Cytochrome P450 Drug Metabolization Polymorphisms

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

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

Greatful!!
Dawn

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.

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.

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!

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. 🙂

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.

"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.