Cytochrome P450 2D6 (CYP2D6) testing

[mr_colt]

Does anyone know if the above enzyme metabolisation testing is avaliable in the UK? If so can it be done on the NHS? I've tried to ask my GP about it to see if it's the cause of my problems with codeine, tramadol etc.

Though he says it's a good possibility; he has left me with the fact finding if I want to get the test done: So can anybody point me in the right direction?

Many Thanks,

mr_colt.

[johnep]

Relevance is? Bet Pharout knows!
johnep

[mr_colt]

I see what you are saying but;

I don't know any clinical chemists and I have exhaustively searched the net but all the sites of interest are in other countries. I was just hoping someone on here might know where to point me to.

Or were you talking about the relevance between CYP2D6 and metabolism of codeine etc? From what I understand; CYP2D6 strips the methyl group off about 10% of the methylmorphine (codeine) turning it into morphine. Obviously people defficient in this enzyme will get little or no analgesic effect. Apparently it is required to properly metabolise a large number of drugs.

More information can be found here: CYP2D6 - Wikipedia, the free encyclopedia (yes i know its a wiki article but appears to be accurate.)

mr_colt.

[pharout]

Originally Posted by mr_colt

I see what you are saying but;

I don't know any clinical chemists and I have exhaustively searched the net but all the sites of interest are in other countries. I was just hoping someone on here might know where to point me to.

Or were you talking about the relevance between CYP2D6 and metabolism of codeine etc? From what I understand; CYP2D6 strips the methyl group off about 10% of the methylmorphine (codeine) turning it into morphine. Obviously people defficient in this enzyme will get little or no analgesic effect. Apparently it is required to properly metabolise a large number of drugs.

More information can be found here: CYP2D6 - Wikipedia, the free encyclopedia (yes i know its a wiki article but appears to be accurate.)

mr_colt.

CYP2D6 metabolism may affect the metabolism of certain drugs, but to what extent is UNKNOWN. The other factor is that does this metabolism result in clinical significance? Probably not in most cases. For example, tricylic antidepressants are 2D6 drugs, metabolized through this pathway, but still work. The third issue is that WHY would we test for it? It would probably be an expensive test and not very cost effective especially for the NHS. Would it change the course of treatment by doing the test? If not, no need for the test. Codeine is a poor pain reliever, and better cough suppressor. Bottom line, it is never a first choice to treat chronic pain. If it is not working, it either means you have developed tolerance to it and must rotate to another opioid, it's not strong enough to begin with for the type of pain you are treating, or the type of pain you're treating is not best treated by opioids. Where we are concerned more about 2D6 is if a drug metabolized through this pathway, has this process inhibited or sped up with a concommitant drug that "induces' or "inhibits" CYP2D6. For example, if someone is on say fluoxetine (Prozac here) and amitriptyline or nortriptyline for sleep, headache or neuropathy, it is standard to check a "amitriptyline" or "nortriptyline" level if on a dose >50mg per day. This is because the CYP2D6 interaction may exacerbate the side effect potential of the tricylic because one "inhibits" and one is "metabolized" through this pathway. I don't think this will ever be a cost-effective choice to test for, because there are always other options to treat the same problem.

[johnep]

Thanks pharout for the good explanation. However, codeine is used by the bucket in the UK 15,30 or 60mg qds along with paracetamol. In my area dihydrocodeine used to much lesser extent.
johnep

[mr_colt]

Thanks for the response,

I managed to bet onto Butrans after months of fighting for the medics to acknowledge that my pain is organic and not neuropathic. All the usual drugs like NSAID's, Trcyclics etc were tried with no effect.

Opioids are the only thing that have ever worked; but codeine, tramadol and DHC were barely effective on the pain. Buprenorphine has done the world of good in turning me from being almost bed-bound to housebound without door-to-door transport I suspose:

5mcg/hr is just not enough for any quality of life though, as I have mentioned in other posts. I have had to move counties to get close enough to an consultant who will script higher doses for someone my age (19) who isn't terminal.

So far it is looking like a trial increase to 10mcg/hr with Temgesic 200mcg sublinguals for breakthrough pain: From a pharm perspective is this a good combo to try? We were also thinking about oramorph for breakthrough but it only has a half-life of 4hrs and wouldnt bup's partial agonist-antagonist properties make it less effective?

mr_colt

[johnep]

Maybe wrong thread, but sure Mr colt knows answer. This is what does pt get exemption for if disabled. Could not find on back of FP10.
johnep

[mr_colt]

Well according to the PPA guidelines, I should qualify for a medical exemption certificate but thats another story. I was highlighting the fact that charge exemption was merely assumed. If the pharmacy wants to deprive the PPA of dispensing fees then its their choice.They might come to regret it at a later date though.

mr_colt.

[pharout]

Originally Posted by mr_colt

Thanks for the response,

I managed to bet onto Butrans after months of fighting for the medics to acknowledge that my pain is organic and not neuropathic. All the usual drugs like NSAID's, Trcyclics etc were tried with no effect.

Opioids are the only thing that have ever worked; but codeine, tramadol and DHC were barely effective on the pain. Buprenorphine has done the world of good in turning me from being almost bed-bound to housebound without door-to-door transport I suspose:

5mcg/hr is just not enough for any quality of life though, as I have mentioned in other posts. I have had to move counties to get close enough to an consultant who will script higher doses for someone my age (19) who isn't terminal.

So far it is looking like a trial increase to 10mcg/hr with Temgesic 200mcg sublinguals for breakthrough pain: From a pharm perspective is this a good combo to try? We were also thinking about oramorph for breakthrough but it only has a half-life of 4hrs and wouldnt bup's partial agonist-antagonist properties make it less effective?

mr_colt

Mr. Colt: you are probably the most educated pt I've come across (assuming you're not a healthcare professional). From a pharm perspective, it is always good to treat chronic pain with a long-acting or "basal" agent and another for breakthrough pain, such as you describe. I would argue that all pain guidelines support this. However, not all practitioners are "used" to prescribing this way or "comfortable" with it. There lies the problem! There are also medico-legal issues with prescribing these medications if something should go awry. ANY breakthrough pain agent will not last more than 4 hours, no matter what the kinetics say! The key to treating pain is to adequately dose the underlying basal agent so that you will not require breakthrough agent. Unfortunately, some patients know this, abuse it and doctors are certainly aware of it. Oramorph here in the U.S. is an extended release morphine product. One would not use this for b/t pain. Partial agonist/antagonists are never used to treat chronic pain, period...If your pain is not neuropathic in origin, not sure why tricyclics tried. Not sure what type of chronic pain you have? Sounds somatic? Low back pain? Paraspinal? It is important to know to choose the right agent. Also if your dose is titrated upward, a titration of <30% is clinically ineffective. You can feel free to send me a private message and I'd be happy to look into your issues.