How can tolerance to Oxycodone suddenly decrease ?

[Unlucky]

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?

 

[Sturnam]

Yes, you are a medical phenomenon. If top doctors don't know why, we probably won't.

I'd think you'd be used to strange stuff happening to you by now, living with a rare neurological disease and what not.

 

[Unlucky]

Ye, Sorry guys my questions are often of a medical nature because my whole life is effected and restricted by my health problems but I only post the ones here that are specifically drug related thinking you guys could explain it as some of you are pretty knowledged in that area.

Yes I have been through so much strange stuff over the past 9 years but honestly it just doesnt get any easier. Everytime Ive posted a topic here its been immideately right after a bad reaction where I've felt hopeless, frustrated and confused by it with my odd symptoms. I'm sorry if my questions annoy you guys but I've got no one to turn to and the doctors have all failed in figuring my odd symptoms.

I only have 3 options left here, its either :

1- Stop opiates alltogether which I cant because of chronic pain and other reasons,

2- Keep taking them whilst hoping the adverse effects dont worsen enough to kill me someday

3- Keep looking for answers hoping one day I will come across a fix or some drug to counteract the effects which is more the purpose of this thread.

 

[seep]

This may be somewhere in your Bluelight file (which has a high text to post ratio), but have you been tested for CYP2D6 polymorphism?

 

[HereIam]

Could be as simple as liver problems

 

[Unlucky]

If you referring to the CYP2D6 liver enzyme genotype testing....I have also suspected this for a while and even talked about this in previous topics that perhaps my liver enzymes are abnormal and either metabolizing too fast or too slow resulting in the adverse reactions, however despite extensive searching I have not been able to find anywhere in Australia that can actually do the CYP2D6 tests to confirm my suspicions.

I have even mentioned it to my Neurologist and Autonomic specialist on many occasions but they too are unsure where the test can be done but now that you have also brought up the same topic again it is a confirmation that perhaps this is in fact the real issue here.

In that case I have been suffering unnecessarily for many years when a simple test could have solved this for me, I guess I have to continue searching harder for a place that can do this for me in Australia,

EDIT: See this why I post this stuff here cause you guys are way better than my doctors who never even mentioned CYP2D6 a a possible issue and if it turns out you guys were right about my liver then I owe it to you guys for helping me change my life, soon as I find a place that can do this test for me I will post back letting yous know if it was correct.

Thanks guys

 

[seep]

There's a lab in Adelaide that does the test, as well as a lab in New Zealand. Type cyp2d6 into the search pane here.

Verified poor metabolizers could probably make some money as study subjects.

 

[WSB15]

Are you taking any other medications (or even supplements/herbs)? Certain drugs can inhibit CYP2D6, which can lead to less oxycodone being metabolized, leading to higher concentrations. This probably isn't the cause but may be exacerbating the problem, causing the recent decline in tolerance. See http://en.wikipedia.org/wiki/Cyp2d6 (inhibitors).

Are there any other medications you're unusually sensitive to?

 

[Unlucky]

Seep your a legend man, I contacted them and they gave me even a closer adress for the test, cheers

WSB15, The only other medication I've been on is betablockers for the past 8 years, there are many other medications that I actually need to take but I avoid due to my sensitivity which has left me very cautious, I wear a medical bracelet to warn paramedics not to administer any morphine, tramadol, hydromorphone, codene, oxycodone or other opiates, anelgesics and even stimulants during an emergency situation as I have had also adverse effects with all of them.

 

[seep]

I contacted them and they gave me even a closer adress for the test, cheers

Glad to hear it. Here's some data on how the isozymes present.

I don't know that there's any treatment. As I understand it, if someone is a poor metabolizer, he likely has no 2D6 activity.

Consensus seems to be that 7% of caucasians have no 2D6 activity. That's quite significant. This test will probably be common in the near future.

 

[white_widow]

!!!DISCLAIMER: I AM NOT A PHYSICIAN!!!

actually, there are only two ways that I'm aware of to cause sudden opiate intolerance. the first is using an opiate antagonist, which is unlikely in your situation since its an experience you would never forget. the other thing you might want to look at is if you're taking an SSRI. sometimes the drugs can interfere with each other, causing one to work harder and one not to work as hard. meaning, if you've recently been put on an antidepressant that is also an SSRI, you may have been metabolizing less opiate for a while, and then if you stopped taking the SSRI long enough for it to leave your system, but continue to take the same dose of the opiate, you may notice an increase in side effects.

 

[Unlucky]

I don't know that there's any treatment.

I was actualy anticipating that the treatment would be based on the results , say if my test came back indicating that I was poor metobolizer due to little or slow CYp2d6 function then I was thinking of taking a CYP2D6 Inducer like Quinidine along with the medication thats causing me the adverse effects or if the tests indicate that I am a ultrarapid metobolizer then I was going to slow my liver function down with a CYP2D6 Inhibitor such as tagamet or grapefruit juice whilst I take my meds.

Its just a fix I came up with but I could be wrong about it, what do you think ?

White Widow I dont take any SSRI's even though Ive been told they could help me, but they also cause me adverse effects which is odd, unless they too are effected by the CYP2D6 ?

 

[kken]

i guess it could help you to some extent. But doubt it helps much with your threshold problem tho. If i recall right CYP2D6 does about 70% of the O-demethylation

 

[seep]

Yeah but I'm reading epidemiology data that says 7% of caucasians have no 2D6 activity, meaning (I haven't looked deeply into this) they translate a mutant that doesn't function and is literally a vestigial protein. So in this scenario there would be nothing to induce.

I hadn't thought about the possibility of being an ultrarapid metabolizer: you make an excellent point there. What is the symptom set for this?

There are other cytochrome P450s that are genetically polymorphic. 2C19 for instance.

*ps: Data are data, but how can 7% of the white population have a congenital inability to process so many xenobiotic substances? Seems counter-intuitive.

 

[Unlucky]

What is the symptom set for this?

- fast metabolizers resulting in reduced analgesic effect but increased adverse effects.

- slow metabolizers resulting in increased toxicity without improved analgesia.


According to Wiki The CYP2D6 function in any particular subject may be described as one of the following:

-poor metabolizer - these subjects have little or no CYP2D6 function
-intermediate metabolizers - these subjects metabolize drugs at a rate somewhere between the poor and extensive metabolizers
-extensive metabolizer - these subjects have normal CYP2D6 function
-ultrarapid metabolizer - these subjects have multiple copies of the CYP2D6 gene expressed, and therefore greater-than-normal CYP2D6 function

http://en.wikipedia.org/wiki/Cyp2d6

 

[seep]

Now I'm starting to want the test too. This is a fickle enzyme.

 

[QuasiStoned]

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.

 

[zzx]

This may be somewhere in your Bluelight file (which has a high text to post ratio), but have you been tested for CYP2D6 polymorphism?

Taken from http://www.purduepharma.com/PI/Prescription/Oxycontin.pdf. Seems a legitimate source to me.

CYP3A mediated N-demethylation is the principal metabolic pathway of oxycodone with a lower contribution from CYP2D6 mediated O-demethylation and in theory can be affected by drugs affecting cytochrome P450 enzymes.

Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone which represents less than 15% of the total administered dose. This route of elimination may beblocked by a variety of drugs (e.g., certain cardiovascular drugs including amiodarone and quinidine as well as polycyclic anti-depressants). However, in a study involving 10 subjects using quinidine, a known inhibitor of cytochrome P450 2D6, the pharmacodynamic effects of oxycodone were unchanged.

The reason why I'm posting is that I have needed pain management for the past week and everything I take just simply sucks and therefore I have been researching opioid metabolism, cyp etc. For example codeine hits me hard and fast with little analgesic effects and it's very short acting. Also if I were to follow the given guideline of 12 hour intervals for taking 10mg time release oxycodone I would be in intense pain for ~4hours or so. The analgesic properties start to wear off 6 hours after taking and the pain kicks in at full effect 8-10 hours after popping the pill. Maybe my doses are/were too low but then again I had enough respiratory depression from one 10mg oxycontin to make me concerned for my health 8) Sorry for offtopic :<

 

[Unlucky]

wow so your having problems with only 10mg as well ? that sucks. Have u tried hydromorphone or fentanyl ? I had excellent pain relief from those but horrible side effects, you might be able to tolerate it bettter than me though.

Seep, if it turns out the problem was with my liver enzymes all along then I would agree its is an exteremly fickle enzyme because I never had problems tolerating drugs prior to the overdose that contributed to my developing this neurological condition but at the same time Im confused that CYPD6 type is asscoiated with skin color, ethnicity and genetic predisposition but I assume it is not a definite trait to determine everyones type.

 

[seep]

Seep, if it turns out the problem was with my liver enzymes all along then I would agree its is an exteremly fickle enzyme because I never had problems tolerating drugs prior to the overdose that contributed to my developing this neurological condition

Generally speaking, gene expression patterns change throughout one's lifetime, and certain exogenous chemicals can activate and accelerate such changes. Whether or not this applies to the P450s is something I've never studied.

The neurological condition you mention was confirmed how?