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Maximum opioid dosing

Morihiro Fujimura, Naoki Izumimoto, Sayoko Kanie, Ryosuke Kobayashi, Satoru Yoshikawa, Shinobu Momen, Mikito Hirakata, Toshikazu Komagata, Satoshi Okanishi, Masashi Iwata, Tadatoshi Hashimoto, Takayuki Doi, Naoki Yoshimura, Koji Kawai
PURPOSE: To clarify the mechanism of inhibitory action of TRK-130 (Naltalimide), a unique µ-opioid receptor partial agonist, on the micturition reflex. METHODS: The effect of TRK-130 on isovolumetric rhythmic bladder contractions (RBCs) was examined in guinea pigs, the effect of which was clarified by co-treatment with naloxone or in spinal cord transection. The effect of TRK-130 on urodynamic parameters was also observed in guinea pigs. In addition, the effect of TRK-130 on bladder contraction induced by peripheral stimulation of the pelvic nerve was investigated in rats...
January 16, 2017: International Urology and Nephrology
Joanne Salas, Jeffrey F Scherrer, Frank David Schneider, Mark D Sullivan, Kathleen K Bucholz, Thomas Burroughs, Laurel A Copeland, Brian K Ahmedani, Patrick J Lustman
Recent studies suggest that longer durations of opioid use, independent of maximum morphine equivalent dose (MED) achieved, is associated with increased risk of new-onset depression (NOD). Conversely, other studies, not accounting for duration, found that higher MED increased probability of depressive symptoms. To determine whether rate of MED increase is associated with NOD, a retrospective cohort analysis of Veterans Health Administration data (2000-2012) was conducted. Eligible patients were new, chronic (>90 days) opioid users, aged 18 to 80, and without depression diagnoses for 2 years before start of follow-up (n = 7051)...
February 2017: Pain
Cheng Wang, Congpin Wang
Neuropathic pain is still considered as incurable disease as current therapies are not ideal in terms of efficacy and tolerability. It is imperative to search for novel drugs to obtain better treatments. Sulforaphane (SFN), a derivative of glucoraphanin present in cruciferous vegetables, exhibits therapeutic effects on inflammation-related diseases. Since inflammation plays an important role in regulating chronic pain, in the present study, we investigated anti-nociceptive effects of SFN and its underlying mechanisms in a neuropathic pain mouse model, sciatic nerve chronic constriction injury (CCI)...
January 4, 2017: Inflammopharmacology
Abdulaziz Al Odhayani, Ayla Tourkmani, Mohammed Alshehri, Hala Alqahtani, Adel Mishriky
The elderly population is increasing throughout the globe, resulting in higher healthcare costs. Potential inappropriate medication (PIM) prescriptions are a major health problem affecting the elderly persons. Due to limited studies in PIM use in primary care and home healthcare in Saudi Arabia, we aim to examine the extent of PIM prescription for and use by elderly patients. This study was carried out with 798 elderly patients, arbitrarily selected from Prince Sultan Medical Military City through the patient register...
January 2017: Saudi Journal of Biological Sciences
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
Shokoufeh Bonakdaran, Mahdi Hassan Zadeh Daloee, Ali Akhoondpoor Manteghi, Mina Akbarirad, Abdollah Firoozi, Fatemeh Akbarirad
INTRODUCTION: Methadone is the most common opioid in use for opioid substitution therapy. The Relation of methadone and electrocardiographic findings is nearly well known while the relationship between its electrocardiographic indexes and hormonal changes are not well recognized. OBJECTIVE: To evaluate the hormonal changes in patients who are taking methadone maintenance treatment (MMT) and its effects on electrocardiographic indexes, in comparison with healthy control groups...
October 26, 2016: Endocrine, Metabolic & Immune Disorders Drug Targets
Steffen T Simon, Irene J Higginson, Sara Booth, Richard Harding, Vera Weingärtner, Claudia Bausewein
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 1, 2010, on 'Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults'. Breathlessness is one of the most common symptoms experienced in the advanced stages of malignant and non-malignant disease. Benzodiazepines are widely used for the relief of breathlessness in advanced diseases and are regularly recommended in the literature. At the time of the previously published Cochrane review, there was no evidence for a beneficial effect of benzodiazepines for the relief of breathlessness in people with advanced cancer and chronic obstructive pulmonary disease (COPD)...
October 20, 2016: Cochrane Database of Systematic Reviews
Sheena Derry, Cathy Stannard, Peter Cole, Philip J Wiffen, Roger Knaggs, Dominic Aldington, R Andrew Moore
BACKGROUND: Opioid drugs, including fentanyl, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for fentanyl, at any dose, and by any route of administration. Other opioids are considered in separate reviews. OBJECTIVES: To assess the analgesic efficacy of fentanyl for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials...
October 11, 2016: Cochrane Database of Systematic Reviews
Jaime R Bastian, Huijun Chen, Hongfei Zhang, Scott Rothenberger, Ralph Tarter, Dennis English, Raman Venkataramanan, Steve N Caritis
BACKGROUND: Buprenorphine is a Food and Drug Administration-approved maintenance therapy for opioid use disorders and is increasingly being used in pregnant women with opioid use disorders as an alternative to methadone. Dosing of buprenorphine in pregnant women is based on the regimen recommended for nonpregnant females and males. Limited data are available defining the pharmacokinetic properties of sublingual buprenorphine administered during pregnancy. OBJECTIVE: This study evaluated the impact of physiological changes associated with pregnancy on the pharmacokinetics of sublingual buprenorphine during and after pregnancy...
January 2017: American Journal of Obstetrics and Gynecology
Emily Wersocki, John Bedson, Ying Chen, Linda LeResche, Kate M Dunn
A comprehensive systematic literature review of reproductive side effects in women aged 18 to 55 years treated with opioids for 1 month or longer for chronic noncancer pain. A search of 7 databases including EMBASE and Medline was undertaken (October 2014 and a limited rerun April 2016). The search contained key words for opioids (generic and specific drug names) and side effects (generic and specific reproductive). Titles were screened using predefined criteria by a single reviewer and abstracts and full texts by 2 independent reviewers...
January 2017: Pain
Beatrice Stenik, Almasa Bass, Candace Bramson, Naama Levy-Cooperman, Bimal Malhotra, Kyle Matschke, Pierre Geoffroy, Kenneth W Sommerville, Gernot Wolfram
OBJECTIVE: To evaluate the abuse potential of ALO-02, an abuse-deterrent formulation comprising pellets of extended-release oxycodone hydrochloride surrounding sequestered naltrexone hydrochloride. DESIGN: Randomized, double-blind, placebo-/active-controlled, 6-way crossover study, with naloxone challenge, drug discrimination, and treatment phases. SUBJECTS: Nondependent, recreational opioid users. METHODS: Oral administration of crushed and intact ALO-02, crushed immediate-release (IR) oxycodone, and placebo...
August 22, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Jacob Hutchins, Ioanna Apostolidou, Sara Shumway, Rosemary Kelly, Qi Wang, Cody Foster, Gabriel Loor
OBJECTIVE: Effective postoperative pain management has been shown to be a positive predictive factor for postoperative recovery following a thoracotomy. The primary objective of this study was to examine the efficacy and safety of continuous paravertebral blockade in managing acute postsurgical pain following unilateral and bilateral single-lung transplantation. DESIGN: The authors conducted a prospective observational trial of patients. SETTING: The study was conducted in an academic university hospital...
May 4, 2016: Journal of Cardiothoracic and Vascular Anesthesia
Barbara Bednarczyk-Cwynar, Natalia Wachowiak, Michal Szulc, Ewa Kamińska, Anna Bogacz, Joanna Bartkowiak-Wieczorek, Lucjusz Zaprutko, Przemyslaw L Mikolajczak
The conjugate 8 was obtained as a result of condensation of 3-hydroxyiminooleanolic acid morfolide (7) and aspirin in dioxane. Analgesic effect of OAO-ASA (8) for the range of doses 0.3-300.0 mg/kg (p.o.) was performed in mice using a hot-plate test. Anti-inflammatory activity was assessed on carrageenan-induced paw edema in rats for the same range of doses. The conjugate OAO-ASA (8) did not significantly change locomotor activity of mice, therefore sedative properties of the compound should be excluded. The compound 8 proved a simple, proportional, dose-dependent analgesic action and expressed strong anti-inflammatory activity showing a reversed U-shaped, dose-dependent relation with its maximum at 30...
2016: Frontiers in Pharmacology
Eunjung Oh, Hyun Joo Ahn, Woo Seog Sim, Jin Young Lee
BACKGROUND: An intravenous form of ibuprofen has recently been approved by the Food and Drug Administration (FDA) and reports are rare on its co-administration with opioids. OBJECTIVES: We researched whether an intravenous ibuprofen-hydromorphone combination is synergistic, additive, or infra-additive on postoperative pain. STUDY DESIGN: A parallel-group, 1:1:1 allocation, randomized, double-blind controlled trial. SETTING: University teaching hospital in Korea...
July 2016: Pain Physician
Jacqueline Gonçalves, Marisa Rangel, Andréia Biolchi, Eveline Alves, Karla Moreira, Luciano Silva, Márcia Mortari
Analgesic therapy is based on the sequential treatment of pain, in which opioids are drugs of last resource and known to be highly effective, but are also responsible for undesirable side effects, tolerance and addiction. There is a need for new drugs with alternative targets in order to minimize side effects and improve treatment efficacy. Mastoparans are an abundant class of peptides in wasp venom and have shown great potential as new drugs, as well as being excellent tools for the study of G-protein-coupled receptors...
September 15, 2016: Toxicon: Official Journal of the International Society on Toxinology
Eyas Raddad, Amy Chappell, Jeffery Meyer, Alan Wilson, Charles E Ruegg, Johannes Tauscher, Michael A Statnick, Vanessa Barth, Xin Zhang, Steven J Verfaille
Therapeutic benefits from nociceptin opioid peptide receptor (NOP) antagonism were proposed for obesity, eating disorders, and depression. LY2940094 ([2-[4-[(2-chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]-3-pyridyl]methanol) is a novel, orally bioavailable, potent, and selective NOP antagonist. We studied NOP receptor occupancy (RO) after single oral LY2940094 doses in rat hypothalamus and human brain by use of liquid chromatography with tandem mass spectrometry (LC-MS/MS) (LSN2810397) and positron emission tomography (PET) ([(11)C]NOP-1A) tracers, respectively...
September 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Anna K M Persson, Lars-Erik Dyrehag, Jonas Åkeson
OBJECTIVE: Early postoperative pain correlates to persisting pain, psychosocial distress, and delayed mobilization with thromboembolic and infectious complications. Electrical pain thresholds (EPT) have shown promising results in being able to predict postoperative pain, but the results are conflicting. The aim of this study was to test whether EPT levels can be used to predict the postoperative pain in patients of both sexes. MATERIALS AND METHODS: One hundred eighty patients scheduled for laparoscopic cholecystectomy were included in this prospective clinical study...
February 2017: Clinical Journal of Pain
Girish R Chopda, Viraj Parge, Ganesh A Thakur, S John Gatley, Alexandros Makriyannis, Carol A Paronis
Daily treatment with cannabinoids results in tolerance to many, but not all, of their behavioral and physiologic effects. The present studies investigated the effects of 7-day exposure to 10 mg/kg daily of Δ(9)-tetrahydrocannabinol (THC) on the diuretic and antinociceptive effects of THC and the synthetic cannabinoid AM4054. Comparison studies determined diuretic responses to the κ-opioid agonist U50,488 and furosemide. After determination of control dose-response functions, mice received 10 mg/kg daily of THC for 7 days, and dose-response functions were re-determined 24 hours, 7 days, or 14 days later...
August 2016: Journal of Pharmacology and Experimental Therapeutics
Kevin J Friesen, Jamie Falk, Shawn Bugden
BACKGROUND: Meperidine (pethidine) is an opioid analgesic that offers little advantage relative to other opioids and several disadvantages including limited potency, short duration of action, and the production of a neurotoxic metabolite (normeperidine) with a long half-life. Older adults are more sensitive to meperidine's side effects and may have diminished renal function which leads to the accumulation of normeperidine. The Institute for Safe Medication Practices has suggested avoiding meperidine in older adults, limiting its dose (≤600 mg/day) and duration of use (≤48 h)...
May 11, 2016: BMC Geriatrics
Philip Krieter, Nora Chiang, Shwe Gyaw, Phil Skolnick, Roger Crystal, Fintan Keegan, Julie Aker, Melissa Beck, Jennifer Harris
Parenteral naloxone has been approved to treat opiate overdose for over 4 decades. Intranasal naloxone, administered "off label" using improvised devices, has been widely used by both first responders and the lay public to treat overdose. However, these improvised devices require training for effective use, and the recommended volumes (2 to 4 mL) exceed those considered optimum for intranasal administration. The present study compared the pharmacokinetic properties of intranasal naloxone (2 to 8 mg) delivered in low volumes (0...
October 2016: Journal of Clinical Pharmacology
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