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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 5 of 5. This is the beginning of the thread.
Posted by Quintal on August 17, 2007, at 18:10:45
I've noticed for a while now that as I've built up tolerance to codeine, after each dose it actually seems to be *causing* pain. It reminds me of those ill-defined aches and pains, like currents running through the body, that one gets on high doses of GHB. Also, there is a mild pain in my back and shoulders. Last night I felt ill after taking my usual dose, so much so that I feared I'd accidentally taken an overdose. A great heaviness descended upon me, accompanied by a wave of sickness, leaving me feeling weak and faint. I'm starting to wonder if I have a bleeding ulcer which the ibuprofen has re-opened now my stomach acid is back on?
Anyway, today I felt much better when I got up so I didn't want to take any codeine in case it made me ill again. I've been fine all day without it - no pain or withdrawal symptoms at all. Yesterday I felt ill all day with it - pain despite taking a larger dose than the day before and a horrible malaise, which is the opposite of the usual effect it has on me. The day before, I ran out of codeine and I felt ill all day without it, withdrawal symptoms and awful aches and pains. So what's going on? I think Larry Hoover once had a similar experience with an opiate, so I'd be interested to hear what happened there.
I'm also thinking about the article I posted a week or so ago on benzodiazepine withdrawal, where the receptors can become locked into the inverse agonist configuration and thereby cause the opposite effect of the drug. I haven't examined that theory carefully, and it may just apply to people suffering lingering withdrawal symptoms after the drug has been discontinued, and therefore be irrelevant to this, but I wonder if there is a technical explanation for this phenomenon? Maybe the best thing to do is taper off to regain tolerance?
I'm thinking of substituting it with Parnate and Xanax for a month or so. I have some Parnate left over from my prescription last October and it's mildly dopaminergic so might take up the slack in my dopamine system. One batch goes off at the end of this month so I need to get it used up anyway and now would be a good time. I also need to stay away from the ibuprofen (in Nurofen Plus) as it cant be good for my poor stomach any more. I actually felt something wobbling around in there today, a fleshy mass of some sort. Not nice, but I'm not going back to the doctor unless it flares up again.
Q
Posted by chiron on August 18, 2007, at 8:50:44
In reply to Paradoxical Reactions and Inverse Agonists, posted by Quintal on August 17, 2007, at 18:10:45
Interesting. Why the body reacts paradoxically and why people react so differently is so interesting to me.
Posted by Quintal on August 18, 2007, at 13:22:16
In reply to Re: Paradoxical Reactions and Inverse Agonists, posted by chiron on August 18, 2007, at 8:50:44
Today I took a small dose of Paramol and it had the usual effect, but I haven't bothered with Nurofen Plus lest it aggravate my ulcer. I think this phenomenon is linked to tolerance, since I've always had typical reactions to opiates and other drugs in the past...
Q
Posted by Larry Hoover on August 28, 2007, at 19:35:00
In reply to Paradoxical Reactions and Inverse Agonists, posted by Quintal on August 17, 2007, at 18:10:45
I've been struggling to answer posts that I've been interested in answering.....this one took me a while to find again.
> I've noticed for a while now that as I've built up tolerance to codeine, after each dose it actually seems to be *causing* pain.
That sounds familiar to me.
> It reminds me of those ill-defined aches and pains, like currents running through the body, that one gets on high doses of GHB.
I'm unfamiliar with that, though.
> Also, there is a mild pain in my back and shoulders. Last night I felt ill after taking my usual dose, so much so that I feared I'd accidentally taken an overdose. A great heaviness descended upon me, accompanied by a wave of sickness, leaving me feeling weak and faint. I'm starting to wonder if I have a bleeding ulcer which the ibuprofen has re-opened now my stomach acid is back on?
I experienced a blend of withdrawal and overdose symptoms from oxycodone, after a period of stable use.
> Anyway, today I felt much better when I got up so I didn't want to take any codeine in case it made me ill again. I've been fine all day without it - no pain or withdrawal symptoms at all. Yesterday I felt ill all day with it - pain despite taking a larger dose than the day before and a horrible malaise, which is the opposite of the usual effect it has on me. The day before, I ran out of codeine and I felt ill all day without it, withdrawal symptoms and awful aches and pains. So what's going on? I think Larry Hoover once had a similar experience with an opiate, so I'd be interested to hear what happened there.
Yes, I certainly did. And my pain doctor denied that the drug was at the heart of it. I was using Oxycontin (sustained release oxycodone) t.i.d. (three times a day), because the drug did not last 12 hours in my body, as it was supposed to. 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. These would occur at roughly the mid-point between doses. I also began to experience abdominal cramping, enhanced pain, insomnia, and other signs of withdrawal, despite remaining at this stable dose (that had worked for a lengthy period of time). I lost so much weight (60 lbs.) that they did exhaustive testing for cancer, yet no one would attribute my suffering to the oxycodone.
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.....so I did the withdrawal at home, alone. I've never been sicker in my life. Not even close.
Anyway, my experience entering into withdrawl confirmed my intuitive understanding of what was happening; I had been in withdrawal, despite maintaining stable dosing of sustained release drug. Although my doctors wouldn't support my interpretation, they certainly validated the outcome. After withdrawal, the adverse symptoms went away.
I found some anecdotal reports of identical experiences on the net, or I feared I'd have lost my mind, thinking myself uniquely f*cked up. There is one doctor who published an account of this syndrome, and called it "downhill spiral syndrome", but it's not much accepted. I think that you can only use opiates for some finite period, and after that, your body finds some way to reject them.> I'm also thinking about the article I posted a week or so ago on benzodiazepine withdrawal, where the receptors can become locked into the inverse agonist configuration and thereby cause the opposite effect of the drug. I haven't examined that theory carefully, and it may just apply to people suffering lingering withdrawal symptoms after the drug has been discontinued, and therefore be irrelevant to this, but I wonder if there is a technical explanation for this phenomenon?
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
Your genes might be switched to different positions, Quintal. You might have been changed by using the drug for as long as you have.
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.
> Maybe the best thing to do is taper off to regain tolerance?
It worked that way for me. I was too scared to take any for a good four months, after I went through that hell.
> I'm thinking of substituting it with Parnate and Xanax for a month or so. I have some Parnate left over from my prescription last October and it's mildly dopaminergic so might take up the slack in my dopamine system. One batch goes off at the end of this month so I need to get it used up anyway and now would be a good time. I also need to stay away from the ibuprofen (in Nurofen Plus) as it cant be good for my poor stomach any more. I actually felt something wobbling around in there today, a fleshy mass of some sort. Not nice, but I'm not going back to the doctor unless it flares up again.
>
> QIbuprofen 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.
Lar
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
This is the end of the thread.
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