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Opioid induced respiratory depression

Almasa Bass, Lynn R Webster, Kyle T Matschke, Bimal K Malhotra, Gernot Wolfram
Background: Abuse of prescription opioids, particularly by intravenous (IV) administration, can cause respiratory depression and death. ALO-02, an abuse-deterrent opioid formulation, is designed to release sequestered naltrexone upon manipulation by crushing, thereby antagonizing the pharmacologic effects of oxycodone. This exploratory post-hoc analysis examined the effects of IV administration of simulated crushed ALO-02 on end-tidal carbon dioxide (EtCO2 ), a surrogate marker of respiratory depression...
2019: Therapeutic Advances in Drug Safety
Eugene A Kiyatkin
Opioid drugs are important tools to alleviate pain of different origins, but they have strong addictive potential and their abuse at higher doses often results in serious health complications. Respiratory depression that leads to brain hypoxia is perhaps the most dangerous symptom of acute intoxication with opioids, and it could result in lethality. The development of substrate-specific sensors coupled with amperometry made it possible to directly evaluate physiological and drug-induced fluctuations in brain oxygen levels in awake, freely-moving rats...
February 5, 2019: Neuropharmacology
Hoani Macfater, Weisi Xia, Sanket Srinivasa, Andrew Graham Hill, Marc Van De Velde, Girsh P Joshi
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a common weight loss operation that is increasingly being managed on an outpatient or overnight stay basis. The aim of this systematic review was to evaluate the available literature and develop recommendations for optimal pain management after LSG. METHODS: A systematic review utilizing preferred reporting items for systematic reviews and meta-analysis with PROcedure SPECific Postoperative Pain ManagemenT methodology was undertaken...
February 4, 2019: World Journal of Surgery
Emilie Eiselt, Jérôme Côté, Jean-Michel Longpré, Véronique Blais, Philippe Sarret, Louis Gendron
Opioid and neurotensin (NT) receptors are expressed in both central and peripheral nervous systems where they modulate nociceptive responses. Nowadays, opioid analgesics like morphine remain the most prescribed drugs for the treatment of moderate to severe pain. However, despite their daily used, opioids can produce life-threatening side effects, such as constipation or respiratory depression. Besides, NT analogs exert strong opioid-independent analgesia. Here, we thus hypothesized that the combined use of opioid and NT agonists would require lower doses to produce significant analgesic effects, hence decreasing opioid-induced adverse effects...
January 29, 2019: European Journal of Pharmacology
Jonathan P Wanderer, James P Rathmell
No abstract text is available yet for this article.
February 2019: Anesthesiology
A Kliewer, F Schmiedel, S Sianati, A Bailey, J T Bateman, E S Levitt, J T Williams, M J Christie, S Schulz
Opioid analgesics are powerful pain relievers; however, over time, pain control diminishes as analgesic tolerance develops. The molecular mechanisms initiating tolerance have remained unresolved to date. We have previously shown that desensitization of the μ-opioid receptor and interaction with β-arrestins is controlled by carboxyl-terminal phosphorylation. Here we created knockin mice with a series of serine- and threonine-to-alanine mutations that render the receptor increasingly unable to recruit β-arrestins...
January 21, 2019: Nature Communications
Marie Joseph
'Opioid induced hyper-algesia' is a paradoxical phenomenon known to occur with high-dose opioid therapy when attempting to control severe pain. The high opioid load leads to exacerbation of existing 'central sensitization' process in the spinal cord dorsal horn and parts of the brain. This situation usually occurs in the clinical context of uncontrolled complex pain with a predominant neuropathic pain component. There is resistance to the analgesic effect of the opioid which worsens with increasing doses. It was not commonly known that in this situation there is often a resistance to the respiratory depression effect of the opioid too caused by similar mechanisms...
January 12, 2019: BMJ Supportive & Palliative Care
Rajalakshmi Nandakumar, Shyamnath Gollakota, Jacob E Sunshine
Early detection and rapid intervention can prevent death from opioid overdose. At high doses, opioids (particularly fentanyl) can cause rapid cessation of breathing (apnea), hypoxemic/hypercarbic respiratory failure, and death, the physiologic sequence by which people commonly succumb from unintentional opioid overdose. We present algorithms that run on smartphones and unobtrusively detect opioid overdose events and their precursors. Our proof-of- concept contactless system converts the phone into a short-range active sonar using frequency shifts to identify respiratory depression, apnea, and gross motor movements associated with acute opioid toxicity...
January 9, 2019: Science Translational Medicine
Yi Zheng, Samuel Obeng, Huiqun Wang, Abdulmajeed M Jali, Bharath Peddibhotla, Dwight Williams, Chuanchun Zou, David L Stevens, William L Dewey, Hamid I Akbarali, Dana E Selley, Yan Zhang
Mu opioid receptor (MOR) agonists have been widely applied for treating moderate to severe pain. However, numerous adverse effects have been associated with their application, including opioid-induced constipation (OIC), respiratory depression, and addiction. Based on previous work in our laboratory, NAP, a 6β-N-4'-pyridyl substituted naltrexamine derivative, was identified as a peripheral MOR antagonist that may be used to treat OIC. To further explore its structure activity relationship, a new series of NAP derivatives were designed, synthesized, and biologically evaluated...
January 4, 2019: Journal of Medicinal Chemistry
Kapil Gupta, Mahesh Nagappa, Arun Prasad, Lusine Abrahamyan, Jean Wong, Toby N Weingarten, Frances Chung
OBJECTIVE: This systematic review and meta-analysis aim to evaluate the risk factors associated with postoperative opioid-induced respiratory depression (OIRD). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed-MEDLINE, MEDLINE in-process, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed and (January 1946 to November 2017). ELIGIBILITY CRITERIA: The inclusion criteria were: (1) adult patients 18 years or older who were administered opioids after surgery and developed postoperative OIRD (OIRD group); (2) all studies which reported both OIRD events and associated risk factors; (3) all studies with reported data for each risk factor on patients with no OIRD (control group) and (4) published articles in English language...
December 14, 2018: BMJ Open
Lisa R Gerak, David R Maguire, James H Woods, Stephen M Husbands, Alex Disney, Charles P France
One consequence of the ongoing opioid epidemic is a large number of overdose deaths. Naloxone reverses opioid-induced respiratory depression; however, its short duration of action limits the protection it can provide. Methocinnamox (MCAM) is a novel opioid receptor antagonist with a long duration of action. This study examined the ability of MCAM to prevent and reverse the respiratory-depressant effects (minute volume [VE]) of heroin in 5 monkeys. MCAM (0.32 mg/kg) was given before heroin to determine whether it prevents respiratory depression; heroin dose-effect curves were generated 1, 2, 4, and 8 days later, and these effects were compared to those of naltrexone (0...
November 21, 2018: Journal of Pharmacology and Experimental Therapeutics
Michael D Raleigh, Federico Baruffaldi, Samantha J Peterson, Morgan Le Naour, Theresa M Harmon, Jennifer R Vigliaturo, Paul R Pentel, Marco Pravetoni
Fentanyl is an extremely potent synthetic opioid that has been increasingly used to adulterate heroin, cocaine and counterfeit prescription pills leading to an increase in opioid-induced fatal overdoses in the US, Canada, and Europe. A vaccine targeting fentanyl could offer protection against fatal overdoses in both recreational drug users and others in professions at risk of accidental exposure. This study focuses on the development of a vaccine consisting of a fentanyl hapten (F) conjugated to keyhole limpet hemocyanin (KLH) carrier protein or to GMP-grade subunit KLH (sKLH)...
November 8, 2018: Journal of Pharmacology and Experimental Therapeutics
Eugene A Kiyatkin
The goal of this work is to consider physiological fluctuations in brain oxygen levels and its changes induced by opioid drugs. This review article presents, as a comprehensive story, the most important findings obtained in our laboratory by using high-speed amperometry with oxygen sensors in awake, freely moving rats; most of these findings were separately published elsewhere. First, we show that oxygen levels in the nucleus accumbens (NAc) phasically increase following exposure to natural arousing stimuli...
2018: Frontiers in Integrative Neuroscience
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
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
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
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
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...
December 2018: Current Opinion in Anaesthesiology
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...
December 2018: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
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
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