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06.10.2017 | Original Article

Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350

verfasst von: Jakob Lykke Poulsen, Christina Brock, Debbie Grønlund, Donghua Liao, Hans Gregersen, Klaus Krogh, Asbjørn Mohr Drewes

Erschienen in: Digestive Diseases and Sciences | Ausgabe 11/2017

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Abstract

Background

Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment.

Aims

To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms.

Methods

A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily.

Results

Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (− 27.5%; P < 0.001 and − 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035).

Conclusion

Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.

Gilson AM, Maurer MA, Ryan KM, Rathouz PJ, Cleary JF. Using a morphine equivalence metric to quantify opioid consumption: examining the capacity to provide effective treatment of debilitating pain at the global, regional, and country levels. J Pain Symptom Manag. 2013;45:681–700.CrossRef

Bell TJ, Panchal SJ, Miaskowski C, et al. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med. 2009;10:35–42.CrossRefPubMed

Müller-Lissner S, Bassotti G, Coffin B, et al. Opioid-induced constipation and bowel dysfunction: a clinical guideline. Pain Med. 2016;7:121–134.

Brock C, Olesen SS, Olesen AE, et al. Opioid-induced bowel dysfunction: pathophysiology and management. Drugs. 2012;72:1847–1865.CrossRefPubMed

Becker G, Blum HE. Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus. Lancet (London, England). 2009;373:1198–1206.CrossRef

Kumar L, Barker C, Emmanuel A. Opioid-induced constipation: Pathophysiology, clinical consequences, and management. Gastroenterol Res Pract. 2014. doi:10.1155/2014/141737.PubMedPubMedCentral

Camilleri M, Drossman DA, Becker G, et al. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol Motil. 2014;26:1386–1395.CrossRefPubMedPubMedCentral

Manchikanti L, Abdi S, Atluri S, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: part 2–guidance. Pain Physician. 2012;15:S67–S116.PubMed

Rao SSC, Rattanakovit K, Patcharatrakul T. Diagnosis and management of chronic constipation in adults. Nat Rev Gastroenterol Hepatol. 2016;13:295–305.CrossRefPubMed

10.

Lee AA, Hasler WL. Opioids and GI motility-friend or foe? Curr Treat Options Gastroenterol. 2016;14:478–494.CrossRefPubMed

11.

Galligan JJ, Akbarali HI. Molecular physiology of enteric opioid receptors. Am J Gastroenterol. 2014;2:17–21.CrossRef

12.

Gaertner J, Siemens W, Camilleri M, et al. Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review. J Clin Gastroenterol. 2015;49:9–16.CrossRefPubMed

13.

Mearin F, Lacy BE, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150:e5.

14.

Wu S-D, Zhang Z-H, Jin J-Z, et al. Effects of narcotic analgesic drugs on human Oddi’s sphincter motility. World J Gastroenterol. 2004;10:2901–2904.CrossRefPubMedPubMedCentral

15.

Helm JF, Venu RP, Geenen JE, et al. Effects of morphine on the human sphincter of Oddi. Gut. 1988;29:1402–1407.CrossRefPubMedPubMedCentral

16.

Rattan S, Culver PJ. Influence of loperamide on the internal anal sphincter in the opossum. Gastroenterology. 1987;93:121–128.CrossRefPubMed

17.

Chowdhury AR, Lorber SH. Effects of glucagon and secretin on food- or morphine-induced motor activity of the distal colon, rectum, and anal sphincter. Am J Dig Dis. 1977;22:775–780.CrossRefPubMed

18.

Göke M, Ewe K, Donner K, et al. Influence of loperamide and loperamide oxide on the anal sphincter: a manometric study. Dis Colon Rectum. 1992;35:857–861.CrossRefPubMed

19.

Wilder-Smith CH, Bettiga A. The analgesic tramadol has minimal effect on gastrointestinal motor function. Br J Clin Pharmacol. 1997;43:71–75.CrossRefPubMed

20.

Read M, Read NW, Barber DC, Duthie HL. Effects of loperamide on anal sphincter function in patients complaining of chronic diarrhea with fecal incontinence and urgency. Dig Dis Sci. 1982;27:807–814.CrossRefPubMed

21.

Bouvier M, Kirschner G, Gonella J. Actions of morphine and enkephalins on the internal anal sphincter of the cat: relevance for the physiological role of opiates. J Auton Nerv Syst. 1986;16:219–232.CrossRefPubMed

22.

Bouchoucha M, Faye A, Arsac M, Rocaries F. Anal sphincter response to distension. Int J Colorectal Dis. 2001;16:119–125.CrossRefPubMed

23.

Lottrup C, Gregersen H, Liao D, et al. Functional lumen imaging of the gastrointestinal tract. J Gastroenterol. 2015;50:1005–1016.CrossRefPubMed

24.

Musial F, Enck P, Kalveram KT, Erckenbrecht JF. The effect of loperamide on anorectal function in normal healthy men. J Clin Gastroenterol. 1992;15:321–324.CrossRefPubMed

25.

Gregersen T, Grønbæk H, Worsøe J, et al. Effects of Sandostatin LAR on gastrointestinal motility in patients with neuroendocrine tumors. Scand J Gastroenterol. 2011;46:895–902.CrossRefPubMed

26.

Dipalma JA, Cleveland MV, McGowan J, Herrera JL. A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. Am J Gastroenterol. 2007;102:1436–1441.CrossRefPubMed

27.

Harris ML, Hobson AR, Hamdy S, et al. Neurophysiological evaluation of healthy human anorectal sensation. Am J Physiol Gastrointest Liver Physiol. 2006;291:G950–G958.CrossRefPubMed

28.

Krogh K, Mosdal C, Gregersen H, Laurberg S. Rectal wall properties in patients with acute and chronic spinal cord lesions. Dis Colon Rectum. 2002;45:641–649.CrossRefPubMed

29.

Alqudah MM, Gregersen H, Drewes AM, McMahon BP. Evaluation of anal sphincter resistance and distensibility in healthy controls using EndoFLIP ©. Neurogastroenterol Motil. 2012;24:e591–e599.CrossRefPubMed

30.

Sørensen G, Liao D, Lundby L, et al. Distensibility of the anal canal in patients with idiopathic fecal incontinence: a study with the Functional Lumen Imaging Probe. Neurogastroenterol Motil. 2014;26:255–263.CrossRefPubMed

31.

Gregersen H. Biomechanics of the Gastrointestinal Tract: New Perspectives in Motility Research and Diagnostics. London: Springer; 2003.CrossRef

32.

Haas S, Liao D, Gregersen H, et al. Increased yield pressure in the anal canal during sacral nerve stimulation: a pilot study with the functional lumen imaging probe. Neurogastroenterol Motil. 2016;29:1–9.

33.

Rao SSC, Azpiroz F, Diamant N, et al. Minimum standards of anorectal manometry. Neurogastroenterol Motil. 2002;14:553–559.CrossRefPubMed

34.

Slappendel R, Simpson K, Dubois D, Keininger DL. Validation of the PAC-SYM questionnaire for opioid-induced constipation in patients with chronic low back pain. Eur J Pain. 2006;10:209–217.CrossRefPubMed

35.

Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32:920–924.CrossRefPubMed

36.

Andresen T, Arendt-Nielsen L, Drewes A, Oksche A, Staahl C. Effect of buprenorphine and fentanyl in experimental induced superficial, deep and hyperalgesic pain. Scand J Pain. 2010;1:174–175.CrossRef

37.

Cheeney G, Nguyen M, Valestin J, Rao SSC. Topographic and manometric characterization of the recto-anal inhibitory reflex. Neurogastroenterol Motil. 2012;24:e147–e154.CrossRefPubMedPubMedCentral

38.

Rattan S. The internal anal sphincter: regulation of smooth muscle tone and relaxation. Neurogastroenterol Motil. 2005;17:50–59.CrossRefPubMed

39.

Bhardwaj R, Vaizey CJ, Boulos PB, Hoyle CH. Neuromyogenic properties of the internal anal sphincter: therapeutic rationale for anal fissures. Gut. 2000;46:861–868.CrossRefPubMedPubMedCentral

40.

Sternini C, Patierno S, Selmer I-S, Kirchgessner A. The opioid system in the gastrointestinal tract. Neurogastroenterol Motil. 2004;16:3–16.CrossRefPubMed

41.

Kromer W. Endogenous opioids, the enteric nervous system and gut motility. Dig Dis. 1990;8:361–373.CrossRefPubMed

42.

Rasmussen OO, Colstrup H, Lose G, Christiansen J. A technique for the dynamic assessment of anal sphincter function. Int J Colorectal Dis. 1990;5:135–141.CrossRefPubMed

43.

Luft F, Fynne L, Gregersen H, et al. Functional luminal imaging probe: a new technique for dynamic evaluation of mechanical properties of the anal canal. Tech Coloproctol. 2012;16:451–457.CrossRefPubMedPubMedCentral

44.

Gourcerol G, Granier S, Bridoux V, et al. Do endoflip assessments of anal sphincter distensibility provide more information on patients with fecal incontinence than high-resolution anal manometry? Neurogastroenterol Motil. 2016;28:399–409.CrossRefPubMed

45.

Monteiro FJR, Regadas FSP, Murad-Regadas SM, Rodrigues LV, Leal VM. Comparative evaluation of the effect of sustained inflation and rapid inflation/deflation of the intrarectal balloon upon rectoanal inhibitory reflex parameters in asymptomatic subjects. Tech Coloproctol. 2007;11:323–326.CrossRefPubMed

46.

Burness CB, Keating GM. Oxycodone/naloxone prolonged-release: a review of its use in the management of chronic pain while counteracting opioid-induced constipation. Drugs. 2014;74:353–375.CrossRefPubMed

47.

Smith K, Hopp M, Mundin G, et al. Single- and multiple-dose pharmacokinetic evaluation of oxycodone and naloxone in an opioid agonist/antagonist prolonged-release combination in healthy adult volunteers. Clin Ther. 2008;30:2051–2068.CrossRefPubMed

48.

Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat Rev Microbiol. 2016;14:273–287.CrossRefPubMedPubMedCentral

49.

Olesen AE, Drewes AM. Validated tools for evaluating opioid-induced bowel dysfunction. Adv Ther. 2011;28:279–294.CrossRefPubMed

50.

Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001;182:11S–18S.CrossRefPubMed

51.

Moore J, Barlow D, Jewell D, Kennedy S. Do gastrointestinal symptoms vary with the menstrual cycle? Br J Obstet Gynaecol. 1998;105:1322–1325.CrossRefPubMed

52.

Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol. 2014;6:71–80.PubMedPubMedCentral

53.

McCrea GL, Miaskowski C, Stotts NA, et al. Gender differences in self-reported constipation characteristics, symptoms, and bowel and dietary habits among patients attending a specialty clinic for constipation. Gend Med. 2009;6:259–271.CrossRefPubMed

Titel: Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350
verfasst von: Jakob Lykke Poulsen
Christina Brock
Debbie Grønlund
Donghua Liao
Hans Gregersen
Klaus Krogh
Asbjørn Mohr Drewes
Publikationsdatum: 06.10.2017
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 11/2017
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-017-4784-7

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Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350

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