Opioid bowel dysfunction

Yuan CS. (2007) Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects. Ann Pharmacother 41 984-993. 

Choung RS, Locke GR 3rd, Zinsmeister AR, Schleck CD, Talley NJ. Opioid bowel dysfunction and narcotic bowel syndrome a population-based study. Am J Gastroenterol 2009 104(5) 1199-204. 

OBD comprises a constellation of GI symptoms including OIC, incomplete evacuation, inhibition of gut peristalsis, bloating, pain, nausea/ vomiting, and increased gastric reflux and tone of intestinal sphincters [3]. Approximately 40% of patients taking chronic opioids for nonmalig-nant pain develop bowel dysfunction [25]. 

Kurz A, Sessler DI. Opioid-induced bowel dysfunction pathophysiology and potential new therapies. Drugs 2003 63 649-71. 

McNichol ED et al Mu-opioid antagonists for opioid-induced bowel dysfunction. Cochrane Database Syst Rev 2008 Apr 16(2) CD006332. 

Tamayo AC, Diaz-Zuluaga PA. Management of opioid-induced bowel dysfunction in cancer patients. Support Care Cancer. 2004 12 613-618. 

The 17 - N- a 11 y I - (n a I o x o n e. 3a) and 17 - /V-c v c lop I opv I m e t h v I (naltrexone, 3b) analogues of oxymorphone (2d) are the prototype opioid receptor antagonists with some selectivity for MOR. They have entered clinical practice as treatments for narcotic overdose (naloxone) and alcoholism or opioid abuse/dependence (naltrexone). The 17-quatemary derivative of naltrexone, methylnaltrexone (4) has recently been introduced into clinical practice as a treatment for opiate-induced bowel dysfunction [1],... 

Multiple clinical trials are currently under way to investigate methyinaltrexone, orally or subcutaneously, in healthy chronic pain patients as a treatment for constipation and opioid-induced bowel dysfunction. Intravenous methyinaltrexone is being investigated to treat and prevent post-operative ileus however, the drug has not yet received approval for these indications. Chronic use of methyinaltrexone for greater than 4 months has not been studied. 

Figure 106,2. Opioid-induced bowel dysfunction (OBD). Opioids increase intestinal fluid absorption, inhibit intestinal secretions and peristalsis, and block propulsive movements in the colon. Constipation and other symptoms associated with OBD occur in 15-90% of cancer patients and may be more distressful and debilitating than pain. Tolerance rarely develops to these symptoms and traditional therapy including stimulants, lubricants, arxf bulk laxatives may not be effective.

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