Problems with Meds and Disease Associations
 

I am not sure how I stumbled upon this concept, and there is not a lot in layman's terms, however, apparently having a mutation (polymorphism) in the drug metabolism enzyme CYP 2D6, is associated not only with drug problems but also with spondyloarthropathies and a few other diseases. It seems most connected in spondyloarthropathies.

Anyway, any one who has issues with medications would be well served to read up on the inability of some folks to metabolize medications. This also may extend to substances in the environment, but not much research has been done yet on this.

I know some PNers have arthritic issues, and I wonder how much overlay there is. Maybe some one can explain this better, as I am in territory that is getting a bit over my head, and I don't know how this relates to debrisoquine hydroxylase deficiency...any chemists, pharmacists or really smart people who can explain is a debrisoquine hydroxylase deficiency the reason that the drugs can't be tolerated, or is it that you can't tolerate debrisoquine hydroxylase?? And, how and why should this be associated with diseases such as Ankylosing Spondylitis?

I really need some answers, because, I am soooo sick of getting sick on this list of drugs, and getting very little relief from the pain med mentioned...and I am wondering why every joint in my body is sore, (enthesitis or enthesopathy) and what this has to do with neuropathy??? Did I get a boatload of bad genes or is this one systemic condition?? I am getting to the end of the internet...again.

BTW, IVIG is helping the neuropathy, a lot...but not the arthropathy, arthritis or other issues.

http://www.fpnotebook.com/Pharm/Meta...02d6Isnzym.htm

Ok, I found that debrisoquine is just a 'substrate', no different than an SSRI, or tricyclic. I don't know why they bothered to name it debrisoquine hydroxylase deficiency. It is just as simple as not being able to metabolize that substance.

Well I have found that I must take the methylcobalamin form of B-12. The other form not only doesn't seem to help much but causes some nasty sides for me. But that's just me.

I've done a bit of research on problems with absorption that people have. If you're having problems with food wouldn't you say it's a good chance you're having issues with drugs and other substances as well?

cyclelops,

I am glad you brought this topic up. And I believe I am one of those people. You are right though, it gets involved! For years I could NOT understand why people could take all kinds of medications and I had issue after issue. And it is not like I didn't give the meds time. I just never, ever got past the SE's or rather, adapted to the medication. In any case, I CANNOT take the nerve meds (Neurontin, Depakote, Lyrica as an example) NOR the SSRI's. Suffice to say I was much worse while on them; extremely sick. I can handle the SHORT ACTING narcotics and the benzodiazepenes however. Also, Prednisone, Kenalog, Celestone; the last two as in injections.

Finally, a pharmacist mentioned CYP450 to me and basically explained to me it was the way I metabolized meds. Or, well, the way that I couldn't. He told me also it gets very, very involved. So, I have a family friend who is a Geneticist and she called me in regards to this subject. She told me that she, herself, is deficient in the CYP450 and always has to cut meds in half or take low doses. I kind of laughed when she said that because I have been cutting mine in half for years and stay with very low doses. But she did recommend asking my Neurologist to run a test to see where I stand on this CYP450. I haven't done so yet but really need to. I keep forgetting to ask. :rolleyes:

In any case, I HAVE to keep the doses low. It doesn't obliterate all the pain; just takes the edge off. And I also have OA all over the place! My spine being the worst. I have also read something in regards to OA and arachidonic acid. I would have to go look it up again. But IF I recall correctly, it is the Cox 2's that inhibit production of it. I could be way off; just seems I read something about it.

I have issues with the Cox 2's as well with the exception of Limbrel which is really a botantical medical food. It DOES help with the OA pain since it ACTS LIKE a Cox 2 but it can also cause stomach upset. Some people swear by it while others don't.

This website...
 

has some interesting information:

http://www.healthanddna.com/drug-saf...n-testing.html

http://www.healthanddna.com/drugchart.html

Thank you Mrs. D., the information was very helpful.

I am going to ask either my PM or Neurologist to run a panel if they will. I was thinking about this. Wouldn't it be nice if ALL docs ran a panel at FIRST? I realize it would probably be expensive and maybe not necessary. But at least it would give them a sort of "blueprint" before prescribing anything. In any case, I have been forever told I am just extremely sensitive to meds and it is all very well documented in my charts. So, I just have to keep the meds low. Again, thank you.

there is a test by Roche...
 

that doctors know about. (hopefully)
http://www.roche.com/med-cor-2005-01-12

The one I put up is a consumer one. I noticed that it has gone up in price. It used to be in the 600 dollar range.

I don't think insurance pays for the first one. You'd have to call your carrier.

I think this subject is long over due. In fact, vitamin/mineral use by the body varies from person to person as much as well.
So far we know thru genetics of 25 enzyme errors that involve the folate pathways. That is only ONE nutrient.

Sadly, I have to say, many doctors do NOT understand this subject. This is the largest hurdle. I would call them all the time with interactions (some very serious) and they would refuse to listen. The subject is very hard to understand, and because they are not trained to believe it, they don't.
And the bottom line is most doctors don't even understand drugs at all! That is why the Big Pharma gets away with what it does these days!

I know I am a slow metabolizer...since one Flexeril lasts me 2 days! So I do not use many RX drugs myself. I find other ways to improve pain, depression, and fatigue. (and those work wonderfully for me).

Kathi

You mentioned that you have OA all over. There is some link with 2D6 and ankylosing spondylitis. They can't say it is causal, but there are links. Parkinson's is also somehow linked.

I have gotten myself down to 2 meds, one is a 2D6, but I take very little, and it takes the edge of pain.

Anesthetics don't work on me. SSRIs cause movement disorders and autonomic meltdowns. Tricyclics the same thing. Allergy pills, ditto.

I did some genealogy and one quarter is utterly Swedish back to 1300 where things kind of stop and I think or am pretty sure, that side is indigenous or what could be called Sami. I can't prove it though. Interestingly, they have a high incidence of spondyloarthropathies, and also 2D6 issues in Sweden. The other quarter is British, and way back to 1600's in this country....again, same names appear over and over the generations. The other side is mutt, which is good.

Insurance won't pay for the genetic testing. It runs 600-1300$. I may have it done. One caveat, every day they find new stuff and not all mutations are discovered. There is not one drug in the 2D6 that I don't have pretty big issues with, so I would be surprised if they did not find a mutation in me.

I am tired of arguing about SSRIs and how good they are for me! Unfortunately, a lot of cancer drugs are in this group too, as is the Alzheimer's drug, and the Zofran I had a reaction to recently. As soon as I tell my GI I had a reaction, he orders more! It goes down the toilet and I tell him, again, I can't take that, and it goes in my chart as an allergy. The Zofran (ondasetron) was a doozy reaction. They pass this drug off as the safest drug on earth. It is an SSRI...

I thought I would die from Tramadol.

Anyway, check out the spondylarthopathies, interesting group of diseases....not related to PN from what I read, but you never know what will crop up in the future.

Mother Nature is going to have to cure me.