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Pharmacology - Naloxone not absorbed myth

Discussion in 'Buprenorphine' started by synonymous, Oct 18, 2010.

  1. synonymous

    synonymous Titanium Member

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    Swim knows the often repeated company line about naloxone not being absorbed sub-lingual and beleaved it was true until he tried both Subutex and Suboxone. Swim has tried both many times now and it is utterly clear to him that naloxone does get absorbed.

    Subutex gives swim nice warm relaxed feeling and back pain goes away completely.Swim feels good all day.

    Suboxone gives swim dizzy nauseous feeling and then he feels achy and sore after a couple of hours. With Suboxone the warm relaxed feeling never really comes but just moments or hints of nice feeling come and go.

    Maybe Swim is just sensitive... Maybe not. How many swimmers have the same experiences?

    Swim knows Australian ambulance service use naloxone nasal spray for heroin over dose. Why would naloxone aborb through nasal mucus membrane but not oral mucus membrane?
    Naloxone is lipophilic enough to cross blood brain barrier and the mucus membrane in mouth is a phospholipid...

    It doesn't add up.
    I have a link for a study showing 50% of patients switched from Subutex to Suboxone had adverse side effects after switch.
    But I can't post a link...
    google this title if you are curious:
    A retrospective evaluation of patients switched from buprenorphine (subutex) to the buprenorphine/naloxone combination (suboxone)
     
  2. Spucky

    Spucky Palladium Member

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    AW: Naloxone not absorbed myth

    The first is "your" Study:


    Source:
    http://www.ncbi.nlm.nih.gov/pubmed/18559110

    Versus



    Source: http://www.ncbi.nlm.nih.gov/pubmed/20450243

    They changed from average 22mg. a Day, so they get ca. 6mg, of Naloxone, that is by far to high


    Imo. it must be logical that the Naloxone had a influence.
    Ie. the Problem of Constipation is much lower in the Suboxone-Group,
    my idea is that Naloxone contribute that!
     
    Last edited: Oct 18, 2010
  3. kailey_elise

    kailey_elise Gold Member

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    Re: AW: Naloxone not absorbed myth

    This is true...I had completely forgotten about the Naloxone factor in Suboxone, in a way.

    I wonder if people who continue to crave while on high dose Suboxone treatment (3 & 4 tablets a day, ie., 24mg/6mg & 32/8mg) aren't, in fact, screwing themselves over with the excessive Naloxone.

    And that probably is a big part of why people, once stabilised on Suboxone (meaning, they've been on it a few weeks & all the other opioids are out of their systems), seem to find 4mg/1mg and less most effective/"euphoric".

    Very interesting.

    ~Kailey
     
  4. Spucky

    Spucky Palladium Member

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    AW: Naloxone not absorbed myth

    @ Kailey-Chan,

    afaik. this high dosage of Subutex/ Suboxone above 8mg. a Day will be not metabolized,
    to give a Patients more than 8mg. a day is a waste of Money!

    Buprenorphine is not made for everyone, some People need stronger Opioids!
    (like Methadone or Diamorphine)

    In the last weeks there is a Witch-hunt going on, suddenly Methadone is the bad one,
    i am a little bit scared that soon "they" (the military-industrial and Pharmaceutical Complex) will allow only Buprenorphine-Products!
     
  5. Eden

    Eden Titanium Member

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    Re: AW: Naloxone not absorbed myth


    WOW! what you surmise with regard to the "less is more" concept just blew my socks off!After all these years I dont know why it didnt occur to me that it was only the folks I have known taking Suboxone and NOT Subutex who have made the claim that less is more. WOW...thanks for the post...I have lots to think about for awhile.
     
  6. kailey_elise

    kailey_elise Gold Member

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    No problem, Eden! :)

    More food for thought - the Suboxone group might additionally find "less is more" because the small doses of Naloxone that do get absorbed act as "Ultra Low Dose Naltrexone" in a way, making the lower doses of buprenorphine more effective than when in the Subutex formulation. :)

    So, for Suboxone at least, taking less is more euphoric because less Naloxone is absorbed, with the potential addition of the opioid working more efficiently BECAUSE of the small amount of Naloxone absorbed!

    Now, this is all theory; I have no studies to back this up. But it makes sense in many ways, and I think there could be something to it!

    ~Kailey
     
  7. dyingtomorrow

    dyingtomorrow Palladium Member R.I.P.

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    SWIM has some anecdotal evidence he could add.

    SWIM has been on and off Suboxone dozens of times. He could attest to what Spucky said, because he noticed that dropping from 16mgs+ down to 8mgs+ felt like no difference at all. He also found that he could drop his dose every 2-3 days by 2mgs and experience almost no noticable effects. Getting down to 1-2mgs the difference became a little more noticiable, but slowly tapering off from there was still not a problem at all. He'd usually go down to .5mgs or less as part of his quick taper.

    However, when he was on Subutex (switching on and off a few times) he noticed a big difference. It was far more difficult to taper off, and the effects of each dose drop were a lot more noticiable.

    SWIM has read medical documentation for Suboxone which indicates that even orally, or to a greater extent nasally, a small amount of Naloxone is still absorbed. SWIM has a theory that this small amount of Naloxone is partially what makes the tapering process so easy with Suboxone. That while most of the receptors are filled with Buprenorphine, a small amount are bound with Naloxone. Other studies have shown that taking low doses of Naloxone at night can induce the body to start producing more endorphins and elevate mood, and this could perhaps explain why it seems like one's tolerance is lowering with Suboxone, and why lower doses can have the same effectiveness after a couple day plateau dose. Alternately, it could just be the Buprenorphine itself, since it has such low receptor activity that the body might feel that it is still lacking in "proper endorphins." Or perhaps both.

    SWIM can also say that, normally he would snort his Suboxone doses as he was tapering down, which, along with the greater bioavailability, would very likely result in a greater amount of Naloxone being absorbed. He noticed a difference in tapering difficulty when he tried using it orally instead of nasally, orally being more difficult, perhaps because he was absorbing less Naloxone.

    Just some theories that have come to SWIM's mind, explaining some of the effects he has experienced between Suboxone and Subutex.
     
  8. Eden

    Eden Titanium Member

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    This is amazing! Can SWIM estimate how many times this comparison has been done? A donkey I know would be highly interested in this information because he(the donkey) has experimented with low-dose Naltrexone etc.:thumbsup:
     
  9. Naked Lunch

    Naked Lunch Silver Member

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    Even if it is absorbed its irrelevant as Naloxone does not reverse Buprenorphine like it does Heroin.
    Straight from a med School handbook BTW.

    How this works in real life, well, who knows...

    I've been taking Subutex and Suboxone legally* (*Hence, the reason why I use "I" )for years and have no problems with it.(I do 3 days on Subutex and 4 on Suboxone and I feel the same everyday.
     
  10. Spucky

    Spucky Palladium Member

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    AW: Re: Naloxone not absorbed myth

    Afaik. this is not 100% true,
    Naloxone drives Buprenorphin away from the Receptor
    but only for a short Time (ca. 20min)

    In a Overdosage a constant Monitoring is needed
    and a 3-5 Times continual injection of Naloxone to reach the safe Haven!
     
  11. catseye

    catseye Gold Member

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    From Cambridge University Opiates Poisoning guide.
    IPPV means intermittent positive pressure ventilation (eg mechanical ventilation).

    As Spucky says, the major problem with using naloxone to counter-act opiates with a long half-life is Naloxones inherently short duration action - so in cases like this close monitoring and re-administration may be needed for 48-72 hrs.

    As naloxone is so short acting and is not easily absorbed orally at low doses, it will have little to no effect if the Suboxone is taken as directed - if it's crushed and injected, well that's another story! John Hopkins University is currently looking at buprenorphine's dose response curve (ie the 'less is more' idea) but haven't released their findings yet. In animal studies, bupe response has a bell shaped distribution curve with very high doses (ie well over the 32mg 'ceiling dose' for humans) producing less results than mid-range doses.

    In response to the OPs original question, my guess is that the reason intra-nasal naloxone is more readily absorbed is for two reasons:
    1) the method of administration is (or should be!) via atomizer which is absorbent-enhancing. Fine particle atomization maximizes nasal bioavailability compared to sprays or drops.
    2) the fact that the nasal mucosal membrane is in close contact with the blood stream (via the nasal mucosal vasculature). It is also directly in contact with the brain through the olfactory mucosal membrane nose-brain pathway (the area of smell at the top of the nasal cavity). Since the olfactory mucosa is in direct contact with the brain, medication can absorb directly from the olfactory mucosa into the brain CSF and actually skip the blood stream/blood brain barrier.

    Its also worth mentioning that the concentration of the nasal administration route - 1mg/1ml - is highly concentrated vs. the small sublingual amounts available in suboxone. :)
     
  12. Eden

    Eden Titanium Member

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    Ok lets break this down: Part One: "...Naloxone does not reverse Buprenorphine like it does Heroin.." Taken in context this is correct. However,does it eventually and when done properly under medical supervision"reverse Buprenorpine? YES.

    The following excerpt is taken from The Journal of The American Society of Anesthesiologists**: (Note:quoted in it's entirety as I believe it is pertinent to the thread.):

    "...Background: The objective of this investigation was to examine the ability of the opioid antagonist naloxone to reverse respiratory depression produced by the μ-opioid analgesic, buprenorphine, in healthy volunteers. The studies were designed in light of the claims that buprenorphine is relatively resistant to the effects of naloxone.
    Methods: In a first attempt, the effect of an intravenous bolus dose of 0.8 mg naloxone was assessed on 0.2 mg buprenorphine–induced respiratory depression. Next, the effect of increasing naloxone doses (0.5–7 mg, given over 30 min) on 0.2 mg buprenorphine–induced respiratory depression was tested. Subsequently, continuous naloxone infusions were applied to reverse respiratory depression from 0.2 and 0.4 mg buprenorphine. All doses are per 70 kg. Respiration was measured against a background of constant increased end-tidal carbon dioxide concentration.
    Results: An intravenous naloxone dose of 0.8 mg had no effect on respiratory depression from buprenorphine. Increasing doses of naloxone given over 30 min produced full reversal of buprenorphine effect in the dose range of 2–4 mg naloxone. Further increasing the naloxone dose (doses of 5 mg or greater) caused a decline in reversal activity. Naloxone bolus doses of 2–3 mg, followed by a continuous infusion of 4 mg/h, caused full reversal within 40–60 min of both 0.2 and 0.4 mg buprenorphine–induced respiratory depression.

    Conclusions: Reversal of buprenorphine effect is possible but depends on the buprenorphine dose and the correct naloxone dose window. Because respiratory depression from buprenorphine may outlast the effects of naloxone boluses or short infusions, a continuous infusion of naloxone may be required to maintain reversal of respiratory depression..."

    Eden added 10 Minutes and 8 Seconds later...

    Part Two: Btw Naked Lunch-this is not in any way to pick on you.This is purely in the interest of accuracy and keeping the thread on track.


    The original comment about Suboxone vs. Subutex made by "dyingtomorrow" is absolutely relevant because the comparison is drawn between partial agonists(Subutex and Suboxone) and really has nothing to do with heroin(full agonist).Again, just trying to keep this discussion on track and accurate :)


    **Van Dorp E. et al. (2006) Naloxone reversal of buprenorphine- induced respiratory depression. Anesthesiology 105 (1): 51-57
     
    Last edited: Dec 1, 2010
  13. Naked Lunch

    Naked Lunch Silver Member

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    Nice to know.:)
     
  14. synonymous

    synonymous Titanium Member

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    Effects of sublingually given naloxone in opioid-dependent human volunteers

    Abstract

    To determine whether sublingual naloxone could precipitate withdrawal in opioid-dependent subjects, naloxone was administered in increasing doses (0–8 mg in four or six sessions conducted over 2 days) to six heroin abusers and three methadone (30 mg/day, p.o.) maintenance patients. Two or three sessions were conducted per day with 2- to 2.5-h intervals between sameday sessions. Naloxone precipitated withdrawal in two of six heroin abusers and in all three methadone subjects. Naloxone is sufficiently absorbed sublingually to precipitate abstinence in dependent subjects, but naloxone doses up to 1–2 mg can be administered sublingually to opioid abusers/addicts without precipitating withdrawal.