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Maximum opioid dosing

Kris Rutten, Wolfgang Schröder, Thomas Christoph, Thomas Koch, Thomas M Tzschentke
Agonists selectively acting at NOP, MOP, DOP and KOP receptors as well as mixed opioid receptor agonists are known to exert anti-hypersensitive efficacy in the rat spinal nerve ligation (SNL) model of neuropathic pain. To investigate the relative contribution of individual opioid receptor activation to the overall efficacy of mixed opioid receptor agonists, selective doses of respective opioid receptor antagonists have to be employed. In order to identify such selective antagonist doses, doses of the selective NOP, MOP, DOP and KOP receptor agonists Ro65-6570, morphine, SNC-80 and U50488H, that produced maximum efficacy without apparent side effects, were challenged by each of the receptor antagonists J-113397 (NOP receptor), naloxone (MOP receptor), naltrindole (DOP receptor) and nor-binaltorphimine (KOP receptor)...
March 7, 2018: European Journal of Pharmacology
M Barletta, S M Ostenkamp, A C Taylor, J Quandt, B D X Lascelles, K M Messenger
Buprenorphine is a partial μ agonist opioid used for analgesia in dogs. An extended-release formulation (ER-buprenorphine) has been shown to provide effective analgesia for 72 hr in rats and mice. Six healthy mongrel dogs were enrolled in a randomized, blinded crossover design to describe and compare the pharmacokinetics and pharmacodynamics of ER-buprenorphine administered subcutaneous at 0.2 mg/kg (ER-B) and commercially available buprenorphine for injection intravenously at 0.02 mg/kg (IV-B). After drug administration, serial blood samples were collected to measure plasma buprenorphine concentrations using liquid chromatography/mass spectrometry detection...
March 9, 2018: Journal of Veterinary Pharmacology and Therapeutics
Nathan R Blue, Cristina Murray-Krezan, Shana Drake-Lavelle, Daniel Weinberg, Bradley D Holbrook, Vivek R Katukuri, Lawrence Leeman, Ellen L Mozurkewich
BACKGROUND: Non-steroidal anti-inflammatory drug use has been shown to increase blood pressure in non-pregnant adults. Because of this, the American College of Obstetricians and Gynecologists suggests avoiding their use in women with postpartum hypertension; however, evidence to support this recommendation is lacking. OBJECTIVES: Our goal was to test the hypothesis that non-steroidal anti-inflammatory drugs, such as ibuprofen, adversely affect postpartum blood pressure control in women with preeclampsia with severe features...
March 2, 2018: American Journal of Obstetrics and Gynecology
Yoanna Skrobik, Matthew S Duprey, Nicholas S Hill, John W Devlin
RATIONALE: Dexmedetomidine is associated with less delirium than benzodiazepines, and better sleep architecture than either benzodiazepines or propofol; its effect on delirium and sleep when administered at night to patients requiring sedation remains unclear. OBJECTIVES: To determine if nocturnal dexmedetomidine prevents delirium and improves sleep in critically ill adults. METHODS: This two-center, double-blind, placebo-controlled trial randomized 100 delirium-free critically ill adults receiving sedatives to receive nocturnal (21:30 to 6:15h) intravenous dexmedetomidine (0...
March 2, 2018: American Journal of Respiratory and Critical Care Medicine
Earl B Ettienne, Edwin Chapman, Mary Maneno, Adaku Ofoegbu, Bradford Wilson, Beverlyn Settles-Reaves, Melissa Clarke, Georgia Dunston, Kevin Rosenblatt
Introduction: Opioid use disorder (OUD) is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an integral component of OUD management, and buprenorphine is often utilized in OUD management due to strong clinical evidence for efficacy. However, interindividual genetic differences in buprenorphine metabolism may result in variable treatment response, leaving some patients undertreated and at increased risk for relapse...
December 2017: Addictive Behaviors Reports
Diana Crisan, Karin Scharffetter-Kochanek, Sabine Kastler, Maria Crisan, Avram Manea, Katja Wagner, Lars Alexander Schneider
BACKGROUND: Children undergoing dermatosurgical procedures require, unlike adults, particular attention; the administration of various analgesics, anesthetics or sedatives requires a thorough knowledge of drug pharmacokinetics and pharmacodynamics. Furthermore, there are concerns that drugs used for sedation/general anesthesia may result in anesthetic/analgesic complications in children undergoing surgery, with a risk of impaired mental development. OBJECTIVES: Based on our clinical experience and a literature review, we illustrate the most commonly used analgesic, anesthetic and sedative drugs in pediatric dermatosurgery, and identify risk factors and complications following dermatosurgical procedures...
February 12, 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Vibhuti Agarwal, Natalie Logie, Christopher G Morris, Julie A Bradley, Ronny L Rotondo, Scott M Bradfield, Daniel J Indelicato
BACKGROUND: Ewing sarcoma of the thoracic spine and chest wall is frequently treated with concurrent chemotherapy and radiation therapy (RT). Treatment-related acute esophagitis can lead to hospitalization and treatment delays. The aim of this study was to analyze the incidence, risk factors, and management of esophagitis in pediatric patients with Ewing sarcoma of the thoracic region. METHODS: We conducted a single-institution retrospective review of patients treated over a 10-year period...
February 12, 2018: Pediatric Blood & Cancer
Hideki Kozono, Hiroshi Yoshitani, Ryoko Nakano
Background: Intractable pruritus in hemodialysis patients can significantly decrease their quality of life and is also associated with poor vital prognosis. Although combined multiple causes of intractable pruritus in these patients have been identified, no existing treatments are proven to be sufficiently effective. We conducted a post-marketing surveillance to follow-up and assess the safety and efficacy of nalfurafine, a selective κ-opioid receptor agonist, for the treatment of intractable pruritus in patients undergoing hemodialysis...
2018: International Journal of Nephrology and Renovascular Disease
Lynn R Webster, Eugene R Viscusi, Colville Brown, Jeffrey M Dayno
BACKGROUND: The development and use of abuse-deterrent (AD) opioids is part of a multifaceted strategy to reduce misuse, abuse, and diversion, while maintaining access for patients with severe pain who may benefit from their analgesic efficacy. Morphine AD, extended-release (ER), injection-molded tablets (morphine-ADER-IMT; ARYMO® ER; Egalet US Inc, Wayne, PA) is approved by the FDA as an AD opioid. As part of the characterization of AD opioids, assessments of their human abuse potential (HAP) are required...
January 25, 2018: Current Medical Research and Opinion
Jeremy C Cornelissen, Samuel Obeng, Kenner C Rice, Yan Zhang, S Stevens Negus, Matthew Banks
Receptor theory predicts that fixed-proportion mixtures of a competitive, reversible agonist (e.g. fentanyl) and antagonist (e.g. naltrexone) at a common receptor (e.g. mu opioid receptors; MOR) will result in antagonist proportion-dependent decreases in apparent efficacy of the mixtures and downward shifts in mixture dose-effect functions. The present study tested this hypothesis by evaluating behavioral effects of fixed-proportion fentanyl/naltrexone mixtures in a warm-water tail-withdrawal procedure in rhesus monkeys (n=4)...
January 12, 2018: Journal of Pharmacology and Experimental Therapeutics
Niraj R Chavan, Kristin B Ashford, Amanda T Wiggins, Michelle R Lofwall, Agatha S Critchfield
Objective  To examine the relationship between antepartum buprenorphine dose for medication-assisted treatment (MAT) of opioid use disorder (OUD) and incident neonatal opioid withdrawal syndrome (NOWS). Study Design  We performed a prospective cohort study of pregnant women with a singleton gestation diagnosed with OUD and receiving buprenorphine for MAT at a tertiary care academic institution from July 2015 to January 2017. We divided the study cohort into two groups-pregnancies with versus without NOWS...
October 2017: American Journal of Perinatology Reports
Elham A Afify, Najlaa M Andijani
Tolerance to the analgesic effect of morphine is a major clinical problem which can be managed by co-administration of another drug. This study investigated the ability of propranolol to potentiate the antinociceptive action of morphine and the possible mechanisms underlying this effect. Antinociception was assessed in three nociceptive tests (thermal, hot plate), (visceral, acetic acid), and (inflammatory, formalin test) in mice and quantified by measuring the percent maximum possible effect, the percent inhibition of acetic acid-evoked writhing response, and the area under the curve values of number of flinches for treated mice, respectively...
2017: Frontiers in Pharmacology
Fanny P Timm, Sebastian Zaremba, Stephanie D Grabitz, Hassan N Farhan, Stefanie Zaremba, Elizabeth Siliski, Christina H Shin, Sandra Muse, Sabine Friedrich, James E Mojica, Tobias Kurth, Satya-Krishna Ramachandran, Matthias Eikermann
Study Objectives: Following extubation in the intensive care unit (ICU), upper airway (UA) edema and respiratory depressants may promote UA dysfunction. We tested the hypothesis that opioids increase the risk of sleep apnea early after extubation. Methods: Fifty-six ICU patients underwent polysomnography the night after extubation. Airflow limitation during wakefulness was identified using bedside spirometry. Correlation and ordinal regression analyses were used to quantify the effects of preextubation opioid dose on postextubation apnea-hypopnea index (AHI) and severity of sleep apnea and whether or not inspiratory airway obstruction (ratio of maximum expiratory and inspiratory airflows at 50% of vital capacity [MEF50/MIF50] ≥ 1) during wakefulness predicts airway obstruction during sleep...
January 1, 2018: Sleep
Jing-Jing Nie, Shen Sun, Shao-Qiang Huang
Background: Oxycodone is a semisynthetic μ-opioid receptor agonist with a potentially good analgesic efficacy in visceral pain. This study aims to compare the efficacy of oxycodone with sufentanil patient-controlled intravenous analgesia (PCIA). Methods: One hundred and twenty primiparas undergoing elective cesarean section were randomized into four groups by different drugs of PCIA: group S (sufentanil 100 μg), group OS1 (sufentanil 70 μg, oxycodone 30 mg), group OS2 (sufentanil 50 μg, oxycodone 50 mg), and group O (oxycodone 100 mg)...
2017: Journal of Pain Research
Eva-Britt Hysing, Lena Smith, Mans Thulin, Rolf Karlsten, Stephen Butler, Torsten Gordh
BACKGROUND AND AIMS: Patients suffering from chronic nonmalignant pain constitute a heterogeneous population in terms of clinical presentation and treatment results. Few data are available about what distinguishes different groups in this huge population of patients with chronic persistent pain (CPP). A subgroup that is poorly studied, consists of the most severely impaired chronic pain patients. At the Uppsala University Hospital Pain Clinic, there is a specialized department accepting the most complex patients for rehabilitation...
October 2017: Scandinavian Journal of Pain
Mary Bond, Kerri A Schoedel, Laura Rabinovich-Guilatt, Maciej Gasior, William Tracewell, Richard Malamut, Yuju Ma, Lynn R Webster
Objective: To assess the intranasal abuse potential of hydrocodone extended-release (ER) tablets developed with CIMA Abuse-Deterrence Technology compared with hydrocodone powder and hydrocodone bitartrate ER capsules (Zohydro ER, original formulation [HYD-OF]). Design: Single-dose, randomized, double-blind, quadruple-dummy, active- and placebo-controlled, crossover study. Setting: One US site. Subjects: Healthy, adult, nondependent, recreational opioid users...
June 14, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Joseph B Wick, Ahilan Sivaganesan, Silky Chotai, Kristin R Archer, Samuel L Posey, Parker T Evans, Joel R Campbell, Clinton J Devin
BACKGROUND: Preoperative opioid use is widespread and associated with worse patient-reported outcomes following spine surgery. OBJECTIVE: To calculate a threshold preoperative morphine equianalgesic (MEA) dose beyond which patients are less likely to achieve the minimum clinically important difference (MCID) following elective surgery for degenerative spine disease. METHODS: The study included 543 cervical and 1293 lumbar patients. Neck Disability Index and Oswestry Disability Index scores were collected at baseline and 12 mo postoperatively...
July 25, 2017: Neurosurgery
Kazuya Fukumura, Takaaki Yokota, Yuko Baba, Juan Camilo Arjona Ferreira
Naldemedine (S-297995) is a peripherally acting μ-opioid receptor antagonist for the treatment of opioid-induced constipation, a common side effect of opioid therapy. We determined the safety, tolerability, and pharmacokinetic profiles of oral naldemedine in healthy volunteers in 2 randomized, double-blind, placebo-controlled, phase 1 studies. In the single ascending dose study, subjects received a single dose of naldemedine (0.1-100 mg; n = 42) or placebo (n = 14). In the multiple ascending dose study, subjects received once-daily naldemedine (3-30 mg; n = 27) or placebo (n = 9) for 10 days...
September 27, 2017: Clinical Pharmacology in Drug Development
Madhavan Seshadri, Ahmed Elsemary, Madhusudan Deepak Thalitaya, Lawrence Chikodzore, Priya Nagalingam
INTRODUCTION: Providing comprehensive services for about 400 patients in the South Herefordshire area, the community mental health team manages cases of varying severity and complexity, ranging from Schizophrenia, to neuroses and disorders of adult personality. Antipsychotic medication remains a mainstay of treatment and management for patients under the team case load; hence a need exists for a detailed look into the prescription patterns of such medications. AIM: The aim of this study was to look into the prescribing patterns of antipsychotics for a sample of 50 patients in the South Herefordshire community team during the year of 2016 (from Jan 2016 to Dec 2016), as well as investigate whether these antipsychotics were licensed to be used for the corresponding diagnoses of these patients...
September 2017: Psychiatria Danubina
Mary Bond, Laura Rabinovich-Guilatt, Sally Selim, Mona Darwish, William Tracewell, Philmore Robertson, Ronghua Yang, Richard Malamut, Philippe Colucci, Murray P Ducharme, Ofer Spiegelstein
BACKGROUND AND OBJECTIVES: Food intake can alter the pharmacokinetics of certain medications, including changes in their oral bioavailability, which is of particular concern for extended-release (ER) opioids because of the high drug loads. Two randomized, open-label studies assessed the effect of food on the pharmacokinetics of single and multiple doses of hydrocodone ER formulated with CIMA(®) Abuse-Deterrence Technology. METHODS: Healthy subjects in fed and fasted states received single 90-mg doses of hydrocodone ER (Studies 1 and 2) or multiple doses of hydrocodone ER (45 mg twice daily on days 2-3, 60 mg twice daily on days 4-5, 90 mg twice daily on days 6-10, and 90 mg once in the morning on day 11) (Study 2)...
December 2017: Clinical Drug Investigation
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