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Opioid induced respiratory depression

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https://www.readbyqxmd.com/read/30242972/pharmacokinetic-study-of-sudaxine-in-dog-plasma-using-novel-lc-ms-ms-method
#1
Ghaith Altawallbeh, Laura Smith, Stephen J Lewis, Simon Authier, Kim Bujold, Benjamin Gaston, Ilya Bederman
CONTEXT: Sudaxine is a novel respiratory stimulant that increases ventilatory drive via NO+ -thiolate signaling and is under development for reversal of opioid-induced respiratory depression and other critical care indications. OBJECTIVE: This study investigates the pharmacokinetic characteristics after intravenous administration of Sudaxine by using a simple LC-MS/MS method. MATERIALS AND METHODS: A sensitive LC-MS/MS method was validated to determine the concentration of Sudaxine in beagle dog plasma after intravenous administration of Sudaxine at (3, 10, 30 and 100 mg/kg)...
September 22, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/30242482/synthetic-opioids
#2
Patrick M Beardsley, Yan Zhang
Opioid abuse has been a global menace for centuries, but the proliferation of synthetic opioids and their use within this current decade have created epidemic-level harms in some countries. According to the United Nations Office on Drugs and Crime, almost 12 million years were estimated loss of "healthy" life resulting in premature death and disability attributable to global opioid abuse just in 2015. Law enforcement and regulatory authorities have been particularly challenged abating the spread of synthetic opioids because soon after controlling the currently recognized abused opioids, their structures are tweaked, and new entities replace them...
September 22, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30236566/preventing-opioid-induced-respiratory-depression-in-the-hospitalized-patient-with-obstructive-sleep-apnea
#3
Carla R Jungquist, Elizabeth Card, Jean Charchaflieh, Bhargavi Gali, Meltem Yilmaz
PURPOSE: To enhance the role of nursing interventions in the management of perioperative opioid-induced respiratory depression (OIRD) in patients with obstructive sleep apnea (OSA). DESIGN: Narrative review of the literature. METHODS: Literature reviewed with emphasis on recommendations by professional and accrediting organizations. FINDINGS: Postsurgical OIRD increases hospital stay (55%), cost of care (47%), 30-day readmission (36%), and inpatient mortality (3...
October 2018: Journal of Perianesthesia Nursing: Official Journal of the American Society of PeriAnesthesia Nurses
https://www.readbyqxmd.com/read/30199635/optimization-of-a-series-of-mu-opioid-receptor-mor-agonists-with-high-g-protein-signaling-bias
#4
Nicole M Kennedy, Cullen L Schmid, Nicolette C Ross, Kimberly M Lovell, Zhizhou Yue, Yen Ting Chen, Michael D Cameron, Laura M Bohn, Thomas D Bannister
While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal βarrestin-mediated signaling because MOR agonist-treated βarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents...
September 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30199402/best-perioperative-practice-in-management-of-ambulatory-patients-with-obstructive-sleep-apnea
#5
Mahesh Nagappa, Yamini Subramani, Frances Chung
PURPOSE OF REVIEW: The perioperative outcome in obstructive sleep apnea (OSA) patients undergoing ambulatory surgery can be potentially impacted by the type of anesthetic technique, fluid management and choice of anesthetic agents. This review highlights the best perioperative practices in the management of OSA patients undergoing ambulatory surgical procedures. RECENT FINDINGS: A recent meta-analysis found that STOP-Bang might be used as a perioperative risk stratification tool...
September 7, 2018: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/30194672/accuracy-of-remote-continuous-respiratory-rate-monitoring-technologies-intended-for-low-care-clinical-settings-a-prospective-observational-study
#6
Kim van Loon, Linda M Peelen, Emmy C van de Vlasakker, Cor J Kalkman, Leo van Wolfswinkel, Bas van Zaane
PURPOSE: Altered respiratory rate (RR) has been identified as an important predictor of serious adverse events during hospitalization. Introduction of a well-tolerated continuous RR monitor could potentially reduce serious adverse events such as opioid-induced respiratory depression. The purpose of this study was to investigate the ability of different monitor devices to detect RR in low care clinical settings. METHODS: This was a prospective method-comparison study with a cross-sectional design...
September 7, 2018: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/30190295/predictors-of-oversedation-in-hospitalized-patients
#7
Jeannine M Brant, Lee Stringer, Lisa R Jurkovich, Nicholas C Coombs, Elizabeth J Mullette, Christy Buffington, Sherry Herbert, David Karera
PURPOSE: Results of a study to determine demographic and clinical characteristics predictive of oversedation and potential opioid-induced respiratory depression (OIRD) in hospitalized patients are reported. METHODS: In a retrospective case-controlled study, an incident reporting database was searched to identify cases of in-hospital oversedation; to form the control group, patients who did not experience an oversedation event while hospitalized were sampled in reverse chronological order until the desired total sample size ( n = 225) was obtained...
September 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/30183460/opposing-mechanisms-underlying-differential-changes-in-brain-oxygen-and-temperature-induced-by-intravenous-morphine
#8
Ernesto Solis, Anum Afzal, Eugene A Kiyatkin
Morphine remains widely used in clinical settings due to its potent analgesic properties. However, one of the gravest risks of all opioids is their ability to induce respiratory depression and subsequent brain hypoxia that can lead to coma and death. Due to these life-threatening effects, our goal was to examine the effects of intravenous (iv) morphine at a wide range of doses (0.1-12.8 mg/kg) on changes in brain oxygen levels in freely-moving rats. We employed oxygen sensors coupled with high-speed amperometry and conducted measurements in the nucleus accumbens (NAc) and subcutaneous (SC) space, the latter serving as a proxy for blood oxygen levels that depend on respiratory activity...
September 5, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/30158150/a-bifunctional-nociceptin-and-mu-opioid-receptor-agonist-is-analgesic-without-opioid-side-effects-in-nonhuman-primates
#9
Huiping Ding, Norikazu Kiguchi, Dennis Yasuda, Pankaj R Daga, Willma E Polgar, James J Lu, Paul W Czoty, Shiroh Kishioka, Nurulain T Zaveri, Mei-Chuan Ko
Misuse of prescription opioids, opioid addiction, and overdose underscore the urgent need for developing addiction-free effective medications for treating severe pain. Mu opioid peptide (MOP) receptor agonists provide very effective pain relief. However, severe side effects limit their use in the clinical setting. Agonists of the nociceptin/orphanin FQ peptide (NOP) receptor have been shown to modulate the antinociceptive and reinforcing effects of MOP agonists. We report the discovery and development of a bifunctional NOP/MOP receptor agonist, AT-121, which has partial agonist activity at both NOP and MOP receptors...
August 29, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/30104829/nalbuphine-pretreatment-for-prevention-of-etomidate-induced-myoclonus-a-prospective-randomized-and-double-blind-study
#10
Mayank Gupta, Priyanka Gupta
Background and Aims: Etomidate induced myoclonus (EM) is a common and hazardous sequel. Premedication with a number of opioids has been shown to effectively attenuate EM. However, there is no reported literature evaluating the effect of nalbuphine pretreatment on EM. The present study was designed to evaluate the efficacy of 0.2 mg/kg nalbuphine intravenous (IV) pretreatment for prevention of EM. Material and Methods: This prospective randomized double-blind and placebo controlled study was conducted in a medical college associated tertiary hospital...
April 2018: Journal of Anaesthesiology, Clinical Pharmacology
https://www.readbyqxmd.com/read/30044299/pharmacological-characters-of-oliceridine-a-%C3%AE-opioid-receptor-g-protein-figure-dash-biased-ligand-in-mice
#11
De-Yong Liang, Wen-Wu Li, Chinwe Nwaneshiudu, Karen-Amanda Irvine, J David Clark
BACKGROUND: A major advancement in the field of analgesic pharmacology has been the development of G-protein[FIGURE DASH]biased opioid agonists that display less respiratory depression than conventional drugs. It is uncertain, however, whether these new drugs cause less tolerance, hyperalgesia, and other maladaptations when administered repeatedly. METHODS: The archetypical µ-opioid receptor agonist morphine and, separately, the G-protein[FIGURE DASH]biased µ-opioid receptor agonist oliceridine were administered to mice...
July 21, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/30012498/bilateral-carotid-sinus-nerve-transection-exacerbates-morphine-induced-respiratory-depression
#12
Santhosh M Baby, Ryan B Gruber, Alex P Young, Peter M MacFarlane, Luc J Teppema, Stephen J Lewis
Opioid-induced respiratory depression (OIRD) involves decreased sensitivity of ventilatory control systems to decreased blood levels of oxygen (hypoxia) and elevated levels of carbon dioxide (hypercapnia). Understanding the sites and mechanisms by which opioids elicit respiratory depression is pivotal for finding novel therapeutics to prevent and/or reverse OIRD. To examine the contribution of carotid body chemoreceptors OIRD, we used whole-body plethysmography to evaluate hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses including changes in frequency of breathing, tidal volume, minute ventilation and inspiratory drive, after intravenous injection of morphine (10 mg/kg) in sham-operated (SHAM) and in bilateral carotid sinus nerve transected (CSNX) Sprague-Dawley rats...
September 5, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/30010438/the-role-of-integrated-pulmonary-index-monitoring-during-morphine-based-intravenous-patient-controlled-analgesia-administration-following-supratentorial-craniotomies-a-prospective-randomized-double-blind-controlled-study
#13
Eren Fatma Akcil, Ozlem Korkmaz Dilmen, Hayriye Ertem Vehid, Ercument Yentur, Yusuf Tunali
OBJECTIVE: Morphine is commonly used in post-operative analgesia, but opioid-related respiratory depression causes a general reluctance for its use. The "Integrated Pulmonary Index" is a tool calculated from non-invasively obtained respiratory and hemodynamic parameters. The aim of this prospective, randomized, double blind, and placebo-controlled study is to determine a more safe and effective dose for morphine in patient-controlled analgesia following supratentorial craniotomy using the "Integrated Pulmonary Index"...
August 5, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/30004934/a-systematic-review-evaluating-neuraxial-morphine-and-diamorphine-associated-respiratory-depression-after-cesarean-delivery
#14
Nadir Sharawi, Brendan Carvalho, Ashraf S Habib, Lindsay Blake, Jill M Mhyre, Pervez Sultan
The prevalence of neuraxial opioid-induced clinically significant respiratory depression (CSRD) after cesarean delivery is unknown. We sought to review reported cases of author-reported respiratory depression (ARD) to calculate CSRD prevalence. A 6-database literature search was performed to identify ARD secondary to neuraxial morphine or diamorphine, in parturients undergoing cesarean delivery. "Highest" (definite and probable/possible) and "lowest" (definite) prevalences of CSRD were calculated...
July 11, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29958218/opioids-for-acute-pain-management-in-patients-with-obstructive-sleep-apnea-a-systematic-review
#15
Crispiana Cozowicz, Frances Chung, Anthony G Doufas, Mahesh Nagappa, Stavros G Memtsoudis
The intrinsic nature of opioids to suppress respiratory function is of particular concern among patients with obstructive sleep apnea (OSA). The association of OSA with increased perioperative risk has raised the question of whether patients with OSA are at higher risk for opioid-induced respiratory depression (OIRD) compared to the general population. The aims of this systematic review were to summarize current evidence with respect to perioperative OIRD, changes in sleep-disordered breathing, and alterations in pain and opioid sensitivity in patients with OSA...
October 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29949201/sedation-scales-do-they-capture-the-concept-of-opioid-induced-sedation
#16
Danielle R Dunwoody, Carla R Jungquist
AIM: The purpose of this study was to explore the concept of opioid-induced sedation and how nurses define and measure sedation in the hospital setting. BACKGROUND: Opioid medications are the primary treatment for acute pain in the postoperative setting. One of the most serious side effects of opioid therapy is excessive sedation and respiratory depression. Nurses have the responsibility of providing effective pain management, while keeping the patient safe from adverse sedation and respiratory depression...
June 27, 2018: Nursing Forum
https://www.readbyqxmd.com/read/29936327/respiratory-depression-in-low-acuity-hospital-settings-seeking-answers-from-the-prodigy-trial
#17
REVIEW
Ashish K Khanna, Frank J Overdyk, Christine Greening, Paola Di Stefano, Wolfgang F Buhre
Predicting episodes or severity of cardiorespiratory decompensation has proved to be challenging in patients with stable surgical or medical conditions, recovering on the general care floor (ward). Critical cardiorespiratory events on hospital floors may be prevented by early detection of deterioration using continuous, electronic cardiorespiratory monitoring (CEM). The PRediction of Opioid-induced Respiratory Depression In Patients Monitored by capnoGraphY (PRODIGY) trial investigates CEM using pulse oximetry and capnography in 1650 patients at 16 centers in North America, Europe, and Asia (ClinicalTrials...
October 2018: Journal of Critical Care
https://www.readbyqxmd.com/read/29927325/inflammation-associated-changes-in-dor-expression-and-function-in-the-mouse-colon
#18
Jesse J DiCello, Ayame Saito, Pradeep Rajasekhar, Emily M Eriksson, Rachel M McQuade, Cameron J Nowell, Benjamin W Sebastian, Jakub Fichna, Nicholas A Veldhuis, Meritxell Canals, Nigel W Bunnett, Simona E Carbone, Daniel P Poole
Endogenous opioids activate opioid receptors (ORs) in the enteric nervous system to control intestinal motility and secretion. The μ-OR mediates the deleterious side effects of opioid analgesics, including constipation, respiratory depression, and addiction. Although the δ-OR (DOR) is a promising target for analgesia, the function and regulation of DOR in the colon are poorly understood. This study provides evidence that endogenous opioids activate DOR in myenteric neurons that may regulate colonic motility...
October 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29913911/buprenorphine-clinically-useful-but-often-misunderstood
#19
Stephen Butler
Background There are a number of false myths about buprenorphine based on unconfirmed animal data, even from isolated animal organs, and early clinical research. These myths came into textbooks on pharmacology and pain about 30 years ago and have been difficult to eradicate. Animal models of pain and pain relief are notoriously unreliable as predictors of human clinical effects. The fact is that in clinical practice there is NO bell-shaped dose-response curve, there is NO plateau on the dose-response curve, and there is NO antagonist effect from buprenorphine on other mu-opioid agonists...
July 1, 2013: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29895890/opioid-receptor-signaling-analgesic-and-side-effects-induced-by-a-computationally-designed-ph-dependent-agonist
#20
Viola Spahn, Giovanna Del Vecchio, Antonio Rodriguez-Gaztelumendi, Julia Temp, Dominika Labuz, Michael Kloner, Marco Reidelbach, Halina Machelska, Marcus Weber, Christoph Stein
Novel pain killers without adverse effects are urgently needed. Opioids induce central and intestinal side effects such as respiratory depression, sedation, addiction, and constipation. We have recently shown that a newly designed agonist with a reduced acid dissociation constant (pKa ) abolished pain by selectively activating peripheral μ-opioid receptors (MOR) in inflamed (acidic) tissues without eliciting side effects. Here, we extended this concept in that pKa reduction to 7.22 was achieved by placing a fluorine atom at the ethylidene bridge in the parental molecule fentanyl...
June 12, 2018: Scientific Reports
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