Pain Management
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Effect of Intranasal Ketamine Vs Fentanyl on Pain
1 PROTOCOL SYNOPSIS 2 STUDY TITLE: 3 Pain Reduction with Intranasal Medications for Extremity Injuries (PRIME): A Randomized Clinical 4 Noninferiority Trial of Intranasal Ketamine vs. Fentanyl 5 6 PROTOCOL TITLE 7 Pain Reduction with Intranasal Medications for Extremity injuries (PRIME) 8 9 PRINCIPAL INVESTIGATOR: 10 Theresa M. Frey, MD 11 Assistant Professor Clinical Pediatrics 12 Division of Pediatric Emergency Medicine 13 Cincinnati Children’s Hospital Medical Center 14 513-636-7966 15 [email protected] 16 17 CO-INVESTIGATORS: 18 Matthew R. Mittiga, MD 19 Todd A. Florin, MD, MSCE 20 Michelle C. Caruso, PharmD, BCPS 21 Nanhua Zhang, PhD 22 Yin Zhang, MS 23 24 I. ABSTRACT 25 26 Introduction: Inadequate pain control in the emergency department, particularly in the pediatric 27 population, is a major health concern. The intranasal route of medication administration is gaining 28 popularity secondary to its rapid onset of action, minimal discomfort for the patient and relative 29 simplicity. When pediatric patients present with moderate to severe pain from traumatic injuries, 30 opioids are currently the most frequently used class of analgesia, but they may not always be the best 31 option for numerous reasons. Sub-dissociative dosing of ketamine has been shown to be an effective 32 alternative to opioids in providing adequate pain relief. 33 34 Objectives: The objectives of this study are to 1) determine if intranasal ketamine is non-inferior to 35 intranasal fentanyl in reduction of pain in children presenting with extremity injuries and 2) define and 36 compare the level of sedation and respiratory side effect profile associated with intranasal ketamine and 37 fentanyl. -
Opioid Tolerance in Methadone Maintenance Treatment: Comparison
Gutwinski et al. Harm Reduction Journal (2016) 13:7 DOI 10.1186/s12954-016-0095-0 RESEARCH Open Access Opioid tolerance in methadone maintenance treatment: comparison of methadone and levomethadone in long-term treatment Stefan Gutwinski*, Nikola Schoofs, Heiner Stuke, Thomas G. Riemer, Corinde E. Wiers and Felix Bermpohl Abstract Background: This study aimed to investigate the development of opioid tolerance in patients receiving long-term methadone maintenance treatment (MMT). Methods: A region-wide cross-sectional study was performed focusing on dosage and duration of treatment. Differences between racemic methadone and levomethadone were examined. All 20 psychiatric hospitals and all 110 outpatient clinics in Berlin licensed to offer MMT were approached in order to reach patients under MMT fulfilling the DSM IV criteria of opiate dependence. In the study, 720 patients treated with racemic methadone or levomethadone gave information on the dosage of treatment. Out of these, 679 patients indicated the duration of MMT. Results: Treatment with racemic methadone was reported for 370 patients (54.5 %), with levomethadone for 309 patients (45.5 %). Mean duration of MMT was 7.5 years. We found a significant correlation between dosage and duration of treatment, both in a conjoint analysis for the two substances racemic methadone and levomethadone and for each substance separately. These effects remained significant when only patients receiving MMT for 1 year or longer were considered, indicating proceeding tolerance development in long-term treatment. When correlations were compared between racemic methadone and levomethadone, no significant difference was found. Conclusions: Our data show a tolerance development under long-term treatment with both racemic methadone and levomethadone. -
Biased Versus Partial Agonism in the Search for Safer Opioid Analgesics
molecules Review Biased versus Partial Agonism in the Search for Safer Opioid Analgesics Joaquim Azevedo Neto 1 , Anna Costanzini 2 , Roberto De Giorgio 2 , David G. Lambert 3 , Chiara Ruzza 1,4,* and Girolamo Calò 1 1 Department of Biomedical and Specialty Surgical Sciences, Section of Pharmacology, University of Ferrara, 44121 Ferrara, Italy; [email protected] (J.A.N.); [email protected] (G.C.) 2 Department of Morphology, Surgery, Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy; [email protected] (A.C.); [email protected] (R.D.G.) 3 Department of Cardiovascular Sciences, Anesthesia, Critical Care and Pain Management, University of Leicester, Leicester LE1 7RH, UK; [email protected] 4 Technopole of Ferrara, LTTA Laboratory for Advanced Therapies, 44122 Ferrara, Italy * Correspondence: [email protected] Academic Editor: Helmut Schmidhammer Received: 23 July 2020; Accepted: 23 August 2020; Published: 25 August 2020 Abstract: Opioids such as morphine—acting at the mu opioid receptor—are the mainstay for treatment of moderate to severe pain and have good efficacy in these indications. However, these drugs produce a plethora of unwanted adverse effects including respiratory depression, constipation, immune suppression and with prolonged treatment, tolerance, dependence and abuse liability. Studies in β-arrestin 2 gene knockout (βarr2( / )) animals indicate that morphine analgesia is potentiated − − while side effects are reduced, suggesting that drugs biased away from arrestin may manifest with a reduced-side-effect profile. However, there is controversy in this area with improvement of morphine-induced constipation and reduced respiratory effects in βarr2( / ) mice. Moreover, − − studies performed with mice genetically engineered with G-protein-biased mu receptors suggested increased sensitivity of these animals to both analgesic actions and side effects of opioid drugs. -
Nitrous Oxide in Emergency Medicine Í O’ Sullivan, J Benger
214 ANALGESIA Emerg Med J: first published as 10.1136/emj.20.3.214 on 1 May 2003. Downloaded from Nitrous oxide in emergency medicine Í O’ Sullivan, J Benger ............................................................................................................................. Emerg Med J 2003;20:214–217 Safe and predictable analgesia is required for the identify these zones as there is considerable vari- potentially painful or uncomfortable procedures often ation between people. He also emphasised the importance of the patient’s pre-existing beliefs. If undertaken in an emergency department. The volunteers expect to fall asleep while inhaling characteristics of an ideal analgesic agent are safety, 30% N2O then a high proportion do so. An appro- predictability, non-invasive delivery, freedom from side priate physical and psychological environment increases the actions of N2O and may allow lower effects, simplicity of use, and a rapid onset and offset. doses to be more effective. Unlike many other Newer approaches have threatened the widespread use anaesthetic agents, N2O exhibits an acute toler- of nitrous oxide, but despite its long history this simple ance effect, whereby its potency is greater at induction than after a period of “accommoda- gas still has much to offer. tion”. .......................................................................... MECHANISM OF ACTION “I am sure the air in heaven must be this Some writers have suggested that N2O, like wonder-working gas of delight”. volatile anaesthetics, causes non-specific central nervous system depression. Others, such as 4 Robert Southey, Poet (1774 to 1843) Gillman, propose that N2O acts specifically by interacting with the endogenous opioid system. HISTORY N2O is known to act preferentially on areas of the Nitrous oxide (N2O) is the oldest known anaes- brain and spinal cord that are rich in morphine thetic agent. -
Opioid Receptorsreceptors
OPIOIDOPIOID RECEPTORSRECEPTORS defined or “classical” types of opioid receptor µ,dk and . Alistair Corbett, Sandy McKnight and Graeme Genes encoding for these receptors have been cloned.5, Henderson 6,7,8 More recently, cDNA encoding an “orphan” receptor Dr Alistair Corbett is Lecturer in the School of was identified which has a high degree of homology to Biological and Biomedical Sciences, Glasgow the “classical” opioid receptors; on structural grounds Caledonian University, Cowcaddens Road, this receptor is an opioid receptor and has been named Glasgow G4 0BA, UK. ORL (opioid receptor-like).9 As would be predicted from 1 Dr Sandy McKnight is Associate Director, Parke- their known abilities to couple through pertussis toxin- Davis Neuroscience Research Centre, sensitive G-proteins, all of the cloned opioid receptors Cambridge University Forvie Site, Robinson possess the same general structure of an extracellular Way, Cambridge CB2 2QB, UK. N-terminal region, seven transmembrane domains and Professor Graeme Henderson is Professor of intracellular C-terminal tail structure. There is Pharmacology and Head of Department, pharmacological evidence for subtypes of each Department of Pharmacology, School of Medical receptor and other types of novel, less well- Sciences, University of Bristol, University Walk, characterised opioid receptors,eliz , , , , have also been Bristol BS8 1TD, UK. postulated. Thes -receptor, however, is no longer regarded as an opioid receptor. Introduction Receptor Subtypes Preparations of the opium poppy papaver somniferum m-Receptor subtypes have been used for many hundreds of years to relieve The MOR-1 gene, encoding for one form of them - pain. In 1803, Sertürner isolated a crystalline sample of receptor, shows approximately 50-70% homology to the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the the genes encoding for thedk -(DOR-1), -(KOR-1) and orphan (ORL ) receptors. -
Recommended Methods for the Identification and Analysis of Fentanyl and Its Analogues in Biological Specimens
Recommended methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES Laboratory and Scientific Section UNITED NATIONS OFFICE ON DRUGS AND CRIME Vienna Recommended Methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES UNITED NATIONS Vienna, 2017 Note Operating and experimental conditions are reproduced from the original reference materials, including unpublished methods, validated and used in selected national laboratories as per the list of references. A number of alternative conditions and substitution of named commercial products may provide comparable results in many cases. However, any modification has to be validated before it is integrated into laboratory routines. ST/NAR/53 Original language: English © United Nations, November 2017. All rights reserved. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. Mention of names of firms and commercial products does not imply the endorse- ment of the United Nations. This publication has not been formally edited. Publishing production: English, Publishing and Library Section, United Nations Office at Vienna. Acknowledgements The Laboratory and Scientific Section of the UNODC (LSS, headed by Dr. Justice Tettey) wishes to express its appreciation and thanks to Dr. Barry Logan, Center for Forensic Science Research and Education, at the Fredric Rieders Family Founda- tion and NMS Labs, United States; Amanda L.A. -
What Are the Treatments for Heroin Addiction?
How is heroin linked to prescription drug abuse? See page 3. from the director: Research Report Series Heroin is a highly addictive opioid drug, and its use has repercussions that extend far beyond the individual user. The medical and social consequences of drug use—such as hepatitis, HIV/AIDS, fetal effects, crime, violence, and disruptions in family, workplace, and educational environments—have a devastating impact on society and cost billions of dollars each year. Although heroin use in the general population is rather low, the numbers of people starting to use heroin have been steadily rising since 2007.1 This may be due in part to a shift from abuse of prescription pain relievers to heroin as a readily available, cheaper alternative2-5 and the misperception that highly pure heroin is safer than less pure forms because it does not need to be injected. Like many other chronic diseases, addiction can be treated. Medications HEROIN are available to treat heroin addiction while reducing drug cravings and withdrawal symptoms, improving the odds of achieving abstinence. There are now a variety of medications that can be tailored to a person’s recovery needs while taking into account co-occurring What is heroin and health conditions. Medication combined with behavioral therapy is particularly how is it used? effective, offering hope to individuals who suffer from addiction and for those around them. eroin is an illegal, highly addictive drug processed from morphine, a naturally occurring substance extracted from the seed pod of certain varieties The National Institute on Drug Abuse (NIDA) has developed this publication to Hof poppy plants. -
Fentanyl Infographic 24X36
FENTANYL WHAT IS IT? Fentanyl can be found in prescription form, introduced to the medical community in the 1960s Fentanyl analogues are now being Fentanyl is a potent synthetic and prescribed to relieve severe pain post-surgery created in clandestine laboratories to opioid analgesic, 50 to 100x or during end-of-life care . In its prescription form, be sold and used illegally. In it's non- more powerful than fentanyl is sold under the brand names Actiq®, prescription form, fentanyl is found in morphine. Duragesic®, and Sublimaze®. When prescribed by a powder form, spiked on blotter paper; physician, fentanyl is often administered via mixed with heroin; or as tablets that injection, transdermal patch, or in lozenges. attempt to mimic other opioids. Effects: Like other opioids, Fentanyl binds to Through Fentanyl's effects on the Euphoria, relaxation, drowsiness, opioid receptors in the reward centers opioid receptors in the brain stem nausea, confusion, constipation, of the brain, increasing dopamine however, it can inhibit normal sedation, tolerance, addiction, levels to cause a surge in endorphins breathing, causing breathing to stop respiratory depression and arrest, and feelings of pleasure. altogether, leading to death. unconsciousness, coma, and death. WHY DOES IT MATTER? 540% While the fast-acting nature of the effects of fentanyl may create a more powerful and immediate euphoria, these increase in fentanyl effects wear off faster, leading to the more immediate return overdose deaths of cravings and discomfort. since 2016 (CDC) With a high profit margin, Fentanyl is often mixed into heroin or is made to mimic the In talking about Fentanyl, you may hear about appearance of other opioids. -
The Effects of the Morphine Analogue Levorphanol on Leukocytes: Metabolic Effects at Rest and During Phagocytosis
The effects of the morphine analogue levorphanol on leukocytes: Metabolic effects at rest and during phagocytosis Nancy Wurster, … , Penelope Pettis, Sharon Lebow J Clin Invest. 1971;50(5):1091-1099. https://doi.org/10.1172/JCI106580. Studies on bacteria have suggested that morphine-like drugs have effects on the cell membrane. To determine the effect of this class of drugs on a mammalian cell, we selected the rabbit peritoneal exudate granulocyte, which undergoes striking membrane changes during phagocytosis. We examined the effect in vitro of the morphine analogue, levorphanol on phagocytosis and metabolism by granulocytes incubated with and without polystyrene particles or live Escherichia coli. Levorphanol (1 or 2 mmoles/liter) decreased: (a) acylation of lysolecithin or lysophosphatidylethanolamine in the medium (which is stimulated about two-fold during phagocytosis) both at rest (40%) and during phagocytosis (60%); (b) uptake of latex particles and Escherichia coli, as judged by electron microscopy; (c) killing of live Escherichia coli (10-fold); (d) 14 14 + CO2 production from glucose-1- C during phagocytosis by at least 80%; (e) K content of granulocytes (35%); (f) oxidation of linoleate-1-14C by 50%, and its incorporation into triglyceride by more than 80%. However, levorphanol stimulated 2 to 3-fold the incorporation of linoleate-1-14C or palmitate-1-14C into several phospholipids. Glucose uptake, lactate production, and adenosine triphosphate (ATP) content are not affected by the drug. Thus, levorphanol does not appear to exert its effects through generalized metabolic suppression. Removal of levorphanol by twice resuspending the granulocytes completely reverses all inhibition. In line with observations on bacteria, it appears that the complex effects of levorphanol on […] Find the latest version: https://jci.me/106580/pdf The Effects of the Morphine Analogue Levorphanol on Leukocytes METABOLIC EFFECTS AT REST AND DURING PHAGOCYTOSIS NANcY WuRsTE, PETER ELSBACH, ERIc J. -
Marijuana Is Cannabis with Tetrahydrocannabinol (THC). Strains Without THC Are Often Classified As Hemp
“COMBATING 21ST CENTURY DRUGS WITH SUCCESSFUL OUTCOMES” William L. Parker CEO American Court & Drug Testing Services [email protected] THE SUPREME COURT OF OHIO SPECIALIZED DOCKETS CONFERENCE Fentanyl and its correlation to fatal overdoses Thursday, October 11, 2018 in Ohio, a relatively new threat called Flakka, 11:45 a.m. – 1:00 p.m. CBD oils and how to incorporate these drugs into an effective drug testing program. Friday, October 12, 2018 1:15 p.m. – 2:30 p.m. FENTANYL Fentanyl is an opioid which is used as a pain medication and together with other medications for anesthesia or to relieve pain in terminally ill cancer patients. Fentanyl is available in a number of forms including by injection, as a skin patch, and to be absorbed through the tissues inside the mouth. Fentanyl about 75 times stronger than morphine for a given amount. Some fentanyl analogues may be as much as 10,000 times stronger than morphine. FENTANYL Fentanyl was created in 1959 by Paul Jannsen, founder of Jannsen Pharmaceutical and first used medically as anesthetic in 1968. Fentanyl patches were first introduced in the mid 1990’s as a pain management treatment for Opiate-tolerate patients. Fentanyl was first used for pain management in cancer patients in 2009. FENTANYL Recreational use of Fentanyl started in the mid 1970’s among medical professionals. The use of Fentanyl – especially from the illegal manufacturing of the drug has increased exponentially over the past three years. Since 2012 Fentanyl related overdoses and deaths have produced staggering statistics in almost every state in the U.S. -
The Main Tea Eta a El Mattitauli Mali Malta
THE MAIN TEA ETA USA 20180169172A1EL MATTITAULI MALI MALTA ( 19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0169172 A1 Kariman (43 ) Pub . Date : Jun . 21 , 2018 ( 54 ) COMPOUND AND METHOD FOR A61K 31/ 437 ( 2006 .01 ) REDUCING APPETITE , FATIGUE AND PAIN A61K 9 / 48 (2006 .01 ) (52 ) U . S . CI. (71 ) Applicant : Alexander Kariman , Rockville , MD CPC . .. .. .. .. A61K 36 / 74 (2013 .01 ) ; A61K 9 / 4825 (US ) (2013 . 01 ) ; A61K 31/ 437 ( 2013 . 01 ) ; A61K ( 72 ) Inventor: Alexander Kariman , Rockville , MD 31/ 4375 (2013 .01 ) (US ) ( 57 ) ABSTRACT The disclosed invention generally relates to pharmaceutical (21 ) Appl . No. : 15 /898 , 232 and nutraceutical compounds and methods for reducing appetite , muscle fatigue and spasticity , enhancing athletic ( 22 ) Filed : Feb . 16 , 2018 performance , and treating pain associated with cancer, trauma , medical procedure , and neurological diseases and Publication Classification disorders in subjects in need thereof. The disclosed inven ( 51 ) Int. Ci. tion further relates to Kratom compounds where said com A61K 36 / 74 ( 2006 .01 ) pound contains at least some pharmacologically inactive A61K 31/ 4375 ( 2006 .01 ) component. pronuPatent Applicationolan Publication manu saJun . decor21, 2018 deSheet les 1 of 5 US 2018 /0169172 A1 reta Mitragynine 7 -OM - nitragynine *** * *momoda W . 00 . Paynantheine Speciogynine **** * * * ! 1000 co Speclociliatine Corynartheidine Figure 1 Patent Application Publication Jun . 21, 2018 Sheet 2 of 5 US 2018 /0169172 A1 -
Patient-Controlled Transdermal Fentanyl Hydrochloride Vs Intravenous Morphine Pump for Postoperative Pain a Randomized Controlled Trial
ORIGINAL CONTRIBUTION Patient-Controlled Transdermal Fentanyl Hydrochloride vs Intravenous Morphine Pump for Postoperative Pain A Randomized Controlled Trial Eugene R. Viscusi, MD Context Patient-controlled analgesia (PCA) with morphine is commonly used to pro- Lowell Reynolds, MD vide acute postoperative pain control after major surgery. The fentanyl hydrochloride Frances Chung, MD patient-controlled transdermal system eliminates the need for venous access and com- plicated programming of pumps. Linda E. Atkinson, PhD Objective To assess the efficacy and safety of an investigational patient-controlled Sarita Khanna, PhD iontophoretic transdermal system using fentanyl hydrochloride compared with a stan- dard intravenous morphine patient-controlled pump. ATIENT-CONTROLLED ANALGE- Design, Setting, and Patients Prospective randomized controlled parallel-group sia (PCA) allows the patient to trial conducted between September 2000 and March 2001 at 33 North American hos- self-administer small doses of pitals, enrolling 636 adult patients who had just undergone major surgery. opioids, such as fentanyl, mor- Interventions In surgical recovery rooms, patients were randomly assigned to in- Pphine, hydromorphone, or meperi- travenous morphine (1-mg bolus every 5 minutes; maximum of 10 mg/h) by a patient- dine, as needed to manage pain. A key controlled analgesia pump (n=320) or iontophoretic fentanyl hydrochloride (40-µg principle of PCA use is that it is initi- infusion over 10 minutes) by a patient-controlled transdermal system (n=316). Supple- ated after titration to patient comfort mental analgesia (morphine or fentanyl intravenous boluses) was administered as needed with loading doses of intravenous (IV) before and for the first 3 hours after activation of the PCA treatments.