Methods of Euthanasia Kay Schwink Iowa State University
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Cyclopropane Anaesthesia by JOHN BOYD, M.D., D.A
Cyclopropane Anaesthesia By JOHN BOYD, M.D., D.A. TLHIS paper is based on my experience of one thousand cases of cyclopropane anaesthesia personally conducted by me since October, 1938, both in hospital and in private. But before discussing these it might be convenient for me to mention here something about the drug itself. HISTORY. Cyclopropane was first isolated in Germany in 1882 by Freund, who also demonstrated its chemical structure, C3H6. He did not, however, describe its anaesthetic properties. Following its discovery it seems to have been forgotten until 1928, when Henderson and Lucas of Toronto, in investigating contaminants of propylene, another anesthetic with undesirable side-effects, and itself'an isomer of cyclopropane, found that the supposed cause of the cardiac disturbances was in reality a better and less toxic anaesthetic. They demonstrated its anaesthetic properties first on animals, and then, before releasing it to the medical profession for clinical trial, they anaesthetised each other, and determined the quantities necessary for administration to man. In 1933 the first clinical trials of cyclopropane were made by Waters and his associates of the University of Wisconsin. In October of that year Waters presented a preliminary report on its anaesthetic properties in man,1 confirming the findings of Henderson and Lucas. Rowbotham introduced it to England first in 1935, and since then its use has spread rapidly throughout the country. PREPARATION. Cyclopropane is prepared commercially by the reduction of trimethylene bromide in the presence of metallic zinc in ethyl alcohol. It is also made commercially from propane in natural gas by progressive thermal chlorination. -
Unnamed Document
Mutations M287L and Q266I in the Glycine Receptor ␣1 Subunit Change Sensitivity to Volatile Anesthetics in Oocytes and Neurons, but Not the Minimal Alveolar Concentration in Knockin Mice Cecilia M. Borghese, Ph.D.,* Wei Xiong, Ph.D.,† S. Irene Oh, B.S.,‡ Angel Ho, B.S.,§ S. John Mihic, Ph.D.,ʈ Li Zhang, M.D.,# David M. Lovinger, Ph.D.,** Gregg E. Homanics, Ph.D.,†† Edmond I. Eger 2nd, M.D.,‡‡ R. Adron Harris, Ph.D.§§ ABSTRACT What We Already Know about This Topic • Inhibitory spinal glycine receptor function is enhanced by vol- Background: Volatile anesthetics (VAs) alter the function of atile anesthetics, making this a leading candidate for their key central nervous system proteins but it is not clear which, immobilizing effect if any, of these targets mediates the immobility produced by • Point mutations in the ␣1 subunit of glycine receptors have been identified that increase or decrease receptor potentiation VAs in the face of noxious stimulation. A leading candidate is by volatile anesthetics the glycine receptor, a ligand-gated ion channel important for spinal physiology. VAs variously enhance such function, and blockade of spinal glycine receptors with strychnine af- fects the minimal alveolar concentration (an anesthetic What This Article Tells Us That Is New EC50) in proportion to the degree of enhancement. • Mice harboring specific mutations in their glycine receptors Methods: We produced single amino acid mutations into that increased or decreased potentiation by volatile anesthetic in vitro did not have significantly altered changes in anesthetic the glycine receptor ␣1 subunit that increased (M287L, third potency in vivo transmembrane region) or decreased (Q266I, second trans- • These findings indicate that this glycine receptor does not me- membrane region) sensitivity to isoflurane in recombinant diate anesthetic immobility, and that other targets must be receptors, and introduced such receptors into mice. -
Management of Chronic Problems
MANAGEMENT OF CHRONIC PROBLEMS INTERACTIONS BETWEEN ALCOHOL AND DRUGS A. Leary,* T. MacDonald† SUMMARY concerned. Alcohol may alter the effects of the drug; drug In western society alcohol consumption is common as is may change the effects of alcohol; or both may occur. the use of therapeutic drugs. It is not surprising therefore The interaction between alcohol and drug may be that concomitant use of these should occur frequently. The pharmacokinetic, with altered absorption, metabolism or consequences of this combination vary with the dose of elimination of the drug, alcohol or both.2 Alcohol may drug, the amount of alcohol taken, the mode of affect drug pharmacokinetics by altering gastric emptying administration and the pharmacological effects of the drug or liver metabolism. Drugs may affect alcohol kinetics by concerned. Interactions may be pharmacokinetic or altering gastric emptying or inhibiting gastric alcohol pharmacodynamic, and while coincidental use of alcohol dehydrogenase (ADH).3 This may lead to altered tissue may affect the metabolism or action of a drug, a drug may concentrations of one or both agents, with resultant toxicity. equally affect the metabolism or action of alcohol. Alcohol- The results of concomitant use may also be principally drug interactions may differ with acute and chronic alcohol pharmacodynamic, with combined alcohol and drug effects ingestion, particularly where toxicity is due to a metabolite occurring at the receptor level without important changes rather than the parent drug. There is both inter- and intra- in plasma concentration of either. Some interactions have individual variation in the response to concomitant drug both kinetic and dynamic components and, where this is and alcohol use. -
Cyclobutane Derivatives in Drug Discovery
Cyclobutane Derivatives in Drug Discovery Overview Key Points Unlike larger and conformationally flexible cycloalkanes, Cyclobutane adopts a rigid cyclobutane and cyclopropane have rigid conformations. Due to the ring strain, cyclobutane adopts a rigid puckered puckered conformation Offer ing advantages on (~30°) conformation. This unique architecture bestowed potency, selectivity and certain cyclobutane-containing drugs with unique pharmacokinetic (PK) properties. When applied appropriately, cyclobutyl profile. scaffolds may offer advantages on potency, selectivity and pharmacokinetic (PK) profile. Bridging Molecules for Innovative Medicines 1 PharmaBlock designs and Cyclobutane-containing Drugs synthesizes over 1846 At least four cyclobutane-containing drugs are currently on the market. cyclobutanes, and 497 Chemotherapy carboplatin (Paraplatin, 1) for treating ovarian cancer was cyclobutane products are prepared to lower the strong nephrotoxicity associated with cisplatin. By in stock. CLICK HERE to replacing cisplatin’s two chlorine atoms with cyclobutane-1,1-dicarboxylic find detailed product acid, carboplatin (1) has a much lower nephrotoxicity than cisplatin. On information on webpage. the other hand, Schering-Plough/Merck’s hepatitis C virus (HCV) NS3/4A protease inhibitor boceprevir (Victrelis, 2) also contains a cyclobutane group in its P1 region. It is 3- and 19-fold more potent than the 1 corresponding cyclopropyl and cyclopentyl analogues, respectively. Androgen receptor (AR) antagonist apalutamide (Erleada, 4) for treating castration-resistant prostate cancer (CRPC) has a spirocyclic cyclobutane scaffold. It is in the same series as enzalutamide (Xtandi, 3) discovered by Jung’s group at UCLA in the 2000s. The cyclobutyl- (4) and cyclopentyl- derivative have activities comparable to the dimethyl analogue although the corresponding six-, seven-, and eight-membered rings are slightly less 2 active. -
Euthanasia of Experimental Animals
EUTHANASIA OF EXPERIMENTAL ANIMALS • *• • • • • • • *•* EUROPEAN 1COMMISSIO N This document has been prepared for use within the Commission. It does not necessarily represent the Commission's official position. A great deal of additional information on the European Union is available on the Internet. It can be accessed through the Europa server (http://europa.eu.int) Cataloguing data can be found at the end of this publication Luxembourg: Office for Official Publications of the European Communities, 1997 ISBN 92-827-9694-9 © European Communities, 1997 Reproduction is authorized, except for commercial purposes, provided the source is acknowledged Printed in Belgium European Commission EUTHANASIA OF EXPERIMENTAL ANIMALS Document EUTHANASIA OF EXPERIMENTAL ANIMALS Report prepared for the European Commission by Mrs Bryony Close Dr Keith Banister Dr Vera Baumans Dr Eva-Maria Bernoth Dr Niall Bromage Dr John Bunyan Professor Dr Wolff Erhardt Professor Paul Flecknell Dr Neville Gregory Professor Dr Hansjoachim Hackbarth Professor David Morton Mr Clifford Warwick EUTHANASIA OF EXPERIMENTAL ANIMALS CONTENTS Page Preface 1 Acknowledgements 2 1. Introduction 3 1.1 Objectives of euthanasia 3 1.2 Definition of terms 3 1.3 Signs of pain and distress 4 1.4 Recognition and confirmation of death 5 1.5 Personnel and training 5 1.6 Handling and restraint 6 1.7 Equipment 6 1.8 Carcass and waste disposal 6 2. General comments on methods of euthanasia 7 2.1 Acceptable methods of euthanasia 7 2.2 Methods acceptable for unconscious animals 15 2.3 Methods that are not acceptable for euthanasia 16 3. Methods of euthanasia for each species group 21 3.1 Fish 21 3.2 Amphibians 27 3.3 Reptiles 31 3.4 Birds 35 3.5 Rodents 41 3.6 Rabbits 47 3.7 Carnivores - dogs, cats, ferrets 53 3.8 Large mammals - pigs, sheep, goats, cattle, horses 57 3.9 Non-human primates 61 3.10 Other animals not commonly used for experiments 62 4. -
Pharmacology – Inhalant Anesthetics
Pharmacology- Inhalant Anesthetics Lyon Lee DVM PhD DACVA Introduction • Maintenance of general anesthesia is primarily carried out using inhalation anesthetics, although intravenous anesthetics may be used for short procedures. • Inhalation anesthetics provide quicker changes of anesthetic depth than injectable anesthetics, and reversal of central nervous depression is more readily achieved, explaining for its popularity in prolonged anesthesia (less risk of overdosing, less accumulation and quicker recovery) (see table 1) Table 1. Comparison of inhalant and injectable anesthetics Inhalant Technique Injectable Technique Expensive Equipment Cheap (needles, syringes) Patent Airway and high O2 Not necessarily Better control of anesthetic depth Once given, suffer the consequences Ease of elimination (ventilation) Only through metabolism & Excretion Pollution No • Commonly administered inhalant anesthetics include volatile liquids such as isoflurane, halothane, sevoflurane and desflurane, and inorganic gas, nitrous oxide (N2O). Except N2O, these volatile anesthetics are chemically ‘halogenated hydrocarbons’ and all are closely related. • Physical characteristics of volatile anesthetics govern their clinical effects and practicality associated with their use. Table 2. Physical characteristics of some volatile anesthetic agents. (MAC is for man) Name partition coefficient. boiling point MAC % blood /gas oil/gas (deg=C) Nitrous oxide 0.47 1.4 -89 105 Cyclopropane 0.55 11.5 -34 9.2 Halothane 2.4 220 50.2 0.75 Methoxyflurane 11.0 950 104.7 0.2 Enflurane 1.9 98 56.5 1.68 Isoflurane 1.4 97 48.5 1.15 Sevoflurane 0.6 53 58.5 2.5 Desflurane 0.42 18.7 25 5.72 Diethyl ether 12 65 34.6 1.92 Chloroform 8 400 61.2 0.77 Trichloroethylene 9 714 86.7 0.23 • The volatile anesthetics are administered as vapors after their evaporization in devices known as vaporizers. -
DOCUMENT RESUME ED 300 697 CG 021 192 AUTHOR Gougelet, Robert M.; Nelson, E. Don TITLE Alcohol and Other Chemicals. Adolescent A
DOCUMENT RESUME ED 300 697 CG 021 192 AUTHOR Gougelet, Robert M.; Nelson, E. Don TITLE Alcohol and Other Chemicals. Adolescent Alcoholism: Recognizing, Intervening, and Treating Series No. 6. INSTITUTION Ohio State Univ., Columbus. Dept. of Family Medicine. SPONS AGENCY Health Resources and Services Administration (DHHS/PHS), Rockville, MD. Bureau of Health Professions. PUB DATE 87 CONTRACT 240-83-0094 NOTE 30p.; For other guides in this series, see CG 021 187-193. AVAILABLE FROMDepartment of Family Medicine, The Ohio State University, Columbus, OH 43210 ($5.00 each, set of seven, $25.00; audiocassette of series, $15.00; set of four videotapes keyed to guides, $165.00 half-inch tape, $225.00 three-quarter inch tape; all orders prepaid). PUB TYPE Guides - Classroom Use - Materials (For Learner) (051) -- Reports - General (140) EDRS PRICE MF01 Plus Plstage. PC Not Available from EDRS. DESCRIPTORS *Adolescents; *Alcoholism; *Clinical Diagnosis; *Drug Use; *Family Problems; Physician Patient Relationship; *Physicians; Substance Abuse; Units of Study ABSTRACT This document is one of seven publications contained in a series of materials for physicians on recognizing, intervening with, and treating adolescent alcoholism. The materials in this unit of study are designed to help the physician know the different classes of drugs, recognize common presenting symptoms of drug overdose, and place use and abuse in context. To do this, drug characteristics and pathophysiological and psychological effects of drugs are examined as they relate to administration, -
Divergent Synthesis of Cyclopropane-Containing Fragments and Lead-Like Compounds for Drug Discovery
Divergent Synthesis of Cyclopropane-Containing Fragments and Lead-Like Compounds for Drug Discovery A Thesis submitted by Stephen John Chawner In partial fulfilment of the requirement for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry Imperial College London South Kensington London SW7 2AZ United Kingdom 2017 1 I confirm that the work presented within this document is my own. Clear acknowledgement has been made when referring to the work of others, or where help has been received. The copyright of this thesis rests with the author and is made available under a Creative Commons Attribution Non-Commercial No Derivatives licence. Researchers are free to copy, distribute or transmit the thesis on the condition that they attribute it, that they do not use it for commercial purposes and that they do not alter, transform or build upon it. For any reuse or redistribution, researchers must make clear to others the licence terms of this work. 2 Acknowledgements Firstly, I would like to thank Imperial College London and Eli Lilly whose combined generosity through a CASE award made my PhD financially possible. I would like to thank my academic supervisor Dr James Bull for providing me with the opportunity to undertake a PhD in his group. I am grateful for the chemistry knowledge that he has shared, his encouragement to present at conferences and the freedom to follow new project ideas. In addition to funding, the CASE award provided me with the opportunity to collaborate with Dr Manuel Cases-Thomas at Erl Wood. Manuel was a constant source of enthusiasm throughout my PhD and has been a joy to work with. -
Appendix D: Important Facts About Alcohol and Drugs
APPENDICES APPENDIX D. IMPORTANT FACTS ABOUT ALCOHOL AND DRUGS Appendix D outlines important facts about the following substances: $ Alcohol $ Cocaine $ GHB (gamma-hydroxybutyric acid) $ Heroin $ Inhalants $ Ketamine $ LSD (lysergic acid diethylamide) $ Marijuana (Cannabis) $ MDMA (Ecstasy) $ Mescaline (Peyote) $ Methamphetamine $ Over-the-counter Cough/Cold Medicines (Dextromethorphan or DXM) $ PCP (Phencyclidine) $ Prescription Opioids $ Prescription Sedatives (Tranquilizers, Depressants) $ Prescription Stimulants $ Psilocybin $ Rohypnol® (Flunitrazepam) $ Salvia $ Steroids (Anabolic) $ Synthetic Cannabinoids (“K2”/”Spice”) $ Synthetic Cathinones (“Bath Salts”) PAGE | 53 Sources cited in this Appendix are: $ Drug Enforcement Administration’s Drug Facts Sheets1 $ Inhalant Addiction Treatment’s Dangers of Mixing Inhalants with Alcohol and Other Drugs2 $ National Institute on Alcohol Abuse and Alcoholism’s (NIAAA’s) Alcohol’s Effects on the Body3 $ National Institute on Drug Abuse’s (NIDA’s) Commonly Abused Drugs4 $ NIDA’s Treatment for Alcohol Problems: Finding and Getting Help5 $ National Institutes of Health (NIH) National Library of Medicine’s Alcohol Withdrawal6 $ Rohypnol® Abuse Treatment FAQs7 $ Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) Keeping Youth Drug Free8 $ SAMHSA’s Center for Behavioral Health Statistics and Quality’s (CBHSQ’s) Results from the 2015 National Survey on Drug Use and Health: Detailed Tables9 The substances that are considered controlled substances under the Controlled Substances Act (CSA) are divided into five schedules. An updated and complete list of the schedules is published annually in Title 21 Code of Federal Regulations (C.F.R.) §§ 1308.11 through 1308.15.10 Substances are placed in their respective schedules based on whether they have a currently accepted medical use in treatment in the United States, their relative abuse potential, and likelihood of causing dependence when abused. -
Halothenoyl-Cyclopropane-1-Carboxylic Acid Derivatives
Europäisches Patentamt *EP001424333A1* (19) European Patent Office Office européen des brevets (11) EP 1 424 333 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: C07D 333/28, A61K 31/381, 02.06.2004 Bulletin 2004/23 A61P 25/00 (21) Application number: 02026597.1 (22) Date of filing: 28.11.2002 (84) Designated Contracting States: • Fariello, Ruggero AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 20091 Bresso (MI) (IT) IE IT LI LU MC NL PT SE SK TR • Salvati, Patricia Designated Extension States: 20091 Bresso (MI) (IT) AL LT LV MK RO SI • Pellicciari, Roberto 20091 Bresso (MI) (IT) (71) Applicant: Newron Pharmaceuticals S.p.A. • Caccia, Carla 20091 Bresso (MI) (IT) 20091 Bresso (MI) (IT) (72) Inventors: (74) Representative: Minoja, Fabrizio, Dr. • Benatti, Luca Bianchetti Bracco Minoja S.r.l. 20091 Bresso (MI) (IT) Via Rossini, 8 20122 Milano (IT) (54) Halothenoyl-cyclopropane-1-carboxylic acid derivatives (57) Compounds of formula (I) benzyloxy, a group -N(R1R2) wherein R1 is hydrogen, 2 linear or branched C1-C4 alkyl, benzyl, phenyl and R is hydrogen or linear or branched C1-C4 alkyl, or R is a glycoside residue or a primary alkoxy residue from ascorbic acid, optionally having one or more hydroxy groups alkylated or acylated by linear or branched C1-C4 alkyl or acyl groups; X is a halogen atom and n 1 or 2 are long lasting inhib- itors of kynurenine 3-monooxygenase (KMO) and po- tent glutamate (GLU) release inhibitors. wherein R is hydroxy, linear or branched C1-C6 alkoxy, phenoxy, EP 1 424 333 A1 Printed by Jouve, 75001 PARIS (FR) EP 1 424 333 A1 Description [0001] The present invention refers to halothenoyl-cyclopropane-1-carboxylic acid derivatives as long lasting inhib- itors of kynurenine 3-monooxygenase (KMO), which are potent glutamate (GLU) release inhibitors. -
Federal Register/Vol. 71, No. 34/Tuesday, February 21, 2006
Federal Register / Vol. 71, No. 34 / Tuesday, February 21, 2006 / Notices 8859 DEPARTMENT OF HEALTH AND DEPARTMENT OF HEALTH AND of the Public Health Service Act to HUMAN SERVICES HUMAN SERVICES conduct directly or by grants or contracts, research, experiments, and Office of the National Coordinator; Office of the National Coordinator; demonstrations relating to occupational American Health Information American Health Information safety and health and to mine health. Community Chronic Care Workgroup Community Consumer Empowerment The BSC shall provide guidance to the Meeting Workgroup Meeting Director, NIOSH on research and prevention programs. Specifically, the ACTION: Announcement of meeting. ACTION: Announcement of meeting. board shall provide guidance on the institute’s research activities related to SUMMARY: SUMMARY: This notice announces the This notice announces the developing and evaluating hypotheses, third meeting of the American Health third meeting of the American Health Information Community Consumer systematically documenting findings Information Community Chronic Care and disseminating results. The board Workgroup in accordance with the Empowerment Workgroup in accordance with the Federal Advisory shall evaluate the degree to which the Federal Advisory Committee Act (Pub. activities of NIOSH: (1) Conform to L. 92–463, 5 U.S.C., App.) Committee Act (Pub. L. 92–463, 5 U.S.C., App.) appropriate scientific standards, (2) DATES: March 22, 2006 from 1 p.m. to address current, relevant needs, and (3) DATES: March 20, 2006 from 1 p.m. to 5 p.m. produce intended results. 5 p.m. ADDRESSES: Hubert H. Humphrey Matters to be Discussed: Agenda items ADDRESSES: Hubert H. Humphrey Building (200 Independence Ave., SW., include a report from the Director, Building (200 Independence Ave., SW., Washington, DC 20201), Conference NIOSH; progress report by BSC working Washington, DC 20201), Conference Room 705A. -
Newborn Anaesthesia: Pharmacological Considerations D
$38 REFRESHER COURSE OUTLINE Newborn anaesthesia: pharmacological considerations D. Ryan Cook MD Inhalation anaesthetics Several investigators have studied the age-related For the inhalation anaesthetics there are age-related cardiovascular effects of the potent inhalation differences in uptake and distribution, in anaes- anaesthetics at known multiples of MAC. At thetic requirements as reflected by differences in end-tidal concentrations of halothane bracketing MAC, in the effects on the four determinants of MAC, Lerman er al. 2 noted no difference in the cardiac output (preload, afterload, heart rate and incidence of hypotension or bradycardia in neonates contractility), and in the sensitivity of protective and in infants one to six months of age. Likewise, cardiovascular reflexes (e.g., baroreceptor reflex). we 3 have noted no age-related differences in the These differences limit the margin of safety of the determinants of cardiac output in developing piglets potent agents in infants. 1-20 days during either halothane or isoflurane Alveolar uptake of inhalation anaesthetics and anaesthesia. Halothane produced hypotension by a hence whole-body uptake is more rapid in infants reduction in contractility and heart rate; in much than in adults. J Lung washout is more rapid in older animals halothane also decreases peripheral infants than in adults because of the larger ratio vascular resistance. In piglets although blood pres- between alveolar minute ventilation and lung sure was equally depressed with isoflurane and volume (FRC) (3.5:1 in the infant vs. 1.3:1 in the halothane, cardiac output was better preserved adult). Increased brain size (ml.kg-J), limited during isoflurane anaesthesia.