News From the End of Life: MNTX shows promise for opioid effects

Parenteral and oral administration of methylnaltrexone (MNTX) has clinical utility in managing opioid bowel dysfunction (OPD) with minimal adverse effects, according to two recently published studies. According to the findings, MNTX may be particularly useful as adjunctive medication in patients with malignancies and to enhance palliative care in terminal cancer patients. It also concluded that the drug prevented morphine-induced bowel paralysis and reduced, in aggregate, the severity of 12 other common side effects of morphine.

In one study, published in the February issue of the American Journal of Surgery, University of Chicago researcher Joseph F. Foss, MD, concluded that MNTX helped manage OPD, a common side effect with opioid drugs. Foss also concluded that the oral drug is effective in promoting laxation in long-term opioid users.

Many patients, particularly those with advanced cancer, are forced to reduce or stop taking opioid analgesics and endure pain rather than experience the debilitating side effects caused by these agents. The recently published journal articles support the belief that MNTX can ameliorate the bowel dysfunction and other incapacitating side effects of opioids.

The second article, also by clinicians at the University of Chicago, reported that MNTX prevented morphine-induced bowel paralysis and reduced, in aggregate, the severity of 12 other common side effects of morphine. In this Phase II study, 12 healthy volunteers experienced a diminution in qualitative measures of opioid side effects, including flushing, difficulty in concentrating, skin itch, dry mouth, nausea and others. In addition, pharmacokinetic data showed that subcutaneous administration of MNTX provided rapid onset of action, with a total drug effect comparable to intravenous or oral administration.

The article, titled "Effects of subcutaneous methylnaltrexone on morphine-induced peripherally medicated side effects: A double-blind randomized placebo-controlled trial," appeared in the Journal of Pharmacology and Experimental Therapeutics (2002; 300:118-123). It was written by Chun-Su Yuan, MD, PhD, and colleagues.

Opioids are widely used for analgesia for chronic pain, after surgery or traumatic injury, or to lessen suffering in advanced cancer. To relieve pain, narcotic medications such as morphine interact with receptors located in the central nervous system — the brain and spinal cord. Opioids, however, also react with peripheral receptors, those outside the central nervous system, resulting in debilitating side effects including constipation, delayed gastric emptying, nausea and vomiting, severe itching, and urinary retention. MNTX is designed to block opioids from activating the peripheral receptors in the body that cause these side effects. As MNTX does not cross the blood-brain barrier, it does not interfere with brain- centered pain relief.