This post is from an article on Medscape. I am sharing it because I have clients with these issues, and these enzymes have impact ~ Causing either extreme sensitivity to a class of medicine (aka Ultra Rapid Metabolizers), or, lack of absorption (aka Slow or Under Metabolizers ) of the same drug can occur.
Many drugs are processed via these pathways. In this article, specifically, they are discussing Opioids such as Codeine/Morphine. Great insight for those that do take pain management medicines and wonder why they are not getting relief.....
Please share, this has impact on many adverse responses, and/or high doses of medicine, than any study I have seen thus far.
Perhaps these findings can guide Clients/Patients and Health Care Providers, on better, individualized care at a personal level, that is much safer than the norm today. Scroll down for the complete article....
We now offer Pharmaco Reports via a CLIA certified lab, extracted from your raw genetic data file. This is included in the 'Complete Plan Consultation' at www.snowdropherbals.com. As always, work with your practitioner to implement any possible changes you deem necessary.
As always,
Be Well, Be Happy, Be Healthy
SnowDropHerbals
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Medscape article on CYP* Enzyme function
Patients with chronic pain who require high doses of opioids to
achieve pain relief show exceptionally high rates of defects of the
cytochrome P450 (CYP450) enzyme system compared with the general
population.
The CYP450 enzyme system is known to play an important role in the
metabolism of opioids, and recent advances in genetic testing allow
for the easy detection of defects to the enzymes.
"We've known for years that among patients with the exact
same pain conditions one may need 500 mg of morphine a day while the
other may need only 50 mg, but we've always wondered why," lead
author Forest Tennant, MD, told
Medscape Medical News.
"It turns out that among high-dose patients, about 85% have
these defects in 1 or more of their CYP450 enzymes." In the
general population, only about 20% to 30% of people have CYP450
defects, he said.
His findings were presented here at the American Academy of Pain
Management (AAPM) 23rd Annual Clinical Meeting.
Emerging Frontier
To evaluate patterns among his own patients with intractable pain,
Dr. Tennant tested 66 patients attending his clinic in West Covina,
California, who required more than 150 mg equivalence of morphine a
day for pain relief.
The patients were tested specifically for the CYP2D6, CYP2C9, and
CYP2C19 enzymes. The results showed that 55 (83.3%) of the 66
patients had 1 or more CYP450 defects, 21 (31.8%) had 2 defects, and
6 (9.1%) had 3 defects.
According to chronic pain management expert Gary M. Reisfield, MD,
genetic research is poised to reveal expansive new insights into the
mechanisms of why some patients respond to medications whereas others
don't.
"Pharmacogenomics represents the emerging frontier for
understanding interindividual variability in opioid efficacy and
toxicity, and in guiding safe and effective opioid pharmacotherapy,"
said Dr. Reisfield, an assistant professor and chief of Pain
Management Services in the University of Florida College of
Medicine's Divisions of Addiction Medicine and Forensic Psychiatry
and Department of Psychiatry in Gainesville, Florida.
"With regard to opioid response, the mu-opioid receptor, the
ATP [adenosine triphosphate]-binding cassette subfamily B, and other
genes are believed to play significant roles," he explained.
With CYP450, a "superfamily" of enzymes responsible for
the metabolism of most opioids, various polymorphisms and variables
in activity can have clinical significance.
The enzymes, for instance, have been implicated as playing a role
in the overactive metabolism of codeine. In a recent case, the US
Food and Drug Administration (FDA) in fact
issued
a warning about the risks associated with codeine after 3
children died and a fourth child nearly died after having been
administered codeine following tonsillectomy and adenoidectomy.
"Once in the body, codeine is converted to morphine in the
liver by an enzyme called cytochrome P450 isoenzyme 2D6 (CYP2D6)
(and) some people metabolize codeine much faster and more completely
than others," the
FDA
wrote in a statement.
"These people, known as ultra-rapid metabolizers, are likely
to have higher-than-normal levels of morphine in their blood after
taking codeine. These high levels can lead to overdose and death,"
the agency said. "The three children who died after taking
codeine exhibited evidence of being ultra-rapid metabolizers."
Conversely, some people are "poor" metabolizers of
codeine, meaning that they have few, one, or no copies of the gene or
CYP2D6, Dr. Reisfield added.
"Such individuals are incapable of metabolizing codeine
morphine, and thus incapable of deriving analgesia from
administration of the medication. Both genetic defects would be
detected through CYP2D6 genotyping."
Drug Seeker or Higher Requirement?
That being said, Dr. Reisfield suggested that the new study's
findings, although intriguing, leave many unanswered questions.
"The study adds to a nascent literature on pharmacogenomics
in opioid therapy," Dr. Reisfield said. "Dr. Tennant
demonstrates an association between CYP 'defects' and requirements
for high opioid dosages. He has not, however, established a causal
association."
The study's limitations include that "the most frequent
defects were in CYP2C19, which plays an inconsequential role in
methadone metabolism, but plays no role in the metabolism of other
opioids," Dr. Reisfield said.
Meanwhile, CYP3A4, an important enzyme for the metabolism of most
opioids, was not genotyped in the study, Dr. Reisfield said.
In addition, the specific opioids used were not identified, which
is important because some opioids, including hydromorphone,
oxymorphone, and morphine, are not metabolized by CYPs, he added.
It's not known whether subjects were receiving other medications
that could have affected CYP metabolic activity.
Dr. Tennant acknowledged that the study would have benefited from
more information from a control group of patients with chronic pain
who did not require the high doses.
"It is unknown just how prevalent severe intractable pain
patients with CYP 450 defects who require high dose opioid therapy
may be compared to the general, chronic pain population, but it is
probably a small percentage," he wrote.
"This study makes it clear, however, that some severe
chronic pain patients have major CYP defects that affect opioid
metabolism and dosage."
At the very least, the findings suggest that CYP450 testing can
represent an important starting point for evaluation when high doses
of opioids are required, Dr. Tennant asserted.
"No one should be called a drug-seeker these days until
you've done the CYP450 testing to see if that patient simply needs
an awful lot more medication than someone else."
Dr. Tennant and Dr. Reisfield have disclosed no relevant
financial relationships.
American Academy of Pain Management (AAPM) 23rd Annual Clinical
Meeting. Abstract 5. Presented September 21, 2012.
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