Share this:
Kelly, Alumna Mentor
@kdubois

Posts: 290
Joined: Mar 24, 2016

Cytochrome P450 Drug Metabolization Polymorphisms

Posted by @kdubois, Sep 13, 2016

Last March, I was diagnosed with multiple cytochrome P450 drug metabolization polymorphisms by Mayo Rochester’s Pharmacogenomics group. (In a nutshell, because of genetic polymorphisms in my liver enzyme system, I do not properly-metabolize most medications.)

Though I’m very thankful for finally having an answer to why I was becoming increasingly more and more ill for 12 years, it’s extremely difficult to find any information about this condition:
• I cannot locate any information regarding the clinical symptoms of having these polymorphisms.
• These polymorphisms are not rare, so I continue to remain stunned that pretty much no one in the medical community has a clue about this issue. Most doctors have nothing beyond a rudimentary understanding based on some P450 info they learned in their first few years of college.
• I cannot find information regarding the possible long-term affects on the body of taking P450 medications when you cannot properly-metabolize them.

At this point, I’ve learned about this via my own research (thank god for the Internet), and actually have to educate my own doctors regarding how to figure out whether or not they can or cannot prescribe a medication for me.

Does anyone know about any good resources for finding information about this issue, or has anyone ever been diagnosed with these? I want to prevent people from having to go through what I went through; this was a horrible experience that almost killed me, and I am certain that many, many people are also suffering from this in a widespread fashion. I’m working to compile information from legitimate sources, as well as a symptom list, to create an online support group.

Thank you!

REPLY

@dawn_giacabazi

The main thing we focus on with our patients is drug toxicities that can be predicted by P450 polymorphism include those exerted by codeine, tramadol, warfarin, acenocoumarol, and clopidogrel. We also evaluate the patients smoking habits because the polymorphic CYP2A6 has a role in nicotine metabolism and smoking behavior.

Drug-drug interactions are of particular importance with respect to adverse effects. In fact, adverse drug reactions (ADRs) are one of the major causes of death, amounting to the fifth leading cause in the United States, encompassing 100,000 deaths annually. In addition, ADRs are also responsible for up to 7% of hospitalizations.

This is why we are working with our physicians to make pharmacogenetic testing become standard practice prior to prescribing and dosing medications.

Smiles
Dawn

Jump to this post

YAY! I’m sure it will take a few years, but it’s necessary. My Pharmacogenomics guy told me that they realize at Mayo that they need to educate their own doctors. Acknowledging this deficit is the first step, and I’m glad that such a powerful-yet-morally-sound organization is leading the way for the remainder of the country.

You’ll find this interesting… when I got my results, I shared them with my brother, who lives in VA. About a week later, he shared a link from a local hospital there who is now including pharmacogenomic testing with all of their newborn screening. So cool!

@dawn_giacabazi

You are certainly in great hands with Mayo Clinics Pharmacogenetics Genetic Testing Dept & Mayo Clinic Labortories. They are the leaders in genetic research!!

Prayers
Dawn

Jump to this post

I have both selfish and unselfish reasons for doing it. Mostly as a heads-up for my daughters. Second, because they will share info with me, if I have the opportunity to find out about something years ahead of time and am then able to alter my life to prevent something from happening, why would I not want to know about it? Third, I firmly believe that this genetics stuff will significantly change/improve medicine for the better, though I know it will take a while. I just hope to still be around to see some of the findings and inventions come to fruition.

Thanks FANTASTIC!! Keep up the great work. 🙂

@dawn_giacabazi

@kdubois Sorry for my delay in response. I unfortunately have a limited knowledge on this particular drug but I do have alittle. It is more importantly the effects of your other medications with the P-450 CYP2C9. Such as anticoagulation drugs -risk of over-anticoagulation in patients on long-term treatment.

Here is a recent article I read that might help alittle. Sounds like you may know more than I. But definitely a topic I will most definitely research. I will see if I can help find a support group.

http://www.townsendletter.com/FebMarch2016/enviro0216.html

Curious: how does your body do at detoxification? Have you notice a significant complication?

I would suggest starting with a genetic specialist.

Many prayers
Dawn

Jump to this post

A symptom overlay like that would be impossible to parse out as a single ideas diagnosis unless it were something aggressively systemic like of course a cancer, or again, lupus or some equally systemic autoimmune disease. To get a handle on it you’d almost have to fall back to a toxicological interpretation and that’s essentially what you did. Every major system in your body was simply decompensating and with that many failures, the usual servo systems that would reestablish homeostasis couldn’t handle it. So, you were dying basically. The weight gain is what jumps out at me and your wondering how many people are being similarly effected. Been through some of that myself, which I attributed to aging, and still do to some degree, but its worth revisiting. Obesity/metabolic syndrome is what starts the cascade of deterioration for a lot of folks these days through different avenues, heart disease, heart failure, cancer, diabetes, even dementia. There is never a single, simple answer for disease although the mind, by nature, seems to crave simplification. This thing you and Dawn @dawn_giacabazi are onto is very close to being a Rosetta Stone however. Kudos to both of you.

@dawn_giacabazi

@kdubois Sorry for my delay in response. I unfortunately have a limited knowledge on this particular drug but I do have alittle. It is more importantly the effects of your other medications with the P-450 CYP2C9. Such as anticoagulation drugs -risk of over-anticoagulation in patients on long-term treatment.

Here is a recent article I read that might help alittle. Sounds like you may know more than I. But definitely a topic I will most definitely research. I will see if I can help find a support group.

http://www.townsendletter.com/FebMarch2016/enviro0216.html

Curious: how does your body do at detoxification? Have you notice a significant complication?

I would suggest starting with a genetic specialist.

Many prayers
Dawn

Jump to this post

“So, you were dying basically.” I totally agree with you! I think I would have been in liver failure this past June and probably dead by the end of this year. For the past four years, I had been to 20 local doctors about this issue, and not a single one had a clue what was wrong with me. I think that half of them thought I was crazy, and the other half believed me but had no clue what was wrong with me.

What stuns me is that every_single_medication_ad_on_TV tells you, “If your liver starts hurting while taking this medication, tell your doctor.” After hearing this last April, I stated loudly back to the TV, “AND THEY WILL HAVE NO CLUE WHAT IS WRONG WITH YOU!” (My 14-year-old thought this was hilarious and replied with, “Down, girl.” LOL.) When TV ads talk about avoiding grapefruit juice with certain meds, they are talking about P450. Funny how I can google things and find answers to problems, but doctors can’t.

“The weight gain is what jumps out at me and your wondering how many people are being similarly effected.” Excellent question! After I got my results, I googled “cytochrome P450” and the name of a pharmacy college in my city, and I randomly-emailed the first professor name I found asking her to meet with me. She replied in less than two hours saying yes, and we ended up meeting for four hours. The one major question she had was “Why did you gain so much weight from this?” She also said that in a pharmacist’s entire career, they learn a ton about this but never actually meet anyone who has them because no one gets tested. So, she’s invited me to speak at her P450 classes. Those will be cool.

Something else that you and @dawn_giacabazi can start thinking about… These same enzymes also metabolize many hormones. Therefore, do I also not properly-metabolize my own hormones? Does this explain my endocrine symptoms? Also…
• Do I have hypersomnia because one of the enzymes that metabolizes melatonin is CYP2C19, and that enzyme in me is Intermediate prior to other drugs making it work even more slowly?
• While pregnant, I was incredibly sick compared to most women — just as my mother was. Well, progesterone production increases significantly and is one of the hormones that causes the nausea and vomiting, and it is also too-slowly-metabolized by my wonky enzymes. Is this why I was so much sicker than most women while I was pregnant?
• I also wonder if I was misdiagnosed with acromegaly (a disorder where you produce too much growth hormone (GH) and insulin-based growth hormone (IGF1)), because I figured out that these P450 enzymes are modulated by — ta da — growth hormone! Maybe if your enzymes aren’t working properly, the GH keep trying and trying? And guess what causes too much IGF1? Growth hormone!

I sent these questions to my two Mayo endocrinologists to mull over (no response expected), so I hope that I’ve catalyzed them to start thinking. I also emailed these questions to a head of Endocrine and Genetics at NIH. He replied with, “Although possible, I am not sure that it is likely.” I actually found this to be a positive response. (I also found it interesting that he copied four other NIH doctors on his response to me. Maybe I was able to get some other brains thinking about these things, too.)

Another thing I also told my Mayo endocrinologists… I feel that once a person is diagnosed with these polymorphisms, Pharmacogenomics should be referring patients to related specialties, such as Endocrine. I also want to know what long-term use of these drugs has done to the other parts of my body, especially my liver.

The problem is, all of this is so new, that science, research, and discovery hasn’t gotten there yet. Bummer.

@dawn_giacabazi

@kdubois Sorry for my delay in response. I unfortunately have a limited knowledge on this particular drug but I do have alittle. It is more importantly the effects of your other medications with the P-450 CYP2C9. Such as anticoagulation drugs -risk of over-anticoagulation in patients on long-term treatment.

Here is a recent article I read that might help alittle. Sounds like you may know more than I. But definitely a topic I will most definitely research. I will see if I can help find a support group.

http://www.townsendletter.com/FebMarch2016/enviro0216.html

Curious: how does your body do at detoxification? Have you notice a significant complication?

I would suggest starting with a genetic specialist.

Many prayers
Dawn

Jump to this post

There’s a concept called “allostatic load” which describes how you hit a tipping point and the downward cascade accelerates. You were probably near that tipping but and had you been older, or had one more stressor, would have gone over. No doubt many people succumb without ever having had any idea what precipitated their final decline. I lived in Oregon not too long ago and the major ‘health’ megaplex I went to in Portland had so many seriously sickly looking people going in and out that it looked like the Court of Miracles. The vast majority were seriously overweight. That’s a trend that it it can be even slightly reversed much suffering will be averted.
As far as this issue causing endocrine disorders, its easy to start over-generalizing once you get momentum. Quite possible, or a complicating factor, much like how a fatty liver wrecks so many things, but the root cause of most endocrine problems probably unlikely.
We’d all like a unified field theory to explain all misery but its never going to materialize is my guess.
Once I get some more clarification of an issue I’m dealing with I’ll look into this, mainly as a way to help weight loss. Shedding 30 lbs would help a lot of things.
This won’t explain everything, but its a very good jump on a lot of problems.

https://en.wikipedia.org/wiki/Allostatic_load

@dawn_giacabazi

@kdubois Sorry for my delay in response. I unfortunately have a limited knowledge on this particular drug but I do have alittle. It is more importantly the effects of your other medications with the P-450 CYP2C9. Such as anticoagulation drugs -risk of over-anticoagulation in patients on long-term treatment.

Here is a recent article I read that might help alittle. Sounds like you may know more than I. But definitely a topic I will most definitely research. I will see if I can help find a support group.

http://www.townsendletter.com/FebMarch2016/enviro0216.html

Curious: how does your body do at detoxification? Have you notice a significant complication?

I would suggest starting with a genetic specialist.

Many prayers
Dawn

Jump to this post

Allostatic load — This perfectly explains what was happening to me! I had my own theory about this, but had no idea that there was a name for it.

I bet this is one factor of, maybe even the main contributing factor to, epigenetic switches being turned on, and perhaps also the cause of conditions such as fibromyalgia.

I truly-and-firmly believe that I was on-the-edge on my final decline. Years and years of feeling more and more ill and battling doctors all while trying to have a normal life (and the stressors of failing at that). It was at this point in August 2015 that I came home from yet another doctor’s appointment crying because I was told once again that I my tests had come back normal and nothing was wrong with me. I finally stopped crying and got mad enough at the situation to call Mayo Clinic and ask if I could come. Thankfully, my insurance requires no referrals to see other doctors.

Looking back now, it’s as if P450 drugs caused me to have a pseudo-acromegaly (with high but not super-high GH and IGF1 levels, which is usually the case, and lacking all physical symptoms). Another good example is that it caused me to have a buffalo hump, yet I always had normal cortisol levels, so no Cushings. When my PCP examined me on August 1, he lifted my hair and quickly said, “Oh my gosh, it’s gone!” The hump was there for years, and was still there when he saw me the previous mid-April.

And I do realize that it could be that I, as an individual, have a super-wonky set of polymorphisms even compared to most people out there. For example, 33% of caucasians like me are CYP2D6 Poor, BUT are they also CYP2C9 Poor/Intermediate and also CYP2C19 Intermediate, etc.? When I came to Mayo a year ago, I was on 12 medications; the more medications you are on, the more likely these issues are likely to occur. BUT, my P450 symptoms actually started in 2005 after adding Celexa to the Nexium that I had started in 2004. (An additional theory I have is that this seems to occur to those of German ancestry more than other caucasians.)

Feeling better is great, but seeing all of my physical symptoms completely disappear from ceasing these drugs seems to have been the most fascinating factor for doctors. Knowing that I have lost 50 pounds in six months solely from ceasing metoprolol, omeprazole, ranitidine, and duloxetine has stunned them.

When you get a chance, please do look into this for yourself. One thing that my Mayo pharmacist said that struck me was, “I feel that every person should have this testing done.” I feel that he’s spot-on with this. He said that for all of the people he had tested from August 2015 through February 2016, most people had at least one polymorphism.

One other battle that I’m still in is getting doctors and pharmacists to realize that there are non-P450 metabolized medications that also inhibit/induce these enzymes. Currently, they stay inside-the-box and don’t consider other meds; they assume that a drug metabolized elsewhere in the body won’t affect things, and they also neglect to consider that things like vitamins. I know these things do because I lived it and felt this happen to me — and the symptoms were exactly the same with these drugs as they were for metoprolol, omeprazole, ranitidine, and duloxetine. I think the problem is that they look things up on sites like clinicalpharmacology.com, which lacks information. Knowing that my clinical symptoms didn’t match what my Mayo pharmacist was telling me (i.e., non-P450 drugs don’t affect this), I did more research and was able to locate a Canadian database that acknowledges that these other drugs and supplements indeed do inhibit/induce, and this exactly-matches my clinical symptoms regarding taking non-P450 drugs / vitamins and inhibiting/inducing P450 enzymes. (It’s called http://www.drugbank.ca, and it was developed by their government and their genome institutes. It’s also acknowledged by some P450 doctors and pharmacists in Germany that I correspond with. These people have another database and also a tool that I’m looking into. The tool let’s you enter your specific polymorphisms and medications and it will give you severity results.)

Liked by JohnWBurns

@dawn_giacabazi @johnwburns @alysebrunella @colleenyoung — I wanted to share the attached photo with you. This is what cytochrome P450 drugs did to me because of my inability to properly-metabolize them. I started ceasing them in January 2016, and by July I had lost 50 pounds — any stopping these P450-metabolized drugs is the only lifestyle change I made. Though I am still detoxing from them, I will be forever grateful to my Mayo doctors for listening to me and suggesting that I have these tests. What my home doctors couldn’t figure out for 12 years, Mayo figured out in only six months.

Interestingly, in December 2015, I was in the patient cafeteria at Mayo and saw a young woman walking by looking for place to sit, so I waved her over to sit with me. We talked about medical stuff, as is normal in that cafeteria, I told her that Mayo was going to perform these Pharmacogenomic tests on me, and I told her that it sounded like she had many of the same issues I was having. We decided to become Facebook friends.

She was able to get into my doctor in Allergy/Immunology, and they decided to perform the testing on her. (I’m not sure why they sent me to the Center for Individualized Medicine but they ordered the tests for her directly from their department.) Anyway, it ends up that she has three of the exact same polymorphisms I have, plus some that I wasn’t tested for (and I have polymorphisms that she doesn’t have). We are now forever-friends and slowly-building our own community of information to help people.

——–

*** Looks like the site removed the sides of my photo. I’ll try to revise and repost. Regardless, it still gives you a good idea regarding what happened to me.

@kdubois

@dawn_giacabazi @johnwburns @alysebrunella @colleenyoung — I wanted to share the attached photo with you. This is what cytochrome P450 drugs did to me because of my inability to properly-metabolize them. I started ceasing them in January 2016, and by July I had lost 50 pounds — any stopping these P450-metabolized drugs is the only lifestyle change I made. Though I am still detoxing from them, I will be forever grateful to my Mayo doctors for listening to me and suggesting that I have these tests. What my home doctors couldn’t figure out for 12 years, Mayo figured out in only six months.

Interestingly, in December 2015, I was in the patient cafeteria at Mayo and saw a young woman walking by looking for place to sit, so I waved her over to sit with me. We talked about medical stuff, as is normal in that cafeteria, I told her that Mayo was going to perform these Pharmacogenomic tests on me, and I told her that it sounded like she had many of the same issues I was having. We decided to become Facebook friends.

She was able to get into my doctor in Allergy/Immunology, and they decided to perform the testing on her. (I’m not sure why they sent me to the Center for Individualized Medicine but they ordered the tests for her directly from their department.) Anyway, it ends up that she has three of the exact same polymorphisms I have, plus some that I wasn’t tested for (and I have polymorphisms that she doesn’t have). We are now forever-friends and slowly-building our own community of information to help people.

——–

*** Looks like the site removed the sides of my photo. I’ll try to revise and repost. Regardless, it still gives you a good idea regarding what happened to me.

Jump to this post

Incredible @kdubois. Thank you for sharing so openly.
PS: I’m afraid that the photo attachment tool on Connect clips all images to the pre-set size.

Amazing!! Thank you for sharing and pray your encouraging success rings loud a amounts many!!

PgX is truly an amazing tool
Dawn

Please login or register to post a reply.