• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio

Please translate results

DixiChik

DixiChik

Bluelighter
Joined
Apr 27, 2015
Messages
972
I am enrolled in pain management, but have extensive GI issues with absorption, metabolism, etc. I had Genetic Testing of enzymes for metabolism of meds, but have no clue what this means. I'm a hard case, which my PM doctor resents. I need someone here to translate these results and make suggestions for possible pain meds that I can tolerate and/or metabolize. TIA for your help. I need it badly!

This patient has genetic variations within the CYP2D6, CYP3A4 and CYP3A5 genes that predict a decrease in the CYP2D6, CYP3A4 and CYP3A5 enzyme function.

Reduced CYP2D6 enzyme function is expected to decrease the conversion of Codeine, Hydrocodone, Oxycodone, Dihydrocodeine or Tramadol to its active form.

Reduced CYP3A4 and CYP3A5 enzyme function is expected to reduce conversion of Ketamine to its active form and slow clearance of Codeine, Hydrocodone, Dihydrocodeine, Oxycodone, Tramadol, Merperidine, Methadone and Fentanyl.

Consider alternative medications such as Morphine, Oxymorphone, or Hydromorphone if not otherwise contraindicated.

Analysis of the CYP2C19 gene predicts normal CYP2C19 related enzymatic function.

I desperately need my PM to be more invested in my "wellness", but that's not happening. I don't understand the science or chemistry. Otherwise I would not have been dragged face down through a year and a half of failed med trials and ALL that implies.

PLEASE HELP ME!
 
Last edited:
The summary is right there:
Consider alternative medications such as Morphine, Oxymorphone, or Hydromorphone if not otherwise contraindicated.
Click to expand...
 
Sadly, it's not that simple. Morphine was one of the first trials (MS Contin). TMI, but my bowels did not move for 11 days creating a borderline obstruction that would have required surgery. I have mal-absorption issues due to gastric bypass in 1987. I don't absorb nutrients, vitamins, etc. This also "hinders" whether or not my pouch can tolerate oral meds. The MS Contin caused extreme chest pain, as in "rolling in the floor, praying for death". The new matrix Fentanyl patch trial failed me this time, for some reason. I had hideous SEs with no relief.

I am currently taking Oxycodone, because PM doesn't think I can metabolize OxyContin. I need extended release.

Dilaudid knocks me out. I can't function. I think Opana might be too expensive.

I know, I'm screwed.

Please tell me if I started this thread in the wrong "category".

Thx.
 
:\ P.S. YES, I take maintenance meds for constipation due to disease-ridden, surgically mutilated GI system. If I didn't take softeners, laxatives, etc. I'd never have a BM. My stomach distends as if I'm pregnant w/multiples. The opiate induced constipation was never discussed with me. I had to find out the HARD WAY that I needed to increase my softeners, and go with Miralax. I cannot afford the Linzess. I have to pay out of pocket for prescriptions. This is also quite the challenge, as relief of any degree seems to come with a huge price tag!
 
codeine and tramadol are not active on their own. they need to be metabolized by the CYP2D6 enzyme (an enzyme that shows great variations among people) into morphine and O-desmethyl-tramadol respectively to have a painkilling effect. the text says you are CYP2D6 deficient so you want painkillers that do not need to be metabolized by this enzyme to be active, such as the ones said to be considered.

your PM is wrong or knows something i don't because other than duration of action, there is no difference between oxycodone and OxyContin.

even though oxycodone and hydrocodone need CYP2D6 to be converted to the morphones, i think they are active on their own also (they should, if you are getting pain relief from your oxycodone) so this should not be a reason to avoid them.

bottom line, tramadol, codeine and some codeine-related painkillers will not be as effective, try other meds.
 
Perhaps the doctor thinks you will not absorb (not metabolize) Oxycontin well due to your GI problems? Oxycontin is oxycodone so there is no reason to think the metabolism will be different.

There are generics for Opana in both IR and ER form but if I remember correctly the ER is not considered equivalent to the brand by the FDA but I am sure you can get it without much effort. They are still relatively pricey, the ER being moreso.
 
I apologize for my ignorance of this stuff. I had such hopes the tests would provide info for PM doctor to direct me, as this is his specialty. He thinks the abuse-proof formulation will prevent absorption (my bad) of OxyContin. PLUS...EXTREMELY expensive.

I'm told the generic of Opana is sub-par, at best. Oh...I've put MUCH EFFORT into all aspects of this. I saw a total of 8 specialists across 3 states, just trying to get help. (see DaVinci Code type threads/posts for DixiChik) I begged for prescription assistance, through state programs and Pharma. I was told that our income exceeds parameters, therefore they could not help me.

My PM asked me on DAY ONE..."How have you existed with this suicidal pain?" "There are pain meds that can give you back your life, but they are expensive".

There seems to be a big ole brick wall in all directions. THANK Y'ALL for your input. Please don't give up on me. I NEED HELP!
 
Last edited:
CYP2D6 deficiency will reduce the painkilling activity (but not totally eliminate) of codeine, dihydrocodeine, tramadol. It's much less relevant to the opioids which aren't prodrugs.
Oxycodone and hydrocodone are not effected as strongly by this enzyme mutation, if those work for you, by all means use them.

The CYP3A4 deficiency means most opioids you consume will actually have a longer and stronger effect than other people: it means the drugs you consume will take longer to be metabolized that particular route, so they stick around longer in your system.

... as for "reduce conversion of ketamine to its active form"... what is that even talking about? Ketamine is the active form, norketamine (the metabolite), is much weaker, and isn't the drug people are after when they use K.

What does this mean? Don't use codeine, dihydrocodeine, or tramadol for opioid pain killers. That's basically it.
 
Last edited:
Much appreciation for everyone's input...I'm told I'm an enigma. :\ I'm a tough case, I guess...don't fit neatly into most doctor's "box". I never knew pain management would be so difficult. I basically have horrific cramps (with no uterus/ovaries), vaginal/rectal pain and crippling bone/spine pain. It shouldn't be that hard, should it?

I struggled so long, resisting the idea of serious "pain killer meds". I took only Darvocet for MANY years. YES, it helped me to cope with the pain and remain highly functional with my career and my life.

I lost my lifelong GP, cancer surgeon, and Darvocet within a year. I really haven't "steadied" from the death spiral that ensued. In late 2013 I traveled to the best specialists I could find in the Southeast. I saw GYNs, GIs, ORTHOs, NEUROs, UROs, rinse, repeat from UMMC to Vanderbilt to UT.

NO ONE wanted to touch me with a ten foot pole. They all pointed fingers toward the "other" as being the source of pain. I figured as much, but felt if residual disease was present, perhaps another extensive surgery could excise it.

NO...They all said "You're old. You hurt. Seek PM." I am. (54) I do. I did.

Hydrocodone provides some relief, but tough on liver/kidneys. PM wants Zohydro, but too expensive.

Oxycodone doesn't ease pain as such. It seems to change my perception. It hits fast, but quickly dissipates before the 6 hour dosing. He started me on 15 mg over a year ago. I'm afraid of this med because I don't want my body to NEED an opiate. I think that I would benefit from long-acting or extended release, but that seems elusive. I'm afraid of all the horror stories of addiction and urban legends. I don't trust my doctor to even stay in this country, even though he is department head/chairman of The Pain Center within my hospital.

I have been SHOCKED by the insanity of rules/regulations of prescribing. My doctor tells me that he cannot prescribe more than 100 per month due to DEA. He also says that if I had become his patient 5 years earlier, this wouldn't have been a problem. Huh?

I regret enrolling in this circus, that makes no sense to me. I would have preferred my GP "managed" my healthcare, but Tramadol could not replace the Darvocet and Hydrocodone became a schedule II. He threw me out with the bath water of CP, rather than "treat" with adequate pain relief.

I sound like a broken record, I know. I also know this site is not for pain management. I've tried other health sites, but am told I'm too graphic and my disease scares the HELL out of people. I just try to be honest, as I wish someone had been (to me) when diagnosed 2 decades ago.

I don't want to get HIGH. I just want to get UP every day with a lower level of pain. I'd rather grind through with pain, though, than feel sedated and drooling. I have to be on point, sharp and competitive whether professional or familial. I cannot bleed in the water. I'm damned if I do and, well you know.

:|

Again, forgive my ignorance, but what are "prodrugs"? Please don't DOG PILE me. I'm fucked enough, believe me. I don't need the cruelty.
 
Last edited:
The hundred per month as per the DEA is an outright lie. The federal government has no quantity limit only a max days supply of 30. Your state law may be more stringent, however. Have you looked into the copay assistance cards? Both Opana and Zohydro, and even Oxycontin have them but there are limits.
 
Many of the patients I work with experience chronic constipation, albeit not opioid induced. A steady regimen of docusate 100mg every morning and 17g mirilax once or twice daily, depending on clinical response, seems to do the trick for many. More resistant cases warrant po bisacodyl or rectal bisacodyl if, as is likely in your case, the enteric coated formulation is not efficacious. Linaclotide is added if the above regimen fails to produce bowel movements.

You mentioned trailing MS Contin, but experiencing severe OIC. Did you experience adequate pain relief? If so, methylnaltrexone, a quarternary amine opioid receptor antagonist has been recently approved for the treatment of OIC and does not cross the blood-brain barrier. It's influence is largely localized in the gastrointestinal track and may be an option to offset the constipation caused by an otherwise effective pain medication.

That's just my two cents.
 
Kittycat...I've questioned his policy as well.

If there is documented medical history that rivals Wikipedia (like mine) why is there an issue? His response is that he and colleagues have made a pact to limit to 100 per month to avoid "red flags".

My interpretation: My case is beyond legit. Perhaps he has other cases (that aren't) where he has over-prescribed, and can't afford the risk of DEA oversight. I cannot make sense out of nonsense.

Re: PAP cards would provide a % off regular costs, but both Zohydro and OxyContin are UBER EXPENSIVE. Like I said earlier, I've jumped through proverbial hoops. There seem to be no "breaks" for middle class working folks, that don't involve bones. I think today's "healthcare system" is one big cluster fuck of medical professionals, politicians and big Pharma. I digress.

The STRESS of the past two years has only made things worse. The root side of the grass is looking better every day.
 
Prodrugs are drugs which are inactive in their current form, but are metabolised by enzymes into an active form.

For example, codeine itself binds weakly to the mu opioid receptor. But it is demethylated at the 3 oxygen position to give morphine, which binds with much higher affinty to mu.

Around 7% of Caucasians are deficient in CYP2D6 (enzyme responsible for demethylation into morphine). This population will not find codeine or any other prodrug requiring metabolism as effective.

Your pain is probably only managed by strong opioids, but what non-opioid analgesics have you used, and to any efficacy? Have you tried methadone? You said oxymorphone is too expensive. Might be worth trying if you haven't already done so, and sort financial problems from there.

As others have said, prodrugs will probably be ineffective for you, but all other opioids should technically be fine, provided you are able to manage the side effects like OIC etc.

I'm no doctor, and don't know how well/if this will work, but just thinking from logic, you could suggest to your doc taking a med to increase CYP3A4 activity, since he has said you can't metabolise oxycodone. I think modafinil does this. It could also possibly eliminate some of the sedation side effects of the opioids you're taking.
 
Last edited:
I think so; if the gene coding for that particular enzyme isn't expressed properly then there will be less enzyme in the liver to modify the drug I believe.

The 2D6 genes code for 2D6 which demethylates the methyl ethers on the drugs.
 
AromaticNitrogen said:
If so, methylnaltrexone, a quarternary amine opioid receptor antagonist has been recently approved for the treatment of OIC and does not cross the blood-brain barrier. It's influence is largely localized in the gastrointestinal track and may be an option to offset the constipation caused by an otherwise effective pain medication.
Click to expand...

Off-topic, but does this drug cross the GI tract into the blood stream? If so, how? The quarternary amine would render lipophobic to cross the GI tract membrane?
 
Oh. Would the patient need to do administer it if treatment is prolonged? Also why can't it be given orally; won't it eventually reach the receptors in the bowels to antagonise? It's quite lipophobic so I'm guessing it wouldn't cross the GIT membrane lots.
 
Last edited:
Thank Y'all...I'm trying to absorb this (no pun intended) but my brain can't process the lingo.

I didn't want to retype my original threads and posts and I don't know how to create a "link" to simplify. It's not that I mind re-typing, but be warned...it's not 140 characters or less.

Remember folks...I'm old school. I speak with a slow Southern drawl. I consider myself a highly educated professional in Architectural Design. I don't know JACK about chemistry. I wish I'd known Jack Kevorkian. I thought a doctor who specializes in pain management would "manage" this information for me, and guide me through this maze. He hasn't. He won't.

I never got to find out if the MS Contin provided pain relief. It exacerbated the tummy issues so severely, it put me in the ditch.

He wanted me on Fentanyl from the first appointment. I resisted for a year, until other meds failed. The matrix (not gel) formulation did not perform well, even at 48 hour dosing.

Yes, he tried Methadone first thing, because he said it was good for lifelong treatment (and cheap). I couldn't tolerate it.

I CAN tolerate the Oxycodone with little SEs, aside from IBC issues, which are pre-existing. It's the OxyContin abuse proofing that prevents absorption.

With major surgeries in my history, I knew Morphine IV was the go-to for pain control in hospital. I was hopeful this would be what would work for me, but no. When a HUG fractured my weak bones last year (yep) I was given a shot of Morphine and Percocet in the ER. That's the best I've felt in 10 years.

The Oxycodone gives me that feeling, but not because it truly relieves the pain. It just makes me not give a damn that the pain is there. The IR Oxycodone, though, leaves me waking in horrid pain because the med has dissipated.

I'm going to try to figure out how to perform "quote" function so that I can address your specific questions as they are posted.

I'm sorry if I'm unclear, or too type-ative. My crap can't be solved in 140 characters or less. If it were easy, I would have done it a long time ago. :!
 
You must log in or register to reply here.
Top