Making Practical Sense of Cytochrome P450
by Forest Tennant, MD, DrPH
 If you’re not somewhat confused by all the background noise
regarding cytochrome P450 (hereafter CYP) opioid metabolism, drug interactions, and
overdoses, you stand singularly alone among your fellow physicians. Given a few critics
condemning opioids as sinister, some pharmaceutical companies claiming their opioid avoids
the evils of drug interactions, and some Government Agencies scolding just about everybody
over opioid overdoses, you should naturally have a little bewilderment as to what the
facts may be and what your practical actions should be. At the request of the publisher of
Practical Pain Management, I am attempting here to summarize the scientific
evidence and develop some simple, quick, practical guidelines regarding genetic opioid
metabolic defects (GOMD). While some knowledge about how the CYP450 enzyme system
metabolizes opioids is essential, the major, critical point is that opioid-prescribing
practitioners need to know that GOMDs are relatively common and can usually be diagnosed
or at least suspected by history. Rather than attempt to laboratory test every patient for
CYP450 defects, the practitioner can almost always suspect a GOMD and develop an
appropriate clinical regimen by asking a few screening questions that are given here in
Table 1. When a GOMD is suspected there are a few do’s and don’ts that can
prevent opioid toxicity and overdose and simultaneously get better therapeutic results. A
major goal of Practical Pain Management is to help prescribers of opioids to do
it safely and with confidence.
Critical Reasons to Diagnose a “Genetic Opioid Metabolic Defect”
(GOMD)
Rather than know the intricate details of the CYP system and opioid metabolism, the
practitioner who prescribes opioids really wants to know if the patient has a GOMD. There
are three characteristics that GOMD patients may present or exhibit:
- Patients will not respond or achieve pain relief with certain opioids.1-3
- Patients will require a high opioid dosage or an unusual opioid regimen.4,5
- Patients may overdose and even die if certain opioids are prescribed to a GOMD patient
(and possibly a normal patient) who is taking an inhibitor or blocker of the CYP450
system. This includes such common drugs as benzodiazepines and antidepressants.6,7
Please refer to the May 2010 issue for the complete text. In the event you need to order a back issue, please click here.
— May 2010
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