Question for Rick

[Guest guest]

This brings to mind something possibly interesting in my case, but it

may have more to do with the process of encapsulating time-release

medicines than to the morphine that was in it: I took morphine for

pain for a long time (eventually the worst of the pain was found to

be due to neuromas in both feet, which were treated with cortisone

shots and I just started taking partial pills and eventually none at

all, so I have been off the morphine now for more than six months and

I now just have more tolerable overall body aches). But I was

prescribed a time-release morphine that was supposed to last 24

hours, and evidently for FDA aprrovals did last 24 hours (or more for

suitable overlap) in most people; for me it was gone from my system

in8-10 hours. If I did not take it three times a day my pain would go

from 3 to10 and back to 3 every day; to maintain the 'even keel'

effect I had to take it three times a day. Another doctor who had

tried me on time-release oxycontin was convinced I was lying when I

said _that_ lasted only 6-8 hours, so convinced was he that, if it

said it was a 12-hour or 24-hour (I forget now which it is supposed

to be) time release, that had to be correct. What might account for

using up a time-release medicine 3 times faster than it should (other

than something obvious like taking it and chewing it, or dissolving

it in some solvent, which I didn't do!)?

>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.

>

>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.

>

>In view of that, you might be interested to know what other

>substances are detoxed at least partially using this enzyme, so you

>can avoid those that are drugs or at least be aware that they could

>be potentiated. Here is the complete list of the ones I have found,

>and there are probably more that I have not found or for which the

>detox has not been completely studied and reported:

>

>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).