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Cytochrome P450 Drug Metabolization Polymorphisms

Just Want to Talk | Last Active: Jan 22, 2017 | Replies (25)

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@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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Replies to "Hi @kdubois, thanks for sharing all of the information with us. Finding an exact cause for..."

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.

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.

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.