Symptoms
Drug therapy with opioids for pain, cough, or diarrhea often results in constipation as an adverse effect. Triggers include, for example, morphine, codeine, oxycodone, tramadol, fentanyl, or buprenorphine. Constipation limits quality of life and can lead to accompanying symptoms and complications such as nausea, vomiting, bloating, abdominal cramps, hemorrhoids, and bowel obstruction. Laxative abuse may also develop. A possible consequence is discontinuation of therapy and inadequate pain relief.
Causes
The cause is due to the binding of opioids to peripheral μ-receptors in the intestine, which decreases the release of acetylcholine. Inhibition of longitudinal and circular muscle movements and increased absorption of fluid in the intestine results. The mechanism is identical for all opioids. Clinical studies suggest that there are differences in the extent of constipation between agents. In contrast, the route of administration plays a minor role, because opioids administered transdermally, parenterally, or sublingually also induce constipation (!)
Diagnosis
A variety of factors influence bowel function and must be considered in treatment, for example, other medications, bedriddenness, or electrolyte imbalances (see also under constipation). A relationship between constipation and opioid therapy is likely but not sufficient, as constipation is a common disorder.
Nonpharmacologic treatment
Any factors that negatively affect bowel function, such as other medications, must be considered. Sufficient exercise and an adapted diet can also have a positive effect (fiber, high-fiber diet, dried figs, prunes, and dates, laxative fruit juices, drinking plenty of fluids).
Drug treatment
Laxatives (selection):
- Macrogols: macrogol 4000, macrogol 3350.
- Sugar and sugar alcohols, e.g., lactulose.
- Isoosmotic laxatives
- Other
Prokinetics promote intestinal activity Opioid antagonists abolish the effects of opioids locally in the intestine:
- Methylnaltrexone (Relistor) was approved in many countries in 2009 for the treatment of opioid-induced constipation in critically ill adults receiving palliative treatment when standard laxatives are not sufficiently effective.
- The fixed-dose combination oxycodone and naloxone was approved in many countries in late 2009. Naloxone is intended to counteract opioid-induced constipation.
- Alvimopan (USA: Entereg).
- Naloxegol (Moventig) was approved in 2015. It is a pegylated derivative of naloxone that is only peripherally active and not centrally active.
Drug switch: Clinical studies suggest a difference in the extent of constipation between agents. In comparison, morphine, codeine and oxycodone are worse tolerated. Transdermal fentanyl, tramadol, methadone, and sublingual buprenorphine appear to be better tolerated. The drug must be discontinued if it is too harsh or if there are complications. Dose reduction usually does not help.
Things to know
The constipating property of opioids is used therapeutically to treat diarrhea. Opioids are used as antidiarrheal agents, such as loperamide or tincture of opium.
