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Opioid induced respiratory depression

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
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
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...
July 19, 2018: European Journal of Pharmacology
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
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
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...
June 28, 2018: Anesthesia and Analgesia
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
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...
June 18, 2018: Journal of Critical Care
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 Elisa Carbone, Daniel P Poole
Endogenous opioids activate opioid receptors (ORs) in the enteric nervous system to control intestinal motility and secretion. The mu OR mediates the deleterious side effects of opioid analgesics, including constipation, respiratory depression and addiction. Although the delta 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 which may regulate colonic motility...
June 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
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
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
Daniel P Radin, Steven Johnson, Richard Purcell, Arnold S Lippa
Neurotrophin dysregulation has been implicated in a large number of neurodegenerative and neuropsychiatric diseases. Unfortunately, neurotrophins cannot cross the blood brain barrier thus, novel means of up regulating their expression are greatly needed. It has been demonstrated previously that neurotrophins are up regulated in response to increases in brain activity. Therefore, molecules that act as cognitive enhancers may provide a clinical means of up regulating neurotrophin expression. Ampakines are a class of molecules that act as positive allosteric modulators of AMPA-type glutamate receptors...
September 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Adeleke D Adewumi, Christine E Staatz, Samantha A Hollingworth, Jason P Connor, Rosa Alati
Prescription opioid use has increased rapidly in developed countries, as have fatalities and other related adverse events. This review examines the intrinsic characteristics of opioids, including their mechanisms of action and pharmacokinetic and pharmacodynamic properties, to determine how the use of a regonised pharmacological remedy for a medically confirmed ailment could result in an accidental fatality. Opioids trigger biological processes that inhibit their own therapeutic effect. Prolonged use of opioids can result in activation of pronociceptive systems, leading to opioid-induced hyperalgesia and tolerance, while opioid metabolites can antagonise the antinociceptive action of the parent drug, also leading to opioid-induced hyperalgesia and tolerance...
May 23, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Sameer Hassamal, Karen Miotto, William Dale, Itai Danovitch
Tramadol is commonly prescribed for pain control because it presents a lower risk for addiction and respiratory depression compared to other opioids. However, tramadol's serotonin and norepinephrine reuptake inhibitory effects result in a unique adverse effect profile. Two such adverse events are serotonin syndrome and seizures. The prevalence of tramadol-induced serotonin syndrome and seizures is modest in the general population, but if left untreated, the morbidity and mortality can be high; therefore, prompt recognition and management is essential...
May 10, 2018: American Journal of Medicine
Armand Drieu la Rochelle, Karel Guillemyn, Maria Dumitrascuta, Charlotte Martin, Valérie Utard, Raphaëlle Quillet, Séverine Schneider, François Daubeuf, Tom Willemse, Pieter Mampuys, Bert U W Maes, Nelly Frossard, Frédéric Bihel, Mariana Spetea, Frédéric Simonin, Steven Ballet
Opioid analgesics, such as morphine, oxycodone, and fentanyl, are the cornerstones for treating moderate to severe pain. However, on chronic administration, their efficiency is limited by prominent side effects such as analgesic tolerance and dependence liability. Neuropeptide FF (NPFF) and its receptors (NPFF1R and NPFF2R) are recognized as an important pronociceptive system involved in opioid-induced hyperalgesia and analgesic tolerance. In this article, we report the design of multitarget peptidomimetic compounds that show high-affinity binding to the mu-opioid receptor (MOPr) and NPFFRs...
April 26, 2018: Pain
Hwoe Gyeong Ok, Su Young Kim, Su Jung Lee, Tae Kyun Kim, Billy K Huh, Kyung Hoon Kim
All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to µ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the β-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the β-arrestin pathway...
April 2018: Korean Journal of Pain
Xiaonan Liang, Zheng Yong, Ruibin Su
Opioid-induced respiratory depression is a major obstacle to improving the clinical management of moderate to severe chronic pain. Opioids inhibit neuronal activity via various pathways, including calcium channels, adenylyl cyclase, and potassium channels. Currently, the underlying molecular pathway of opioid-induced respiratory depression is only partially understood. This study aimed to investigate the mechanisms of opioid-induced respiratory depression in vivo by examining the effects of different pharmacological agents on fentanyl-induced respiratory depression...
June 11, 2018: Neuroscience Letters
James D Boghosian, Anita Luethy, Joseph F Cotten
Thyrotropin releasing hormone (TRH) is a tripeptide hormone and a neurotransmitter widely expressed in the central nervous system that regulates thyroid function and maintains physiologic homeostasis. Following injection in rodents, TRH has multiple effects including increased blood pressure and breathing. We tested the hypothesis that TRH and its long-acting analog, taltirelin, will reverse morphine-induced respiratory depression in anesthetized rats following intravenous or intratracheal (IT) administration...
July 2018: Journal of Pharmacology and Experimental Therapeutics
Chenchen Yu, Mei Yuan, Haiying Yang, Xiaomei Zhuang, Hua Li
Fentanyl is a rapid-acting, short duration opioid analgesic agent. In recent years, increased prescription and illicit use of fentanyl drugs have led to major safety concerns and a growing death toll. However, the causes of fentanyl-induced fatal adverse effects have not been thoroughly researched. This study investigated P-glycoprotein (P-gp) modulated blood-brain barrier penetration of fentanyl and its resulting toxicity in vitro and in vivo. ATPase assays were performed together with bi-directional transport assays using Caco-2 cells in the presence and absence of tariquidar, a P-gp inhibitor, to confirm the P-gp substrate property of fentanyl...
July 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
K Jonkman, E van Rijnsoever, E Olofsen, L Aarts, E Sarton, M van Velzen, M Niesters, A Dahan
BACKGROUND: Opioids can produce life-threatening respiratory depression. This study tested whether subanaesthetic doses of esketamine stimulate breathing in an established human model of opioid-induced respiratory depression. METHODS: In a study with a randomised, double blind, placebo controlled, crossover design, 12 healthy, young volunteers of either sex received a dose escalating infusion of esketamine (cumulative dose 40 mg infused in 1 h) on top of remifentanil-induced respiratory depression...
May 2018: British Journal of Anaesthesia
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