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I would sure like to know the answer to that looming question if anybody can enlighten me. It actually illustrates how and why buprenorphine is more tightly bound to the mu-1 receptor compared to naloxone.In fact, van Vorp and colleagues demonstrated this well showing that although naloxone can reverse burpenorphine, the naloxone dose must be huge and continuous. You can’t have it both ways folks; either naloxone reverses buprenorphine or buprenorphine blocks naloxone![AOT examples include morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, and others.] One of the most misunderstood opioids among clinicians is buprenorphine, and even more especially when combined with naloxone in the branded form of Suboxone®.If a patient has a scheduled or elective surgery with an active prescription for any buprenorphine product, the approach is not too difficult, but it requires an understanding of pharmacology, rational polypharmacy, but most importantly, common sense.Imagine bringing a patient to surgery on a naloxone (Narcan®) intravenous continuous infusion that you cannot stop for at least 2-3 days post-operatively.Envision trying to treat that severe pain with acute opioid therapy (AOT) but that with each sequential dose escalation, your attempts remain futile because naloxone is blocking the AOT from combining at the site of action, the mu-2 opioid receptors.Because naloxone can block heroin and other opioids from stimulating the receptors while not itself stimulating them, it can precipitate opioid withdrawal and is classified as an opioid receptor “antagonist.” The buprenorphine/naloxone mixture in Suboxone is touted to reduce the possibility of illicit use by injection if an attempt is made to abuse the Suboxone by a parenteral route, presumably because “naloxone antagonizes the opioid effect”. Repeat after me…at normal therapeutic doses, naloxone will never see that mu receptor because buprenorphine has a higher binding affinity, a longer half-life, and therefore naloxone is not capable of reversing it.In fact, to the contrary, it’s more believable that buprenorphine could reverse naloxone.

For now however, the bottom line is…USE COMMON SENSE!Here’s the figure from Jones’ writing with italicized dialogue from his article.Heroin, Buprenorphine, and Naloxone Effects at the Mu Opioid Receptor Heroin, buprenorphine, and naloxone (represented above by blue polygons) produce contrasting effects because they interact differently with the brain’s mu opioid receptors (red pentagons).Even the manufacturer (Reckitt Benckiser) admits to this, as seen in a 2004 Johns Hopkins University School of Medicine writing entitled “Practical Considerations for the Clinical Use of Buprenorphine“.How then did Reckitt Benckiser ever convince the FDA that this is a necessary or safer combination compared to buprenorphine alone? Jones shares a diagram that is ironically referenced to the eminent Suboxone manufacturer, Reckitt Benckiser.

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