: if I take some ethanol (which I know is still debatable as an inducer of CYP2D6, but I'm getting desperate here!), would it cancel out the inhibiting effect of the fluoxetine and allow me to convert codeine to beautiful morphine once more? Or will it do sweet F-all?

Cheers.
 
Regardless of whether it would work (which I actually think it would to a small degree), I would strongly advise against taking ethanol to facilitate opioid binding. Hello Mr. reasonable-chance-of-respitory failure imo
 
Well, not that this is an indication of future safety or in any way responsible drug use, but I've taken fair amounts of alcohol with codeine in the past when attempting potentiation and I'm still here. Also, I live literally round the corner from a hospital... my housemates (aware of what I'm taking and the risks) could literally carry me there in 30 seconds.

Thanks for the reply, in return... here's something interesting I just found whilst researching the topic and want to share! -

As you probably know, codeine is also metabolized to codeine-6-glucuronide by UGT2B7 which is partly responsible for its [codeine's] effects. I've been curious about the possibility of inducing UGT2B7 for a while now and just found a chart which gives answers!

http://www.pharmacologyweekly.com/content/pages/ugt-enzymes-medications-herbs-substrate-inhibitor-inducer

Although the only thing currently listed as an inducer of UGT2B7 is bartbiturates, there's some other interesting points to note... mostly that nicotine is an inducer of UGT1A1 which is responsible for converting morphine to M3G and M6G.

Anyhoo, derailing my own thread here!
 
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i haven't been able to find any other UGT2B7 inducers besides barbiturates. however, quinine(tonic water) and naproxen sodium(aleve) inhibit UGT2B7. i use these two combined(in addition to cimitidine) to delay glucosination of hydrocodone/oxycodone, and thus elongating their duration of action.
 
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I meant a new thread to share the UGT enzymes chart, I think a few people will want to see this, but if you don't think there will be interest then okay.

I've seen a few people mention that promethazine induces 2D6, but out of the many substrate/inhibitor/inducer charts I've seen for Cytochrome P450, not one of them says anything about this. Do you have a source?

Here's one chart that lists ethanol as an inducer of 2D6 and not 3A4 (the pdf file in the first post).

Interesting about the quinine and naproxen though, cheers for that! :D
 
i was wrong. ethanol is an inducer of 2D6, and promethazine inhibits 2D6 instad of induces. also, St. Johns Wort induces 2D6 according to MrBlonde:

Mr Blonde said:
Promethazine is actually an inhibitor of CYP2D6.

That wikipedia quote about morphine 'not being metabolized by the CYP450 system' is bullshit. Morphine is metabolized by the CYP3A4 enzyme, amongst others, and grape fruit juice will work to slow down this metabolism.

To be honest with you OP, most of these antihistamines are not incredibly potent inhibitors of the enzymes so I would not worry too much about them. There are some SSRIs that are potent inhibitors of CYP2D6 though which would have an effect on the metabolism of codeine to morphine.

As for inducing CYP2D6 to produce more morphine, the most readily available inducers are ethanol and St Johns Wort. One or two standard drinks 45 minutes before codeine should help. I'm not sure about dosing for St John's Wort, but there might be something about it here on Bluelight. Try out a dose or two before your codeine.

The rest of the inducers I am aware of are scheduled and probably hard to get... phenobarbital is one. Some of the others are steroids, NSAIDS or heavy-duty antibiotics. They should be listed on a CYP450 chart somewhere out there. I can't be bothered to reference mine right now. :p
Click to expand...

source: http://www.bluelight.ru/vb/threads/511261-Converting-Codeine-into-more-Morphine?
 
St John's Wort is an inducer of 2D6, but it is also an inducer of 3A4 (source: chart linked in last post), which I'm sure is a bad thing but for the life of me I can't remember why.

Anyone want to elaborate on that?
 
i think you should be fine after 1-2 weeks. the fluoxetine is probably out of your system by now
 
Cheers. Also, we may have an answer. Had two Stella Cidre between 21:30 GMT and 22:15 GMT, then took my dose of codeine at 22:25 GMT. Feeling pretty fucking awesome right now! Though as you said, it may be that the fluoxetine has worn off.
 
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