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Opioid constipation

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https://www.readbyqxmd.com/read/28213593/randomised-double-blind-parallel-group-placebo-controlled-study-to-evaluate-the-analgesic-efficacy-and-safety-of-vvz-149-injections-for-postoperative-pain-following-laparoscopic-colorectal-surgery
#1
Srdjan S Nedeljkovic, Darin J Correll, Xiaodong Bao, Natacha Zamor, Jose L Zeballos, Yi Zhang, Mark J Young, Johanna Ledley, Jessica Sorace, Kristen Eng, Carlyle P Hamsher, Rajivan Maniam, Jonathan W Chin, Becky Tsui, Sunyoung Cho, Doo H Lee
INTRODUCTION: In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery...
February 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28204957/insights-into-the-role-of-opioid-receptors-in-the-gi-tract-experimental-evidence-and-therapeutic-relevance
#2
James J Galligan, Catia Sternini
Opioid drugs are prescribed extensively for pain treatment but when used chronically they induce constipation that can progress to opioid-induced bowel dysfunction. Opioid drugs interact with three classes of opioid receptors: mu opioid receptors (MORs), delta opioid receptors (DOR), and kappa opioid receptors (KORs), but opioid drugs mostly target the MORs. Upon stimulation, opioid receptors couple to inhibitory Gi/Go proteins that activate or inhibit downstream effector proteins. MOR and DOR couple to inhibition of adenylate cyclase and voltage-gated Ca(2+) channels and to activation of K(+) channels resulting in reduced neuronal activity and neurotransmitter release...
February 16, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28182123/long-term-safety-and-analgesic-efficacy-of-buprenorphine-buccal-film-in-patients-with-moderate-to-severe-chronic-pain-requiring-around-the-clock-opioids
#3
Martin Hale, Veronica Urdaneta, M Todd Kirby, Qinfang Xiang, Richard Rauck
BACKGROUND: This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids. METHODS: The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients) or were recruited de novo for this study (n=61) were enrolled in this study...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28181146/when-people-with-opioid-induced-constipation-speak-a-patient-survey
#4
Robert S Epstein, J Russell Teagarden, Ali Cimen, Mark Sostek, Tehseen Salimi
INTRODUCTION: Opioid-induced constipation (OIC) is a common consequence of opioid use for chronic pain. OIC creates problems for patients independent of their pain syndromes, in addition to threatening pain treatment effectiveness. Healthcare practitioners need to be alert to how patients talk about OIC so that it is not missed. Using a survey mechanism, we sought patient expressions of the personal impact OIC imposes on how they are able to live their lives and on meanings that symptom relief would produce...
February 8, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28176913/peripherally-acting-%C3%AE-opioid-receptor-antagonists-as-treatment-options-for-constipation-in-noncancer-pain-patients-on-chronic-opioid-therapy
#5
REVIEW
Joseph V Pergolizzi, Robert B Raffa, Marco Pappagallo, Charles Fleischer, Joseph Pergolizzi, Gianpietro Zampogna, Elizabeth Duval, Janan Hishmeh, Jo Ann LeQuang, Robert Taylor
Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28168885/methylnaltrexone-versus-naloxone-for-opioid-induced-constipation-in-the-medical-intensive-care-unit
#6
Cristian Merchan, Diana Altshuler, John Papadopoulos
BACKGROUND: Opioid-induced constipation (OIC) is common in critically ill patients; it leads to complications that can increase hospital stay and, rarely, bowel perforation. Opioid antagonists are considered a logical approach to treat OIC; however, the agent of choice has yet to be determined. OBJECTIVE: To assess the effectiveness and safety of enteral naloxone (NTX) versus subcutaneous methylnaltrexone (MNTX) for the treatment of OIC in the medical intensive care unit...
March 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28162731/-480-oral-methylnaltrexone-does-not-negatively-impact-analgesia-in-patients-with-opioid-induced-constipation-and-chronic-noncancer-pain
#7
L Webster, J Peppin, J Harper, R Israel
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28158929/the-analgesic-and-anti-inflammatory-effects-of-salvinorin-a-analogue-%C3%AE-tetrahydropyran-salvinorin-b-in-mice
#8
K F Paton, N Kumar, R S Crowley, J L Harper, T E Prisinzano, B M Kivell
BACKGROUND: Drugs activating the mu opioid receptor are routinely used to treat severe acute and chronic pain. Unfortunately, side effects including nausea, constipation, respiratory depression, addiction and tolerance can limit clinical utility. In contrast, kappa opioid receptor (KOPr) agonists, such as Salvinorin A (SalA), have analgesic properties with little potential for abuse. METHODS: We evaluated SalA and the novel analogue β-tetrahydropyran Salvinorin B (β-THP SalB) for the ability to modulate pain and inflammation in vivo...
February 3, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28152820/using-a-qopi-based-template-to-monitor-appropriate-evaluation-of-constipation
#9
Bruce S Lin, Nanette Robinson, Thomas William Malpass, Vincent J Picozzi, Prakash Vishnu, Lynne Patricia Taylor, Gurkamal S Chatta, Cathleen M Goetsch, David Michael Aboulafia, Joseph K Rosales
: 94 Background: A common symptom in patients being treated with opioid analgesics is constipation, which is often underreported by patients and therefore undertreated by providers. The Quality Oncology Project Initiative (QOPI) has identified constipation as one of the benchmark symptoms to be monitored in order to obtain certification. At Virginia Mason Medical Center, we had previously identified constipation as a symptom which was not adequately addressed in the medical record, and implemented a template-based initiative to increase its evaluation...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28146271/liposomal-bupivacaine-infiltration-at-the-surgical-site-for-the-management-of-postoperative-pain
#10
REVIEW
Thomas W Hamilton, Vassilis Athanassoglou, Stephen Mellon, Louise H Strickland, Marialena Trivella, David Murray, Hemant G Pandit
BACKGROUND: Despite multi-modal analgesic techniques, acute postoperative pain remains an unmet health need, with up to three quarters of people undergoing surgery reporting significant pain. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained-release analgesia. OBJECTIVES: To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain...
February 1, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28143720/strategies-for-combating-opioid-induced-constipation-targeted-mechanisms-to-maintain-pain-control-without-compromise
#11
Michael J Brennan, Steven P Stanos
No abstract text is available yet for this article.
January 29, 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/28142305/effects-of-acute-and-repeated-treatment-with-the-biased-mu-opioid-receptor-agonist-trv130-oliceridine-on-measures-of-antinociception-gastrointestinal-function-and-abuse-liability-in-rodents
#12
Ahmad A Altarifi, Bethany David, Karan H Muchhala, Bruce E Blough, Hamid Akbarali, S Stevens Negus
RATIONALE: TRV130 (oliceridine; N-[(3-methoxythiophen-2-yl)methyl]-2-[(9 R)-9-pyridin-2-yl-6-oxaspiro[4.5]decan-9-yl]ethanamine) is a novel mu opioid receptor (MOR) agonist that preferentially activates G-protein versus β-arrestin signaling pathways coupled to MORs. Prevailing evidence suggests that TRV130 and other G-protein-biased MOR agonists may produce therapeutic analgesic effects with reduced adverse effects compared to existing MOR agonists. OBJECTIVES: This study compared the effects of acute and repeated TRV130 administration on measures of antinociception, gastrointestinal function, and abuse liability in rodents...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28127938/an-open-label-randomized-bioavailability-study-of-alternative-methods-of-oral-administration-of-naloxegol-in-healthy-subjects
#13
Khanh Bui, Bruce Birmingham, Ulysses Diva, Bruce Berger
Naloxegol is a peripherally acting μ-opioid receptor antagonist approved as an orally administered tablet for the treatment of opioid-induced constipation. Patients with swallowing difficulties may benefit from alternative approaches to the oral administration of the whole-tablet formulation of naloxegol. This open-label, randomized, 4-period, 4-treatment, crossover, single-dose study (NCT02446171) evaluated the pharmacokinetic (PK) characteristics of crushed naloxegol 25-mg tablets (suspended in water) administered orally or by nasogastric tube and a naloxegol solution compared with the commercially available 25-mg tablet formulation in healthy volunteers...
January 27, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28105279/nanoconjugated-nap-as-a-potent-and-periphery-selective-mu-opioid-receptor-modulator-to-treat-opioid-induced-constipation
#14
Guoyan G Xu, Olga Yu Zolotarskaya, Dwight A Williams, Yunyun Yuan, Dana E Selley, William L Dewey, Hamid I Akbarali, Hu Yang, Yan Zhang
Opioids are the mainstay for cancer and noncancer pain management. However, their use is often associated with multiple adverse effects. Among them, the most common and persistent one is probably opioid-induced constipation (OIC). Periphery selective opioid antagonists may alleviate the symptoms of OIC without compromising the analgesic effects of opioids. Recently our laboratories have identified one novel lead compound, 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-pyridyl)acetamido]morphinan (NAP), as a peripherally selective mu opioid receptor ligand carrying subnanomolar affinity to the mu opioid receptor and over 100-folds of selectivity over both the delta and kappa opioid receptors, with reasonable oral availability and half-life, and potential to treat OIC...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28059433/a-12-week-extension-study-to-assess-the-safety-and-tolerability-of-naloxegol-in-patients-with-noncancer-pain-and-opioid-induced-constipation
#15
Lynn Webster, Raj Tummala, Ulysses Diva, Jaakko Lappalainen
OBJECTIVE: To compare the long-term safety and tolerability of naloxegol with placebo in patients with opioid-induced constipation (OIC) and noncancer pain. DESIGN: Twelve-week, multicenter, randomized, double-blind, parallel-group phase 3 extension study (KODIAC-07, NCT01395524). SETTING: Clinical investigation centers in the United States. PATIENTS: Adult outpatients (N = 302) with confirmed OIC who had completed a 12-week pivotal phase 3 study (KODIAC-04, NCT01309841)...
November 2016: Journal of Opioid Management
https://www.readbyqxmd.com/read/28053617/characterization-the-response-of-korl-icr-mice-to-loperamide-induced-constipation
#16
Ji Eun Kim, Woo Bin Yun, Ji Eun Sung, Hyun Ah Lee, Jun Young Choi, Yeon Shik Choi, Young Suk Jung, Kil Soo Kim, Dae Youn Hwang
Animal models of constipation induced with drugs and diet have been widely employed to investigate therapeutic effects and the action mechanism of drugs against this disease. ICR mice were selected to produce this disease model through oral administration of loperamide (Lop), even though SD rats are commonly utilized in studies of constipation. To compare the responses of ICR mice obtained from three different sources to constipation inducers, alterations in stool number, histopathological structure, mucin secretion and opioid-receptor downstream signaling pathway were measured in Korl:ICR (Korea FDA source), A:ICR (USA source) and B:ICR (Japan source) injected with low and high concentrations of Lop (LoLop and HiLop)...
December 2016: Laboratory Animal Research
https://www.readbyqxmd.com/read/28035588/clinical-pharmacokinetics-and-pharmacodynamics-of-naloxegol-a-peripherally-acting-%C3%A2%C2%B5-opioid-receptor-antagonist
#17
REVIEW
Khanh Bui, Diansong Zhou, Hongmei Xu, Eike Floettmann, Nidal Al-Huniti
Naloxegol is a peripherally acting µ-opioid receptor antagonist approved for use as an orally administered tablet (therapeutic doses of 12.5 and 25 mg) for the treatment of opioid-induced constipation. Over a wide dose range (i.e. single supratherapeutic doses up to 1000 mg in healthy volunteers), the pharmacokinetic properties of naloxegol appear to be time- and dose-independent. Naloxegol is rapidly absorbed, with mean time to maximum plasma concentration of <2 h. Following once-daily administration, steady state is achieved within 2-3 days and minimal accumulation is observed...
December 29, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28034973/opioid-induced-constipation-and-bowel-dysfunction-a-clinical-guideline
#18
Stefan Müller-Lissner, Gabrio Bassotti, Benoit Coffin, Asbjørn Mohr Drewes, Harald Breivik, Elon Eisenberg, Anton Emmanuel, Françoise Laroche, Winfried Meissner, Bart Morlion
OBJECTIVE:  To formulate timely evidence-based guidelines for the management of opioid-induced bowel dysfunction. SETTING:  Constipation is a major untoward effect of opioids. Increasing prescription of opioids has correlated to increased incidence of opioid-induced constipation. However, the inhibitory effects of opioids are not confined to the colon, but also affect higher segments of the gastrointestinal tract, leading to the coining of the term "opioid-induced bowel dysfunction...
December 29, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28024664/long-term-use-of-opioids-in-210-officially-registered-patients-with-chronic-noncancer-pain-in-taiwan-a-cross-sectional-study
#19
Tso-Chou Lin, Luo-Ping Ger, Joseph V Pergolizzi, Robert B Raffa, Ju-O Wang, Shung-Tai Ho
BACKGROUND/PURPOSE: Prescribing opioids for chronic noncancer pain has been strictly regulated for two decades in Taiwan. The aim of this study was to survey the patients' perspectives and potential drawbacks following long-term use of opioids. METHODS: An observational cross-sectional survey using the Taiwanese version of Brief Pain Inventory was conducted among outpatients with chronic noncancer pain registered by the Taiwan Food and Drug Administration. Patients were also asked about their sexual behavior, depression, opioid misuse behaviors, and use of complementary and alternative medicine...
December 23, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28019066/opioid-analgesic-use-among-patients-presenting-with-acute-abdominal-pain-and-factors-associated-with-surgical-diagnoses
#20
D Khemani, M Camilleri, A Roldan, A D Nelson, S-Y Park, A Acosta, A R Zinsmeister
BACKGROUND: The prevalence of chronic opioid use among non-cancer patients presenting with acute abdominal pain (AAP) is unknown. The aim was to characterize opioid use, constipation, diagnoses, and risk factors for surgical diagnoses among non-cancer patients presenting with AAP to an emergency department (ED). METHODS: We performed a retrospective, observational cohort study of all (n=16,121) adult patients (88% from MN, IA and WI) presenting during 2014 with AAP...
December 25, 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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