codeine to morphine: what's the enzyme?

Specialties Pain


I just read that approximately 1 in 14 Caucasians lacks the enzyme needed to convert codeine into morphine and therefore codeine does not do it for these folks. (Pharmacology for Nursing Care, 5th edition, by Lehne; page 76)

WOW - that seems like a high number of cases. Have you guys experienced patients with this problem? Do you buy the 1 in 14 number? And the book says that the patients LACK the enzyme, not that they are deficient in its quantity... so that sounds like the patient would get absolutely NO relief (no enzyme available to catalyze the reaction)...

WHAT is the enzyme (:angryfire arrrrrrrrrrrgh - book did not mention the enzyme name)

Thanks for all comments,


Specializes in 5 yrs OR, ASU Pre-Op 2 yr. ER.

Steven Yale, MD

Codeine is a drug that has been used for years to treat mild and moderate pain. One of the ways that it is metabolized results in the formation of morphine, which is believed to be the metabolite that makes codeine effective as a pain reliever.

The vast majority of clinically useful drugs are degraded by a small number of metabolic pathways, mainly microsomal P-450 enzymes located in the liver, and to a lesser extent, in the small intestine. A form of P-450 enzyme referred to as CYP2D6 metabolizes about 20% of the clinical drugs. Extensive studies on the CYP2D6 gene over the last decade have identified at least 53 alleles, and of these, more than 20 are known to significantly alter the metabolism of CYP2D6 substrates. CYP2D6 activity ranges from complete absence to ultra-rapid metabolism.

The ability of CYP2D6 to metabolize codeine to morphine is absent in 7% of the white population. This means that millions of patients get less pain relief from codeine because their particular variant of the CYP2D6 gene is unable to convert codeine into morphine.

In this study, it is planned to investigate a subpopulation of the Marshfield Clinic patients that have a medical history of relative codeine insensitivity to identify their genetic polymorphisms and to stratify this subpopulation into groups exhibiting pharmacokinetic differences in codeine metabolism.

prmenrs, RN

4,565 Posts

Specializes in NICU, Infection Control.

There'll be a pop quiz on that material in the morning. Whew!!!

z's playa

2,056 Posts

For years my mother and I have been saying to doctors that codeine does no better than tylenol for pain relief. Now I know why. Thanks!

Or at least it comes close enough to an explanation for me.

jnette, ASN, EMT-I

4,388 Posts

Specializes in Hemodialysis, Home Health.

Very interesting... thanx ! Learned something new again today.

So......... is there a way to find out if you are one of the 7% on whom codeine would have no affect? So one wouldn't be wasting their time, money, and doc's patience? :rolleyes:


264 Posts

Specializes in MICU.

"thank you.... thank you very much"

You need to be in an Elvis mood when ya read this:Melody: :smokin:


41 Posts

Do like me, get a tibia fracture and try convincing the ER staff (in the middle of the night) that the codeine/paracetamol combo tablets they gave me earlyer didnt work ;)


4,516 Posts

Do like me, get a tibia fracture and try convincing the ER staff (in the middle of the night) that the codeine/paracetamol combo tablets they gave me earlyer didnt work ;)

Now we've got a snappy comeback to snooty staff who roll their eyes if codeine doesn't work for us. (and we will take our patients seriously when they tell US that ) :)

Great information!!


11 Posts

Does lacking this enzyme affect other drugs as well? My husband has always said that morphine does nothing for his pain but in 95% of his hospital admissions that require pain meds, they always insist on giving him morphine. Although the doctors don't say anything, we assume that they think that he is just drug seeking as they insist that morphine is the strongest pain med available. When the doctor asks if he is allergic to any meds, he will tell them that morphine doesn't work for him but they insist on giving it anyway. It wasn't until his brother was given morphine for a post-surgical procedure, and got no relief, that I began to think that it may be a genetically inherited trait.


65 Posts

I have the same problem with Percocet... but codeine works fine for me.

After my kidney transplant I was getting Percocet and practically crying from the pain. I asked if there was anything else ordered for pain, and the nurse said, "Just Tylenol with codeine." I begged her to bring me the Tylenol 3-- and within about a half hour I was able to tolerate the pain and finally get some sleep.

I guess if they know about the lacking enzyme for codeine, it must hold true for every other narcotic out there... I hope they develop a test so that people who have had surgery don't have to play a guessing game about which pain drug will or won't work for them.


4,516 Posts

I have seen this phenom in practice many times in critical care where we use lots of I have some good info to back my observations! :)

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