Re: Sara's drug sensitivities

March 5, 2006

Rich, can you please explain what " steroid rage from cortisone "

means? What happens physically inside as well as any outward

manifestations of such a thing going on?

Thanks...

>

> Hi, Sara.

> [...]

To check this out, the next step was to find out what other

substances are detoxed using this enzyme to see whether any of them

would ring a bell in your case. Well, lo and behold, it turns out

that UGT2B7 is also used to detox morphine and related opiates,

Diflucan and the androgenic steroids, among others. And, of course,

you reported terrific problems with anesthesia which likely involved

morphine or other related opioids , particular effectiveness of

Diflucan in knocking out your yeast infections, and steroid rage

from cortisone. So based on these observations, I think there is a

good possibility that you do have a polymorphism in your UGT2B7

enzyme.

[...]

March 5, 2006

On Mar 5, 2006, at 4:47 PM, rvankonynen wrote:

> Hi, Sara.

>

> I think I may have a small piece of your story figured out. Here's

> the rundown:

Rich, I am boggled. Really.

I'm getting ready to send you my full " story' (maybe later this

evening) as requested. I'm updating it to include the past nine

months -- amazing to see how much change there's been in my condition.

>

> In trying to understand a case, one of the first things I do is to

> study the unusual things that are reported. One of the things you

> have reported is is an unusual sensitivity to Naproxen. As you

> probably know, the body views drugs as toxins, and uses its detox

> system to get rid of them. If a person has higher than normal

> sensitivity to a particular drug, it often means that there is

> something amiss with the particular part of the detox system that

> normally gets rid of that drug. As a result, when such a person

> uses the drug at what is a normal dosage and dosing frequency for

> most people, which is based on how fast the normal detox system is

> able to get rid of the drug, this person experiences much stronger

> effects than normal, because the drug rises to higher concentrations

> and has a longer biological half-life in their body than in that of

> a normal person.

The naproxen thing was one small detail out of a great many (and,

frankly, one I've used to good advantage over the years -- it's great

to have something in the house that works that well). Interestingly,

it has not affected me nearly so strongly in recent months, perhaps

due to the glutathione shots?

My understanding -- I seem to recall that this even made it into the

Canadian case def -- is that it's very common for PWCs to be

extremely sensitive to many drugs. If your glutathione hypothesis

proves correct, could that be one explanation for this long-observed

phenomenon?

> O.K., so the first step was to find out how the detox system

> normally gets rid of Naproxen. It turns out that it does this by

> the pathway known as glucuronidation, one of the Phase II detox

> pathways. Glucuronidation of a particular drug or endogenous toxin

> takes place by means of one or more of the isoforms of the enzyme

> uridine 5'-diphosphoglucuronosyltransferase, or UGT, for short. In

> the case of Naproxen, it was reported last year (Bowalgaha et al.,

> PMID #16187975) that the main isoform of UGT involved is UGT2B7.

> So my suspicion was that you inherited a genetic polymorphism

> inUGT2B7.

>

> To check this out, the next step was to find out what other

> substances are detoxed using this enzyme to see whether any of them

> would ring a bell in your case. Well, lo and behold, it turns out

> that UGT2B7 is also used to detox morphine and related opiates,

> Diflucan and the androgenic steroids, among others. And, of course,

> you reported terrific problems with anesthesia which likely involved

> morphine or other related opioids , particular effectiveness of

> Diflucan in knocking out your yeast infections, and steroid rage

> from cortisone. So based on these observations, I think there is a

> good possibility that you do have a polymorphism in your UGT2B7

> enzyme.

It's true that a little bit of any of these drugs goes a very long

way for me. Sometimes (like when I'm taking morphine post-op, for

example), that's a good thing. Sometimes (like when I take cortisone

and turn into the Incredible Red-Headed Hulk) it's not so good.

I've tried to explain this phenomenon to anesthesiologists the last

several times I've had surgery. They seem universally inclined to

ignore me, and way overmedicate anyway, leaving me confused,

panicked, sick, and miserable for days. Maybe if I include this

information next time, they'll take me more seriously....? It's a

hope. <g>

> Among the drugs, morphine and related opiates, Diflucan, the 1,4

> benzodiazepines, including Valium, Librium, Dalmane, Xanax and

> others; Naproxen; Voltaren; ketoprofen; ibuprofen (Motrin, Advil,

> Nuprin); fenoprofen (Nalfon); clofibric acid; and Retrovir. Among

> the endogenous substances, hyodeoxycholic acid (a component of

> bile); estriol (a form of estrogen produced during pregnancy); and

> the androgenic steroids dihydrotestosterone, androsterone and

> androstane-3 alpha, 17-beta-diol (3 alpha-diol).

Well now, there, see? I was just writing in my history about my

overstrong reaction to testosterone gel, despite the fact that my

blood tests show I'm very low in that area.

Much explained. I'm beyond grateful, and am excited to see what else

might come up that could prove useful.

Sara

March 5, 2006

Rich,

A lot of this sounds like my situation. Naproxen made me very sick also,

although I don't have any problem with ibuprofen. When I had knee surgery

under general anesthesia 20 years ago, I awoke, with difficulty, to somebody

slapping me -- it had been that hard to get me conscious again. I also have

problems with exogenous estriol and DHEA (although you didn't mention the

latter, I'm thinking it probably undergoes the same detoxification process

in the body?). About 10 years ago I tried using mild anabolic steroids (for

wasting syndrome-- they use it with AIDS patients) under the guidance of a

doctor, and it made me really ill and no one could see why. Would you

suggest calcium-d-glucarate as a way of dealing with this deficiency?

I'm working on answering all those questions that you asked me, and I'll

probably be able to post it tomorrow.

Thanks,

Ellen