One Size Opioid Dose Does Not Fit All

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…and there is good reason for this.  To believe otherwise is indeed credulous.  Although I will introduce scientific reasons to support that one person’s 100mg morphine equivalent dose is another person’s 200mg morphine equivalent dose, I will start by looking at it in simplest terms. 

In the most straightforward example, consider that a single opioid dose in a 150 pound person may not achieve the same benefit or toxicity as it would in a 300 pound person – and believe me, I have plenty of patients in each of these categories.  By example, consider the sweet taste of 1 teaspoonful of sugar in a 4 ounce cup of coffee versus 1 teaspoonful in an entire pot.  Surely the least concentrated pot with just 1 teaspoonful of sugar will be bitterer (more pain for the heavier patient). The role of pharmacogenomics 1

From a scientific perspective, the amount of active drug in the blood may be more or less, depending on how the body processes or metabolizes the drug.  This is not the same from patient to patient, and in fact can be explained by various patient phenotypes.  This is something that can be easily determined in patients by employing pharmacogenetic testing. In fact, an entire science known as pharmacogenomics has evolved that helps explain why some patient might respond better or worse to one drug (or a particular dose) compared to another drug.  In short, pharmacogenetics variability could explain why a single drug could cause different patients on the same dose of the same drug (identical height, weight, and gender) to have efficacy with toxicity; efficacy with no toxicity; no efficacy and no toxicity; or no efficacy and significant toxicity.  Seems crazy right?  Not really, especially if you’re the patient or the clinician trying to justify an unusual dose or third tier drug option!

Different opioids undergo different metabolic pathways.  Some are metabolized to more active drugs, some are metabolized to less active drugs, some are metabolized to inactive drugs, and others are metabolized to all or some of the above.  There are individual enzymes in the liver known as cytochrome P450 enzymes, abbreviated CYP 450.  The most common of the enzymes for opioid metabolism are 2D6, 3A4, and 2B6.

Select examples of liver enzyme Phase I metabolism:

Codeine (no activity) (2D6) –>  morphine (more potent and active)
Codeine (no activity) (3A4) –> norcodeine (inactive)

Hydrocodone (active) (2D6)–> hydromorphone (more potent and more active)
Hydrocodone (active) (3A4) –> norhydrocodone (far less potent and less active)

Oxycodone (active) (2D6)–> oxymorphone (more potent and more active)
Oxycodone (active) (3A4) –> noroxycodone (inactive)

Patients may be one of the various phenotypes for each of these enzymes (2D6, 3A4) above and they can be a different type for each enzyme: 

Poor metabolizer – Intermediate metabolizer = Extensive metabolizer (considered normal, with two wild type alleles) – Ultra-rapid metabolizer

  • Imagine then what could happen if a patient was an ultra-rapid metabolizer of 2D6 and given codeine. They would convert the codeine rapidly to morphine and in fact this has been responsible for deaths in infants that ingested breast milk from an ultra-rapid 2D6 metabolizing mom. 
  • Imagine what would happen if a patient was a poor 2D6 metabolizer and couldn’t convert oxycodone to its more active form of oxymorphone (it wouldn’t work as well). 
  • Imagine then what could happen if a patient was an ultra-rapid metabolizer of 2D6 and given oxycodone, and at the same time was prescribed erythromycin which is a potent inhibitor of 3A4 – this would result in much higher levels of oxymorphone that could be toxic because degradation to the less active oxycodone metabolite, noroxycodone is blocked.

Aside from all this, the drug needs to combine to an opioid receptor.  OPRM1 (Opioid Receptor Mu-1) is a gene that codes for the mu opioid receptor which is where endorphins and opioids combine to cause analgesia and euphoria. Depending on the patient’s genotype or OPRM1 variability, this too could affect one’s ability to respond to opioid therapy.  If there’s minimal OPRM1, the patient will be a poor responder; if there’s an overabundance, the patient will respond to a lower opioid dose or could overdose more easily. 

There are many more enzymes involved and various phases to opioid metabolism.  In fact, the oral absorption or lack thereof is often dependent on yet another enzyme known as abcb1 (p-glycoprotein).  This same enzyme is responsible for carrying some opioids across the blood brain barrier.  Not only is this variable among patients, but like the CYP 450 enzymes outlined above, it is variable among patients.  Even more of an issue is that production or inhibition of these enzymes occurs with certain drugs.  For example, the Hepatitis C drug telaprevir can enhance methadone absorption from the gastrointestinal tract and also enhance absorption into the brain.  This could happen within 48 hours of taking a single dose of newly prescribed telaprevir.  And we wonder why so many people die from methadone – it is not just about “overdosing” by taking too much. It is far more complex!

So there you have it.  Although this is a very narrow and simplistic overview, it is intended to demonstrate reasons why not everybody responds to or tolerates the same drugs or the same dose.  There are of course many other factors related to the drug chemistry, type of pain, and much more.  But the drug interactions and pharmacogenetics variability described herein is at least a starting point for our blog followers.

 As always, comments are welcome!

 

 

25 thoughts on “One Size Opioid Dose Does Not Fit All

  1. QUESTION: Are there any (practical) tests that can be done to discover how my body processes the opioid medications, in order to utilize pain management more effectively?

    After the change in the opioid laws, my doctor drastically changed my treatment that he had me on for over two years. My current medications help very little for the pain, and it has greatly limited my lifestyle. I struggle just getting out of bed now, and I am at a loss of what to do.

    Thank you. This article is very informative. I appreciate the time and effort that goes into helping so many people.

    1. Vince,

      Yes. This is called pharmacogenetic testing. Certain enzymes that are responsible for metabolizing various opioids may be ordered individually or as a panel.

  2. Too Bad that not all doctors are not like Dr Fudin! but most are not as they do not keep updated on the medical field they practice or maybe not educated just skipping thru med school for the prominence and surely not caring for the patient and the suffering Docs like this are far and few between.
    The article on metabolism and dosages was right on spot We would have less suffering with pain
    I had only 2 doctors that explained my pain and the dosages just like Dr Fudin that I was on and shared this with the Pharmacy I was getting my meds filled at that time which relieved there concerns.
    Wonderful article I hope all pain doctors read .

  3. 15 years ago my psychiatrist / pain doctor heard me say one sentence that changed mt life for the next two years (his retirement). My entire life, since early childhood, I’d had to get 4 shots of novicaine while getting even the smallest cavity filled. My psychiatrist knew I needed very high doses of MS Contin to get mild relief for my disintegrating, bulging discs; but after hearing about my experience at the dentist, specifically having to stop the drilling every ten minutes for another shot, my shrink realized I was metabolizing medicines extremely quickly.
    I realized that every doctor after him ignored me when I told them about this. In their eyes, I had a huge tolerance, or had reached the point where no narcotics could help me.
    The reality was and is; I get satisfactory relief if I take 3 times the highest allowed dose of MS Contin, OxyContin, dilaudud.
    I just realized that due to my pain doctors ignoring my super high metabolism, I’ve had to unconsciencely find a way to live with one third or less the dose I need. I’d get one months presciption; I’d take the snout that allowed me to live any type of quality life at all for a week. Then take a tiny dose the rest of the month, so I wouldn’t become ill from withdrawal. I guess I believed one week without pain was better than nothing. By the way, on the triple dose, I was never drowsy, tired, slow, out of it- never in the least. These doctors gave me no choice; they labeled me as having become totally tolerant, or as a drug seeking addict. Tomorrow I am going to tell me new doctor about this and get genetically tested so I can live pain free, without the stigma that has always accompanied me and my reaction to my pain medication, I believe my new doctor is good enough to understand this issue, and will at Keats research it. Ten years of being told I’m a hopeless case or an addict nearly broke my spirit and will to go on. I’m not going to be ashamed anymore; it’s the doctors who are unaware of these metabolizing issues who ought to be ashamed.
    I’d forgotten how my shrink, so many years ago, hit the nail on the head, and went to the trouble of making sure ai got the doses ai needed. So many doctors have told me, “if you get no relief from this dose, you won’t get it from a hiigher dose, your opioid saturated” caused me years of misery, guilt, and pain. This article reminded me of that diagnosis years ago; it reminded me why I do get almost total relief from doses that would kill 2 normal people. I pray my doctor has heard of rhis, will learn even more, and stop blaming me because I get relief at “ridiculously high doses.” My first Vicodin prescription went from 10/325 to taking 5 10/325 pills, by my neurologists order. Somehow he spotted it over a decade ago, too. This article tells me, “Im not a drug seeker; I haven’t built up a tolerance over the years, I’m not opiate saturated. I simply was never given the doses that worked, aside from those yow doctors. ”
    I’m praying my new pain doctor will see the light with me. Thank you.

  4. Excellant article and why don’t all doctors consider this? I’m so tired of doctors telling me that if they give me 5 Oxy 30mg a day, it might kill me or make me too sleepy when I explained to them that I was for four years taking 450-600mgs of Oxycodone per day without an adverse effects (due to hyper metabolism while taking phenytoin with it.) but I do notice that the complaints from people of sweating, lethargy, allergies, etc., are all symptoms of withdrawal not opiate use.

    1. I am also NA and research taught my we have longer roots in teeth, require far more drug to have any procedure anywhere in our bodies; I also had larger needs to pain relief; Vicodin ok daily but sharp dentist pain requires percodan!
      I learned we also could not tolerate most generic drugs as filling affects us!

      You inspire me because I had already come to the same conclusion about Adderall! I take it at night to sleep better the generic is horrible; another issue we have; asked why I didn’t want generic I said if generic is as good as brand why do they cost less they have cheaper materials that will upset me badly!l

      And I know you are right about patients being in withdrawal from too low a dose; I know once I reach my limit, I don’t want to escalate! Because why? I have to stay near level 5-6 mostly with my drugs as percodan not available due to CDC war on pain patients!

  5. Thank you so much. I am past the 120mg acceptable level and have been for years. I have been fighting chronic pain for 20 years so of course I have a tolerance. Last month the pharmacist decided to not fill one of my prescriptions even though I had no problems with the same medications for 6 months at the same pharmacy. This battle that you help us with affects so many and is so scary. I am scared of losing my ability to even walk to the bathroom. My medication doesn’t make me high nor does it take away the pain completely. Doctors that care are being threatened by the DEA. Pharmacies are encouraged to report them in Tennessee. My prayer and hope is that we have more caring individuals such as yourself in my lifetime.

  6. According to the opiophobe zealots there DOES seem to be a consensus on what size opioid dose fits all. The problem is that size is 0 as in (zip, nothing, zero). I was turned away from having my methadone filled at Baptist Medical Center because I wasn’t using the right pharmacy (I was ‘awarded the privilege’of using only one of their 7 pharmacies to fill my schedule II Rx after 5+yrs as a patient there). The one I was supposed to use was out so instead of filling at one two blocks away I needed to come back Mon and drive another hour and a half out of my way.(it was 4pm Fri and day 32 on a 30 day Rx). Nothing pays like loyalty! I would hate to see how they treat people who just wander in off the street (their pharmacies are open to the public as well). What does this have to do with the topic? It could have sent me into pharmacy crawl mode which could be held against me because of profiling now being done on the disabled who fill Rx for opioids on their Plan D medicare insurance. Profiling?

    As torturous as the ‘pharmacy crawl’ has been for those disabled and in pain there appears there is going to be even MORE negative fallout that we could not foresee. As much as we would like to, or are under contract w/ pain doctors to do, use only one pharmacy, that has become near impossible for most. Unfortunately it can come back to haunt us as if we had done something wrong. Here is how:

    Information below from link: http://www.hematology.org/Advocacy/Policy-News/2014/3300.aspx

    Title: Potential Policy Fixes to Curb Medicare Part D Opioid Abuse
    Published on: October 22, 2014

    Medicare Payment Advisory Commission (MedPAC) is an advisory body to Congress.
    minus hospice and cancer patients the total number of patients prescribed opiates (counted are those who filled even just one Rx) equals roughly 10 million. Here are their findings on the 10 million opioid ‘users’.

    “The top 5% of opioid users account for 69% ($1.9 billion) of total spending on opioids. Users in this percentile, on average, fill twenty-three opioid prescriptions per year at a direct cost of $3,716 per person. 29% receive prescriptions from four or more prescribers, and 31% fill prescriptions at three or more pharmacies.

    Under authority granted by Section 6405 of the Affordable Care Act, the Center for Medicare and Medicare Services (CMS) has enacted changes that will go into effect on June 1, 2015. Physicians prescribing opioids to Part D beneficiaries will now have to be enrolled in Medicare, prescriptions ordered by unauthorized physicians will be denied, and Medicare enrollment will be revoked for abusive prescribing. CMS is also working to develop a tool that will monitor abuse by both prescribers and pharmacies.

    MedPAC discussed a policy proposal to utilize “lock-ins” for the distribution of opioids. A lock-in limits the number of prescribers or pharmacies that can issue a medication, and it can be utilized in many different ways. At-risk patients could be locked-in to single prescribers, or a single pharmacy could be locked-in to distribute all opioids within a geographic area (e.g., a state).

    While these policies might prevent opioid abuse, they could burden physicians and patients by limiting access to pharmacies for legitimate opioid use. Findings regarding the effectiveness of the coming 2015 changes will be analyzed by CMS and may be reviewed by MedPAC in fall 2015. Additional measures, such as lock-ins, will be considered after that time.” end

    Have 2 or 3 surgeries in addition to your PM doctor or PCP who normally writes your Rx? What about PM practices that use more than one doctor to write Rx for patients? I’ve had 3 write mine this year from the same practice? (too many prescribers for opioids) ? Pharmacy crawled a few months? (too many pharmacies used) You could easily be profiled as an abuser. Having my PM doctor allowing my surgeons to write for additional pain medication now doesn’t look as good as it did at the time. Switching main pharmacies and filling at two hospital pharmacies for surgeries may appear ABNORMAL and another RED FLAG. 5 doctors writing me an Rx in a year? On the surface it looks downright scandalous, OMG 5 doctors wrote NARCOTICS FOR ONE PATIENT!!!! That’s what scares me, these zealots never look much farther than on the surface.

    I wonder how all the addiction specialist psychiatrists sleep at night? They must know that there is much less ‘proof’ or evidence (reasoning against COT) of psychological disease(s) than pain conditions yet they write freely and unimpeded for large amounts of anti-depressants, stimulants, anti-psychotics, anxiety medications (now addiction meds) on nothing more than the patients report of symptoms? All of which have significantly longer and more severe side effect profiles including w/drawal syndroms than opioids; some like tardive dyskenisia being permanent. This seems a little hypocritical to me but that’s just my opinion.

    *Not sure how you revoke enrollment if physicians are not enrolled, am I missing something?

  7. Dr. Fudin, I found your article concise and easy to understand even though I’ve been disabled and therefore an active layman-researcher, as well as an active advocate-activist-counselor for approx. 17 yrs. due to living with 3 Autoimmune Arthritic Diseases. (ie: severe RA, moderate Lupus & Sjogrens) I also have Polyneuropathy plus other associated diseases, syndromes, et al. Neverthelesss, this is an excellent read for the beginner as well as those of us who have been disabled for many, many years.

    I thank you for making it clear for all to understand. Great Job! I will be re-posting in the many social media outlets that I’m involved.

    Many Blessings,
    Rev. Anthony

    1. You are the first “Reverend” I’ve located in my research. I received my first ministerial “license” in 1950. Ordained since 1956. Taught in 4 Bible colleges in 3 countries in 2 languages. I’ve been in pain management since 1980. (Arthritis & gout; botched laminectomy with spinal fluid leaks; torn rotator cuff; cancer stage 3.5 w/chemo; poly neuropathy, and several diseases not associated with pain management; ( inner ear tumor, bradycardia, etc. etc! I also had a successful career as an elementary school teacher. My point is this. I recently become aware of the general belief in pain management that everyone in pain management treatment is believed to be a drug abuser. Who would want to go to a church where the pastor was a drug abuser or have their kids taught by a drug abuser? Yet I have been abused by a pain medicine clinic. For 85 years my life and my word were all that was necessary. Now a broken automobile make me a bad driver??? Any such personal experiences? Or don’t your people know? Blessings! Pastor Barbara

  8. THIS WAS VERY INTERESTING AS I HAVE BEEN ON THE PAIN RELIEF ROLLERCOASTER FOR OVER 10 YEARS AND I HAVE SLOWLY BECOME ALMOST BEDRITTEN IN THE PROCESS. ( the reason for caps is due to RA in my hands as well running rapid thru my body, due to several kidney failures and a compromised kidney function of 50% I can’t take the biologics to prevent the progression)

    TO CONTINUE I AM CERTAIN THAT SINCE THE DEA IS RUNNING OUR MEDICAL DECISIONS THAT EVERY STATE WILL BE REQUIRING THAT ANY PAIN RELATED ILLNESS OR INJURIES BE SEEN BY A PAIN DOCTOR. THIS PUTS SUCH A BURDEN ON THE PATIENTS AS YOUR PCP RELEASES YOU TO A PMD WITH ONLY ONE MONTH RX OF MEDS. IT IS EXTREMLY HARD TO FIND PMD’S MUCH LESS GET AN OPPOINTMENT WITHIN A MONTH, THEREFORE YOU HAVE PATIENTS WHO ARE IN EXTREME PAIN WITH AN ANXIETY LEVEL OF 10 AND STRESS OFF THE CHARTS. THIS WILL AND DOES LEAD PEOPLE TO THE STREETS THUS ENFORCING THE BLACK MARKET OF WHICH THE DEA IS RESPONSIBLE FOR RIDDING THEM FROM OUR BORDERS……HUMMM…..SOMETHING IS WRONG WITH THIS PICTURE.
    FIRST, THE MEDICAL COLLEGES NEED TO PUT AN EMPHASIS ON THE NEED FOR PAIN MANAGEMENT DOCTORS, IN ADDITION WHY NOT HAVE THIS A REQUIREMENT FOR ALL DOCTORS, INDEPTH, NOT JUST A DAY LECTURE. THIS WOULD GIVE THEM THE KNOWLEDGE OF WHEN KAND HOW TO PASS ON A PATIENT.
    SECOND, GENETIC TESTING FOR PAIN SHOULD BE DONE AS AN SOP ON ALL PAIN PATIENTS. WITH THIS IN THEIR POCKET DOCTORS WOULDNT HAVE TO PUT PATIENTS ON THE PAIN MANAGEMENT ROLLERCOASTER!!!! THIS WOULD BE A MUCH BETTER WAY, THE PATIENT HAS THE RIGHT MEDICINE, THE DOCTOR HAS MORE TIME FOR THE NUMBER ONE KILLER IN AMERICA, AND THE INSURANCE COMPANIES, WELL THEY WOULDNT BE SUCKING THE LIFE OUT OFNTHE POCKET BOOKS OF EVERY PATIENT AND THE DOCTOR COULD TREAT MORE, DOES THAT NOT COME OUT A WIN FOR ALL??? COULD BE!!!
    LAST, AS AN ADVOCAT OF LEGALIZATION OF CANNABIS, I BELIEVE THAT IT SHOULD ALSO BE INCLUDED IN THE STUDIES OF HOW OUR BRAINS WORK TO RELIEVE PAIN AND HOW THIS MEDICINE IS A VIABLE SOURCE JUST AS OPIATES ARE OR USING BOTH AS NEEDED, IT SHOULD BE A PATIENTS CHOICE. IN STUDIES ALREADY IT HAS BIEEN PROVEN TO BE AN EXCELLANT CHRONIC PAIN MEDICINE.
    AGAIN, I FOUND THIS TO BE VERY INTERESTING. IT COULDNT HAVE BEEN AT A BETTER TIME AS TOMORROW I WILL BE TRAVELING TWO HOURS TO SEE MY PAIN MANAGEMENT DOCTOR, THE TENTH PLUS IN THE LAST 20 OR SO YEARS. IT IS SAD TO HAVE TO GO SO FAR TO SEE A DOCTOR THAT CARES ABOUT A PATIENTS HEALTH AND PAIN. I AM SO THANKFUL THAT MY FRIEND MILLIE PUT THIS OUT ON THE CHRONIC PAIN SUPPORT GROUP, WE ALL LEARN MORE FROM EACH OTHER THAN FROM MEDICAL SITES OR EVEN OUR OWN DOCTORS!!!! LOOK FORWARD TO LEARNING AND READING MORE.
    THANK YOU FOR YOUR WORK ON THIS SUBJECT AND FOR PUTTING IT IN WRITTING SO WE ALL CAN LEARN FROM ALL YOUR WORK INTO PAIN AND HOW TO RELIEVE PATIENTS SUFFERING!!!!!
    SINCERELY,
    MICHELLE STROZIER

    1. Michelle, well stated! Thank you so much for your comment. I agree 100%!
      My prayers are with you as I live with 3 Autoimmune Arthritic Diseases plus Polyneuropathy and several other associated diseases, syndromes, et al. Believe me, I KNOW P-A-I-N! I’m talking about daily excruciating pain.
      I’m in the process of getting a Pain Pump that will hopefully give my life back to me, at least to some extent so I may be more productive and in service to others.
      Be Blessed! My prayers are with you!
      Rev. Anthony

    2. The problem with cannabis is it’s expensive for my level of pain; also, eating it in food will help greatly; I need 4 doses of 25 mg each a day it’s extremely effective so be aware you cannot replace your pain meds totally I just wish I were rich; states should have required pot shops to carry a minimum of 400 pain patients who could get care packages weekly! Maybe naive estimate but these people make fortunes for pennies and this could have involved tax breaks and such but it’s worth discussion!

  9. Thank you Dr. Fudin!!!! While the role of 2D6 and 3A4 in metabolizing opioids has received a fair amount of attention in the pain management literature, the variable activity level of opioid receptors AND of the absorption have been virtually absent. From 25 years of taking care of chronic pain patients (average of 15 years of continuous disabling pain at the time of my retirement) there is no doubt in my mind that the roles of metabolism, receptor activity and absorption rate are major factors affecting any one persons response to a dose.

    The caveat about methadone absorption and transport across the blood brain barrier is especially poignant.

    Thank you again!

  10. In 1999, the Kentucky Distillers’ Association formed the Kentucky Bourbon Trail tour to give visitors a firsthand look at the art and science of crafting Bourbon, …maybe we should put a limit on Bourbon measured in fingers and how much can be had each day by a alcoholic. Lets limit the amount of Bourbon and other type liquor drinkers can have to lessen deadly automobile accidents caused by alcoholics. Just because alcohol can be bought at any corner liquor store doesn’t make it right to drink till you blackout. This may not have anything to do with this blog but alcoholics don’t live in severe intractable pain each day, their addicted to alcohol a drug in itself much more destructive to the organs of the human body. I wonder if the toxicity is equal in a 150 pound person compared to a 250 pound person.
    Alcoholism is a slow but for sure disease when used then abused daily, in whatever amounts you decide to consume. But O those bad opioids and those pain in the butt chronic pain sufferers, what will they think of next to make innocent people suffer a little bit more as time passes us by.
    People forget what you say and what you did, but people never forget how you made them feel.

  11. As always, Dr Fudin, your articles are a lifeline to me as an advocate for others with my rare genetic disease that causes terrible pain. I was particarly interested in your mention of erythromycin and wondered if Levaquin could also affect OxyContin & Dilaudid?

    Thank you for being here! I quote you enough that my pain physician is aware of the issues you raise as well as familiar with your name! He’s a very responsible doctor and I thank God every day for you both!

    1. Barbie, Thank you for your mind words. Levoquon will not affect either of those. It will however elevate cardiac risk when combined with methadone. Dilaudid is not metabolized through the CYP 450 system. Instead, it undergoes only .PHASE 2 metabolism.

      1. Wow, no wonder then that Dilaudid (that I only received a few doses of , once, when in the hospital for surgery) is the only opiods I had that actually ELIMINATED my pain !!

  12. Dr. Fudin,

    Thanks for this easily comprehendable explanation as to WHY the “cookie cutter” approach to limiting of opioid medications is not only impractical, a terrible way to practice medicine. Proof, once again, that legislators have no business involving themselves in your complex world of pharmacology.

    I feel like I have far better understanding of why this system does not work, but I cannot change the laws. Indiana has recently followed the path of Kentucky’s HB 1 law and made it likely that many general practitioners will be referring their long term patients to pain specialists as a result.

    Another tragic example with possible deadly consequences as patients are forced to undergo withdrawal and unnecessary pain that can lead to elevated heroin usage statistics as well as suicides. It is truly heart breaking to see the trend continue into my home state now.

    A little off topic, I wanted to say that I had made a statement that I left the Opposition Page due to ethical reasons. I wanted to clear this up. I simply had a difference of opinion and chose to leave. Please do not withdraw support from this page and the absolutely wonderful work they do there. My apologies for any misunderstandings. All negative issues with Ms Purcell are strictly my issues and should not detract from the positive and productive mission her and her team continue to work diligently on to fight for chronic pain patients’ rights.

    Sincerely,
    Kim Miller

  13. Wonderful review, but narrow and concise as you stated.

    For lay readers, it might be helpful to mention that even 25+ years ago, there was an evolving consensus that opiate doses for equal pain relief might vary as much as 25-fold from person to person. It was an eye-opener to physicians back then to discover that opiates were rather unique drugs in defying the usual physiological rules of dose-vs-response. The most recent pharmacogenomics review I’ve read suggests it may be as much as 40-fold!

    The recent rash of anti-scientific “guidelines” promoted by PROP and other stakeholders in the war-on-drugs asserting that no one should be prescribed more than 120-mg morphine dose equivalents is therefore profoundly ill-conceived, frankly ignorant of real pharmacological science, and likely to succeed only in driving many people back to the street in search of relief.

    So the DEA, PROP and others IMHO are actually going to be the best sales force ever for the mafia and drug cartels for a new expansion of their dirty business.

    1. I was an RN for over 30yrs in RI largest and best top ten nationwide hospitals in U.S. I as a nurse have had plenty of experience with people and each persons level of pain varies. When you give them a score to pick 1-10, someone will say 10 always and have a slow heart rate, be moving well and another patient will say 4, takes short shallow breaths, tears in eyes and in fetal position. You must listen to the patient but observe and use your other signs to judge of where you might want to begin, not to mention heart rate. I recently turned 70yrs old (young at heart) , from age 36yrs, I was sick in a hospital after birth of last child got sick and was there for 3 wks, until it was determinded I had pluersy and pericarditis. Not a pleasant combo, I might add. Since then I have never been well, test after to r/0 evervthing from MS (36 yr old daughter just dx this mo) me lupus r/o, rheumatoid arthritis out,. I have had white plaque in my brain, no reason given, I have aortic anny., at the root of aorta,, being watched for 5-6 years, no change. I have had a cardiac ablation at Mass. General in 2000 by Dr. Ruskin, successful, thank God, could not count or breathe, rate was so fast. I went to the hospital approx. every 3 mo to be converted. Still don’t have NSR. Br bx, neg., 2 vag repairs, last one with mesh has to be removed to poor reaction to the mesh. 3 C/S, 2 Hernia Repairs, 1 with mesh and now a hernia beside it that everyone is afraid to touch. 36 yrs ago after hospitalization it was suggested I go to doc that just specialized in Fibro. At that time there were 2 women that shared an office in Kent County. I have all 18 points , that Fibro Pts, have, I have Fibro fog, I was tested sometime after that time at Butler Hospital in Prov., and went thru many hours of testing, as I recal 4-5, extrememly tiring. They said I did OK, but what they would describe as Fibro Fog. About 15 years later those docs had given up their practice and I found a doc in Landmark Hospital, can’t think of his name. He had a full program and I worked through that looking for help. I took Meditation Class, Stretching classed, Swimming, in conjunction with this I went to Accuputure and Massasage. For the last 3 years of my involvement I suggested a Fibromyalgia Day for the Sate of RI and withLandmark Hospital and the Arthritis Founday, I was able to get Procolations for those 3 years, Declaring May 12th, Nationl Awarness Day. We had docs, speakers from Congress and the Senate, free lunch from one of the Phamacarology Services, and I spoike as a nurse and a patient and the effect on the family. Then that doc disappeared. Now I know you don’t agree with this, but durning that that time, for a total of 30 years, I was on Vicofin 750mg 3-4 tabs, prn. Some days I needed all four and some days none. I never abused. My MD trusted me and kept me on it.I had no where to go, they didn’t even have pain clinics then. I only got 1 /2 hrs of almost no pain, but coullllld go out with my graddaughter , and could go to a funcrion and stay a while and enjoy life. Now I have, no doc, no one that understatnds, no meds. I feel I worked my whole life helping people an now there is no one to help me. My GP is new to me, my other one retired, this one doesn’t seem interested. I have felt since I retired 8 yrs. ago, I just sit here day after day and only have death to look forward. If you could please get back to me. I would like to go to Boston, I feel they are always one step ahead of the game. Thanks for listening. Don’t think I ever put it all down on paper before. Bev Sawyer,R.I. 401-251-3511 I know I have some good life ahead of me and I would love to be able to attend. Thank you for letting me spill my guts. I know it is going to snow or rain, tonight everything hurts so badly I went to bed at 7pm, after walking into TJ Maxx, leaning on a cart and hurting so badly, I left. One more thing I have all eighteen point for Fibro……..Could you get back to me either way, please, feeling very despert.

    2. Sorry but I must disagree with the “start low, titrate slowly” method. Time and time again it has been shown that when pain patients are left to their own devices their use will increase and then plateau and maintain. As one who has been on oxycodone 30mg 4 per day for five years and withdrawal the entire time, I say, “hogwash”! Yes when taking phenytoin concommittently and hyper metabolizing Oxy, I was taking 450-600mgs a day without an any adverse effects. But prior to that and now that Im no longer receiving the phenytoin,6 per day provides adequate pain relief without any adverse effects. My tolerance hasn’t increased in five years and it seems unlikely that it will. Why the withdrawal? Im forced to attempt to take only four per day to continue with pain management. Even though the makers of roxicodone clearly state that they are to be taken every four hours unless opiate naive, doctors continue to expect folks to stay there forever. I believe users o ly i crease usage until they reach their true natural tolerance. Start low, go slow, creates addiction. Just start them a bit higher and stop when they say stop.

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