Emerging therapies for patients with symptoms of opioid-induced bowel dysfunction
Open accessAbstract
Opioid-induced bowel dysfunction (OIBD) comprises gastrointestinal (GI) symptoms, including dry mouth, nausea, vomiting, gastric stasis, bloating, abdominal pain, and opioid-induced constipation, which significantly impair patients' quality of life and may lead to undertreatment of pain. Traditional laxatives are often prescribed for OIBD symptoms, although they display limited efficacy and exert adverse effects. Other strategies include prokinetics and change of opioids or their administration route. However, these approaches do not address underlying causes of OIBD associated with opioid effects on mostly peripheral opioid receptors located in the GI tract. Targeted management of OIBD comprises purely peripherally acting opioid receptor antagonists and a combination of opioid receptor agonist and antagonist. Methylnaltrexone induces laxation in 50%-60% of patients with advanced diseases and OIBD who do not respond to traditional oral laxatives without inducing opioid withdrawal symptoms with similar response (45%-50%) after an oral administration of naloxegol. A combination of prolonged-release oxycodone with prolonged-release naloxone (OXN) in one tablet (a ratio of 2:1) provides analgesia with limited negative effect on the bowel function, as oxycodone displays high oral bioavailability and naloxone demonstrates local antagonist effect on opioid receptors in the GI tract and is totally inactivated in the liver. OXN in daily doses of up to 80 mg/40 mg provides equally effective analgesia with improved bowel function compared to oxycodone administered alone in patients with chronic non-malignant and cancer-related pain. OIBD is a common complication of long-term opioid therapy and may lead to quality of life deterioration and undertreatment of pain. Thus, a complex assessment and management that addresses underlying causes and patomechanisms of OIBD is recommended. Newer strategies comprise methylnaltrexone or OXN administration in the management of OIBD, and OXN may be also considered as a preventive measure of OIBD development in patients who require opioid administration.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Activation of mu-opioid receptors in the gut wall inhibits pathways within the enteric nervous system, which in turn reduce motility, delay gastric emptying, and slow intestinal transit.
“Activation of mu-opioid receptors in the gut wall inhibits pathways within the enteric nervous system, which in turn reduce motility, delay gastric emptying, and slow intestinal transit (172).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [172]
OUD has been associated with bowel dysfunction including constipation while using and diarrhea during detoxification.
“OUD has been associated with bowel dysfunction including but not limited to constipation while using and diarrhea during detoxification (172).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [172]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Stool form scale as a useful guide to intestinal transit time
Lewis, S. J., & Heaton, K. W. (1997) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365529709011203 · Cited by 3,244 · see citing works
Caraceni, A. T., Hanks, G. W., Kaasa, S., Bennett, M., Brunelli, C., Cherny, N. I., Dale, O., Conno, F. D., Fallon, M., Hanna, M., et al. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70040-2 · Cited by 1,247 · see citing works
Morphine and alternative opioids in cancer pain: the EAPC recommendations
Hanks, G. W., Conno, F. D., Cherny, N. I., Hanna, M., Kalso, E. A., McQuay, H. J., Mercadante, S., Meynadier, J., Poulain, P., Ripamonti, C. I., et al. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1680 · Cited by 861 · see citing works
Strategies to Manage the Adverse Effects of Oral Morphine: An Evidence-Based Report
Cherny, N. I., Ripamonti, C. I., Pereira, J. L., Davis, C. L., Fallon, M., McQuay, H., Mercadante, S., Pasternak, G. W., & Ventafridda, V. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.9.2542 · Cited by 625 · see citing works
Methylnaltrexone for Opioid-Induced Constipation in Advanced Illness
Thomas, J., Karver, S. B., Cooney, G. A., Chamberlain, B. H., Watt, C. K., Slatkin, N. E., Stambler, N., Kremer, A. B., & Israel, R. J. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0707377 · Cited by 589 · see citing works
Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire
Marquis, P., de la Loge, C., Dubois, D., Mcdermott, A., & Chassany, O. (2005) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520510012208 · Cited by 586 · see citing works
BELL, T. J., Panchal, S. J., Miaskowski, C. A., Bolge, S. C., Milanova, T. F., & Williamson, R. (2008) · Pain Medicine · doi:10.1111/j.1526-4637.2008.00495.x · Cited by 500 · see citing works
Ahmedzai, S. H., & Brooks, D. (1997) · Journal of Pain and Symptom Management · doi:10.1016/s0885-3924(97)00082-1 · Cited by 475 · see citing works
Management of cancer pain: ESMO Clinical Practice Guidelines
Ripamonti, C. I., Bandieri, E., & Roila, F. (2011) · Annals of Oncology · doi:10.1093/annonc/mdr390 · Cited by 447 · see citing works
Function of opioids in the enteric nervous system
Wood, J. D., & Galligan, J. J. (2004) · Neurogastroenterology & Motility · doi:10.1111/j.1743-3150.2004.00554.x · Cited by 372 · see citing works
18. Cancer Pain Relief and Palliative Care
Eguchi, K. (2010) · Nihon Naika Gakkai Zasshi · doi:10.2169/naika.99.104b · Cited by 368 · see citing works
Tack, J., van Outryve, M., Beyens, G., Kerstens, R., & Vandeplassche, L. (2009) · Gut · doi:10.1136/gut.2008.162404 · Cited by 347 · see citing works
Naloxegol for Opioid-Induced Constipation in Patients with Noncancer Pain
Chey, W. D., Webster, L. R., Sostek, M. B., Lappalainen, J., Barker, P. N., & Tack, J. F. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1310246 · Cited by 328 · see citing works
Bouras, E. P., Camilleri, M., Burton, D., Thomforde, G., Mckinzie, S., & Zinsmeister, A. (2001) · Gastroenterology · doi:10.1053/gast.2001.21166 · Cited by 306 · see citing works
Methylnaltrexone for Reversal of Constipation Due to Chronic Methadone Use
Yuan, C., Foss, J. F., O’Connor, M. F., et al. (2000) · JAMA · doi:10.1001/jama.283.3.367 · Cited by 298 · see citing works
Meißner, W., Leyendecker, P., Mueller‐Lissner, S., Nadstawek, J., Hopp, M., Ruckes, C., Wirz, S., Fleischer, W., & Reimer, K. (2008) · European Journal of Pain · doi:10.1016/j.ejpain.2008.06.012 · Cited by 257 · see citing works
Mercadante, S., Casuccio, A., Fulfaro, F., Groff, L., Boffi, R., Villari, P., Gebbia, V., & Ripamonti, C. I. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.11.2898 · Cited by 250 · see citing works
Adjuvant Analgesics in Cancer Pain Management
Lussier, D., Huskey, A., & Portenoy, R. K. (2004) · The Oncologist · doi:10.1634/theoncologist.9-5-571 · Cited by 249 · see citing works
Management of cancer pain: ESMO Clinical Practice Guidelines
Jost, L., & Roila, F. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq224 · Cited by 227 · see citing works
Opioid-Induced Bowel Dysfunction
Brock, C., Olesen, S. S., Olesen, A., Frøkjaer, J., Andresen, T., & Drewes, A. (2012) · Drugs · doi:10.2165/11634970-000000000-00000 · Cited by 225 · see citing works
The management of constipation in palliative care: clinical practice recommendations
Larkin, P. J., Sykes, N. P., Centeno, C., Ellershaw, J., Elsner, F., Eugene, B., Gootjes, J. R. G., Nabal, M., Noguera, A., Ripamonti, C. I., et al. (2008) · Palliative Medicine · doi:10.1177/0269216308096908 · Cited by 217 · see citing works
Vondráčková, D., Leyendecker, P., Meißner, W., Hopp, M., Szombati, I., Hermanns, K., Ruckes, C., Weber, S., Grothe, B., Fleischer, W., et al. (2008) · Journal of Pain · doi:10.1016/j.jpain.2008.06.014 · Cited by 210 · see citing works
Low-Dose Oral Naloxone Reverses Opioid-Induced Constipation and Analgesia
Liu, M., & Wittbrodt, E. T. (2002) · Journal of Pain and Symptom Management · doi:10.1016/s0885-3924(01)00369-4 · Cited by 204 · see citing works
Oral naloxone reverses opioid-associated constipation
Meißner, W., Schmidt, U., Hartmann, M., Kath, R., & Reinhart, K. (2000) · Pain · doi:10.1016/s0304-3959(99)00185-2 · Cited by 203 · see citing works
Sobczak, M., Sałaga, M., Storr, M., & Fichna, J. (2013) · Journal of Gastroenterology · doi:10.1007/s00535-013-0753-x · Cited by 203 · see citing works
Samer, C. F., Daali, Y., Wagner, M., et al. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00709.x · Cited by 201 · see citing works
Rentz, A. M., Yu, R., Müller-Lissner, S. A., & Leyendecker, P. (2009) · Journal of Medical Economics · doi:10.3111/13696990903430481 · Cited by 191 · see citing works
Portenoy, R. K., Thomas, J., Boatwright, M. L. M., Tran, D. N. H., Galasso, F. L., Stambler, N., von Gunten, C. F., & Israel, R. J. (2008) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2007.12.005 · Cited by 182 · see citing works
Holzer, P. D. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2003.12.004 · Cited by 180 · see citing works
Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain
Tuteja, A. K., BISKUPIAK, J. E., Stoddard, G. J., & Lipman, A. G. (2010) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2009.01458.x · Cited by 177 · see citing works
Simpson, K. H., Leyendecker, P., Hopp, M., Müller-Lissner, S. A., Löwenstein, O., Andrés, J. A. D., Ferrarons, J. T., Bosse, B., Krain, B., Nichols, T., et al. (2008) · Current Medical Research and Opinion · doi:10.1185/03007990802584454 · Cited by 177 · see citing works
The Declaration Montreal: Access to pain management is a fundamental human right
Cousins, M. J., & Lynch, M. E. (2011) · Pain · doi:10.1016/j.pain.2011.09.012 · Cited by 170 · see citing works
Yuan, C., Foss, J. F., Osinski, J., Toledano, A. Y., Roizen, M. F., & Moss, J. (1997) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(97)90197-1 · Cited by 169 · see citing works
Central and peripheral actions of morphine on intestinal transit.
Stewart, J. J., Weisbrodt, N. W., & Burks, T. F. (1978) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)31262-0 · Cited by 169 · see citing works
Ahmedzai, S. H., Nauck, F., Bar‐Sela, G., Bosse, B., Leyendecker, P., & Hopp, M. (2011) · Palliative Medicine · doi:10.1177/0269216311418869 · Cited by 161 · see citing works
Methylnaltrexone for treatment of opioid-induced constipation in advanced illness patients.
Slatkin, N. E., Thomas, J., Lipman, A. G., et al. (2009) · PubMed · Cited by 160 · see citing works
Löwenstein, O., Leyendecker, P., Hopp, M., Schutter, U., Rogers, P., Uhl, R., Bond, S. J., Kremers, W. K., Nichols, T., Krain, B., et al. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560902796798 · Cited by 158 · see citing works
Paulson, D. M., Kennedy, D. T., Donovick, R. A., Carpenter, R. L., Cherubini, M., Techner, L. M., Du, W., Ma, Y., Schmidt, W. K., Wallin, B., et al. (2005) · Journal of Pain · doi:10.1016/j.jpain.2004.12.001 · Cited by 157 · see citing works
Michna, E., Blonsky, E. R., Schulman, S. L., Tzanis, E. L., Manley, A. L., Zhang, H., Iyer, S. S., & Randazzo, B. P. (2011) · Journal of Pain · doi:10.1016/j.jpain.2010.11.008 · Cited by 153 · see citing works
Oxycodone: a review of its use in the management of pain
Riley, J. L., Eisenberg, E., Müller-Schwefe, G. H. H., Drewes, A. M., & Arendt‐Nielsen, L. (2007) · Current Medical Research and Opinion · doi:10.1185/030079908x253708 · Cited by 153 · see citing works
Gastrointestinal Tract Recovery in Patients Undergoing Bowel Resection
LUDWIG, K. A. (2008) · Archives of Surgery · doi:10.1001/archsurg.143.11.1098 · Cited by 152 · see citing works
Peptide opioid antagonist separates peripheral and central opioid antitransit effects.
Shook, J. E., Pelton, J. T., Hruby, V. J., & Burks, T. F. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)11008-2 · Cited by 145 · see citing works
Büchler, M. W., Seiler, C., Monson, J. R. T., et al. (2008) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2008.03696.x · Cited by 140 · see citing works
Busby, R. W., Kessler, M. M., Bartolini, W. P., Bryant, A. P., Hannig, G., Higgins, C. S., Solinga, R. M., Tobin, J. V., WAKEFIELD, J. D., Kurtz, C. B., et al. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.199430 · Cited by 140 · see citing works
Sloots, C. E. J., Rykx, A., Cools, M., Kerstens, R., & Pauw, M. D. (2010) · Digestive Diseases and Sciences · doi:10.1007/s10620-010-1229-y · Cited by 134 · see citing works
Laxatives or methylnaltrexone for the management of constipation in palliative care patients
Candy, B., Jones, L., Goodman, M. L., Drake, R., & Tookman, A. J. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003448.pub3 · Cited by 131 · see citing works
Potet, F., Bouyssou, T., Escande, D., & Baró, I. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29223-5 · Cited by 128 · see citing works
Slappendel, R., Simpson, K. H., Dubois, D. J., & Keininger, D. L. (2005) · European Journal of Pain · doi:10.1016/j.ejpain.2005.03.008 · Cited by 121 · see citing works
Webster, L. R., Dhar, S., Eldon, M. A., Masuoka, L. K., Lappalainen, J., & Sostek, M. B. (2013) · Pain · doi:10.1016/j.pain.2013.04.024 · Cited by 117 · see citing works
Desta, Z., Wu, G. M., Morocho, A. M., & Flockhart, D. A. (2002) · Drug Metabolism and Disposition · doi:10.1124/dmd.30.3.336 · Cited by 113 · see citing works
Treatment of opioid-induced gut dysfunction
Holzer, P. D. (2007) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.16.2.181 · Cited by 109 · see citing works
Ford, A. C., Brenner, D. M., & Schoenfeld, P. (2013) · The American Journal of Gastroenterology · doi:10.1038/ajg.2013.169 · Cited by 106 · see citing works
Ueberall, M., Müller-Lissner, S. A., Buschmann-Kramm, C., & Bosse, B. (2011) · Journal of International Medical Research · doi:10.1177/147323001103900106 · Cited by 105 · see citing works
Sandner‐Kiesling, A., Leyendecker, P., Hopp, M., Tarau, L., Lejčko, J., Meißner, W., Ševčík, P., Hakl, M., Hřib, R., Uhl, R., et al. (2010) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2010.02360.x · Cited by 99 · see citing works
Low absolute bioavailability of oral naloxone in healthy subjects
Smith, K. J., Hopp, M., Mundin, G., Bond, S. J., Bailey, P., Woodward, J., & Bell, D. (2012) · International Journal of Clinical Pharmacology and Therapeutics · doi:10.5414/cp201646 · Cited by 97 · see citing works
Mu-opioid antagonists for opioid-induced bowel dysfunction
McNicol, E. D., Boyce, D. B., Schumann, R., & Carr, D. B. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006332.pub2 · Cited by 96 · see citing works
Mori, T., Shibasaki, Y., Matsumoto, K., et al. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.204313 · Cited by 88 · see citing works
Holzer, P. D., Ahmedzai, S. H., Niederle, N., Leyendecker, P., Hopp, M., Bosse, S. B., Spohr, I., & Reimer, K. (2018) · Journal of Opioid Management · doi:10.5055/jom.2009.0015 · Cited by 87 · see citing works
Parolaro, D., Sala, M., & Gori, E. (1977) · European Journal of Pharmacology · doi:10.1016/0014-2999(77)90227-8 · Cited by 86 · see citing works
Yuan, C. (2000) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2000.105037 · Cited by 84 · see citing works
Abramowitz, L., Béziaud, N., Labreze, L., et al. (2013) · Journal of Medical Economics · doi:10.3111/13696998.2013.851082 · Cited by 83 · see citing works
Methylnaltrexone Treatment of Opioid-Induced Constipation in Patients with Advanced Illness
Chamberlain, B. H., Cross, K. L., Winston, J. L., et al. (2009) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2009.02.234 · Cited by 82 · see citing works
Meeting the Challenges of Opioid-Induced Constipation in Chronic Pain Management – A Novel Approach
Reimer, K., Hopp, M., Zenz, M. W., et al. (2008) · Pharmacology · doi:10.1159/000165778 · Cited by 80 · see citing works
Systemic and central effects of morphine on gastroduodenal motility
Thörn, S., Wattwil, M., Lindberg, G., et al. (1996) · Acta Anaesthesiologica Scandinavica · doi:10.1111/j.1399-6576.1996.tb04417.x · Cited by 77 · see citing works
Wirz, S., Wittmann, M., Schenk, M., Schroeck, A., Schaefer, N., Mueller, M., Standop, J., Kloecker, N., & Nadstawek, J. (2008) · European Journal of Pain · doi:10.1016/j.ejpain.2008.09.005 · Cited by 74 · see citing works
Löwenstein, O., Leyendecker, P., Lux, E. A., et al. (2010) · BMC Clinical Pharmacology · doi:10.1186/1472-6904-10-12 · Cited by 70 · see citing works
Novel opioid antagonists for opioid-induced bowel dysfunction
Diego, L., Atayee, R. S., Helmons, P., et al. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.592830 · Cited by 70 · see citing works
Yu, C. S., Chun, H.-K., Stambler, N., et al. (2011) · Diseases of the Colon & Rectum · doi:10.1007/dcr.0b013e3182092bde · Cited by 68 · see citing works
Ahmedzai, S. H., Leppert, W., Janecki, M., Pakosz, A., Lomax, M., Duerr, H. E., & Hopp, M. (2014) · Supportive Care in Cancer · doi:10.1007/s00520-014-2435-5 · Cited by 66 · see citing works
Self-citationPrucalopride: safety, efficacy and potential applications
Quigley, E. M. M. (2011) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x11423706 · Cited by 66 · see citing works
Yuan, C., & Israel, R. J. (2006) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.15.5.541 · Cited by 64 · see citing works
Management of bowel problems in older people: an update
Potter, J. M., & Wagg, A. (2005) · Clinical Medicine · doi:10.7861/clinmedicine.5-3-289 · Cited by 64 · see citing works
Methylnaltrexone and Gastrointestinal Perforation
Mackey, A. C., Green, L., Greene, P., & Avigan, M. (2010) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2010.01.011 · Cited by 63 · see citing works
Schutter, U., Grunert, S., Meyer, C. G., et al. (2010) · Current Medical Research and Opinion · doi:10.1185/03007991003787318 · Cited by 62 · see citing works
Variations in demethylation of N-methylnaltrexone in mice, rats, dogs, and humans
Kotake, A. N., Kuwahara, S. K., Burton, E. G., et al. (1989) · Xenobiotica · doi:10.3109/00498258909043176 · Cited by 61 · see citing works
Knudsen, A. K., Brunelli, C., Klepstad, P., Aass, N., Apolone, G., Corli, O., Montanari, M., Caraceni, A. T., & Kaasa, S. (2012) · Pain · doi:10.1016/j.pain.2011.12.005 · Cited by 60 · see citing works
Rentz, A., de Jonge, P. V. H., Leyendecker, P., & Hopp, M. (2011) · Current Medical Research and Opinion · doi:10.1185/03007995.2010.535270 · Cited by 60 · see citing works
Gastrointestinal symptoms among inpatients with advanced cancer
Kömürcü, Ş., Nelson, K. A., Walsh, D., et al. (2002) · American Journal of Hospice and Palliative Medicine® · doi:10.1177/104990910201900513 · Cited by 59 · see citing works
Leppert, W. (2012) · Współczesna Onkologia · doi:10.5114/wo.2012.28792 · Cited by 57 · see citing works
Self-citationPatient assessment of a novel therapeutic approach for the treatment of severe, chronic pain
Nadstawek, J., Leyendecker, P., Hopp, M., et al. (2008) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2008.01820.x · Cited by 56 · see citing works
Smith, K. J., Hopp, M., Mundin, G., Bond, S. J., Bailey, P., Woodward, J., Palaniappan, K., Church, A., Limb, M. C., & Connor, A. L. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.563236 · Cited by 56 · see citing works
Rosti, G., Gatti, A., Costantini, M., et al. (2010) · PubMed · Cited by 55 · see citing works
McNicol, E. D., Boyce, D. B., Schumann, R., & Carr, D. B. (2007) · Pain Medicine · doi:10.1111/j.1526-4637.2007.00335.x · Cited by 54 · see citing works
Cloutier, C., Taliano, J., O’Mahony, W. F., Csanadi, M., Cohen, G., Sutton, I., Sinclair, D. M., Awde, M., Henein, S., Robinson, L. R., et al. (2013) · Pain Research and Management · doi:10.1155/2013/164609 · Cited by 53 · see citing works
Role of oxycodone and oxycodone/naloxone in cancer pain management
Leppert, W. (2010) · Pharmacological Reports · doi:10.1016/s1734-1140(10)70316-9 · Cited by 53 · see citing works
Self-citationPorreca, F., Cowan, A., Raffa, R. B., & Tallarida, R. J. (1983) · Life Sciences · doi:10.1016/0024-3205(83)90843-3 · Cited by 50 · see citing works
Smith, K. J., Hopp, M., Mundin, G., et al. (2008) · Clinical Therapeutics · doi:10.1016/j.clinthera.2008.11.008 · Cited by 49 · see citing works
Cuppoletti, J., Chakrabarti, J. L., Tewari, K. P., & Malinowska, D. H. (2012) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-012-9406-6 · Cited by 46 · see citing works
Dunlop, W., Uhl, R., Khan, I., Taylor, A., & Barton, G. (2012) · Journal of Medical Economics · doi:10.3111/13696998.2012.665279 · Cited by 46 · see citing works
Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms
Iyer, S. S., Randazzo, B. P., Tzanis, E. L., Schulman, S. L., Zhang, H., Wang, W., & Manley, A. L. (2011) · Value in Health · doi:10.1016/j.jval.2010.11.003 · Cited by 44 · see citing works
Beneficial effects of naloxone in a patient with intestinal pseudoobstruction.
Schang, J. C., & Devroede, G. J. (1985) · PubMed · Cited by 42 · see citing works
Pain Management in Patients with Cancer: Focus on Opioid Analgesics
Leppert, W. (2011) · Current Pain and Headache Reports · doi:10.1007/s11916-011-0201-7 · Cited by 41 · see citing works
Self-citationHigh doses of oxycodone–naloxone combination may provide poor analgesia
Mercadante, S., Ferrera, P., & Adile, C. (2011) · Supportive Care in Cancer · doi:10.1007/s00520-011-1205-x · Cited by 40 · see citing works
Methylnaltrexone for Opioid‐Induced Constipation in Pediatric Oncology Patients
Rodrigues, A., Wong, C., Mattiussi, A., et al. (2013) · Pediatric Blood & Cancer · doi:10.1002/pbc.24615 · Cited by 39 · see citing works
Slatkin, N. E., Lynn, R. B., Su, C. G., et al. (2011) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2011.02.015 · Cited by 38 · see citing works
Clemens, K. E., Quednau, I., & Klaschik, E. (2011) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2011.02634.x · Cited by 37 · see citing works
Coluzzi, F., & Ruggeri, M. (2014) · Current Medical Research and Opinion · doi:10.1185/03007995.2014.894501 · Cited by 37 · see citing works
Interventional Therapies for Cancer Pain Management: Important Adjuvants to Systemic Analgesics
Eidelman, A., White, T., & Swarm, R. A. (2007) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2007.0075 · Cited by 35 · see citing works
Oxycodone/Naloxone in the Management of Patients with Pain and Opioid–Induced Bowel Dysfunction
Leppert, W. (2013) · Current Drug Targets · doi:10.2174/13894501113149990210 · Cited by 35 · see citing works
Self-citationWeschules, D. J., Bain, K. T., Reifsnyder, J., et al. (2006) · Pain Medicine · doi:10.1111/j.1526-4637.2006.00184.x · Cited by 34 · see citing works
Kuusniemi, K., Zöllner, J., Sjövall, S., Huhtala, J., Karjalainen, P. A., Kokki, M., Lemken, J., Oppermann, J., & Kokki, H. J. (2012) · Journal of International Medical Research · doi:10.1177/030006051204000516 · Cited by 34 · see citing works
Clinical status of methylnaltrexone, a new agent to prevent and manage opioid-induced side effects.
Yuan, C. (2004) · PubMed · Cited by 34 · see citing works
Blagden, M., Hafer, J., Duerr, H. E., Hopp, M., & Bosse, B. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12463 · Cited by 33 · see citing works
Novel therapies for constipation
Thayalasekeran, S. (2013) · World Journal of Gastroenterology · doi:10.3748/wjg.v19.i45.8247 · Cited by 33 · see citing works
Hermanns, K., JUNKER, U., & Nolte, T. (2012) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2012.648615 · Cited by 32 · see citing works
Pharmacokinetic and pharmacodynamic considerations for the current chronic constipation treatments
Müller-Lissner, S. (2013) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2013.773972 · Cited by 31 · see citing works
Mu-opioid antagonists for opioid-induced bowel dysfunction
McNicol, E. D., Boyce, D. B., & Carr, D. B. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006332 · Cited by 31 · see citing works
Methylnaltrexone for the treatment of opioid-induced constipation
Bader, S., Dürk, T., & Becker, G. (2012) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.12.63 · Cited by 30 · see citing works
The opioid bowel syndrome: A review of pathophysiology and treatment
Davis, M. P. (2005) · Journal of Opioid Management · doi:10.5055/jom.2005.0035 · Cited by 29 · see citing works
Validated tools for evaluating opioid-induced bowel dysfunction
Olesen, A. E., & Drewes, A. M. (2011) · Advances in Therapy · doi:10.1007/s12325-011-0006-4 · Cited by 29 · see citing works
Webster, L. R., Slevin, K. A., Narayana, A. K., et al. (2013) · Pain Medicine · doi:10.1111/pme.12184 · Cited by 29 · see citing works
Cuomo, A., Russo, G., Esposito, G., Forte, C. A., Connola, M., & Marcassa, C. (2013) · American Journal of Hospice and Palliative Medicine® · doi:10.1177/1049909113510058 · Cited by 28 · see citing works
Metabolism of Intravenous Methylnaltrexone in Mice, Rats, Dogs, and Humans
Chandrasekaran, A., Tong, Z., Li, H., et al. (2010) · Drug Metabolism and Disposition · doi:10.1124/dmd.109.031179 · Cited by 28 · see citing works
Rauck, R. L. (2013) · Drugs · doi:10.1007/s40265-013-0084-5 · Cited by 27 · see citing works
Shaiova, L., Rim, F., FRIEDMAN, D., et al. (2007) · Palliative & Supportive Care · doi:10.1017/s147895150707023x · Cited by 27 · see citing works
Gatti, A., Casali, M., Lazzari, M., et al. (2012) · Advances in Therapy · doi:10.1007/s12325-012-0074-0 · Cited by 26 · see citing works
Kang, J. H., Lee, G., Shin, S. H., et al. (2013) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2013.02.009 · Cited by 26 · see citing works
Managing opioid-induced constipation in advanced illness: focus on methylnaltrexone bromide
Clemens, E. (2010) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s4301 · Cited by 24 · see citing works
Methylnaltrexone: the evidence for its use in the management of opioid-induced constipation
Deibert, P. (2009) · Core evidence · doi:10.2147/ce.s8556 · Cited by 23 · see citing works
Comelon, M., Wisløff‐Aase, K., Raeder, J. C., Drægni, T., UNDERSRUD, H., Qvigstad, E., Bjerkelund, C. E., & Lenz, H. (2013) · Acta Anaesthesiologica Scandinavica · doi:10.1111/aas.12051 · Cited by 21 · see citing works
Lipman, A. G., Karver, S. B., Cooney, G. A., et al. (2011) · Journal of Pain & Palliative Care Pharmacotherapy · doi:10.3109/15360288.2011.573531 · Cited by 21 · see citing works
Abramowitz, L., Béziaud, N., Caussé, C., et al. (2013) · Journal of Medical Economics · doi:10.3111/13696998.2013.851083 · Cited by 21 · see citing works
Michna, E., Weil, A. J., Duerden, M. E., et al. (2011) · Pain Medicine · doi:10.1111/j.1526-4637.2011.01189.x · Cited by 17 · see citing works
Evaluation of methylnaltrexone for the reduction of postoperative vomiting and nausea incidences.
Moerman, I., Franck, P., & Camu, F. (1995) · PubMed · Cited by 17 · see citing works
Holzer, P. D. (2004) · Neuroscience Letters · doi:10.1016/s0304-3940(03)01384-3 · Cited by 16 · see citing works
Sykes, N. P. (2012) · CRC Press eBooks · doi:10.1201/b13476-15 · Cited by 14 · see citing works
Caraceni, A. T. (2011) · Palliative Medicine · doi:10.1177/0269216310395871 · Cited by 13 · see citing works
Lazzari, M., Sabato, A. F., Caldarulo, C., Casali, M., Gafforio, P., Marcassa, C., & Leonardis, F. (2013) · Current Medical Research and Opinion · doi:10.1185/03007995.2013.866545 · Cited by 13 · see citing works
Sykes, N. P. (2015) · doi:10.1093/med/9780199656097.003.0203 · Cited by 10 · see citing works
Prevalencia y severidad de la disfunción intestinal inducida por opioides
Gálvez, R., Provencio, M., Cobo, M., et al. (2013) · Atención Primaria · doi:10.1016/j.aprim.2013.08.007 · Cited by 10 · see citing works
Mechanisms and Management of Constipation in the Cancer Patient
Basta, S., & Anderson, D. L. (1998) · Journal of Pharmaceutical Care in Pain & Symptom Control · doi:10.1300/j088v06n03_03 · Cited by 9 · see citing works
A Review of the Treatment of Opioid-induced Constipation with Methylnaltrexone Bromide
Abarca, F. M., Saclarides, T. J., & Brand, M. I. (2010) · Clinical Medicine Insights Therapeutics · doi:10.4137/cmt.s1168 · Cited by 6 · see citing works
Unexpected Side Effect of Methylnaltrexone
Stettler, A., & Zulian, G. B. (2013) · Journal of Palliative Medicine · doi:10.1089/jpm.2013.0264 · Cited by 5 · see citing works
Utilization of methylnaltrexone (relistor) for opioid-induced constipation in an oncology hospital.
Watkins, J. L., Eckmann, K. R., Mace, M. L., et al. (2011) · PubMed · Cited by 5 · see citing works
Centeno, C., Carranza, O. E., Zuriarrain, Y., et al. (2013) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2013.08.009 · Cited by 4 · see citing works
Frankish, P. D. (2011) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789814273923_0004 · Cited by 4 · see citing works
Itopride in the treatment of kinetic disorders of gastrointestinal tract
Chojnacki, J. (2011) · Gastroenterology Review · doi:10.5114/pg.2011.23139 · Cited by 3 · see citing works
Vickery, R., Webster, L. R., Li, Y., et al. (2013) · Journal of Pain · doi:10.1016/j.jpain.2013.01.661 · Cited by 2 · see citing works
Caon, M. (2016) · Springer eBooks · doi:10.1007/978-981-10-2332-3_9 · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [72]Targin® (oxycodone hydrochloride and naloxone hydrochloride dihydrate) [package insert] Cambridge, UK Mundipharma International 2011 Polish
- [75]Reimer K Hopp M Zenz M Meeting the challenges of opioid-induced constipation in chronic pain management – a novel approach Pharmacology 2009 83 1 10 17 18957874
Cited by
Sorted by citations
Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model
Wang, F., Meng, J., Zhang, L., Johnson, T., Chen, C., & Roy, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-21915-8 · Cited by 238 · see citing works
Nutritional implications of opioid use disorder: A guide for drug treatment providers
Chavez, M. N., & Rigg, K. K. (2020) · Psychology of Addictive Behaviors · doi:10.1037/adb0000575 · Cited by 38 · see citing works
A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health
Wiss, D. A. (2019) · Frontiers in Public Health · doi:10.3389/fpubh.2019.00193 · Cited by 41 · see citing works
Rapid assessment of nutrition services in Los Angeles substance use disorder treatment centers
Wiss, D. A., Schellenberger, M., & Prelip, M. L. (2019) · Journal of Community Health · doi:10.1007/s10900-018-0557-2 · Cited by 25 · see citing works
The Role of Nutrition in Addiction Recovery
Wiss, D. A. (2019) · The Assessment and Treatment of Addiction · doi:10.1016/b978-0-323-54856-4.00002-x · Cited by 20 · see citing works
Registered dietitian nutritionists in substance use disorder treatment centers
Wiss, D. A., Schellenberger, M., & Prelip, M. L. (2018) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2017.08.113 · Cited by 14 · see citing works
- Authors
- Leppert, W.
- Affiliations
- Poznan University of Medical Sciences (PL)
- Corresponding author
- Leppert, Wojciech
- ORCID
- Leppert, Wojciech
- Venue
- Drug Design Development and Therapy
- Publisher
- Informa UK Limited
- Published
- 2015-04
- Volume
- 9
- Pages
- 2215
- ISSN
- 1177-8881 (ISSN-L)
- PMC
- PMC4404965
- OpenAlex
- W2021478061
- Cited by
- 72
- References
- 139
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 7 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 14 · 2016: 11 · 2015: 2
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Design Development and Therapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (acceptedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- opioid-induced bowel dysfunction, opioid-induced constipation, methylnaltrexone, naloxegol, opioid antagonists, opioid agonists, laxatives, prokinetic agents, cancer pain, chronic non-cancer pain, opioid withdrawal
- MeSH terms
- Analgesics, Opioid, Gastrointestinal Diseases, Gastrointestinal Motility, Humans, Narcotic Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
