Drug info - Potentiation using Grapefruit Juice or Cimetidine

[crizzle]

So my understanding is that Cymetedine (Tagamet) potentiates the effects of opiates by the inhibition of the enzyme CYP2C6, while Grapefruit Juice potentiates the effects of opiates by the ihibition of the enzyme CYP3A4.

My question is, what is the difference? How does the inhibition of each enzyme uniquely potentiate the effects of opiates? Also, would the inhibition of both enzymes cause greater potentitation?

I have looked around and do not see this topic discussed yet, surprisingly.

crizzle added 9 Minutes and 36 Seconds later...

Wait, I just read this. This makes it look like GFJ inhibition of CYP2C6 is a myth and that both GFJ and cimetidine inhibit CYP3A4.


http://www.drugs-forum.com/forum/sho...ghlight=cyp2d6

I would really like to have some feedback regarding this. It seems like there still are many people that have the idea that GFJ inhibits CYP2C6 (including myself).

[crackcityrocker]

from experience grapefruit juice should increase length and intensity of experience. cimetidine will increase the peak time. swim would assume that using both together should potentiate opiates further, as they inhibit different enzymes. it would be good practice to decrease the starting dose, though. as has been said plenty of times on this sight, if it isnt strong enough for swiy he can always up the dosage, but never decrease it.

http://www.drugs-forum.com/forum/sho...t=10884&page=2

EDIT: just read the link in the post above, swim hasnt seen that before. swim isnt so sure now if using both GFJ and cimetidine together will increase effects. he has a feeling it might, but better to wait for someone more in the know to shed some light on this.

[crizzle]

thanks crack, but i really am looking for more than anecdotal feedback. I would like to understand exactly the mechanisms by which each substance potentiates the opiate effects.

[crackcityrocker]

well from what i understand, CYP3A4 metabolizes certain opiates into non-active drugs. so when CYP3A4 is inhibited, morphine (as an example) is broken down into normorphine (non-active) slower, increasing the time of the experience.

thats all i got. like i said, someone else will come along and shed some light on this im sure.

[crizzle]

anyone else? i know there are some smartys out there

[Herbal Healer 019]

Certain opiates are metabolized into certain substances, active or inactive & more or less potent via the CYP3A4 & CYP2D6 liver enzymes.

So depending on what the opiate in question is metabolized into, one should use either GFJ or Cimetidine accordingly for purposes of potentiation. SWIM doesn't know of any opiates that are potentiated by CYP2D6 inhibitors (cimetidine, etc..).

More specifically tho:

Hydrocodone is metabolized via CYP2D6 & into hydromorphone (more potent) & norhydrocodone (via CYP3A4). Norhydrocodone is psychoactively inactive thus by inhibiting the CYP3A4 enzyme, hydrocodone is metabolized into hydromorphone to a greater extent by the CYP2D6 liver enzyme because the CYP3A4 enzyme is busy metabolizing the inhibitor (Grapefruit juice, etc..)

so if you know what the opiate in question is metabolized into & via what liver enzyme, you'll know which inhibitor will work most synergesically with said drug.

Hope that sums it up more clearly