Editor's Memo
by Forest A. Tennant, MD, DrPH
 Pain patients who
require a very high dosage of opioids for pain relief remain, to a great extent, a
mystery. Just why the 100 pound woman needs 2 grams of morphine a day and a 250 pound man
requires a fraction of this dose may be bewildering, but science is beginning to provide
some understanding as to why this situation commonly exists.
For starters we know that the amount of liver enzymes, particularly P450, may be
genetically different in individuals. Consequently, they may dramatically increase in some
patients following chronic opioid administration but not in others. Hence rapid metabolism
of opioids may or may not exist in a patient. The new kid on the block of opioid
metabolism is the gastrointestinal tract. Pain specialists from Maine to Miami are
beginning to identify patients who appear to malabsorb some opioids. Scan the Tables in
the blood level study published in the last issue (March 2006; Vol. 6, Issue 2).
You’ll see some patients who take very high opioid dosages but have very low or
modest blood levels. The opposite also exists. Clearly malabsorption of opioids is common.
But why?
Science has given us one fact to chew on. The small intestine is loaded with opioid
receptors. That’s why opioid medications can be constipating and compounds that
contain an opioid antagonist like naloxone or naltrexone may well treat constipation. But
opioid receptors in the intestinal wall obviously have some important physiologic
function. Transport of nutrients across the wall into the blood? Immune function? No one
quite knows, but these receptors may well behave like those in nerve tissue in that they
may increase in size or number when challenged with chronic coating by external opioids.
Could these receptors be genetically deficient in some patients and fail to execute
transport of opioids from the intestinal lumen into blood?
Pain clinics are now starting to see a number of patients who are referred for abdomen
and pelvis pain. These patients usually have had surgery for an intestinal disease or
endometriosis. The pain is related to adhesions or neuropathy, and these patients tend to
exhibit considerable opioid malabsorption, particularly if there has been intestinal or
gastric surgery.
Another possibility causing malabsorption is infection. A few years ago, some
colleagues and I noted that heroin addicts being treated with methadone maintenance had a
high prevalence of elevated titers to the parasite, Giardia. After a short course of
antibiotics, the addicts believed their daily methadone dose was more potent and lasted
longer. We presented this paper at the American Society of Addiction Medicine Annual
Conference, but it went over like the proverbial lead balloon. The addictionologists
basically told us that addicts were parasitic enough for them, and we should take our
little, wiggly critters elsewhere. Who knows? Maybe we should dust off that old data and
even pounce on those parasites again.
We’re clearly at this point. Malabsorption should be sought, recognized, and
diagnosed in pain patients who require high dosages of opioids. Diabetics are known to
develop a malabsorption state and the “leaky gut syndrome” is certainly an
all-too-common occurrence in the severely ill. All pain clinics have their fair share of
the severely ill. In collecting the opioid blood levels reported here, some physicians
were already conducting a type of “Opioid Tolerance Test.” They would have the
patient take their usual oral opioid dosage in front of them and the patient’s blood
would be drawn about 1 to 2 hours later. And lo and behold. Sometimes there just
wasn’t much opioid in the blood. Bingo! That’s malabsorption!
Isn’t it time we treat our local gastroenterologist to dinner and pick his brain
about the stomach? We just might gain a new member for the pain team.
—Forest A. Tennant, MD, DrPH
Editor in Chief
— April 2006
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