EDS Drug Metabolism

Note: the EDNF.org website is in the process of moving, so links to it may not work.  Once the new site is stable, I’ll update the links – 12/14/13

Thank you, SASO, for another page of excellent information and references!

EDS can result in altered medication metabolism

Dr. Tennent’s explanation about diffences in the CYP450 enzyme: http://www.ednf.org/index.php?option=com_content&task=view&id=2241

Opioid Metabolism – Howard S. Smith, MD – http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704133/

CYP2D6 (http://en.wikipedia.org/wiki/CYP2D6) which if deficient can cause odd interactions, sensitivities or apparent allergies while other may not have any effect at all, which can include opiates. There can be normal, reduced, and non-existent CYP2D6 function:

  • poor metaboliser—little or no CYP2D6 function, something anecdotally found in quite a few EDSers
  • intermediate metabolizers;
  • extensive metaboliser—normal CYP2D6 function;
  • ultrarapid metaboliser—multiple copies of the CYP2D6 gene, with greater-than-normal CYP2D6 function (and could have even a fatal reaction from a first-time or even small dose of some medications or illicit drugs).

When to Suspect a Patient has CYP2D6 Deficiency (http://www.practicalpainmanagement.com/treatments/pharmacological/opioids/non-responsive-pain-patients-cyp-2d6-defect)

  • Patient who reports a past or present history of non-responsiveness to codeine, hydrocodone, oxycodone, or tramadol.
  • Patient who reports better pain relief with Darvocet-N-100 than hydrocodone (Vicodin®) or oxycodone (Percocet®).
  • A patient who gives a history of significant toxicity or adverse reaction when they have taken specific Beta-Blockers, anti-depressants, or anti-psychotics.

A blood test for some cytochrome P450 genotypes has been available since 2005 so that we can now identify some people who will clear liver metabolized drugs from their body differently than the norm. People with two abnormal alleles will exhibit the least enzymatic activity and are referred to as poor drug metabolizers. Those individuals who have one normal (*1) allele and one abnormal (i.e., *10), are referred to as heterozygote’s and will exhibit intermediate drug metabolism. It is also possible for about 2% of whites and >25% of Saudi Arabians to have duplication of the functional *1 gene and results in ultra drug metabolism. Up to 13 copies of CYP-2D6 in the same person have been reported.

http://www.ncbi.nlm.nih.gov/pubmed/14996240 Genetic polymorphism [of P-450] can lead to important potential clinical consequences for some opioids, anticonvulsants (phenytoin), benzodiazepines (diazepam), muscle relaxants (succinylcholine), antidepressants (imipramine, nortriptyline, venlafaxine), typical neuroleptics, alcohol, antihypertensives (propranolol, timolol), local anesthetics (procainamide), L-dopa, nicotine, and warfarin.

http://www.medpagetoday.com/MeetingCoverage/APA/9355 Testing depressed inpatients for abnormalities in cytochrome P450 drug-metabolizing enzymes may be warranted, a researcher said here.

About 20% of patients hospitalized for depression had at least three defects in CYP450 genes, reported Gualberto Ruaño, M.D., Ph.D., of Genomas Inc. in Hartford, Conn., at the American Psychiatric Association annual meeting here.

He said these patients tended to do poorly on initial treatment with standard drugs. Defects in drug-metabolizing enzymes may be an important reason, he said.

http://www.multigen-diagnostics.com/MultiGENTechnology/GeneticTestingforDrugMetabolism.aspx

Genetic Testing for Drug Metabolism

Human body routinely takes in nutrients ( Carbohydrates, fats protein, vitamins, minerals and water for optimum cellular functions. However, additional complex biochemicals such as caffeine, drugs( Plavix) and toxins enter the body. These complex chemicals are broken down to make pharmacologically active and/or inactivate before they are excreted through the kidneys. Break down of these chemicals are carried out in the liver by metabolizing enzymes including cytochrome P450 (Cyp450) which forms the major group. Out of the 57 Cyp450 enzymes, 15 are associated with drug metabolism. Based on the genetic variations of these enzymes and their combination, drug metabolism is grouped into four categories; extensive ( normal) metabolizer, intermediate metabolizer, poor metabolizer, and ultra-rapid metabolizer. Therefore, testing for these genetic variations can help in the proper dosage preventing potential adverse side effects.

More than 25% of the drugs are metabolized by CYP2D6 which including cancer drugs( e.g tamoxifen) antidepressants(e.g.Fluoxetine) and anti narcotic analgesics ( e.g Codeine). Enzyme CYP2C19 metabolizes hormones, and precescription drugs (e.g Omerprazole,Clomipramine and Clopidogrel-Plavix) warfarin by CYP2C9.

Partial list of different enzymes required for example medications list…see which match up with the medications you take to know what enzymes are required…or which ones you tried that didn’t work and which enzymes were required for those: http://medicine.iupui.edu/clinpharm/ddis/ClinicalTable.aspx

A more complete list: http://www.cnsspectrums.com/userdocs/ArticleImages/08CNS_Q&Atable1(big).jpg

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6 thoughts on “EDS Drug Metabolism

  1. Kendra Neilsen Myles

    Some day I will write my whole story about how I figured out that I am a poor metaboizer for the CYP2D6 pathway and it wasn’t just from the test to screen for it. However, this is where I’m having a tough time with the topic in my last comment about the affects of adderall on cfs, narcolepsy, brain fog, etc. It’s been a life changing med for me, but it goes through this pathway. I taken an uber low-dose, but it’s not the dose I need and my doc doesn’t want me to take it more than 1x a day due to concerns with toxicity. I will be calling genelex tomorrow to ask about this specific med, because nothing else works like it and it helps me function.

    Liked by 1 person

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    1. Yvonne DeLisle Spitek

      It’s good to see this and know there are others that understand. I do have a doctor that gives me adderall and it has made a HUGE difference in my life. I wasn’t able to function or be a part of my family before adderall because I was unconscious 80% of the time due to chronic fatigue syndrome. My serotonin levels are below 10 and we are unable to get them any higher than 28 ever.

      My pain levels unfortunately are worse than ever. It is chronic, debilitating, and I am becoming more depressed than ever because I just can’t physically function. I can’t get a doctor to truly believe me and even if they do pain med don’t really work anyway! I tried to have the pain pump put in and the doctor punctured my spine and the blood patch repair didn’t take. I was flat on my back for three months. Soooo I eventually had the Neuro Stimulator put in my back. Well because of my “EDS” skin I woke up with over 30 staples instead of stitches. I went through all. Of that for the thing not to work properly… THEN to top it off… My pain doctor for over five years refused to see me anymore because he charge me an office copy of almost $2000.00 for a TriCare patient. Wouldn’t see me even though I offered to make payments until I got the bill down to under $500.00. I have since been try to survive without pain meds and done nothing but continually think about ending my life because I don’t know how much more pain I can physically or mentally take. I have completely lost faith in the medical community !!!

      I didn’t mean to ramble like this really. It just came pouring out. I guess the pain I’m in right now is so bad it took over. People need to know we are HUMAN and we are SUFFERING!!!!

      Thank you for allowing me to pour out myself here

      Sincerely,

      Yvonne Spitek
      Speejink@gmail.com

      Liked by 2 people

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      1. Tammy

        I know exactly how you feel. I have been dealing with chronic pain for over 3 years and before that I was working full time as an RN. I’m in the process of trying to get into a different pain doctor and waiting on my family Dr to order me something till I can get in. It’s a constant battle. I was on morphine Long acting (2) a day and short acting (4 ) a day they told me I had to be weaned off befire going to the new pain clinic because they don’t prescribe morphine so I stopped it all together and went thru dt’s that was awful but I’m doing what I was told. I had an appt at a new clinic and they called me the morning of my appt and said we don’t have a contract with your insurance company but we are working on it so check back in a month so of course now I’m taking nothing and hurt so bad everyday.

        Liked by 1 person

        Reply
  2. Nathaniel Edwards

    As someone with Psoriatic Arthritis and a chronic pain patient, most opiates have produced horrible side effects similar to drinking too much caffeine. Oxycodone was unbearable and morphine produced a deep spaced effect that reduced my overall productivity.

    Hydrocodone in lower doses is bearable but after taking both Oxycontin and Oxycodone IR and Morphine, it’s clear that opiates do not produce the standard effects within my system.

    Even with Norco, If I take more than my usual daily tapered dose (end of prescription cycle I usually have tens of tablets left) I will feel the caffiene effect which is very uncomfortable, though pain relief is available with Norco/Hydrocodone.

    In a way, this is an added benefit of bolstering against potential abuse. At the pain clinic where I obtain medication, the doctor stated that the vast majority of patients are high risk and abuse is common. I am like some freak of nature deemed low risk.

    Liked by 1 person

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  3. BirdLoverInMichigan

    I wonder if I have any Saudi blood because I must be an Ultra Metabolizer. I know I’m part German Jew. I can’t tolerate opioids or general anesthesia very well at all. I suffer the worst side effects…breathing difficulties, turn grey, excessive sweating, etc. In fact, a dentist used laughing gas on me last year and I felt as if my head was about to explode, and wondered in that instant if I was going to die. Thankfully he saw me raise my hand and stopped it in time. How fitting I have the progressive pain disorder EDS. (Crowd laughs).

    Gotta love life’s twists…

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