Nearly 50 percent of patients who receive opioid drugs like
morphine for pain management during cancer treatment experience
severe opioid-induced constipation. Now, a new study shows that a
drug called methylnaltrexone is effective in blocking constipation
while leaving the analgesic effect of opioids intact.
``By preventing this debilitating but little-discussed problem,
methylnaltrexone could substantially enhance the quality of the
last months of life for terminal cancer patients and others who
depend on opioid pain relievers,'' said Dr. Chun-Su Yuan, an
assistant professor of anesthesia and critical care at the
University of Chicago and the study's lead author.
The researchers opted not to study cancer patients to avoid any
possible interference in their pain management. Instead, the
investigators studied 22 volunteers who were taking the drug
methadone for the treatment of heroin addiction. Methadone is a
synthetic opioid that has actions very similar to those of
morphine.
All 22 participants suffered from opioid-induced constipation,
and about 60 percent of all methadone users experience this
gastrointestinal side effect. In the study, 11 people received
intravenous methylnaltrexone, while the remaining 11 received a
placebo.
Ten of the 11 participants who received methylnaltrexone had an
``immediate response'' to the first infusion. The eleventh person
required a second methylnaltrexone infusion before experiencing
relief.
``By immediate response, we mean you did not want to be between
the subject and the bathroom,'' said study co-author Dr. Joseph
Foss, an assistant professor of anesthesia at the University of
Chicago.
Only an intravenous version of methylnaltrexone was tried in
this study. However, in a separate trial, an oral version is being
studied in patients with advanced cancer who are taking opioids at
St. Christopher's Hospice near London.
The 11 subjects in the current study who received the placebo
continued to have constipation. The report appears in the January
19 issue of the Journal of the American Medical Association
(www.jama.com).
Because none of the methylnaltrexone subjects experienced opioid
withdrawal symptoms, the researchers concluded that
methylnaltrexone did not block the effects of methadone in the
brain. According to the investigators, this suggests that
methylnaltrexone should be effective in treating cancer patients
receiving opioids too. Often, cancer patients would rather give up
their medication and subsequent pain relief than experience the
severe constipation associated with opioids.
The researchers also measured oral-cecal transit time -- the
amount of time it takes food to travel from the mouth to the
beginning of the large intestine -- because opioids are known to
slow the digestive process.
For subjects on methadone, the average oral-cecal transit time
was around two hours and 10 minutes, about twice the normal time.
However, for methadone patients who received methylnaltrexone, this
time dropped from 132.3 minutes to 54.5 minutes.
Methylnaltrexone is derived from the well-studied drug
naltrexone, which is known to block the overall effects of opioids.
However, adding a methyl group prevents the drug from passing the
blood-brain barrier, which keeps many chemicals in the blood from
entering and affecting the brain. Therefore, methylnaltrexone only
blocks opioid effects outside of the brain, specifically in the
gastrointestinal system.
Yuan, Foss and two other co-authors on the study hold
methylnaltrexone-related patents.
