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    Zohydro And A New Obstacle To Medical Innovation
    By Matthew Lazenka | May 8th 2014 09:37 AM | 5 comments | Print | E-mail | Track Comments
    One of the major goals of pharmaceutical companies is to get through FDA approval so that they can begin selling a drug on the market. 

    This step is so important that pharmaceutical companies actually make decisions regarding drugs in their pipeline based on the results of other drug approvals. 

    Further, pharmaceutical companies will choose safe diseases to initially test drugs, even if there is no preclinical indication that the drug will be effective for those diseases.  For instance, they go the ocular route because that is not a systemic administration of drugs.  

    Even though the FDA is a huge stumbling block, Congress has decided to become an even bigger stumbling block.  This is where Zohydro comes in.  It is one such drug that was approved by the FDA despite receiving disapproval in a vote of 11-2 by an advisory panel.  The FDA, in its approval, made it clear that Zohydro showed strong enough efficacy in reducing pain and suffering when weighed against its potential abuse liability. 

    Although it is very true that there is an increase in the number of those who are dependent on opiates, it is also true that not all patients find relief with currently available opiates.  The interesting thing here is that the discussions of Zohydro show a complete ignorance in the media of what potency means in pharmacological terms. 

    Potency is usually defined as how much drug is necessary to produce an effect.  Basically, etorphine is 1000X more potent than morphine, which means it would take 1 milligram of etorphine to produce the same effect as 1 mg of morphine.  So even though less etorphine is necessary, it has no bearing on the effect of etorphine.  Etorphine has about the same efficacy as morphine. 

    In the medical profession, fentanyl is more potent and slightly more efficacious than morphine.  Buprenorphine is ~25-50 times more potent than morphine, but it has lower efficacy because it is a partial agonist.  Therefore, people in the media get it wrong when they say that buprenorphine is more potent because they have no clue what potency means.  This stems from the liberal arts education where Webster’s dictionary is considered the end all for understanding things. 

    To wit, potency is defined as “the strength or effectiveness of something.”  That is true for non-pharmacological discussions, but absolutely false when it comes to medications.

        Now, the issue at hand is that Congress wants to ban a slow release formulation of hydrocodone because 1) Joe Manchin’s daughter is CEO of a company that sells oxycodone and 2) because they would rather see patients suffer than do something that would actually reduce opioid abuse, but know they will get brownie points for pretending like they care about their constituents (Mitch McConnell). 

    For Congress, especially Democrats, it looks good when you attack companies that you claim are trying to make opioid abuse worse.  Because both Democrats and Republicans in Congress are supporting this, it is being touted as a big step forward for Congress.  It also proves that really bad ideas for America can be bipartisan too.   The problem, however, for those in the medical sciences is that, if this ban is successful, Congress will now have the power to trump the “experts” at the FDA.  Drug companies will have to consider whether their competitor has a mom or dad in Congress before embarking on certain medical innovations.

     The science, in a lot of ways does not back up the claims of these Congressmen.  My focus will be on just a 2013 study in Pain, which assessed attitudes of opioid abusers.  It showed that a significantly greater number of individuals (44.7% vs 29.4%) preferred oxycodone over hydrocodone because the "high" was better. 

    Hydrocodone was the drug of choice for risk-averse people, those who were unlikely to abuse heroin.  Oxycodone was preferred by the group that was young and risk-tolerant.  Therefore, the issue at hand is that Joe Manchin’s daughter sells the drug that is more likely to lead to risky opioid use and abuse.  Joe Manchin is not asking to ban oxycodone because his daughter’s company makes money off of it. 

    The only reasonable argument in this whole debate, is that slow release hydrocodone comes in a form that can be crushed and snorted, like the initial release of oxycodone.  However, data suggests that it is unlikely that the scale of this abuse will reach the magnitude of oxycodone abuse because the high is not as good, as reported in peer-reviewed research.  Likewise, risk-averse people are more likely to take hydrocodone.  Eventually, an uncrushable form of slow release hydrocodone will be developed, but, until then, the FDA agrees that some pain suffers would benefit from Zohydro now. 

    I happen to agree that reducing pain is preferable to adding one new obstacle to medical innovation so that one’s child will not lose market share with her company. Finally, more research needs to be done on whether uncrushable forms of opioids is actually a good deterrent.  It's possible that it may force more users into abusing heroin. 

    If Joe Manchin and Mitch McConnell were advocating for more research dollars to stem opioid abuse, along with banning a drug, then maybe I would believe their intentions were earnest.

    Comments

    Thank you!

    Your article is a red herring for it misses the fact opioids lack evidence of long term effectivenes for any chronic pain condition except Tramadol for neuropathic pain. RCT's for opioids show most drop out due to side effects or lack of rewarding effect. People in pain don't exist for the commercial interests of Big Pharma- in case no one told you.
    But getting back to opioids it is remarkable these ancient meds still are used in the post-genomic era- i guess no one told you there is an innovation gap in pharmaceutical companies. But again, opioids are merely antipathic medicines with no regenerative or curative properties. Instead of the opioid economy for painful conditions we would be much better off with a stem cell economy for painful conditions.
    If you wish to discuss "science" maybe you need to mention 50% of studies are so poor they go unpublished and that Dr. Collins at NIH a few months ago indicated that efforts at ensuring research reliability of medical research are "hobbled"- Oh and need I mention many pain specialists are under federal investigation for promoting opioids?
    You have provided a biased "bandwagon" thinly veiled plug for the opioid economy-maybe you need to do more homework on the issue before providing such a slanted view of opioids.

    brain2bewild
    I am not always sure how to respond to crazy, but I am pretty sure the post genomic era started millions upon millions of years ago.  I am also not sure what a stem cell economy is, but if it replaces the dollar as currency, I am all for it.    I also don't know where the 50% of studies part comes from.  I guess, if I understand your point, is that opiates are not great pain relievers, especially for neuropathy, fibromyalgia, etc.  I have to agree with you on that, and I am actively doing research to find effective non-opiate drugs.  The issue here is that if I were to find an effective drug, pharmaceutical companies may not want to pursue it because of what happened to Zohydro.  That is my major concern here.  Also, I am tired of people using the term potency when what they really mean is efficacy.  
    Post genomic era began after the human genome was mapped and guys like Collins told us by 2010 we would have so much better treatment for diseases as a result of being in the post-genomic era. In 2010 Collins and his pal Hamburg at the FDA said it might be another ten years before the promises of the post-genomic era are realized.
    It is good you realize that opioids are ill conceived medication for pain as they assume pain is nothing more than maldynia- that pain is not physiological but merely pathological- yeah it is one of the distinctions made by the pain specialists-although, frankly i dont know anyone with arthritis pain that doesnt have arthritis- but that is something that is lost on the pain specialists. SO if Big Pharma wants to create new medication that are approved by the FDA they should get over their innovation gap instead of trying to create "new and improved opioids" or repurpose old medications. So the FDA isnt the problem- as i see it- the problem is the innovation gap- and so Big pharma when it comes to pain care needs to develop safe and effective new drug entities-maybe the need to learn triz or engage in the circle of trust or have some LENS neurofeedback or neuroptimal for their researchers for drugs like Zohydro are ill conceived and reflect more of the innovation gap then they do problems at the fda. And yeah the 9 functions of my medial prefrontal cortex are well methylated today,

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