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    Hydroxyzine and oxycodone metabolism/potentiation 
    #1
    As a pain patient who has started to develop a tolerance to my 10/325 percocets (every 6 hours), I have a few questions.

    I am also prescribed hydroxyzine in 25mg caps. I know that hydroxyzine, like other 1st generation anti-histamines, inhibits CYP450 2d6 (among others).

    It is my understanding, that oxycodone is metabolized to oxymorphone (among other metabolites) by 2d6, meaning that, if inhibited (albeit somewhat weakly) by hydroxyzine, analgesic effect will be lower as oxycodone is weaker than oxymorphone.

    However, I've seen very frequently that people say to take hydroxyzine with or shortly before taking opioids (somewhere I saw an alleged 50% increase in effect).

    Now, can anyone address these issues? Anyone have personal experience with hydroxyzine and oxycodone SPECIFICALLY?

    Thanks.
     

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    #2
    Hydroxyzine is the best sedative anti histamine on the market, period (with maybe cyclizine)...

    Take it 20mn before taking your oxy.

    Others will chime in as to why and how metabolization interactions do occur.
     

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    #3
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    Oxycodone is metabolized into oxymorphone by CYP2D6/CYP3A4.

    Hydoxyzine does not have any effect on 3A4, and according to some studies the inhibition of enzyme 2D6 is of not much pharmacological significance.

    The potent anti-histamine effect of hydroxyzine far outweighs its inhibition of enzyme 2D6.

    Related reading:

    http://www.ncbi.nlm.nih.gov/pubmed/9616188
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076582/
    Last edited by baooozs; 31-01-2013 at 18:48. Reason: 2D6
     

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    #4
    Bluelighter synthetix's Avatar
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    Woo! Finally someone proves and agrees with me that hydroxyzine sucks for opiate potentiation! High five.
     

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    #5
    Quote Originally Posted by debaser View Post
    Hydroxyzine is the best sedative anti histamine on the market, period (with maybe cyclizine)...

    Take it 20mn before taking your oxy.

    Others will chime in as to why and how metabolization interactions do occur.
    What is the effect of this in your experience?

    Oxycodone is metabolized into oxymorphone by CYP2D6/CYP3A4.

    Hydoxyzine does not have any effect on 3A4, and according to some studies the inhibition of enzyme 2D6 is of not much pharmacological significance.

    The potent anti-histamine effect of hydroxyzine far outweighs its inhibition of enzyme 2D6.

    Related reading:

    http://www.ncbi.nlm.nih.gov/pubmed/9616188
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076582/
    So the incredible amount of people that recommend hydroxyzine for opioids is just due to the increased sedation? It seems strange, especially when reports of stronger subjective effects and longer duration of effects is reported.

    First article information:
    These data demonstrate that classic histamine H1 receptor antagonists, available in over-the-counter preparations, inhibit CYP2D6 in vitro. Furthermore, the CYP2D6-inhibitory concentrations of these antihistamines are in the range of their expected hepatic blood concentrations, suggesting that, under specific circumstances, clinically relevant interactions between classic antihistamines and CYP2D6 substrates might occur.
    Regarding 2D6:
    Oxycodone is extensively metabolised in the liver, mainly via CYP3A4 to the inactive metabolite noroxycodone (47% of the dose), by 6-keto reduction to the most likely inactive metabolites, α- and β-oxycodol (8% of the dose), and via CYP2D6 to the active metabolite oxymorphone (11% of the dose), which is mainly found in a conjugated form in plasma....Serum concentrations of oxycodone (p=0.49), oxymorphone (p=0.12) and the ratio oxymorphone/oxycodone (p=0.15) did not differ between users and non-users of CYP2D6 inhibitors.
    Therefore, if both studies are accurate, the CYP2D6 inhibitory aspects of hydroxyzine have little to do with increased effect of duration. This is what I was referring to regarding oxymorphone, although I had no idea it was such a small percentage of the dose. Maybe 3A4 inhibition is the main cause of increased effect and duration...?

    Regarding CYP3A4:
    Total daily dose and use of CYP3A4 inhibitors displayed positive association. This means that increasing the dose and inhibition of the CYP3A4 metabolic pathway favour increased oxycodone serum concentrations...Users of CYP3A4 inhibitors are predicted to have 60% higher oxycodone serum concentrations than non-users...Formation of noroxycodone [hypothesized to be inactive] by CYP3A4 is the major elimination pathway of oxycodone
    It seems that 3A4 inhibition is really the way to go. Since oxycodone is NOT a prodrug (and is still quite potent agonist in its own regard), this would result in an increased analgesic effect. I couldn't find anything saying hydroxyzine inhibits CYP3A4 though....

    So why do so many people recommend it? People who have tried/still use this combo PLEASE chime in.

    Thanks.
    Last edited by infraredz; 31-01-2013 at 20:06.
     

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    #6
    Personally i would always use an Antihistamine when taking Opiates, although only to counteract the itch.
     

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    #7
    Quote Originally Posted by pally pete View Post
    Personally i would always use an Antihistamine when taking Opiates, although only to counteract the itch.
    And did you see any increased effect?
     

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    #8
    Quote Originally Posted by infraredz View Post
    And did you see any increased effect?
    Not really no.

    The best way to increase effects for me was to drink a load of white grapefruit juice and tonic water 30-60 minutes before dosing on Opiates.
     

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    #9
    Anyone tried grapefruit seed extract?
     

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    #10
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    I may have not concluded appropriately in my first post, but hydroxyzines' inhibition of 2D6 is negligible therefore does not have any or very little bearing on oxycodone-oxymorphone conversion, and its inhibition of 3A4 is non-existent.

    In theory hydroxyzine should depotentiate oxycodone due to its minor inhibition at 2D6, therefore anyone experiencing increased potency from hydroxyzine is due to its powerful anti-histamine effect, and its own analgesic mechanism, but certainly not its activity at liver enzymes.

    Even cimetidine which is a moderate but stronger inhibitor of 2D6 than hydroxyzine is reported to increase the potency/duration of oxycodone. This is also partially a myth. Cimetidine will increase oxycodone plasma levels and also its duration due to 2D6/3A4 inhibition, but at the huge cost of potency as it will hinder the oxycodone-oxymorphone conversion.
    Last edited by baooozs; 01-02-2013 at 00:10. Reason: 2D6
     

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    #11
    Quote Originally Posted by Chromophobia View Post
    I may have not concluded appropriately in my first post, but hydroxyzines' inhibition of 2D6 is negligible therefore does not have any or very little bearing on oxycodone-oxymorphone conversion, and its inhibition of 3A4 is non-existent.

    In theory hydroxyzine should depotentiate oxycodone due to its minor inhibition at 3A4, therefore anyone experiencing increased potency from hydroxyzine is due to its powerful anti-histamine effect, and its own analgesic mechanism, but certainly not its activity at liver enzymes.

    Even cimetidine which is a moderate but stronger inhibitor of 3A4 than hydroxyzine is reported to increase the potency/duration of oxycodone. This is also partially a myth. Cimetidine will increase oxycodone plasma levels and also its duration due to 3A4 inhibition, but at the huge cost of potency as it will hinder the oxycodone-oxymorphone conversion.
    Hydroxyzine inhibits 3A4? I was wondering about that but couldn't find a source.

    • What about the anti-histamine effect potentiates opiates?

    • What is the analgesic mechanism for hydroxyzine? Is this why it's prescribed with opiates for analgesic purposes (Which is my ONLY concern)?

    • The oxymorphone metabolism is fairly negligible it seems, being only 11% of the metabolites of oxycodone. Now, oxymorphone is a more potent opioid, but oxycodone is by no means a pro-drug and is significantly potent in its own regard right?
     

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    #12
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    As a pain patient it sounds as though you've just grown a tollerance to what you are currently Rx'd. Why go through all the troubles of potentiation which is usually not all that effective once a tollerance is built. IMO you'd be much better off to just speak candidly with your doctor.

    ~BLUA~ || ~?s PM me~
     

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    #13
    Bluelighter laCster's Avatar
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    Dude .....oxymorphone has really nothing to do with the effects of oxycodone, really the metabolization of oxycodone into.oxymorphone is very very very minimal, and likely has nothing to do with the effects felt when taking oxycodone.

    I Know this to be true because I myself, and many others I have spoken to attest to tagamet , a potent 2D6 inhibitor, to INCREASE the effects and duration of oxycodone exponentially. If oxymorphone had anything to do with the effects felt from taking oxy, than tagamet would make the effects of oxy feel weaker

    There is no point in arguing whether or not hydroxyZine affects hepatic enzymes in this situation because it really doeant matter because again, the production of oxymorphone has nothing to do with the high of oxy
     

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    #14
    Quote Originally Posted by bronson View Post
    As a pain patient it sounds as though you've just grown a tollerance to what you are currently Rx'd. Why go through all the troubles of potentiation which is usually not all that effective once a tollerance is built. IMO you'd be much better off to just speak candidly with your doctor.
    My issue is that I've only been taking this for 3 weeks and will not likely take it for much longer (ie before my next visit with my doctor). Also, I do not want to take anything stronger/increase dosage because of my fear of withdrawal (which is already going to happen since I have a tolerance). Therefore, I am looking for a way to make the analgesic effects of my current 10/325 percocets last longer. I was taking them every 4 hrs at first, then he brought me down to every 6 hrs and recently I am having breakthrough pain in addition to even some discomfort within 3 hrs of taking the med.

    I am very interested in the relationship between hydroxyzine and oxycodone in respect to potentiation (especially of analgesic effect). Also, as to why they were/are prescribed together to pain patients.

    Side note: injury was broken ribs and vertebrae in early January...

    Quote Originally Posted by laCster View Post
    Dude .....oxymorphone has really nothing to do with the effects of oxycodone, really the metabolization of oxycodone into.oxymorphone is very very very minimal, and likely has nothing to do with the effects felt when taking oxycodone.

    I Know this to be true because I myself, and many others I have spoken to attest to tagamet , a potent 2D6 inhibitor, to INCREASE the effects and duration of oxycodone exponentially. If oxymorphone had anything to do with the effects felt from taking oxy, than tagamet would make the effects of oxy feel weaker

    There is no point in arguing whether or not hydroxyZine affects hepatic enzymes in this situation because it really doeant matter because again, the production of oxymorphone has nothing to do with the high of oxy
    This is what I believe and why I am more interested in CYP3A4 and Grapefruit Extract.

    Like the original article that Chromophobia posted (Thank you, by the way!), the amount of oxycodone converted to oxymorphone is only 11% and oxycodone is in itself still powerful as an analgesic. I could see this being more relavent in a pro-drug situation, but oxycodone has a high affinity for various opioid receptors even compared to oxymorphone (although oxymorphone is stronger, but not enough to worry abut since it's only 11%.
    Last edited by bronson; 01-02-2013 at 02:44. Reason: post merge
     

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    #15
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    ^ Sorry I meant 2D6 in my last paragraph. Even though cimetidine is a 3A4 inhibitor also but not hydroxyzine.

    Anti-histamines are naturally sedating, take them in tandem with a strong opioid and many will notice an increase in that respect.

    Hydroxyzines' analgesic properties are unclear to me due to restricted journal access on select studies, but it is definitive that they exist and in some studies that they increase the analgesic benifit of opioids.

    Bronchodilator activity, and antihistaminic and analgesic effects have been demonstrated experimentally and confirmed clinically.
    http://www.pfizer.com/files/products/uspi_vistaril.pdf

    Analgesia obtained when 10 mg of morphine was combined with 100 mg of hydroxyzine was significantly superior to that obtained with morphine alone.
    http://www.anesthesia-analgesia.org/content/59/9/690

    Oxycodone is moderately potent on its own but one can't neglect its metabolites which are not limited to but include oxymorphone, codeine, and morphine. Nonetheless oxycodone is not a prodrug because it is not fully dependant on cytochrome P-450 enzymes and metabolites for its analgesic efficacy.

    Edit:

    Quote Originally Posted by laCster View Post
    Dude .....oxymorphone has really nothing to do with the effects of oxycodone, really the metabolization of oxycodone into.oxymorphone is very very very minimal, and likely has nothing to do with the effects felt when taking oxycodone.

    I Know this to be true because I myself, and many others I have spoken to attest to tagamet , a potent 2D6 inhibitor, to INCREASE the effects and duration of oxycodone exponentially. If oxymorphone had anything to do with the effects felt from taking oxy, than tagamet would make the effects of oxy feel weaker
    ^This = 100% subjective

    Two studies on the pharmacokinetics of oxycodone:

    http://www.ncbi.nlm.nih.gov/pmc/arti...381353/?page=1

    http://www.chem.agilent.com/Library/...990-3815EN.pdf

    The second study shows less but definitely non-negligible serum levels of noroxymorphone.
    Last edited by baooozs; 01-02-2013 at 00:25.
     

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    #16
    Bluelighter laCster's Avatar
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    Hydroxyzine will increase sedation and analgesia through synergism of effects, NOT potentiation.

    Potentiation is done by inhibiting liver enzymes to increase the duration of effects, or in the case of a prodrug like codeine, to increase the amount of the parent drug produced. Also, for drugs such as amphetamines, potentiation could mean raising stomach ph to increase the amount absorbed. Usually, potentiation doesn't increase the pain killing effects of drugs that don't rely on a metabolite for pain killing effects, but rather to increase the duration effects.

    Synergism on the other hand is a result of targeting other receptors in the brain to help incrwase analgesia of opiates. An example would be hydroxyzine and opiates. Hydroxyzine acts as a serotonin receptor antagonist, and anti histamine which makes the opiates feel more effective. Another example would be adding a muscle relaxer such as klonopin or soma. These drugs target different receptors other than opiate receptors to aide in pain reduction by relaxing the muscles. anoother very good synergism is Pregabalin or gabapentin with opiates. I can personally attest to lyrica or gabapentin to be one of the best non narcotic pain killers especially when combined with opiates.

    Some things to help with pain, definitely stick with hydroxyzine, it helps alot with pain. In addition try a muscle relaxer such as benzo with such. properties such as valium/klonopin or opt for another.muscle relaxer like flexeril or carisoprodol . Pregabalin and or gabapentin are also an excellent choice and really really help with pain. These are my favorite as a pain patient. Marihuana is also an excellent synergizer with opiates and help with pain.

    My favorites to help with pain....
    1. Pregabalin / gabapentin
    2. Marijuana
    3. Benzo with muscle relaxant props such as klonopin or valium
    4. Hydroxyzine
    5. Muscle relaxers like flexeril

    You can try potentiators aswell to make the oxy last longer. Tagamet aka cimitidine is excellent and is sold OTC all across amaerica

    Good luck
     

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    #17
    Quote Originally Posted by laCster View Post
    Hydroxyzine will increase sedation and analgesia through synergism of effects, NOT potentiation.

    Potentiation is done by inhibiting liver enzymes to increase the duration of effects, or in the case of a prodrug like codeine, to increase the amount of the parent drug produced. Also, for drugs such as amphetamines, potentiation could mean raising stomach ph to increase the amount absorbed. Usually, potentiation doesn't increase the pain killing effects of drugs that don't rely on a metabolite for pain killing effects, but rather to increase the duration effects.

    Synergism on the other hand is a result of targeting other receptors in the brain to help incrwase analgesia of opiates. An example would be hydroxyzine and opiates. Hydroxyzine acts as a serotonin receptor antagonist, and anti histamine which makes the opiates feel more effective. Another example would be adding a muscle relaxer such as klonopin or soma. These drugs target different receptors other than opiate receptors to aide in pain reduction by relaxing the muscles. anoother very good synergism is Pregabalin or gabapentin with opiates. I can personally attest to lyrica or gabapentin to be one of the best non narcotic pain killers especially when combined with opiates.

    Some things to help with pain, definitely stick with hydroxyzine, it helps alot with pain. In addition try a muscle relaxer such as benzo with such. properties such as valium/klonopin or opt for another.muscle relaxer like flexeril or carisoprodol . Pregabalin and or gabapentin are also an excellent choice and really really help with pain. These are my favorite as a pain patient. Marihuana is also an excellent synergizer with opiates and help with pain.

    My favorites to help with pain....
    1. Pregabalin / gabapentin
    2. Marijuana
    3. Benzo with muscle relaxant props such as klonopin or valium
    4. Hydroxyzine
    5. Muscle relaxers like flexeril

    You can try potentiators aswell to make the oxy last longer. Tagamet aka cimitidine is excellent and is sold OTC all across amaerica

    Good luck
    Thank you. I actually already take 3600mg of Gabapentin a day, as well as 30mg of Clorazepate (Tranxene which is a prodrug for desmethyldiazepam), but have been taking these for a long time and have an immense tolerance to them unfortunately.

    I think potentiation is ideally what I want, especially an increase in duration. Other than Tagamet, any other suggestions?
     

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    #18
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    Quote Originally Posted by laCster View Post
    Hydroxyzine will increase sedation and analgesia through synergism of effects, NOT potentiation.

    Potentiation is done by inhibiting liver enzymes to increase the duration of effects, or in the case of a prodrug like codeine, to increase the amount of the parent drug produced. Also, for drugs such as amphetamines, potentiation could mean raising stomach ph to increase the amount absorbed. Usually, potentiation doesn't increase the pain killing effects of drugs that don't rely on a metabolite for pain killing effects, but rather to increase the duration effects.

    Synergism on the other hand is a result of targeting other receptors in the brain to help incrwase analgesia of opiates. An example would be hydroxyzine and opiates. Hydroxyzine acts as a serotonin receptor antagonist, and anti histamine which makes the opiates feel more effective. Another example would be adding a muscle relaxer such as klonopin or soma. These drugs target different receptors other than opiate receptors to aide in pain reduction by relaxing the muscles. anoother very good synergism is Pregabalin or gabapentin with opiates. I can personally attest to lyrica or gabapentin to be one of the best non narcotic pain killers especially when combined with opiates.

    Some things to help with pain, definitely stick with hydroxyzine, it helps alot with pain. In addition try a muscle relaxer such as benzo with such. properties such as valium/klonopin or opt for another.muscle relaxer like flexeril or carisoprodol . Pregabalin and or gabapentin are also an excellent choice and really really help with pain. These are my favorite as a pain patient. Marihuana is also an excellent synergizer with opiates and help with pain.

    My favorites to help with pain....
    1. Pregabalin / gabapentin
    2. Marijuana
    3. Benzo with muscle relaxant props such as klonopin or valium
    4. Hydroxyzine
    5. Muscle relaxers like flexeril

    You can try potentiators aswell to make the oxy last longer. Tagamet aka cimitidine is excellent and is sold OTC all across amaerica

    Good luck
    ^ Pharmacologically you're wrong. Both cimetidine and hydroxyzine depotentiate oxycodone. Hydroxyzine is a mild 2D6 inhibitor and cimetidine is a moderate inhibitor of 3A4 and 2D6.

    As I explained and as you repeated hydroxyzine will increase the sedation of opioids therefore spiking perceived potentiation, and cimetidine will increase duration of oxycodone* by inhibition of enzymes also spiking perceived potentiation.


    Quote Originally Posted by infraredz View Post
    Thank you. I actually already take 3600mg of Gabapentin a day, as well as 30mg of Clorazepate (Tranxene which is a prodrug for desmethyldiazepam), but have been taking these for a long time and have an immense tolerance to them unfortunately.

    I think potentiation is ideally what I want, especially an increase in duration. Other than Tagamet, any other suggestions?
    ^Your only options are GABA agonists and cannabis. With GABA agonists being highly addictive.
    Last edited by baooozs; 01-02-2013 at 00:48. Reason: Oxycodone*
     

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    #19
    Quote Originally Posted by Chromophobia View Post
    ^ Pharmacologically you're wrong. Both cimetidine and hydroxyzine depotentiate oxycodone. Hydroxyzine is a mild 2D6 inhibitor and cimetidine is a moderate inhibitor of 3A4 and 2D6.

    As I explained and as you repeated hydroxyzine will increase the sedation of opioids therefore spiking perceived potentiation, and cimetidine will increase duration by inhibition of enzymes also spiking perceived potentiation.




    ^Your only options are GABA agonists and cannabis. With GABA agonists being highly addictive.
    Well what about Cimetidine or Grapefruit juice extract? All I want is to be able to take less opioid, less often with the same pain relief... and it sounds like thats what Cimetidine and (I think) grapefruit juice do.
     

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    #20
    Bluelighter laCster's Avatar
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    Um ok, tagmet isn't a strong inhibitor, but mind saying why I am wrong?
    How the fuck do they potentiate oxy, you sir are quite wrong. You obviously don't know what your are talking about because oxycodone is highly.metabolized through cytochrome 450 and tagmet definitely increases the duration of oxy. Your post also contradicts yourself. First you say tagamet and hydroxyzine and tagamet depotentiates oxy, then you say ir potebtiates it and increase duration? Which one is it? Finally, "spiking perceived potentistion" doesn't make sense at all dude. What? First there is no spike in levels I'd you take an inhibitor, and the potentiation is not simply perceived, it is not placebo whatsoever which is why on many medical websites there are interactions that say tagamet and gfj increase the duration Nd effects.


    Infrared, disregard what chromaphobe said, tagmet will definitely increase Increase the duration of oxycodone, it is not placebo.
    Go with cimitidne, it is more reliable and easier to dose

    Chrome, this forum is not about telling people they are wrong, so next time when you want to think only about yourself, remember this isn't your thread
     

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    #21
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    Well cimetidine will certainly increase bioavailability and half-life significantly but unfortunately you'll have to sacrifice some potency.

    Give it a go, you're the only one who can evaluate its benefit to you. I would suggest you do the same with hydroxyzine because as I mentioned before its inhibition of liver enzymes is mild, it has its own analgesic mechanism, and could add to the sedation of oxycodone therefore increasing relaxation.

    Chrome, this forum is not about telling people they are wrong, so next time when you want to think only about yourself, remember this isn't your thread
    I'm not even sure how to respond to that. When someone called you out on amphetamine and MDMA serotonin syndrome, I provided the study to back your statement up. My aim is not not to prove you wrong, but to state the facts. This is why it's called drug discussion, not LaCsters experiences.

    Here is someone else that agrees and is objective:

    There is a common misconception among opioid users in this forum, other forums, & on the street, and that is: a good potentiator for opiates or opioids is cimitidine (more commonly known as tagamet).

    The theory is that because cimitidine inhibits the CYP3A4 liver enzyme which is responsible for breaking down many opiates/oids into inactive metabolites (noroxycodone, norhydrocodone, etc..) that the opiate/opioid in question will have an increased effect & longer duration. While this is true to a certain extent, there is a vital peice of information regarding the pharmokinetics of cimitidine & it's enzyme inhibition that is widely overlooked by the opiaficionados out there.

    See not only does cimitidine inihibit the CYP3A4 enzyme it is also an inhibitor of a wide range of isozymes of the P450 enzyme system. In addition to the CYP3A4 enzyme, cimitidine (tagamet) also inhibits CYP1A2, CYP2C9, CYP2C19, CYP2E1, & most importantly the CYP2D6 liver enzyme.

    The opiates/opioids codeine, hydrocodone, & oxycodone are all CYP2D6 substrates meaning they all involve metabolism by the enzyme CYP2D6 on some level. Specifically codeine as many, if not all, of us well know metabolizes into morphine via CYP2D6, hydrocodone is metabolized into hydromorphone via CYP2D6, & oxycodone is metabolized into oxymorphone via CYP2D6.

    These metabolites I have just mentioned are all much stronger than codeine, oxycodone, & hydrocodone alone thus they are NOT good candidates for cimitidine (tagamet) potentiation unlike many benzodiazapines.

    Hope that helps...Remember kids, eat your grapefruit.
    http://www.drugs-forum.com/forum/sho...d.php?t=103590

    I can find you several on bluelight pointing out the same facts.

    How the fuck do they potentiate oxy,
    I said depotentiate.

    you sir are quite wrong. You obviously don't know what your are talking about because oxycodone is highly.metabolized through cytochrome 450 and tagmet definitely increases the duration of oxy
    They decrease oxycodone-oxymorphone conversion by inhibiting 2D6/3A4 respectively. Please try and read and comprehend accurately as I won't repeat my logic again.

    From df:

    SWIM agrees that cimitidine IS in fact a potentiator to a degree but also an inhibiter of greater levels of euphoria that could be acheived with the combination of a CYP3A4 only inhibitor and a CYP2D6 inducer.

    Because Cimitidine is a potent CYP3A4 inhibitor it does potentiate opiates in that it increases the duration through inhibiting the enzyme responsible for eliminating the drug through inactive metabolites (CYP3A4) but because it has the potent ability to drastically reduce the amount of morphine created by codeine, hydromorphone created by hydrocodone, and oxymorphone created by oxycodone via CYP2D6 inhibition it isn't the most suitable potentiator for opiates.

    And actually the amounts of active and significantly more potent metabolites of codeine, hydrocodone, and oxymorphone are definately significant especially with codiene which is basically euphorically inactive without being converted into morphine via CYP2D6.

    Here are the percentages for the afformentioned CYP2D6 substrates.

    Hydrocodone- -Hydromorphone= a maximum yield of 25%

    Oxycodone- -Oxymorphone= average yield of 15%

    Codeine- -Morphine= average yield of 10%

    So with a CYP2D6 inducer thrown into the mix these conversions become significantly higher, conversly, a CYP2D6 inhibitor such as tagamet (cimitidine) would lower the yields of the more potent metabolites created via CYP2D6

    I hope that makes sense.
    Last edited by baooozs; 01-02-2013 at 01:32.
     

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    #22
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    Quote Originally Posted by Chromophobia View Post
    Well cimetidine will certainly increase bioavailability and half-life significantly but unfortunately you'll have to sacrifice some potency.

    Give it a go, you're the only one who can evaluate its benefit to you. I would suggest you do the same with hydroxyzine because as I mentioned before its inhibition of liver enzymes is mild, it has its own analgesic mechanism, and could add to the sedation of oxycodone therefore increasing relaxation.
    Wrong , cimitidine does not increase bioavailability and again you contradicted yourself first you say it increases bioavailability which would essentially increase potency and effects, and then you say tagamet will decrease potency9 you dknt make sense. Next time bring in some sources and facts besides what you believe to be true.

    Also, the dude doesn't care about relaxation, he wants pain relief. Pissed me off when you tell me I'm wrong when I'm trying to help someone and all you care about is arguing.


    Infrared..
    I prefer cimitidine because it inhibits multiple enzymes and isn't as volatile as grapefruit juice. Gfj is alright, but you have to drink multiple cups and sometimes the effects are weaker and other stronger. Oxycodone was my DOC for years and I used to extensively and was very interested in getting more bang for my buck by potentiation. I have utilized both grapefruit juice and tagamet, and tagamet is all around better . It's easy to carry around as they are just pills , it is easy to measure your dose and easy to swallow a pill or two, and IMO/IME tagamet was more effective
     

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    #23
    Again, we are referencing CYP2D6 when it has been established that it is relatively insignificant (because oxymorphone is only 11% of the metabolites of oxycodone). I feel that, maybe, Grapefruit Juice extract is the way to go since it somewhat specifically, inhibits CYP3A4 and not 2D6 (or at least, not a lot).
     

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    #24
    Bluelighter laCster's Avatar
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    Yah I overreacted, I didn't mean to flip out lol. No hard feelings chrome...

    However, I.still stand that oxycodone doesn't need to rely on oxymorphone for effects. The metabolization is so minimal it doesn't really matter. Unlike codeine or hydrocodone, oxycodone has a relatively low(strong) Ki value which is somewhere between 10-20 Nm which means it is quite a potenet opioid
    Also another internet forum is not an ideal source , it is more persuasive to post studies and such

    Quote Originally Posted by infraredz View Post
    Again, we are referencing CYP2D6 when it has been established that it is relatively insignificant (because oxymorphone is only 11% of the metabolites of oxycodone). I feel that, maybe, Grapefruit Juice extract is the way to go since it somewhat specifically, inhibits CYP3A4 and not 2D6 (or at least, not a lot).
    Idk how many times I have to say this, oxymorphone has nothing to do or very very very minimal effects felt from oral

    http://paincenter.wustl.edu/c/BasicR...linPharm06.pdf


    In this link, the experiementers gave subjects a high dose of quinidine , a very potent 2D6 inhibitor, and the effects were relatively the same if jot stronger. From this they concluded that oxynorphone has nothing to do with the effects felt from oxy. In the very last paragraph. The study states that the metabolites did not affect in a good or bad way the effects of the parent drug oxycodone. Finally and most important, the.metabolites of oxy including oxymorphone were barely, if completely not at all, were able to cross the blood brain barrier into the cns. This shows that even if you took a 2D6 inducer with oxycodone ad were a super fast 2D6 metabolizer and were able to produce more than normal amounts of oxymorphone, the oxymorphone wouldn't even be able to pass through the BBB which means you wouldn't feel jack shit from the oxymorph even if you were a freak metabolizer!!!

    Point closed
    Last edited by bronson; 01-02-2013 at 02:57. Reason: post merge
     

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    #25
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    ^ That's one study and done in rats. I would find it surprising that a 15% yield of oxymorphone is negligible. I will attempt to get that study from the user.

    As the studies I posted mentioned serum levels of oxymorphone are nearly half of those of oxycodone done in chromotographical laboratories. It would be illogical to ignore that in the same way that codeine-morphine conversion can't be ignored.

    several of which are thought to be active metabolites to some extent, although a study using conventional oral oxycodone concluded that oxycodone itself, and not its metabolites, is predominantly responsible for the drug's opioid effects on the brain.[3]
    http://en.wikipedia.org/wiki/Oxycodone

    The study in rats mentioned is the one you provided.

    From the data sheet itself:

    Metabolism

    Oxycodone hydrochloride is extensively metabolized to noroxycodone, oxymorphone, and their glucuronides. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Oxymorphone, although possessing analgesic activity, is present in the plasma only in low concentrations. The correlation between oxymorphone concentrations and opioid effects was much less than that seen with oxycodone plasma concentrations. The analgesic activity profile of other metabolites is not known.

    The formation of oxymorphone, but not noroxycodone, is mediated by cytochrome P450 2D6 and, as such, its formation can, in theory, be affected by other drugs
    The two main metabolites are oxymorphone--which is also a very potent analgesic
    http://www.ncbi.nlm.nih.gov/pubmed/17525040
    Last edited by baooozs; 01-02-2013 at 02:07.
     

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