Awesome CYP-450 Chart!

[Blowmonkey]

Alright, cool. A suggestion from my side would be to compile all of these helpful threads into one or two stickies instead of all of the above, OD sees a lot of threads daily and it would help make it a bit more readable, 6-7 permanent threads on the front page take up a lot of space.

 

[soundphaRm]

Yeah, I kind of agree with that...
We'll work something out (condense, combining, etc.)...

 

[axl blaze]

you still want this to be stickied? I'll do it.

if not, just gimme a good talking to, soundpharm

 

[soundphaRm]

:D

Enjoy!

 

[Thisisnew]

Thanks, this is a great resource

 

[SpellmanT7]

Very good resource for BL use.

I'd still recommend purchasing the last PDR interactions handbook. The minor advantage over this chart in that it details enzyme reactions on three levels - i.e. minor/significant/predominant.

 

[sonic]

^ Good to know. I'll have to check that handbook out.

 

[soundphaRm]

^^...hmm...

I didn't get the last copy of the interactions handbook, because not much had changed...

But, now I might have to go update my PDR collection(s)- specifically the interactions guide...

Thanks! :D

 

[SpellmanT7]

I just want to make sure that I don't exaggerate the features of the 2006 PDR too much:

The chart equivalent to that posted on BL is essentially the same but a minor reaction is represented as a blank circle, a significant one as a half shaded circle and a predominant one is a filled circle.

(actually, co-dominant because more than one enzyme can and is represented as having such a status)

Just wanted to make sure that anybody expecting greater detail than this didn't purchase/upgrade to the latest version believing it offered anything more in the way of detail.

 

[sonic]

^ I have a couple of questions if you don't mind looking it up for me.

1) How strong of an inducer of CYP2D6 is alcohol?
2) How strong of an inhibitor of CYP3A4 and CYP2D6 is cimetidine?

 

[SpellmanT7]

^ I have a couple of questions if you don't mind looking it up for me.

1) How strong of an inducer of CYP2D6 is alcohol?
2) How strong of an inhibitor of CYP3A4 and CYP2D6 is cimetidine?

Cimetidine is listed as a "moderate" inhibitor of CYP3A4 and CYP2D6 (semi shaded circle). In the main section of the book - 'Interaction Monographs', It states:

(regarding interaction between 2D6 Substrates/2D6 Inhibitors (Moderate) and also interactions between 3A4 Substrates/3A4 Inhibitors (Moderate))

CYP Inhibitors have been labelled "moderate" because a) the serum concentration of the inhibitor drug required to effectively inhibit the cytochrome enzyme (ie, inhibition constant (Ki) as established via in vitro studies) may be acheived in some patients during the course of therapy (especially in higher doses); or b) in vivo pharmacokinetic studies have demonstrated a two- to fivefold increase in the serum concentration of a probe substrate (one known to be primarily metabolized by the enzyme of interest) in the presence of the inhibitor drug administrered in standard doses.


Unfortunately there is no data regarding alcohol and enzyme reaction.

 

[sonic]

^ Thanks for the info!

 

[Gaz_hmmmm]

My memorys really gone down the shitter lately and I was wondering which receptor it is that it is that affects opi's i.e. turns codeine into morphine and also blocks/slows down the break down of opi's in your system?

Thank you

 

[johanneschimpo]

Cyp450 2d6

 

[soundphaRm]

^^...correct.

But, codeine in and of itself is a prodrug, so you don't want to inhibit the metabolism of codeine, as codeine is metabolised into morphine (in vivo) by the CYP-450 (2D6) enzyme, which is responsible for codeine's effects orally...
...but, for other opiate/oid substrates, inhibiting this enzyme should result in a longer duration of effect(s), as it would be metabolised slower by the liver.

 

[Gaz_hmmmm]

So grapefruit is a no no when it comes to codeine and dihydrocodeine?

 

[majhookup]

Will two substrates potentiate each other. (ie hydrocodone and alprazolam)

 

[soundphaRm]

^^...yes, two substrates/meds, esp. the one's that you've mentioned will potentiate/synergize each other.

 

[soundphaRm]

So grapefruit is a no no when it comes to codeine and dihydrocodeine?

That's right. You definitely don't want to inhibit the metabolism of codeine, since it's metabolised into morphine, which gives you the effects you seek.

The same holds true for dihydrocodeine, which is metabolised by O-demethylation [via the same hepatic pathway: CYP-450 (2D6)], into dihydromorphine.

So, in short, grapefruit/juice (and/or cimetidine...i.e. Tagamet) would be a "no-no" with codeine/dihydrocodeine, because you want them to be metabolised into morphine & dihydromorphine, respectively. This is what makes them prodrugs.

I hope that helped and didn't confuse you more...

 

[majhookup]

Just to get the most mileage out of my hydros. I should drink some g.f. juice, take some tagament, diphenhydramine, plaquenil (I take it for Lupus) then wait a predetermined amount of time, take my hydros and then I just read a thread that stated )eating fatty foods after your meds kick in would increase bioavailability). Then I should get a stronger, longer effect? Are there certain amounts of each inhibitor that I should take and a certain amount of time to take each inhibitor to achieve maximum lift-off?
I ask these questions because I do have real pain issues and I also like to feel that opiate buzz we all opiate users know so well. Anyway to overcome tolerance in anyway....