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Re: Paradoxical Reactions and Inverse Agonists » Larry Hoover

Posted by Quintal on August 30, 2007, at 16:32:33

In reply to Re: Paradoxical Reactions and Inverse Agonists » Quintal, posted by Larry Hoover on August 28, 2007, at 19:35:00

>Rather than bridging with I.R. oxycodone (as Percocet), I was switched from b.i.d. to t.i.d., and was stable at about 100 mg/day. I began to experience signs of sympathetic activation, including sweats and faints and panic attacks.

Thanks for the response Larry. I noticed increased anxiety and panic attacks after about six months of continuous use, but mine usually occurred after each dose, not between when I was withdrawing - so that's why I thought it was paradoxical. Same with the pain, some days it would work as normal, but as I built up tolerance I'd notice I'd notice it seemed to be causing pain in my neck and shoulders. I don't have any pain there in my unmedicated state, so that's what I found puzzling.

>I was told that withdrawal from the drug would necessitate my enrolling in a methadone program, which would exclude me from my habitual medical supports. Instead of receiving my drugs at monthly intervals, I would be require to go out daily, and travel to another city, to receive methadone. I was too ill, and unable to manage all that driving due to pain, to even consider that option.....

Yeah, it can be very inconvenient and traumatic for people therapeutically dependent on drugs of abuse to be treated in the same unit as illicit drug abusers. I believe Heather Ashton has made the same case for benzodiazepines, and I would attest to that. Most of the people there seemed to be hardened criminals. Also, the drug counselors were unprepared for dealing with serious psychiatric problems, and I imagine the same would be true of pain management.

>so I did the withdrawal at home, alone. I've never been sicker in my life. Not even close.

Pity you didn't have a bit of Mirapex to take the edge off? It does work, it's not a complete substitute, but it can definitely ease suffering. I think it would be interesting to explore the potential of using dopamine agonists in this way - to withdraw patients dependent on therapeutic doses of opiates in the outpatient setting. I've mentioned this to addiction specialists and it's met with extreme hostility, for reasons not grounded in science or medicine. I have a feeling the same would be true of pain specialists, though I'd like to think otherwise.

>Whoa, I'm been rather verbal, eh? This is the point I wanted to address, in fact. You might want to consider epigenetics, sometimes epigenomics. Prefix taken from the Greek that means "on, upon, at, by, near, over, on top of, toward, against, among." In other words, genes subject to the environment they occupy. We've already identified a number of genetic "switches", molecular changes in the DNA or its immediate environment, that turn genes on or off. These include methylation, histone complexes (proteins that wrap the DNA), and RNA that serves one purpose, to bind to and regulate DNA. Some of these effects even are capable of being passed along to the next generation (some experiments have shown grandparent to grandchild transfer), so the once ridiculed alternative to natural selection proposed by Lamarck, that the giraffe passed on its long neck by reaching for branches might yet have some validity.....Here's a recent study in rats, that hit the news: http://www.world-science.net/othernews/070814_obesity.htm

I saw the results of that study in the health section of The Sun of all places. My biology teacher once told us about the possibility of 'genetic memory', and I remember being intrigued at the time, I suppose this is what she was talking about? So what parts of my gene expression might have been upregulated/downregulated or switched on/off?

>That said, I do use small doses of oxycodone, when I cannot stand the pain. I just cannot foresee myself using it the way I once did. I use it with trepidation, and with some reserve.

I feel much the same way about Xanax.

>Ibuprofen is not usually associated with stomach problems, although chronic use can do you in. Buffering it with food is possibly all you need to do.

I had no problems with ibuprofen until I started taking it on an empty stomach to feel the 'mood elevating' effect more strongly after tolerance developed. This seems to have caused considerable damage, and I can't tolerate any amount of ibuprofen any more, even with food. I noticed a strong smell, similar to ammonia fumes, when taking my Nurofen Plus/Paramol combo on a n empty stomach. I don't know if it can actually produce ammonia, or whether it was a generic 'chemical' tang. A similar thing happened with a slice of Red Leicester on an empty stomach last week - stench of damp cow and overwhelming fumes which I managed to extinguish with some Gaviscon liquid, so I'm inclined to think it has something to do with the hyperacidity of my stomach.

Q


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