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Oral Opioids: Not for Everybody

Editor's Memo: November 2015

Recently I was referred an emergency case of a 55-year-old woman who was bed-bound, lethargic, depressed, had a feeble pulse, cold extremities, and complained of constant, severe abdominal pain. Her serum cortisol level was < 1.0 mg/ml.

Her underlying medical problem was inflammatory bowel disease (IBD) and she had undergone 28 abdominal surgeries, mostly intestinal resections to remove 90% of her small and large intestines. In order to evacuate, she had to use a special syringe apparatus in her lower abdomen.

Her pain, which had previously been treated with oral opioids, proved to be rather easily managed with a fentanyl patch, injectable hydromorphone for breakthrough pain, and hydrocortisone replacement. While a fentanyl lozenge or film may have been another option, her health plan would only pay for an injectable drug.

Thanks to this relatively simple, non-oral opioid regimen, she was ambulatory within 60 days, carrying on normal activities of daily living, had reasonable pain control, and normal serum cortisol levels.

Prior to being referred to me, the woman had visited over 20 prestigious medical and university centers to obtain pain relief—and all had tried in vain to manage her pain with every oral opioid on the commercial market.

The pathetic point of this case is that numerous physicians, including pain specialists, apparently did not know that a patient has to have a functioning small intestine to successfully metabolize oral opioids.1,2

Opioid Malabsorption

At least one-third of the intractable pain patients referred to me in the past 2 years due to poor pain control cannot totally rely on oral opioids for pain control. Some of the pathologic conditions that may impair small intestine opioid metabolism and absorption are apparently increasing in incidence and prevalence in the general population, and include diabetic gastroparesis, bariatric surgery, spine surgery, autoimmune disease, abdominal-pelvic surgeries, and traumatic brain injury (Table 1).3-6 Simply put, any pathologic condition that interferes with intestinal motility, enzymatic pathways, or floral activity may interfere with opioid metabolism and transport into the serum.3-6

Although the mechanisms and causes of opioid malabsorption are not precisely understood, some basic facts are known. The wall of the small intestine contains opioid receptors, which likely help control bowel motility and assist transport of opioids from the intestinal lumen into the serum.

Next to the liver, the small intestine contains the highest concentration of cytochrome P450 enzymes.7,8 Normally, most oral opioids are absorbed into the serum through the small intestine, and travel to the liver where they are metabolized by cytochrome P450 enzymes, or alternatively by a metabolic pathway usually called “glucuronidation.”9-12

Those opioids that are metabolized via CYP enzymes include codeine, hydrocodone, oxycodone, tramadol, fentanyl, and methadone. Some of these opioids (prodrugs) are metabolized to metabolites for analgesic effectiveness and for elimination from the body to prevent a toxic build-up.

Those opioids that are unaffected or mildly affected by CYP450 include morphine, hydromorphone, oxymorphone, and tapentadol. In my clinical experience, CYP450 defects are one of the major causes of opioid malabsorption.

A healthy intestinal flora or biome is critical for the metabolism and transport of opioids and other medicinal agents into the serum.5 The intestine contains more nerves than the brain. The neural innervation of the small intestine is complex and controlled by spinal connections as well as the vagus nerve, which emanates in the cranium and passes downward through the neck to help control intestinal motility. Dysautonomia may, therefore, result from traumatic brain injury and neck trauma, spinal surgeries, and spinal inflammatory disease or arachnoiditis.

Regardless of specific cause, the failure of the small intestine to transport adequate amounts of opioids (and other nutrients and medications) from inside the intestinal lumen into the serum should be called opioid malabsorption.

The percentage of pain patients who can’t effectively utilize oral opioids and have opioid malabsorption is clearly on the increase.

Role of Non-Oral Opioids

Pain patients should be evaluated for opioid malabsorption before they are prescribed an oral opioid, especially patients who have undergoing previous GI surgeries or have history of GI issues. When patients state that oral opioids aren’t effective, and demand a higher and higher oral dosage, it well may be that they have one of the many causes of opioid malabsorption.

One last point, everyone is trying to reduce opioid dosages these days. If opioid malabsorption is overlooked, the patient may be given a high oral opioid dose in an attempt to compensate. A non-oral opioid route of administration may decrease the overall need for opioids plus give the patient much better pain relief.

Last updated on: November 10, 2015
First published on: November 1, 2015
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