Opioids and Constipation
Once patients need specialized pain care, approximately 90% of them will receive opioids.
Up to 100 million American adults have chronic pain.1 Once patients need specialized pain care, approximately 90% of them will receive opioids.2 Opioid use is widespread: in 2010, US physicians prescribed enough opioid analgesics to medicate every American adult around-the-clock for 1 month.3 The large quantities of prescribed opioids in circulation have attracted national attention, incited regulatory concern, and created widespread potential for opioid-induced constipation (OIC).2
When patients develop severe cancer-related, noncancer, and end-of-life pain, opioids are the most effective treatment; however, they have several adverse effects.4,5 OIC is predictable: up to 90% of opioid-treated patients in clinical trials experience constipation, and real-world studies report constipation rates of 40% to 62%.6 OIC is manageable, but prescribing clinicians often fail to anticipate, identify, or treat it.7-14 In addition, OIC pain may rival that caused by the conditions for which opioids are prescribed.15
OIC: A DIFFERENT CONSTIPATION
Many clinicians are surprised to learn that OIC is physiologically different than functional constipation. Regular constipation usually occurs subsequent to poor dietary choices, inactivity, or dehydration. OIC follows interrupted receptor activity. The gastrointestinal tract’s enteric neurons synthesize and release many neurotransmitters, including endogenous opioids. Endogenous opioids bind to 3 opioid receptors—mu, kappa, and, to a lesser extent, delta—to provide analgesia and control bowel function.16,17 Endogenous opioids slow the overactive gut to maintain homeostatic gut function. However, they have shorter half-lives than exogenous opioids: all endogenous opioids (except endorphin) are rapidly metabolized after performing their intended functions.
OIC develops when long-lived exogenous opioids create several changes—slower motility, altered fluid balance, sluggish mental status (leading to hampered mobility), and increased luminal fluid absorption18—when opioid agonists bind to mu-opioid receptors in the enteric nervous system.16,17 OIC creates needless suffering (Figure19-22).
ADDRESS OIC IMMEDIATELY
Clinicians should address potential constipation in all patients who start long-term opioids. Unfortunately, clinicians often fail to address constipation. Consider this: of 489 patients treated with opioid analgesics in 2015, 27% reported no laxative use, 25% had insufficient laxative use, and 48% had sufficient laxative use. During follow-up, 21% to 28% of patients used no or insufficient laxatives.6
Data from a recent study show that patients and their health care providers have different interpretations of the impact of OIC, the effectiveness of laxative treatment, and the impact of OIC on pain control. This study looked at patients treated with a daily morphine-equivalent dose of 30 mg for 4 weeks or longer. At baseline, 25% of health care providers were unaware of their patients’ laxative treatment status, and only 55% of patient—health care provider pairs reported the same plan for laxative use. Twenty-four weeks later, the majority of patients were dissatisfied with their OIC care, but their health care providers believed their patients were “moderately satisfied.” These discordant perceptions complicated pain management and demonstrated a need for greater communication.23
The economics of untreated OIC in the United States are noteworthy. Patients with noncancer pain who develop OIC have significantly higher (more than double) total health care costs than patients who do not develop OIC, regardless of age or residing in a community or a long-term care facility.24
TREATMENT OPTIONS FOR OIC
Prescribers and pharmacists should advise patients to maintain adequate hydration and, if possible, increase their physical activity. Increasing dietary fiber may help some patients, but it is not appropriate for all. Patients who are debilitated, have a suspected bowel obstruction, or cannot hydrate adequately should not fiber-load. Most patients should also be treated prophylactically with a stool softener and a laxative.
Among the traditional laxatives, no one agent is more effective than another. Patients may need to try different laxative classes, use more than 1 laxative type, or adjust their dosing schedule to reach the desired effect. When traditional laxatives are inadequate, clinicians should consider adding an agent specifically indicated for treating OIC25 (Table26-28).
Pharmacists need to advise patients to use prophylactic and intensive bowel management regimens, and pharmacy staff should be vigilant in identifying patients who need counseling. Coordinating care among health care professionals proactively manages the burden of OIC in patients with chronic pain.
Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy.
- Institute of Medicine Committee on Advancing Pain Research, Care, and Education. Relieving Pain in America: a Blueprint for Transforming Prevention, Care, Education, and Research. Washington, DC: National Academies Press; 2011.
- CDC grand rounds: prescription drug overdoses—a US epidemic. CDC website. cdc.gov/mmwr/preview/mmwrhtml/mm6101a3.htm. Published January 13, 2012. Accessed January 22, 2016.
- Prescription painkiller overdoses in the US. CDC website. cdc.gov/vitalsigns/PainkillerOverdoses/index.html. Published November 2011. Accessed January 22, 2016.
- Manchikanti L, Helm S II, Fellows B, et al. Opioid epidemic in the United States. Pain Physician. 2012;15(3 suppl):ES9-ES38.
- Holzer P. Opioid receptors in the gastrointestinal tract. Regul Pept. 2009;155(1-3):11-17. doi: 10.1016/j.regpep.2009.03.012.
- Coyne KS, Margolis MK, Yeomans K, et al. Opioid-induced constipation among patients with chronic noncancer pain in the United States, Canada, Germany, and the United Kingdom: laxative use, response, and symptom burden over time. Pain Med. 2015;16(8):1551-1565. doi: 10.1111/pme.12724.
- Cook SF, Lanza L, Zhou X, et al. Gastrointestinal side effects in chronic opioid users: results from a population-based survey. Aliment Pharmacol Ther. 2008;27(12):1224-1232. doi: 10.1111/j.1365-2036.2008.03689.x.
- Coyne KS, LoCasale RJ, Datto CJ, Sexton CC, Yeomans K, Tack J. Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review. ClinicoEcon Outcomes Res. 2014;6:269-281. doi: 10.2147/CEOR.S61602.
- Camilleri M. Opioid-induced constipation: challenges and therapeutic opportunities. Am J Gastroenterol. 2011;106(5):835-842. doi: 10.1038/ajg.2011.30.
- Panchal SJ, Müller-Schwefe P, Wurzelmann JI. Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden. Int J Clin Pract. 2007;61(7):1181-1187.
- Allan L, Hays H, Jensen NH, et al. Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic noncancer pain. BMJ. 2001;322(7295):1154-1158.
- Brown RT, Zuelsdorff M, Fleming M. Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain. J Opioid Manage. 2006;2(3):137-146.
- Penning-van Beest FJ, van den Haak P, Klok RM, Prevoo YF, van der Peet DL, Herings RM. Quality of life in relation to constipation among opioid users. J Med Econ. 2010;13(1):129-135. doi: 10.3111/13696990903584436.
- Rosti G, Gatti A, Costantini A, Sabato AF, Zucco F. Opioid-related bowel dysfunction: prevalence and identification of predictive factors in a large sample of Italian patients on chronic treatment. Eur Rev Med Pharmacol Sci. 2010;14(12):1045-1050.
- Opioid-induced constipation. American Chronic Pain Association website. theacpa.org/opioid-induced-constipation. Accessed January 24, 2016.
- Höllt V. Opioid peptide processing and receptor selectivity. Annu Rev Pharmacol Toxicol. 1986;26:59-77.
- Manara L, Bianchetti A. The central and peripheral influences of opioids on gastrointestinal propulsion. Annu Rev Pharmacol Toxicol. 1985;25:249-273.
- Gudin JL, Lembo AJ, Brennan MJ. Evolving management of opioid-induced constipation in patients with chronic pain. Medscape Website. medscape.org/viewarticle/826041. Published June 16, 2014. Accessed January 24, 2016.
- Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med. 2009;10(1):35-42. doi: 10.1111/j.1526-4637.2008.00495.x.
- Looström H, Akerman S, Ericson D, Tobin G, Götrick B. (2011) Tramadol-induced oral dryness and pilocarpine treatment: effects on total protein and IgA. Arch Oral Biol. 2011;56(4): 395-400. doi: 10.1016/j.archoralbio.2010.10.019.
- Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001;182(5A suppl):11S-18S.
- Gupta S, Patel H, Scopel J, Mody RR. Impact of constipation on opioid therapy management among long-term opioid users, based on a patient survey. J Opioid Manag. 2015;11(4):325-338. doi: 10.5055/jom.2015.0282.
- Datto C, LaCasale R, Wilson H, Coyne K. Discordance between patient and healthcare provider reports of the burden of opioid-induced constipation. Poster 187, American Academy of Pain Medicine, 31st Annual Meeting, March 2015, National Harbor, MD. painmed.org/2015posters/poster187.pdf. Accessed January 26, 2016.
- Wan Y, Corman S, Gao X, Liu S, Patel H, Mody R. Economic burden of opioid-induced constipation among long-term opioid users with noncancer pain. Am Health Drug Benefits. 2015;8(2):93-102.
- Tariq SH. Constipation in long-term care. J Am Med Dir Assoc. 2007;8(4):209-218.
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