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Treating opioid-induced constipation with methylnaltrexone bromide

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Medicines Management provides essential evidence-based information on medicines and prescribing for nurse prescribers and those involved in administering medicines. This week we look at treating opioid-induced constipation with methylnaltrexone bromide.

Last year a selectively acting peripheral mu-opioid receptor antagonist, methylnaltrexone bromide, was licensed for the management of opioid-induced constipation (OIC) in the UK.

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Background

Effective symptom management is a cornerstone of palliative care, yet opioid-induced constipation continues to be problematic. The concern for quality of life is embedded in palliative care but patients have identified loss of dignity as a major concern. This includes loss of privacy, particularly during intimate care such as washing, toileting, catheterisation and bowel interventions. Patients also worry about losing control of their bodily functions. Thus appropriate end-of-life bowel care is essential.

OIC requires specific treatment

Between 50% and 80% of all patients requiring palliative care cite constipation as a major concern, with over 80% of these requiring laxative therapy (Goodman and Wilkinson, 2005; McMillan et al, 2000). OIC is a common and distressing side-effect of opioids that may affect palliative care patients during their disease process. This has a profound effect on their quality of life and cannot always be satisfactorily managed by the use of laxatives. As a result patients can require bowel interventions that are both invasive and uncomfortable.

Opioid receptors and constipation

There are three main classes of opioid receptor - mu, kappa and delta. These receptors are responsible for mediating the peripheral and central action of opioids. The opioid receptors in the central nervous system mediate the analgesic action of opioids but it is the activation of the peripheral mu-opioid receptors in the gastrointestinal (GI) tract that leads to the constipating effects of opioids. Opioids have a range of effects on the GI tract:

  • They delay gastric emptying by causing constriction of the pyloric sphincter, which leads to impaired faecal transit through the ileocaecal sphincter into the colon, resulting in a weakening of the gastrocolic reflex;

  • They decrease the propulsive peristaltic action of the gut but increase the non-propulsive activity, leading to more efficient absorption of water and electrolytes. This results in faeces becoming hard and dry;

  • They enhance internal anal sphincter tone which weakens the defecation reflex leading to defecation difficulties.

The combination of hard, dry faeces together with defecation difficulties results in the physiological characteristics of constipation.

Practice Points

  • Appropriate end-of-life bowel care is essential to maintain patient dignity

  • Methylnaltrexone bromide is used to manage opioid-induced constipation

  • It is given by the subcutaneous route

  • It provides an effective bowel action between 30 minutes and four hours after the injection, without affecting the quality of the opioid analgesia

  • Side-effects are identified as mild to moderate experiences of abdominal pain, nausea, diarrhoea and flatulence

  • Patients maintain their normal laxative regimen when methylnaltrexone bromide is prescribed

Methylnaltrexone bromide

Methylnaltrexone bromide blocks the action of opioids by acting on mu-opioid receptors. A randomised, placebo-controlled trial of adult patients with advanced illness (for example incurable cancer and end-stage COPD) and with a life expectancy of one month or less was carried out using the drug.

The study showed that a subcutaneous injection of methylnaltrexone bromide (0.15mg/kg) led to an effective bowel action between 30 minutes and four hours after the injection, without affecting the quality of the opioid analgesia (Thomas et al, 2008). The most common adverse reactions were mild to moderate experiences of abdominal pain, nausea, diarrhoea and flatulence.

Conclusion

This medicine may avoid the need for bowel interventions that are both invasive and uncomfortable, and give nurses a therapeutic option to discuss with patients.

Author
Gaye Kyle, MA, BA, DipED, RGN,
is honorary senior lecturer, Thames Valley University and University of Ulster.

References

Goodman, M., Wilkinson, S. (2005) Constipation management in palliative care: a survey of practices in the United Kingdom. Journal of Pain and Symptom Management; 29: 3, 238-244.

McMillan, S. et al (2000) Management of pain and pain-related symptoms in hospitalised veterans with cancer. Cancer Nursing; 23: 327-336.

Thomas, J. et al (2008) Methylnaltrexone for opioid-induced constipation in advanced illness. The New England Journal of Medicine; 358: 22, 2332-2343.

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