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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

Hi @kdubois, thanks for sharing all of the information with us. Finding an exact cause for a diagnosis or understanding the complexity of certain diseases can be frustrating, but I’m so happy that you continue to reach out within the Connect community. I’m bringing in @dawn_giacabazi and @johnwburns into this conversation as well, because I know they will be able to provide valuable insights.

Please keep the community posted on your journey. @kdubois, do you have any of the research you mention readily available to share?

I think @dawn_giacabazi is way more current on this than I am. Kudos to you for having the patience and savvy to triangulate on it. Not intuitively obvious and I’ll bet its a lot more common that anyone suspects. I have a history of drug reactions and I suspect that this is the root cause.

It seems like Mayo is on the bleeding edge but I haven’t drilled down on it. Too many other irons in the fire.

There’s this overview but I’m sure you’re past that.

http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-alerts.asp

Looking forward to more information.

Just found what Dawn sent me.

http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-testing.asp

@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

@alysebrunella

Hi @kdubois, thanks for sharing all of the information with us. Finding an exact cause for a diagnosis or understanding the complexity of certain diseases can be frustrating, but I’m so happy that you continue to reach out within the Connect community. I’m bringing in @dawn_giacabazi and @johnwburns into this conversation as well, because I know they will be able to provide valuable insights.

Please keep the community posted on your journey. @kdubois, do you have any of the research you mention readily available to share?

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Not quite yet. I’ve been gathering info, but I need to organize it. I just created a Facebook group called “Cytochrome P450 Support” and have posted only a few of informational links. At this point, the group is Public. What’s also missing out there is an explanation how each time a medication is added to or removed from a person’s regimen, the entire thing morphs and changes because so many drugs metabolized by P450 enzymes can also inhibit and/or induce these enzymes — sometimes even the very enzyme necessary to metabolize the drug itself.

@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

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Thank you for the info… I’ll definitely read.

***WHAT’S REALLY SCARY is that even if you don’t have polymorphisms, these medications can mess you up because they still inhibit/induce (mainly inhibit) the enzymes from working properly.*** These are drugs like Nexium, Zantac, Cymbalta, Prozac, etc.

From the nine (9) tests, my results yielded six (6) polymorphisms. I’m CYP2D6 Poor, CYP2C9 Intermediate (possibly Poor due to currently-undetectable polymorphism), and CYP2C19 intermediate. I’m CYP1A2 Extensive/Normal unless induced, and then I’m UltraRapid. Plus, I have sensitivities to Warfarin and Allopurinol. They even figured out that Tamoxifen, a cancer-fighting drug, will actually give me cancer if I am given it after menopause.

I can’t share my Mayo Genome Report due to HIPAA, but let’s just say that it was VERY colorful compared to the sample on the CIM web site.

I’m glad that you called it “detoxification” above. That’s what I call it because I had no other term to call it. Coming off of them slowly, I stopped taking my last P450 drug on March 11, 2016, and between January and July, I lost 50 pounds and pretty much every single symptom in the list below*** has completely disappeared.

During all of this (2004 – 2016), based on the symptoms below, I was misdiagnosed with a rare endocrine condition called acromegaly despite lacking the clinical physical symptoms of the condition. This resulted in a slew of unnecessary medical treatments, including a brain surgery which caused brain damage.

***My symptom list…

– Constant weight gain that I couldn’t lose and that kept slowly-climbing. (When I saw my PDP in January 2016, I was considered obese at just under 200 pounds. When I saw him in April 2016, I was then considered overweight and about 172 pounds. When I saw him on August 1, 2016, his jaw dropped when he first looked at me; I weighed 150 pounds and had a BMI of 23 (normal weight). The only thing I changed during this time was that I stopped taking P450 drugs.

– Body-wide edema. I felt like I was engorged, and I remember telling several doctors that I felt like I was “full of medication.”
o My face was so swollen that the bows of my glasses left indentations on the sides of my face for years, and I could feel my face jiggle when driving.
o Fat pads developed at my belly, upper back (buffalo hump), on my sides above my hips, and above my collarbones.
o Pitting edema in my legs.
o My feet were a half-size bigger.
o My breasts became a full size bigger and always extremely very firm. I also experienced leakage that could not be explained via prolactin lab tests.
o Swollen right hand, then right forearm, then left hand, then left forearm. I couldn’t see my knuckles for years.
o The back of my tongue was swollen for years. I couldn’t even sing.
o When I bent forward, my abdomen felt tight like it was about to pop.

– Lymphadenopathy
o Swollen lymph node under my chin
(sub mental gland) that I could feel with my hand and was painful.
o Borderline swollen lymph nodes found on my pancreas.

– Visceral hypersensitivity and pain: I can feel both liver lobes, the head of my pancreas, parts of my small intestine, and my right ovary separately.

– Sicca Syndrome:
o Chronic dry mouth
o Chronic dry eyes – no longer able to wear contact lenses

– Pain:
o Constant body wide aches.
o Sometimes, my legs between hips and knees would hurt. Sometimes shoulders.
o Liver enlargement and pain (both lobes; first off-and-on and then constant) (this was the worst symptom; the right lobe hurt more than the left; my doctors in Rochester, NY kept telling me that you can’t feel with your internal organs, but they are incorrect. Mayo called this visceral pain.
o Kidney pain.
o Small intestine swelling and pain (first off-and-on and then constant)
o Minor bouts of pain in the head of my pancreas
o Intermittent kidney pain
o Pointed pain in right side of neck and in front of neck
o Headache (different from my normal headaches)

– Nasal sores inside of my nose that leaked clear fluid

– Dermatological:
o Bumps on the back of my upper arms
o Cysts that would open on my face and in my hair that would leak clear fluid

– Excessive, exhaustive fatigue

– Whenever I caught a cold/virus, I would always be sicker and longer than every other person in my family. Even my elementary school-aged kids noticed this.

– Odd smell coming from my body
o Skin, armpits, and vagina
o Originally like campfire smoke or combustion engine exhaust; once I ceased P450 meds and started detoxing, it changed to smell more like chemicals or burnt plastic

– Facial flushing despite no physical activity

– Hyperhidrosis (profuse sweating)
o Profuse sweating invoked by minimal activity and feeling extremely hot inside. Once this sweating started, it wouldn’t stop if I stopped moving around.
o Profuse sweating invoked by covering up the back of my neck, wrists, ankles, and torso. I wore my hair up for years.
o I didn’t need to wear a winter coat for a decade, and I live in Western New York.
o Night sweats while sleeping; I would have to woke up in the middle of the night in the winter to change clothes because they were soaked.

– Shortness-of-breathe feeling in my lungs and coughing

– Malaise (general unwell feeling)

– Emotional/crying for no reason plus unusually irritable

– Mild sore throat off and on

– Low-grade fever off and on

– Bouts of nausea; minor bouts of vomiting

– Borderline low blood sugar off and on

– Ovarian cysts, pain, and spotting (right side only)
o It started a few months after I was prescribed my second P450 drug in 2005 and then stopped before 2006 began.
o It started again in April 2016 after I stopped all P450 drugs, during what I call my detox time.

– Brain fog and worsening memory issues (which cleared-up once I ceased all P450 medications)

– Many friends and nurses told me that my skin was gray-colored.

I started taking my first P450 drug in 2004, and then as time went on more and more were added to my regimen — sometimes to treat the pain and other symptoms that these very medications were causing. Despite having a liver that always hurt and was enlarged for years, I never became jaundiced, and my liver labs always came back normal.

@johnwburns

I think @dawn_giacabazi is way more current on this than I am. Kudos to you for having the patience and savvy to triangulate on it. Not intuitively obvious and I’ll bet its a lot more common that anyone suspects. I have a history of drug reactions and I suspect that this is the root cause.

It seems like Mayo is on the bleeding edge but I haven’t drilled down on it. Too many other irons in the fire.

There’s this overview but I’m sure you’re past that.

http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-alerts.asp

Looking forward to more information.

Just found what Dawn sent me.

http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-testing.asp

Jump to this post

The fact that it’s not an intuitively obvious problem is definitely a reason for it’s lack of diagnosis. I asked my Mayo Pharmacist is these are rare, and he replied with , “No, but they are very rarely diagnosed because the testing isn’t widely available.”

I actually promoted Mayo to figure this out for me. Last November, I wrote my primary in endocrinology an email stating that I was sure that a medication I was on was making me sick, and I added that I had had odd reactions to medication my entire life. Not really adverse reactions, but really weird reactions. So I asked him if drug hypersensitivity was a thing, and if so if they could refer me to Allergy/Immunology. He immediately referred me, and I wasn’t able to get in until January, but I had a free day during my December week there, so I checkered into an appointment with Dr. Daniel Maddox. He suspected P450, but wasn’t sure. I told him that I had read something about P450 recently, and he told me to find it when I got home and email him. After a few exchanges, we were certain that I had a P450 issue, and he referred me to Pharmacogenomics. What I liked the most about him was that he seemed genuinely-pleased that I had done research and was able to talk to him about this stuff.

If you suspect that you also have P450 polymorphisms, wait until January-ish and look into having it done by Mayo then. Trust me on this one.

Bittersweet story about this… I saw my local nephrologist today. Before I left, she thanked me saying that she’s been able to learn a ton from me because of this P450 issue, plus she said, “Don’t take this the wrong way, and this is going to sound weird, but you are probably the perfect person for this P450 thing to happen to.” I was like, “Ummm… whatttta?” She said that because I’m “savvy” and have taken the time to educate myself and advocate for myself — mostly because for years and years, I kept pushing and pushing and pushing doctors and was willing to travel until someone figured out the answer — and especially because I was the one who asked Mayo to test me for drug hypersensitivity — that I have done more than just save my own life. I told her that I’ve always just been kinda feisty, that I just knew that I was genuinely ill and wasn’t going to allow any doctor to tell me otherwise, and that I just had to keep going until this was figured out.

Then I asked what other people do, and she replied with, “They just give up.” :’-(

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

@alysebrunella

Hi @kdubois, thanks for sharing all of the information with us. Finding an exact cause for a diagnosis or understanding the complexity of certain diseases can be frustrating, but I’m so happy that you continue to reach out within the Connect community. I’m bringing in @dawn_giacabazi and @johnwburns into this conversation as well, because I know they will be able to provide valuable insights.

Please keep the community posted on your journey. @kdubois, do you have any of the research you mention readily available to share?

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My zen lesson with this came with metoprolol, plaquenil and duloxetine. I hit the trifecta. Apparently some drugs are both indices and substrates and I won’t pretend to understand that dynamic. Most people are probably more likely to run into this when they get older and hit a situation like treatment resistant hypertension, where they pile drugs on. Add some psychoactive stuff and you’re off and running. As far as educating a doctor I won’t even try because the knowledge is in many cases just not out there in terms of chemical soups overplayed onto biochemical individuality. The message is probably to take fewer drugs, period, if possible, and stick with those that have been around long enough to have accumulated a lot of patient years and consequently understanding.
Things are crazy enough when you have an autoimmune disease that associates with a lot of drug reactions, e.g. Lupus.
I’ll check out the FB page.

@johnwburns

I think @dawn_giacabazi is way more current on this than I am. Kudos to you for having the patience and savvy to triangulate on it. Not intuitively obvious and I’ll bet its a lot more common that anyone suspects. I have a history of drug reactions and I suspect that this is the root cause.

It seems like Mayo is on the bleeding edge but I haven’t drilled down on it. Too many other irons in the fire.

There’s this overview but I’m sure you’re past that.

http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-alerts.asp

Looking forward to more information.

Just found what Dawn sent me.

http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-testing.asp

Jump to this post

You are your best advocate!! Not many people are confident enough to do that. You should be very proud of yourself. Sorry the road has been so difficult. As I have learned from my own complicated journey, it is through our trials we become stronger both for ourselves and GREAT advocates for others who can not do it for themselves.

Smiles
Dawn

@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

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Yes, they are! I’m so glad that I decided to come to Mayo, which I did on my own without any doctors at home helping me. After seeing my test results, they asked me to take part in their NGS study. I’m stoked for this!

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

@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

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Thank you for agreeing to be apart of the NGS study. You will help many patients with your sacrifice.

Greatful!!
Dawn

@alysebrunella

Hi @kdubois, thanks for sharing all of the information with us. Finding an exact cause for a diagnosis or understanding the complexity of certain diseases can be frustrating, but I’m so happy that you continue to reach out within the Connect community. I’m bringing in @dawn_giacabazi and @johnwburns into this conversation as well, because I know they will be able to provide valuable insights.

Please keep the community posted on your journey. @kdubois, do you have any of the research you mention readily available to share?

Jump to this post

Your trifecta had two of my bad meds! Metoprolol is on my red list; took it for nine years and Mayo put it on my DO NOT TAKE list. Duloxetine is on my yellow list, but I consider it red based on clinical symptoms.

Yeah, many drugs inhibit or induce the same enzyme that the drug itself needs to get out of the body’s system. It a drug inhibits, and you then add another drug in that also inhibits, your decrease the body’s ability to metabolize drugs that are substrates of that enzyme even more. It can go on and on…. it’s just crazy!

I was put on Metoprolol because I’m allergic to sulfa and all sulfa derivatives, so P450 heart meds was what my docs here at home were trying for my hypertension. Now we know that those can’t be used, so Mayo is having me try to the drug approach via the the low sodium DASH diet. Two grams of sodium per day maximum. I’m starting tomorrow.

Yeah, doctors definitely don’t understand the intricacies of this, and they definitely don’t understand that each and every patient they meet will be entirely different.

Interestingly, many old-school drugs, such as spironolactone, are usually not P450-metabolized. (This gives rise to big pharm.’s role in everything. Hmmmm…)

Funny you mention lupus… I actually got drug-induced lupus from a drug not on the lists of drugs causing drug-induced lupus. It’s a rarely-used endocrine drug, so there’s no data about it.

As few drugs as possible — absolutely!

One other thing… I gained so much weight while on these drugs, and lost so much when coming off of them, that I wonder if, in addition to poor diet, America is “fat” because everyone is taking so many medications. I actually wasn’t fat; I was engorged with edema and what I call “P450 junk.” I am certain that some portion of these medications remain in my system because at times I can smell an odd odor coming from my body — like chemicals or burnt plastic.

@johnwburns

I think @dawn_giacabazi is way more current on this than I am. Kudos to you for having the patience and savvy to triangulate on it. Not intuitively obvious and I’ll bet its a lot more common that anyone suspects. I have a history of drug reactions and I suspect that this is the root cause.

It seems like Mayo is on the bleeding edge but I haven’t drilled down on it. Too many other irons in the fire.

There’s this overview but I’m sure you’re past that.

http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-alerts.asp

Looking forward to more information.

Just found what Dawn sent me.

http://mayoresearch.mayo.edu/center-for-individualized-medicine/drug-gene-testing.asp

Jump to this post

Agreed! After learning so much stuff, in addition to learning how to navigate the system, helping others do the same is just the right thing to do.

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