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Opioid tolerance

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https://www.readbyqxmd.com/read/28548207/pharmacometric-modeling-of-naloxegol-efficacy-and-safety-impact-on-dose-and-label
#1
N Al-Huniti, D Zhou, H Xu, S Aksenov, K H Bui, R Fox, G Helmlinger, D Stanski
Naloxegol is a peripherally acting μ-opioid receptor antagonist that was developed for the treatment of opioid-induced constipation. Modeling and simulation of naloxegol efficacy and tolerability informed selection of doses for phase III studies and provided comprehensive dosage recommendations for the naloxegol US package insert.
May 26, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28535569/reinstituting-the-bolus-new-reasoning-for-an-existing-technique
#2
Porter W McRoberts, Jason E Pope, Catalina Apostol
Improved intrathecal (IT) pump technology is increasing the accuracy of IT opioid bolus dosing and promising advances in pain therapy. Opioid bolus dosing can be used with a minimal continuous infusion or it can function as the sole therapy. Bolus-only dosing is characterized by minimal use of opioid (often less than 1 mg of IT morphine). It achieves adequate pain control while reducing tolerance and possibly opioid-induced hyperalgesia. It may prevent receptor saturation, and provide a "washing out" of the opioid receptor that prevents the observed dose escalation resulting from continuous infusions...
May 2017: Pain Physician
https://www.readbyqxmd.com/read/28533287/trv0109101-a-g-protein-biased-agonist-of-the-%C3%A2%C2%B5-opioid-receptor-does-not-promote-opioid-induced-mechanical-allodynia-following-chronic-administration
#3
Michael Koblish, Richard Carr, Edward R Siuda, David H Rominger, William Gowen-MacDonald, Conrad L Cowan, Aimee L Crombie, Jonathan D Violin, Michael W Lark
Prescription opioids are a mainstay in the treatment of acute moderate to severe pain. However, chronic use leads to a host of adverse consequences including tolerance and opioid-induced hyperalgesia (OIH), leading to more complex treatment regimens and diminished patient compliance. Patients experiencing OIH paradoxically experience exaggerated nociceptive responses instead of pain reduction after chronic opioid usage. The development of OIH and tolerance tend to occur simultaneously and, thus, present a challenge when studying the molecular mechanisms driving each phenomenon...
May 22, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28530786/morphine-for-chronic-neuropathic-pain-in-adults
#4
REVIEW
Tess E Cooper, Junqiao Chen, Philip J Wiffen, Sheena Derry, Daniel B Carr, Dominic Aldington, Peter Cole, R Andrew Moore
BACKGROUND: Neuropathic pain, which is caused by a lesion or disease affecting the somatosensory system, may be central or peripheral in origin. Neuropathic pain often includes symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the nervous system. Opioid drugs, including morphine, are commonly used to treat neuropathic pain...
May 22, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28530501/palliative-care-for-advanced-heart-failure-in-a-department-of-veterans-affairs-regional-hospice-program-patient-selection-a-treatment-protocol-and-clinical-course
#5
George J Taylor, Dorothy M Lee, Catalin F Baicu, Michael R Zile
BACKGROUND: Palliative care for advanced heart failure (HF) is generally recommended. However, few reports have focused on the particulars of treatment, or the clinical course of HF on a specific treatment regimen. OBJECTIVE: Palliation adequate to allow patients to avoid HF admission and die at home. METHODS: Patients from a veterans administration regional practice with multiple, recent hospital admissions were enrolled in community hospice programs...
May 22, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28527421/a-phase-iii-randomized-multi-center-double-blind-placebo-controlled-study-of-safety-and-efficacy-of-lofexidine-for-relief-of-symptoms-in-individuals-undergoing-inpatient-opioid-withdrawal
#6
Charles W Gorodetzky, Sharon L Walsh, Peter R Martin, Andrew J Saxon, Kristen L Gullo, Kousick Biswas
BACKGROUND: Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. METHODS: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal...
May 10, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28525497/enhanced-recovery-after-surgery-for-suspected-ovarian-malignancy-a-survey-of-perioperative-practice-among-gynecologic-oncologists-in-australia-and-new-zealand-to-inform-a-clinical-trial
#7
Kristina Lindemann, Peey-Sei Kok, Martin Stockler, Peter Sykes, Alison Brand
OBJECTIVES: The objective of this survey was to review the current standard of perioperative care of patients with suspected advanced ovarian cancer in Australia and New Zealand in order to determine the level of equipoise for specific interventions. METHODS: In May 2016, a web-based questionnaire (SurveyMonkey Inc, Palo Alto, CA) was sent to all gynecologic oncologists in Australia and New Zealand (n = 56). Descriptive statistics were used. RESULTS: Response rate was 75%...
June 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28516342/pharmacokinetic-bioequivalence-studies-of-an-extended-release-oxycodone-hydrochloride-tablet-in-healthy-japanese-subjects-under-fasting-and-fed-conditions-without-an-opioid-antagonist
#8
Kaoru Toyama, Hidetoshi Furuie, Kana Kuroda, Hitoshi Ishizuka
Oxycodone is a semisynthetic opioid used for the treatment of moderate to severe pain. Two separate studies were conducted to assess the pharmacokinetic bioequivalence of a newly formulated oxycodone hydrochloride extended-release tablet to a marketed oxycodone product in Japan under fasting and fed conditions. Each study was a randomized, open-label, single-dose, single-center, two-period, two-way crossover study. Healthy male Japanese subjects received the oxycodone 10-mg products under fasting and fed conditions...
May 17, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28515426/tolerability-of-opioid-analgesia-for-chronic-pain-a-network-meta-analysis
#9
Zengdong Meng, Jing Yu, Michael Acuff, Chong Luo, Sanrong Wang, Lehua Yu, Rongzhong Huang
Aim of this study was to study the tolerability of opioid analgesia by performing a network meta-analysis (NMA) of randomized-controlled trials (RCTs) which investigated effectiveness of opioids for the management of chronic pain. Research articles reporting outcomes of RCT/s comparing 2 or more opioid analgesics for the management of chronic pain were obtained by database search. Bayesian NMAs were performed to combine direct comparisons between treatments with that of indirect simulated evidence. Study endpoints were: incidence of adverse events, incidence of constipation, trial withdrawal rate, and patient satisfaction with treatment...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507734/adverse-effect-profile-comparison-of-pain-regimens-with-and-without-intravenous-acetaminophen-in-total-hip-and-knee-arthroplasty-patients
#10
Alyssa Gallipani, A Scott Mathis, Hoytin Lee Ghin, Germin Fahim
BACKGROUND: The use of adjunct, non-opioid agents is integral for pain control following total hip and knee arthroplasty. Literature comparing safety profiles of intravenous acetaminophen versus opioids is lacking. OBJECTIVE: To determine whether there is a difference in frequency and type of adverse effects between intravenous acetaminophen-treated and non-intravenous acetaminophen-treated patients. Primary safety endpoints included any adverse effect noted in the electronic medical record post-surgically...
2017: SAGE Open Medicine
https://www.readbyqxmd.com/read/28499376/benefits-of-preparing-for-childbirth-with-mindfulness-training-a-randomized-controlled-trial-with-active-comparison
#11
Larissa G Duncan, Michael A Cohn, Maria T Chao, Joseph G Cook, Jane Riccobono, Nancy Bardacke
BACKGROUND: Childbirth fear is linked with lower labor pain tolerance and worse postpartum adjustment. Empirically validated childbirth preparation options are lacking for pregnant women facing this problem. Mindfulness approaches, now widely disseminated, can alleviate symptoms of both chronic and acute pain and improve psychological adjustment, suggesting potential benefit when applied to childbirth education. METHODS: This study, the Prenatal Education About Reducing Labor Stress (PEARLS) study, is a randomized controlled trial (RCT; n = 30) of a short, time-intensive, 2...
May 12, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28493329/risk-to-heroin-users-of-polydrug-use-of-pregabalin-or-gabapentin
#12
Abigail Lyndon, Suzanne Audrey, Claudia Wells, Erica S Burnell, Suzanne Ingle, Rob Hill, Matthew Hickman, Graeme Henderson
AIM: To examine the risk to heroin users of also using gabapentin or pregabalin (gabapentoids). DESIGN: Multi-disciplinary study: we (a) examined trends in drug-related deaths and gabapentoid prescription data in England and Wales to test for evidence that any increase in deaths mentioning gabapentin or pregabalin is associated with trends in gabapentoid prescribing and is concomitant with opioid use; (b) interviewed people with a history of heroin use about their polydrug use involving gabapentin and pregabalin; and (c) studied the respiratory depressant effects of pregabalin in the absence and presence of morphine in mice to determine whether concomitant exposure increased the degree of respiratory depression observed...
May 10, 2017: Addiction
https://www.readbyqxmd.com/read/28493170/eluxadoline-a-review-in-diarrhoea-predominant-irritable-bowel-syndrome
#13
Gillian M Keating
Eluxadoline (Truberzi(®)) is an orally administered, minimally absorbed agent that acts locally in the gastrointestinal tract as a mixed µ-opioid receptor agonist and δ-opioid receptor antagonist. The randomized, double-blind, placebo-controlled, multinational, phase 3 IBS-3001 and IBS-3002 trials examined the efficacy of eluxadoline in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). The composite response rate (i.e. the proportion of patients with improvement in both worst abdominal pain and stool consistency on ≥50% of days; primary endpoint), was significantly higher in patients receiving eluxadoline 100 mg twice daily than in those receiving placebo after 12 and 26 weeks' therapy...
June 2017: Drugs
https://www.readbyqxmd.com/read/28490343/roadside-opioid-testing-of-drivers-using-oral-fluid-the-case-of-a-country-with-a-zero-tolerance-law-spain
#14
Inmaculada Fierro, Mónica Colás, Juan Carlos González-Luque, F Javier Álvarez
BACKGROUND: Opioids can impair psychomotor performance, and driving under the influence of opioids is associated with an increased risk of accidents. The goals of this study were i) to determine the prevalence of opioids (heroin, morphine, codeine, methadone and tramadol) in Spanish drivers and ii) to explore the presence of opioids, more specifically whether they are used alone or in combination with other drugs. METHODS: The 2008/9 DRUID database regarding Spain was used, which provided information on 3302 drivers...
May 10, 2017: Substance Abuse Treatment, Prevention, and Policy
https://www.readbyqxmd.com/read/28489639/evaluation-of-analgesia-tolerance-and-the-mechanism-of-action-of-morphine-6-o-sulfate-across-multiple-pain-modalities-in-sprague-dawley-rats
#15
Jai Shankar K Yadlapalli, Navdeep Dogra, Anqi W Walbaum, William D Wessinger, Paul L Prather, Peter A Crooks, Maxim Dobretsov
BACKGROUND: Morphine-6-O-sulfate (M6S) is a mixed μ/δ-opioid receptor (OR) agonist and potential alternative to morphine for treatment of chronic multimodal pain. METHODS: To provide more support for this hypothesis, the antinociceptive effects of M6S and morphine were compared in tests that access a range of pain modalities, including hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold tests. RESULTS: Acutely, M6S was 2- to 3-fold more potent than morphine in HPT and PST tests, specifically, derived from best-fit analysis of dose-response relationships of morphine/M6S half-effective dose (ED50) ratios (lower, upper 95% confidence interval [CI]) were 2...
May 4, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28488261/use-of-tramadol-in-psychiatric-care-a-comprehensive-review-and-report-of-two-cases
#16
Ansgar Rougemont-Bücking, Franziska Gamma, Jaak Panksepp
Tramadol is widely prescribed for treating acute and chronic forms of pain. It is a weak mu-receptor opioid agonist and also increases concentrations of serotonin and noradrenaline within the limbic system of the brain. The therapeutic range of tramadol is relatively wide. Compared with other opioid agonists, there is little risk for developing tolerance and for abuse. Recent models of depression emphasise the subjective experience of a depressive mood as being, in part, a psychologically painful state. It is well established that psychological stress due to social separation/loss, disruption or be-trayal of pre-existent significant interpersonal bonds is mediated by the activation of the mammalian PANIC (separation-distress) system...
May 10, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28474563/opioids-and-the-blood-brain-barrier-a-dynamic-interaction-with-consequences-on-drug-disposition-in-brain
#17
Catarina Chaves, Fernando Remião, Salvatore Cisterninoa, Xavier Declèves
Opioids are widely used in pain management whose effects are due to binding to classical opioid receptors and/or Toll-like receptors (TLR) present at the central nervous system (CNS). At the blood-brain barrier (BBB), several influx and/or efflux transporters are expressed, such as the ATP-binding cassette (ABC) P-glycoprotein (P-gp, ABCB1), Breast Cancer Resistance Protein (BCRP, ABCG2) and multidrug resistance-associated proteins (MRP, ABCC) transporters, and solute carrier transporters (SLC), and are responsible for the transport of many xenobiotics from the brain into the bloodstream or vice versa...
May 3, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28470370/high-dosage-of-a-fixed-combination-oxycodone-naloxone-prolonged-release-efficacy-and-tolerability-in-patients-with-chronic-cancer-pain
#18
Francesco Amato, Silvia Ceniti, Sergio Mameli, Giovanni M Pisanu, Renato Vellucci, Vincenzo Palmieri, Leonardo Consoletti, Dorotea Magaldi, Paolo Notaro, Claudio Marcassa
PURPOSE: Opioids are associated with side effects in the treatment of moderate-to-severe chronic cancer pain. Oral combination of opioid agonist-antagonist oxycodone-naloxone (OXN-PR) attenuates gastrointestinal side effects; however, evidence on high-dose OXN-PR treatment is scant. This study evaluates the efficacy and tolerability of high-dose OXN-PR in chronic cancer pain. PATIENTS AND METHODS: This was a multicenter, prospective 60-day observation on consecutive cancer patients with uncontrolled moderate-severe chronic pain or intolerant to other analgesics, who were switched at entry visit (T0) to OXN-PR ≥80 mg daily...
May 3, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28458170/down-in-the-valley-trajectories-of-injection-initiation-among-young-injectors-in-california-s-central-valley
#19
Jennifer L Syvertsen, Catherine E Paquette, Robin A Pollini
BACKGROUND: Injection drug use initiation represents a critical point of public health intervention, as injection increases risk for blood borne infections including Hepatitis C and HIV. In this paper, we explore pathways to injection initiation among youth (≤30) in the rural context of California's Central Valley, where rates of injection drug use are among the highest in the nation. METHODS: We draw on semi-structured qualitative interviews with 20 young injectors to examine drug use histories, including the factors that participants associated with their transition to injection drug use...
April 27, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28456745/oprm1-methylation-contributes-to-opioid-tolerance-in-cancer-patients
#20
Chi T Viet, Dongmin Dang, Bradley E Aouizerat, Christine Miaskowski, Yi Ye, Dan T Viet, Kentaro Ono, Brian L Schmidt
Cancer patients in pain require high doses of opioids and quickly become opioid-tolerant. Previous studies have shown that both chronic cancer pain and high dose opioid use lead to mu-opioid receptor down-regulation. In this study we explore down-regulation of OPRM1, the mu-opioid receptor gene, as a mechanism f,or opioid tolerance in the setting of opioid use for cancer pain. We demonstrate in a cohort of 84 cancer patients that high dose opioid use correlates with OPRM1 hypermethylation in peripheral leukocytes of these patients...
April 26, 2017: Journal of Pain: Official Journal of the American Pain Society
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