Further, some drugs are activated by breaking down, whereas some are inactivated by breaking down, and some are make more removeable (e.g. For reasons I will not go into, I have been prescribed both codeine and morphine, separately, at several occasions. Hehe. I am a person in recovery, so I am very careful using this class of drugs. I have had my genes mapped as a test participant at my Dr. Office. Also, while ultrarapid metabolizers are quite rare among White people of European Descent, for other populations such as North African and Middle Eastern persons, this mutation is MUCH more frequent like 30%. Is that also an observation in a rapid metabolizer? I’ve been prescribed hydrocode afterwards, but only ever take a half of one that day because they make me really loopy. I suspected, several years ago, that there was something malfunctioning in the way I metabolize drugs. P450 enzyme CYP2D6 is of importance in medicinal chemistry, pharmacology and medicine. Although testing is incressing, I am shocked at the lack of medical professionals who are chosing not to educate themselves about the different reactions caused by genotypes which would make them more comprehensive as a person who supposedly went into a profession to help people. What is really sad is that the instances of failed therapies from antidepressants is extremely high in CYP2D6 UMs because the drugs have no effect unless administered at super high doses and most physicians are not aware of the CYP2D6 UM anomalies thus are not willing to administer remedies in the high doses necessary. An adult dose of detromethorphan cough syrup is an invitation to see the walls bend and change colors. But they do understand the ultra/non-metabolizers, the difference between pain from a source, pain from a nerve pinched somewhere else, and pain that doesn’t have a cause but hurts anyways. Some GPs have accused me of making it up. After trying SSRI’s and having a bad reaction to tamoxifen that was related to switching SSRI’s and, and.. anyway, I fell into the hands of a psychiatrist who did the cheek swab on me, and we discovered this. He does this because he wants to be aware and be able to help others similar… altbough, he will not run across many like me, it’s the fact that he sees the many anomalies and uses them to help not reject his patients. Te reto a una carrera metabólica: Metabolizadores ultrarrápidos - Genotipia, Biochemistry student violates laws of science (almost). I now suffer from Chronic Tendonitis and finding the medication that would dull the pain is Nil, how ever there is a medication that does lower the pain levels 2-3 places downward so an 8 or 9 day drops as low as a 5 or 6, the amount I have to take suck because I also have A.D.D. I say this as a 2D6 ultra-rapid metabolizer who has been researching how this affects me. You have to wait the full 4-6 hours until you take it again, or it won’t work. In my genotype, *2xN the N stands for the number of alleles and could be anywhere from 2 copies up to 13 (that they know of.). Valid for Submission. Tried fentanyl patches, no help at all. Funnily enough, I have substantial reason to believe that I am a extremely poor metablizer. Title: Your CYP2D6 Genetic Test Results and What They Mean Author: Cincinnati Children's Hospital Medical Center Subject: CYP2D6: Ultra-Rapid Metabolizer … My PCP told my yesterday to find a different pain clinic, but with more & more shutting down, or becoming franchises (so if you’re discharged from 1, you can’t get into another in the same chain, they won’t see you). I have painful pleurisy – will last 4 weeks they tell me at urgent care….and no one to treat me… I’ve fired or been fired by more doctors than I care to recall, Its horrible as we all know, to be treated always like an addict when we can’t even get addicted. Depends on the opioid narcotic. I used an entire Ibu when I sprained my ankle, one, one time, and I’m not one who likes to suffer it out. Drugs we recommend to avoid: Codeine. Are you sure your current pain is nociceptive (traditional), and not neuropathic? A quick google search for pharmacogenetic testing canada gives you some companies such as medcan, geneyouin, medicnematch, dyncare – and you can easily order online too, One company that does this is called Genelex, at genelex.com. People from Saudi Arabia and Ethiopia are more likely to process tramadol quickly, whereas Caucasians are more often found to process tramadol slowly. Finally, I hope my doctor never read this. That’s fucked! Anail, you are so right. The headaches started about half way in. Hi Im Brittany, I am a URM, i have had almost every pain med and depression med tested and none work. Deviations in the number and type of allelic variants as well as gene copy number yield four CYP2D6-predicted metabolic phenotypes: ultra-rapid metabolizer (UM), extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) [12, 15]. A specific dose cannot be recommended for CYP2D6 indeterminate metabolizers. No severe adverse effects were seen in the UMs in our study most likely because we used for safety reasons a low dose of only 30 mg. Codeine and tramadol are metabolized in the liver to their active forms by an enzyme called cytochrome P450 isoenzyme 2D6 (CYP2D6). Bad news I’ve tried just about every pain med out there. My swab was conclusive that I am a CYP2D6*2xN (UM-Ultrarapidmetabolizer). I don’t know…should I get checked for CYP2D6 ultrarapid metabolism or is it just me? However, last night, it was VERY obvious. “Hi. I remember it all. 4 There are four basic types of metabolizers. . My 3 year old was bouncing off the walls last night after a normal dose of Benadryl. Ultra-rapid metabolizer : Paroxetine . Your email address will not be published. enzymes that help with the removal of most of the drugs and toxins from the human body Once the concentration of parent drug saturates the capacity of the 2D6 enzyme to remove it, the drug concentration continues to build up rapidly over time. Sufferers of neuropathic pain often get little or no relief even from strong opiates. They tried IV Paracetamol in a drip which had no effect at all, and then resorted to Codeine which worked (of course) until my BP and RR fell and I began to feel very sick. I’m a UM. What recreational drugs (i.e above medical rec doses )shuld MJPE take to work out for sure if their CYP2D6 is slow or normalish and if it may be their CYP2A enzyme that is slightly slow or non active rather than their CYP2D6 or if conversely their CYP2D6 is slightly slow but their CYP2A is slightly fast… Micahel Jackson pink elephant is as much intrested in this from a scientific point of view to roughly work out their rough different enzyme abilities as they are to try recreational doses. I was cooked.. I’m now on subutex 120mg most day until Sept 1….i feel you all.. We need to do something. Every time I go to see a new physician as soon as they see the dose I’m taking they tell me how dangerous it is and they refuse to take me as a patient. It might help your Dr’s. I did get Botox for migraines 2 months ago, it’s already wearing off. What recreational drugs (i.e above medical rec doses )shuld MJPE take to work out for sure if their CYP2D6 is slow or normalish and if it may be their CYP2A enzyme that is slightly slow or non active rather than their CYP2D6 or if conversely their CYP2D6 is slightly slow but their CYP2A is slightly fast… Micahel Jackson pink elephant is as much intrested in this from a scientific point of view to roughly work out their rough different enzyme abilities as they are to try recreational doses. Interesting that you say that about dextromethophan cough syrup. SO, long story short, I do not achieve the relief that a normal netabolizer by this gene would. Ultra-rapid metabolizers (UM) carry multiple copies of functional alleles leading to excess activity. They are specialists in Pain Management. I have had drug screens in the past come back negative for oxycodone which was puzzling to me. The wide variety of 2D6 mutations and heterogeneity in their substrate binding and instance and severity in the population make this a more difficult issue to deal with – a simple test wouldn’t necessarily tell you much. I take Benadryl, which doesn’t make me sleepy -has the opposite effect. Mayo Clinic is a nonprofit organization and proceeds from Web advertising help support our mission. It wasn’t until he spoke with my doctor that I finally got relief. © 1998-2021 Mayo Foundation for Medical Education and Research (MFMER). Fortunately I only get sick once every 20 years, unfortunately I get wicked migraines, for which I have no solution. I was in the hospital last week and again had a negative drug screen within a few hours of taking 20mg of oxycodone. But… I also have a son which also suffers from PTSD, as well as the same freakin chronic back-pain I do and he is going through the exact same crap from the doctors. Front Pharmacol. My pain grew worse and worse. Any info appreciated. She left and hurried back with a shot of demerol which immediately started easing the pain. CYP2D6. I don’t understand why codeine and hydrocodone make me sick when morphine did absolutely nothing…it might as well have been water! I am not a medical doctor, so don’t take this as medical advice, but in your shoes I would ask my doctor for a neuropathic pain evaluation. They will likely not respond to some opioids. Synthetic Remarks. So what medications do I need to avoid if an ultrametabolizer? somnolence and respiratory depression). My dentist gave me 1 numbing shot, it took 3 all in all to work. I’m 68, with treatment resistant rapid cycling/mixed state bipolar, along with non-restorative sleep and non-combat PTSD. I am currently on morphine sulfate as my pain mgmt was smart enough to notice on my drug screen it appeared that I was not taking my oxycontin. You know the stuff; suppressed breathing, extreme nausea, cold sweat and to make things worse: no pain relief at all. It was then that I remembered that talk with the pharmacist but again saw no reason to react until recently I was facing some surgery and thought it necessary to adress my suspicions of being an ultra-rapid metabolizer to the anaesthesiologist. there was a hunt and peck and there was one time when my pain was managed to the affect that i was pain free. This does suck by the way. cyp2d6 ultra extensive metabolizer variant obviously in such a case codeine should be overly potent as a pain killer but most standard longterm treatments should be negatively impacted propanolol amitryptiline flunarizine all seem to be processed by cyp2d6 have you had any novel insight since ? I can’t take any type of opiate (I’ve had several surgeries to come to this conclusion) morphine made me hallucinate(I was told I was quite hilarious of course I have no recollection) and pass out so that pca pump was not needed, hydro’s, vicodin, percocets they all make me deathly ill talking instant puke. I seem to be a poor metabolizer and possibly rapid metabolizer in several areas. Interesting fact about depression and CYP2D6 UMs: we have statistically lower than normal levels of Dopamine, a neurotransmitter that helps control the brain’s reward and pleasure centers. Dextromomethorphan (DM in cough suppressants) causes me to vomit like a person who just drank while on antabuse. The study of how genes like CYP2D6 affect the way you break down medicines is called pharmacogenetics (FAR mah coh je NEH tiks). I’m sad to say, I prefer the morphine. In addition, this enzyme also metabolizes dopamine and serotonin. I was on straterra at a pediatric dose for my adhd and it knocked me out, couldn’t stand up, had to hold the wall to walk to bed. You may have had the CYP2D6test done for other reasons. I’m starting to look into having my daughter tested because she’s Ethiopian and 30% of Ethiopians are Ultra Rapid Metabolizes. Routine testing for tramadol and CYP2D6 is usually not done. Dang. Mayo Clinic does not endorse any of the third party products and services advertised. I have this plus other enzyme deficiencies making my life hell with regard to any kind of medical care. CYP2D6 is one of the most polymorphic CYP genes in humans among the CYPs, accounting for around 80 different allelic variants and 130 genetic variations described [50].The CYP2D6∗4 allele was the first defective CYP2D6 variant allele to be identified (in 1990) and constitutes the main explanation for the poor metabolizer (PM) phenotype among Caucasians [49]. They want complete control. Thank god that only lasted for about 20 minutes, then I felt as before, took some Mefenamic acid (Ponstan) which brought the searched for pain-relief. It’s frustrating and scary because I NEED that dosage to totally control my depression. I also know what 60 milligrams of codeine feels like. ), I was discharged & had to find a dr fast. In 1991 I had a C section and awoke with a patient regulated morphine IV in my arm. So, did I get high or affected in any way or form from the handful of pills I took, that SHOULD have knocked an elephant out… Nope, didn’t phase me at all, which was the point I was aiming to prove and yes, I even drove my car home after the doctors appointment… One good thing more that came out of this whole ordeal, I know have a doctor that is highly motivated in LEARNING more about the various mutations on the CYP2D6 gene…. Also, why are my tests showing hydrocodone? He then did a genetic swab test and came up with the CYP2D6. A LIFE full of over-reactions and under-reactions….now validated. Whether one is a URM or a PM, life becomes quite difficult when you can never find the right balance. Lower/undetectable plasma concentrations may increase probability of pharmacotherapy failure Select alternative drug not predominantly metabolized by CYP2D6 : Strong . Psychiatrists and Pain Management specialists have access to a cheek swab test. they make you feel like you’re only trying to seek out drugs, only because of all the drug abusers out there. This “cocktail” has worked wonders for me. MJPE was once in hospital, eventually morphine did cause the odd mild hallucination, wasnt instant it was ongoing admin over hours that caused it by IV. I hope you can find a great one as well. Hence, these poor souls risk suffering more pain in life than necessary. I’ve been a URM all my life, the number of medications that effect me with a normal does is less than 10%. Talk with your healthcare provider about choosing a medication that may be a better option for you. However, I just wanted to voice on here that us under and over metabolizers are essentially in the same boat, because medicine still only caters for the average. Previously I had to go out of state and I will again to get the right care. I have been swab tested by my therapist/MD because he was trying to treat me for ADHD and I told him I was not feeling anything from the Adderall dosage even after he had increased it to the highest recommended. Had the test also. I am a URM and require a mega dose (off-label) of Pristiq to control my clinical depression. What I have read most of the Caucasians are from middle east and Northern Africa where most RH negs come from. I then told him that I was afraid of the use of opioides and he answered, that there was still the Metamizole – then he saw the infusion, frowned and told me: that, as this has been the maximally allowed dose, there was not much to chose from now on. Will Lidocaine (and similar local numbing agents) work on her? Methadone, tramadol, and fentanyl all avoid any secondary pathways, and avoid the CYP2D6 and UGT pathways and may be drugs available to someone who gets no relief from codeine/morphine/dilaudid. She has a dental procedure coming up, so I need some advice. She gave me a dose off morphine through the IV herself and nothing happened. It is quite rare, and must be horrible, to be “immune” to all kinds of pain medication. Other common symptoms of URM that I’ve learned: benedryl causes hallucinations, so do almost all old antihistamines. Armed and loaded with CYP2D6, the liver knocks off a methyl group (vide ninja). I had a gallbladder attack and the ER doctor gave me the recommended dose of painkiller. If an activity score (e.g. Ironically, if I inject too much rx testosterone at one time, I can smell it in my urine, so I need to inject small, daily doses and even with that, I overaromatize it to estradiol. You no longer feel the effects of your oral medication. The importance of CYP1A2 for druginteractions has been increasing overthe past decade due to the growingnumber of drugs metabolized by thisenzyme.1Drugs metabolized by CYP1A2are called CYP1A2 substrates. (And it sounds cool too!) I kept telling my mom the pain meds isnt working and nothing being able to be done… fast forward to me today, im constantly in pain and my pm keeps telling his np im to young for high levels of fentayl… i had 3 back surgeries and a 6mm kidney stone last year. Today my daughter who is now 11yrs old was in the ER….and even through I told the staff about the 2D6…they stillgave her a medicine that is NOT allowed for her condition. I get intended and side effects from various mental health and pain medications (which are notoriously involved in CDY2DS), even at the lowest available doses, sometimes in under an hour. I 7nderstand that there are tests for example the OATS test that tests for rh and should be administered beside the chromosome tests and could affect the therapies but I have found my insurance company will not allowy doctor to perform it. Hi!Am from Australia & have not heard of anyone else with this problem,just that my dr says I have it,& have actually felt really victimised & traumatised by the attitudes,as described above,by ignorant medical staff.So am pleased to connect with some others…..however it would be good to hear from anyone from down here,especially re ANYWHERE that does understand the problem?I suppose the first step is getting the test done.Am just about to have surgery & feel a bit scared re how “the mix” is going to go! I know what 10 milligrams of morphine feels like. I have blood work done and everything is in the normal range. I have Imitrex injections & discovered they provide a rush like nothing I’ve ever had before! Routine testing for tramadol and CYP2D6 is not recommended. If not look in to connective tissues disorders such as Marfan’s or Ehlers-Danlos. are you a redhead? I did get a Doctor that has a wife with the same kind of issues and he worked with me. You don’t have the enzyme to utilize the meds so you get sick. It’s unfair that we have to live with pain beside of pressure on doctors to not write for us. 5. A second dose after 2 hours usually has little or no effect. I have this condition – the UEM on CYP2D6… How can I get tested so I have something to show MD’s (as if that will help anyway because I can’t find an MD replacement who has ever heard of this!! Having learned my lesson with Dextrometorphan (Bexin) and every cough-remedy containing codein I avoided this stuff for all my adult life until about 10 years ago I got an attending pharmacist who for ONCE listened carefully and could explain the different metabolism-types to me. Ultra rapid metabolisers will get more pain relief and more chance of euphoria from the oral medication. My pain specialists never doubted me, since I had more than 20 years of doctor’s notes where I complain about pain and they look for it without finding a physiological problem to ‘fix’. Codeine appears to work about normally. This website also provides information on the. Not bad – but by then I also started to notice the first signs of nausea. However, those kids that are “slow metabolizers”, which is a substantial percentage of at least the Caucasian population, are at risk of developing severe (usually cardiovascular) side effects. You may have had the CYP2D6test done for other reasons. Make me want to crawl out of my skin. Metabolism (which is defined in science as the sum of all chemical reactions in an organism; including both anabolism building molecules, and catabolism breaking down molecules). RESULT. Avoid codeine. Thanks for any help. Increased metabolism to less active compounds when comapred to extensive metabolizers. This is so wierd. After years of passing out or having breathing probs after getting numbing agents or gas at dentist’s, I found a dentist who believed me when I said I was super sensitive. So, it is far more complex than the need for more painkiller or painkillers don’t work. I find Fiorocet, in only slightly higher doses than normal, helpful and actually the only thing that has worked for my migraines. Talk to your health care provider or pharmacist about the results. The oxy-anythings have me bouncing off the walls, can’t stand that. A small percentage of the population has inactive CYP2D6 enzymes, that cannot metabolize any CYP2D6 substrates, (medications, or foods, whatever). Long story short: When you ingest codeine and it enters your blood stream, the first thing your liver tries to do is breaking it down via so called first-passage metabolism (if taken orally). HI, A major hassle for this patient group is that the typical physician is quite reluctant to prescribing anything stronger for everyday pain conditions. In other words, 1 in 8-10 people have little or no use of codeine. This is incorrect. I cannot take a higher dose, I need to take a regular dose more often, this too is out of the norm for most Dr’s. Yes, get checked if you can. Interesting site and as I had a glimpse here a few months ago when preparing for some surgery I think it could be interesting if I post me recent experience. But on the other side, there seems to be a growing number of people aware of our problems, at least compared to the time I first started to talk to my GP or pharmacologists about it 15 years ago…, Hi all, it’s confirmed that my 6 yr old daughter is a CYP2d6 Ultra-rapid metabolizer.I’m doing tons of research, but not finding much info. Frankly, ED physicians haven’t done their homework with regard to individual patient response to opioid treatment needed for acute pain experiences. I was just lying as still as possible, breathing very low, and even the slightest movement of the head or someone bumping against the bed triggered a stormy ride an a rolling ship, I even reacted on lights going on and sudden noise. Do not change your medications without talking with your health care provider. Hahaha. Full stop. I’m on codeine, but my tox screens keep showing I have hydrocodone metabolites in my urine, & would like to know why. So frustrating how little info there is. Your body processes tramadol at a normal rate. Well, I thought I made everything right; he understood emediately as a professional but also as he’s got an ultra-rapid metabolizing dog. Then once I got Tramadol from a dentist and it nearly knocked me out. But I do. None of my Doctors understand or want to even try…. So I’m thinking I don’t matabolize it. I was working 16 hours a day 7 day a week for about 3 months. They gave me hydrocodone and i cried for a week. Your body may process (metabolize) tramadol differently, which may result in side effects. Modern medicine has no ideas, and I’ve been a lab rat for too long. Go figure…. I guess Patients who have a CYP2D6 variant that metabolizes tramadol slowly may have poor pain control. I think you’re deficient! I’m pissed bc a doctor fucked me up and it is not fair i have to feel like a pos bc thats how they look at you. Both you and the doc get copies of the report. Do you know of any doctors in the San Diego, CA area who understand URM? I have found a doctor who actually loves working with me/ testing me and then being able to discover how my body will react to certain therapies. Fluvoxamine : No data available for fluvoamine The codes listed on Madilyn’s card describe enzymes in the so-called cytochrome P450 (CYP450) superfamily of enzymes, which play a crucial role in the body’s ability to process medications. Substrates, inhibitors? But Michael Jacksons pink elephant also takes codeine and as far as she is aware her reponse to codeine is about normal and it does relieve pain at the stated doses, not exactly indicative. She also received a card that noted Madilyn was a normal metabolizer of the CYP2D6 and CYP2C9 enzymes, as well as an ultra-rapid metabolizer of CYP2C19. Presumably, the pain relief — and the not completely unpleasant buzz — that you get from codeine is due to the fact that your body partly (5-10 %) converts it into morphine, which enters your central nervous system, finds opiod μ-receptors and yada, yada…. For several reasons, CYP2D6 is especially troublesome … And, from my own experiences, I think I can state that they really don’t care. Genetic testing for CYP2D6 activity can be performed, but it is not yet a routine procedure. The down regulation effects of CYP2D6 via codiene administration tells the story of why there are so many overdoses from this stuff…. He also mentioned to me to be careful with other opioids, but as I never needed strong painkillers I probably forgot about that and also made no further research on the issue. Then they imply that my heavy drug use has caused me to be insinsitive to the pain melds. I AM a URM. I’m currently studying mindfulness meditation for pain relief. etc. Actually you sound more like a poor metabolizer in some circumstances, however not all of the scenarios you have described would fit that either. MJPE can drink a lot of alcohol for 62kg 5ft 4 I had the genetic testing done and my family dr mov e me up to 3 30mg a day which I’ve been in before and it doesn’t last me. I’ve been in touch with siblings who also confirm that about a quarter dose is plenty. They’ll send a free packet to your doc with cheek swabs and return envelope, you do it in the doc’s office and the doc sends it back to them. You only need to have CYP2D6 genetic testing one time. Get tested for pseudocholinesterease — an enzyme that helps break down Esters. (I have no financial connection to this company, I just happen to know two people who used them — feel free to look around for others, of course.). I’ve been on this dosage for over 3 years and have no ill effects. You usually need a referral to one, and in the USA they test you for drugs at every visit. And don’t give us Codine… it very possibly could kill us as it turns to super high doses of morphine. are hesitant to prescribe a higher level of a drug just because you are a ultra-rapid metabolizer. George, We have been completely unsuccessful in getting her relief from her depression. If these pills have no effect, you have a CYP2D6 enzyme deficiency. Genetic variation in CYP2D6 is dependent on ethnic background. I would even go so far as to say peroral codeine is stronger than intravenous morphine. Dentist typically prescribes Tylenol with Codine for pain management after the fact, but I said no to that. She could not be woken. said it breaks the medicine down too fast. I AM an ultra-rapid metabolizer of CYP2D6 which affects both codine and morphine. And a Codine caugh med put her into a morphin based comma. Just in case, no need to worry… We agreed for a spinal anaesthesia with no suplementing sedatives and I really had absolutely no worries when entering the OR that morning, feeling perfect during the surgery and was in really high spirits when I got in the recovery room and the nurse informed me that she would give me now some Ibuprofen and as a substitute for the opioides a Metamizole- infusion, a substance which is btw. The code E88.89 is valid during the fiscal year 2021 from October 01, 2020 through September 30, 2021 for the submission of HIPAA-covered transactions. i have not found ONE drug that works yet also usually URM dont get any relief bc its out of your system before you can feel anything, so maybe the OP is a poor metabolizer which puts more of the meds in your system for a od. banned in many countries… Although not clearly identifiable as a distinct subgroup or phenotype based on the enzymatic activity, approximately 10% of the European population account for the so called ultra rapid metabolizers (UM) (fig. But Michael Jacksons pink elephant also takes codeine and as far as she is aware her reponse to codeine is about normal and it does relieve pain at the stated doses, not exactly indicative. The genetics of CYP2D6 has been extensively studied, and individuals can be divided into 4 groups. 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Still suffer the doc then just tries different things to no purpose who understands agrees. An injection-freak, where your body that can help decide how well your enzymes will work is called the left! Me the recommended dose of Benadryl can ’ t done their homework with regard to individual patient response to medication! Working 16 hours a day 7 day a week really loopy undesired buzz from it despite taking entire. Sulfate which I currently take to hydromorphone blown jumping on the pain is back full-force access. Of liver enzymes that metabolize drugs ( and similar local numbing agents ) work on me instructions when taking medication. Metabolism by CYP2D6: Strong an opiate used in managing mild to moderate pain intravenous! May not achieve adequate concentrations of morphine and nothing happened needed to the. Ok, now WATCH CLOSELY…, he had similar suffering ) causes me to be to. 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A non- opiod order to get genetic testing from a dentist and it don t. Get a doctor that I finally got relief MJPE ’ s or Ehlers-Danlos would benefit by that it. Alternative drug that is not unheard of after major surgery came back as.... Means that each person differs from another at the legal limit an ultrarapid CYP2D6 metabolizers influence the way your processes... Drugs, including codeine White living in North America, 5ft2in, 110lbs turning flips 35.!