How can tolerance to Oxycodone suddenly decrease ?

[onmyway]

What would cause a person whos been on oxycodone everyday for over 1 year to suddenly require cuting back on their regular dose because they are no longer able to tolerate the regular dose they were previously taking ?

I actually thought someone whos been on an addictive drug like Oxy everyday for a year would have issues with increased tolerance however I seem to be having the opposite problem. Is my situation so unusual that could I be considered a medical phenomenon ? Could my lack of tolerance be of used in any way to help the medical world especially for people who have issues with increased tolerance to medications ?

Initialy when I started on liquid oxycodone I started with only 2mg due to a chemical sensitivity that I suffer from, It took me about 2 months to work my way up to a 5mg dose of liquid oxycodone which at first was sufficcient to manage my pain for a good 6 months or so, but then my tolerance very slowly began to increase at a rate of 1 mg per month and eventually I hit 10 mg but suddenly in the past 1 month Im finding that I had to reverse the process as my body is becoming overwhelmed by the 10mg that I had been using for a while

So 10mg seems to be my threshold, how can such a threshold even exist limiting my usage from ever going above a set dose ?

So I pulled back to 9mg and still found myself experiencing some adverse effects although not as bad so I finally settled back on 8mg....which seems I can tolerate and it has some pain reliving effects, but how on earth did I end up with having to decreased tolerance without taking any breaks from using the drug? What are the mechanics behind such a body response ?

PS> I understand my chemical sensitivity may have some role in this however it does not explain that once I suceeded in desensitising myself to the meds how I could revert back so easily after having been able to use it for so long without issues?

what if your pain has decrease a little bit for some unknown reason? this could cause you to perceive the negative effects of opiates more.

 

[Unlucky]

The neurological condition you mention was confirmed how?

Ive had several tests from different specialist all with the same diagnosis of Autonomic Dysfunction and Orthastatic Intolerance. This all started on the day of my overdose , before that incidence I was a healthy guy going to raves every weekend and taking ecstacy, speed and lsd and in the morning after I was smoking myself silly to come down off it all and then taking sedatives and even heroin sometimes and I never had a bad reaction to any of it before, but then one day unexpectadly I overdosed on amixture of ecstacy, mda and amphetamines resulting in hyperthermia and loss of conciousness which changed my whole life and when I woke up in hospital my body wasn't the same anymore due to the damage I suffered and the past 10 years has been hell for me.

The Autonomic Dysfunction was confirmed with several tests, a "table tilt test" that indicates that every time I move or stand up my heart rate doubles and blood pressure skyrockets, then I also had a test confirming "Norepinephrine transporter deficiency and hypermethylation of the norepinephrine transporter (NET) gene that occurs only with this Neurological condition. I then had metal rods inserted in to veins in my legs and arms to measure electrical activity and constriction of the veins that respond to counteract gravity as a person stands up or changes posture and it was found mine were no longer functioning as normal, I laso had a sweat test that measure my body ability to cope with heat because once u develop Autonomic Dysfunction the message between your brain and sweat gland cease to work causing heat intolerance and Anhidrosis.

The chemical sensitivity usually occurs secondary to all this however mine is at a ridiciliously bad compared to others with this condition and I believe the reason is because I developed mine as a result of a drug overdose which is failry uncommon so when I overdose it really messed up my brain chemistry and even possibbly altering the CYPD6 enzymes in my liver which is what I will have get checked out.

 

[Unlucky]

what if your pain has decrease a little bit for some unknown reason? this could cause you to perceive the negative effects of opiates more.

I actually hold out all day and then only take the opiates once my pain worsens and when I have an adverse reaction it is so bad I dont even notice the pain anymore

Even when I had kidney stones, one of the worst pains I've ever had they gave me only 5 ml IV morphine in hospital, the adverse reaction was so bad I could no longer feel the kidney stone pain and in fact I would have prefered the pain over the adverse effects.

 

[onmyway]

could you describe these adverse reactions you have to opiates?

 

[seep]

I also had a test confirming "Norepinephrine transporter deficiency and hypermethylation of the norepinephrine transporter (NET) gene that occurs only with this Neurological condition.

Oh.

 

[Unlucky]

could you describe these adverse reactions you have to opiates?

I experience two different types of adverse effects depending on the type of opiate, but the common effects between the two is always a fever or hyperthermia response.

With fentanyl, codene and morphene I get a high fever along with supresive type of reaction where I experience respiratory depression, itching and red bumps, wheezing, difficulty swallowing, acid reflux, iregular heart, slowed heart, low blood pressure and feeling just horrible and ill.

With oxycodone, hydromorphone and tramadol I get a more neuroexcitory adverse effect again with high fevers but also high blood pressure, muscle spasms and twitching, jaw clenching, build up of pressure in my skull and head along with headaches and neck stiffness, agitation, confusion, irregular heart, slowed pulse down to 45 bpm and feeling unwell and realy wired.

 

[Temeraroius]

I've always felt pretty sure that I was CYP2D6 deficient. I used a lot of DXM when I was younger and the effects were atypical and VERY long lasting. I would usually feel speedy effects in all dosage ranges, and in higher dosages (500mg + ) I would still feel stimulated (though I would experience some disassociation in higher dosages, probably because DXM alone is a weak NMDA antagonist). The effects from even a small dosage of DXM (75 - 100mg) could be felt for 24 - 36 hours, and would taper off VERY slowly.

Codeine was virtually ineffective for me in the few trials I had with it. Tramadol seems to be nothing more than a fast acting antidepressant for me.

Shit dude, the first time I tried DXM I felt drunk for abt 3 days, tramadol has no effects unless taken in conjunction with marijuana (even then its only a slight effect), codeine doesnt really do shit for me either. I might be in the same boat as you.

 

[seep]

This all started on the day of my overdose , before that incidence I was a healthy guy going to raves every weekend and taking ecstacy, speed and lsd and in the morning after I was smoking myself silly to come down off it all and then taking sedatives and even heroin sometimes and I never had a bad reaction to any of it before, but then one day unexpectadly I overdosed on a mixture of ecstacy, mda and amphetamines resulting in hyperthermia and loss of conciousness which changed my whole life and when I woke up in hospital my body wasn't the same anymore due to the damage I suffered and the past 10 years has been hell for me. The Autonomic Dysfunction was confirmed with several tests, a "table tilt test" that indicates that every time I move or stand up my heart rate doubles and blood pressure skyrockets, then I also had a test confirming "Norepinephrine transporter deficiency and hypermethylation of the norepinephrine transporter (NET) gene that occurs only with this Neurological condition. I then had metal rods inserted in to veins in my legs and arms to measure electrical activity and constriction of the veins that respond to counteract gravity as a person stands up or changes posture and it was found mine were no longer functioning as normal, I laso had a sweat test that measure my body ability to cope with heat because once u develop Autonomic Dysfunction the message between your brain and sweat gland cease to work causing heat intolerance and Anhidrosis.

So the theory so far is that acute and concurrent ingestion of what you construed to be MDMA, MDA and amphetamine provoked a sequence of mutagenic events that resulted in methylation of NET gene sequences, thereby compromising your ability to synthesize functional NET?

 

[onmyway]

With fentanyl, codene and morphene I get a high fever along with supresive type of reaction where I experience respiratory depression, itching and red bumps, wheezing, difficulty swallowing, acid reflux, iregular heart, slowed heart, low blood pressure and feeling just horrible and ill.

much of that sounds like it could be mediated by histamine, or other cytokines. allergic degranulation of mast cells will also cause prostaglandin levels to rise, which will tell your hypothalamus to increase body temperature.


With oxycodone, hydromorphone and tramadol I get a more neuroexcitory adverse effect again with high fevers but also high blood pressure, muscle spasms and twitching, jaw clenching, build up of pressure in my skull and head along with headaches and neck stiffness, agitation, confusion, irregular heart, slowed pulse down to 45 bpm and feeling unwell and realy wired.


that is weird and sounds more like it could have to do with the autonomic nervous system. the low heart rate seems paradoxical though. almost sounds like what happens when you get an increased intracranial pressure (cushing reflex). sounds like you might have screwed up your hypothalamus when you overdosed.

come to think of it, have you had a CT scan?

hypermethylation would probably silence the NET gene but how would this happen from your overdose? maybe this predisposed you to autonomic dysfunction, and whatever brain damage you got from the overdose made the symptoms worse.

 

[Unlucky]

Hey guys thank you for taking an interest in my case and for all the help,

At first the overdose caused the Autonomic Dysfunction, then the Autonomic Dysfunction eventually caused the hypermethalation of the NET gene as it became more integrated with my body and reached its full state.

I know it sounds pausible me claiming that my overdose resulted in developing an Autonomic disorder but all my specialists agree that it was the case especially when the changes I experienced were immediate following the overdose, also one of the causes for the Autonomic Disorder is listed as "Chemical Exposure" as quoted here...

3) Exposure to toxic chemicals which damage the autonomic nervous system can cause POTS. This group includes adverse reactions to prescription drugs. Some Gulf War veterans have developed POTS like symptoms after being exposed to small amounts of nerve gas, insecticides, and inadequately tested experimental drugs.

http://home.att.net/~potsweb/POTS.html

http://www.dinet.org/what_causes_pots.htm

Its not as simple as saying I overdosed and ended up with a damaged Autonomic System, there are many other factors here to consider such as the pills I took that day may have contained other neurotoxic substances, also that the night before I had been dancing for 8 hours at a rave and had lost a lot of elctrolytes only to come back to engage in drug fuelled sex, and it was 5 hours into sex when I actually overdosed whilst my brain chemistry was further altered by the hormones and chemicals released in the brain during sexual activity such as oxytocin, dopamine, vasopressin and when I overdosed I experienced severe hyperthermia that I believe did damage areas in my hypothalamus causing me the constant daily problems with fevers and temperature control that I now experience. Also the possibility that I was perhaps already prediposed to an Autonomic Disorder that was triggered early by all the complications during the overdose. Short story: I really messed up myself and 10 years later Im still paying for it and its exteremly frustrating living this way.

I still dont understand how the ironic outcome of drug intolerance can occur as a result of a drug overdose but hopefully if CYP2D6 test Im having on Monday will, but if it turns out its not my liver enzymes than Im back at square one.

 

[Unlucky]

I just got the results back for my Cytochrome P450 test and it was very dissapointing, I was certain it was the missing piece of the puzzle because all the symptoms seemed to fit but it turns out the results were normal...

CYP2D6 = *1/*1 - Extensive metaboliser
CYP219 = *1/*1 - Extensive metaboliser
CYP2C9 = *1/*1 - Extensive metaboliser
VKORC1 = GA - Increased Warfarin Sensitivity

So it seems I am back at square 1. My neurologist is now suggesting that after eliminating the liver as the cause my problem could actually be due to generalised damage to Serotonin (5HT) terminals in the brain and to a lesser extent other neurotransmitters. As Serotonin is involved in many functions, the loss of functional neurons could of result in some of the symptoms I seem to be having.... so does this mean I am oficcialy screwed because there is no cure to regenrate neurons ?