DOCSLIB.ORG

Comparative Effects of Halogenated Inhaled Anesthetics on Voltage-Gated Na؉ Channel Function Wei Ouyang, Ph.D.,* Karl F

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparative Effects of Halogenated Inhaled Anesthetics on Voltage-Gated Na؉ Channel Function Wei Ouyang, Ph.D.,* Karl F Anesthesiology 2009; 110:582–90 Copyright © 2009, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Comparative Effects of Halogenated Inhaled Anesthetics on Voltage-gated Na؉ Channel Function Wei Ouyang, Ph.D.,* Karl F. Herold, M.D., Ph.D.,† Hugh C. Hemmings, Jr., M.D., Ph.D.‡ ؉ Background: Inhibition of voltage-gated Na channels (Nav) neurotransmitter release by the potent inhaled (volatile) is implicated in the synaptic actions of volatile anesthetics. We 2,3 ϩ anesthetics. The voltage-gated Na channel (Nav)su- studied the effects of the major halogenated inhaled anesthetics perfamily consists of 9 distinct genes that encode for the (halothane, isoflurane, sevoflurane, enflurane, and desflurane) ␣ on Na 1.4, a well-characterized pharmacological model for Na channel-forming -subunit (Nav1.1–1.9), each with tis- v v 4 effects. sue-dependent expression and functions. The potent ؉ ␣ ϩ Methods: Na currents (INa) from rat Nav1.4 -subunits heter- inhaled anesthetics inhibit native neuronal Na chan- Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/110/3/582/367953/0000542-200903000-00024.pdf by guest on 29 September 2021 ologously expressed in Chinese hamster ovary cells were analyzed nels5–7 as well as heterologously expressed mammalian by whole cell voltage-clamp electrophysiological recording. Naϩ channel ␣-subunits.8–11 However, the relative po- Results: Halogenated inhaled anesthetics reversibly inhibited tencies and channel-gating effects of various inhaled an- Nav1.4 in a concentration- and voltage-dependent manner at clinical concentrations. At equianesthetic concentrations, peak esthetics have not been compared in detail. Although Ϸ ϩ INa was inhibited with a rank order of desflurane > halothane Na channel blockade is of enormous therapeutic im- enflurane > isoflurane Ϸ sevoflurane from a physiologic hold- portance for cardiac dysrhythmias, acute and chronic ing potential (–80 mV). This suggests that the contribution of -؉ pain states, seizure disorders, and possibly general anes Na channel block to anesthesia might vary in an agent-specific ϩ manner. From a hyperpolarized holding potential that mini- thesia, systemic administration of Na channel blockers is associated with severe cardiac and central nervous mizes inactivation (–120 mV), peak INa was inhibited with a 4 rank order of potency for tonic inhibition of peak INa of halo- system side effects. Effects of anesthetics on central thane > isoflurane Ϸ sevoflurane > enflurane > desflurane. nervous system and peripheral Nav isoforms are there- Desflurane produced the largest negative shift in voltage-depen- fore likely to be involved in their anesthetic and some of dence of fast inactivation consistent with its more prominent voltage-dependent effects. A comparison between isoflurane their agent-specific nonanesthetic effects. and halothane showed that halothane produced greater facili- We characterized the effects of five potent inhaled tation of current decay, slowing of recovery from fast inactiva- anesthetics on the function and gating of rat Nav1.4 tion, and use-dependent block than isoflurane. ␣-subunits heterologously expressed in Chinese hamster Conclusions: Five halogenated inhaled anesthetics all inhibit ovary cells. The skeletal muscle Naϩ channel isoform a voltage-gated Na؉ channel by voltage- and use-dependent ,؉ Nav1.4 is expressed at the neuromuscular junction mechanisms. Agent-specific differences in efficacy for Na 12 channel inhibition due to differential state-dependent mecha- where it regulates muscle excitability. Nav1.4 function nisms creates pharmacologic diversity that could underlie sub- is inhibited by local anesthetic and antidepressant drugs, tle differences in anesthetic and nonanesthetic actions. and it provides a well-characterized model for studies of Naϩ channel pharmacology that is amenable to genetic 13–17 ␥ manipulation for detailed structure-function studies. BOTH ligand-gated ion channels, including GABAA ( - aminobutyric acid, type A) receptors, glycine receptors, The halogenated alkane halothane and methylethyl neuronal nicotinic acetylcholine receptors, and N-meth- ethers isoflurane, sevoflurane, enflurane, and desflurane represent the principal volatile anesthetics employed yl-D-aspartic acid–type glutamate receptors, as well as 2ϩ ϩ clinically in the modern era. Detailed kinetic character- voltage-gated ion channels, including Ca channels, K ϩ channels, and Naϩ channels, represent promising molec- ization of their Na channel blocking effects is impor- ular targets for various general anesthetics.1 Depression tant for identifying common and/or distinct features that of presynaptic action potential amplitude involving Naϩ might contribute to agent-specific pharmacological pro- channel blockade has been implicated in inhibition of files. We report here that all five anesthetics inhibit Nav1.4 at concentrations in the clinical range in propor- tion to their potencies for producing anesthesia in vivo, * Research Associate, ‡ Professor and Vice Chair of Research, Departments of ϩ Anesthesiology and Pharmacology, Weill Cornell Medical College, New York, which provides additional support for Na channel New York; † Postdoctoral Associate, Department of Anesthesiology, Weill Cor- blockade as a plausible mechanism of inhaled anesthetic nell Medical College, and Department of Anesthesiology and Intensive Care, Campus Mitte, Charite´ University Medicine Berlin, Berlin, Germany. action. In addition, agent-specific differences in their Received from the Department of Anesthesiology, Weill Cornell Medical Col- relative potencies and involvement of state-dependent lege, New York, New York. Submitted for publication July 8, 2008. Accepted for mechanisms could contribute to differences in their cen- publication November 18, 2008. Supported by grant GM 58055 from the National Institutes of Health, Bethesda, Maryland, (to Dr. Hemmings), and by fellowship tral and peripheral pharmacodynamic properties. HE4554/5-1 from the Deutsche Forschungsgemeinschaft, Bonn, Germany (to Dr. Herold). Drs. Ouyang and Herold contributed equally to this study. Address correspondence to Dr. Hemmings: Department of Anesthesiology, Materials and Methods Box 50, LC-203, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065. [email protected]. Information on purchasing re- Cell Culture prints may be found at www.anesthesiology.org or on the masthead page at the Chinese hamster ovary cells stably transfected with rat beginning of this issue. ANESTHESIOLOGY’s articles are made freely accessible to all ␣ readers, for personal use only, 6 months from the cover date of the issue. Nav1.4 -subunit (a gift from S. Rock Levinson, Ph.D., Anesthesiology, V 110, No 3, Mar 2009 582 INHALED ANESTHETIC EFFECTS ON NAV1.4 583 Professor, Department of Physiology and Biophysics, Uni- pette (diameter, 0.15 mm) positioned 30–40 ␮m away versity of Colorado Health Sciences Center, Denver, Colo- from patched cells. Concentrations of volatile anesthet- rado) were cultured in 90% (v/v) Dulbecco’s Modified ics were determined by local sampling of the perfusate at Eagle Medium, 10% (v/v) fetal bovine serum, 300 ␮g/ml the site of the recording pipette tip and analysis by gas G418 (Invitrogen, Carlsbad, CA), 100 units/ml penicillin, chromatography as described.5 and 100 ␮g/ml streptomycin (Biosource, Rockville, MD) under 95% air/5% CO2 at 37°C. Cells were plated on glass Statistical Analysis coverslips in 35-mm plastic dishes (Becton Dickinson, IC50 values were calculated by least squares fitting of data to Franklin Lakes, NJ) 1–3 days before electrophysiological ϭ ϩ Ϫ ϫ the Hill equation: Y 1/(1 10((logIC50 X) h)), where recording. Y is the effect, X is measured anesthetic concentration, and h is Hill slope. Activation curves were fitted to a Boltzmann Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/110/3/582/367953/0000542-200903000-00024.pdf by guest on 29 September 2021 Electrophysiology ϭ ϩ equation of the form G/Gmax 1/(1 e(V1/2a – V)/k), where Cells attached to coverslips were transferred to a plas- G/G is normalized fractional conductance, G is maxi- tic Petri dish (35 ϫ 10 mm) on the stage of a Nikon max max mum conductance, V1/2a is voltage for half-maximal activa- ECLIPSE TE300 inverted microscope (Melville, NY). The ϩ tion, and k is the slope factor. Na conductance (GNa) was culture medium was replaced, and cells were superfused ϭ calculated using the equation: GNa INa/(Vt –Vr), where INa at 1.5–2 ml/min with extracellular solution containing ϩ ϩ is peak Na current, Vt is test potential, and Vr is Na reversal (in mM): NaCl 140; KCl 4; CaCl2 1.5; MgCl2 1.5; HEPES ϭ potential (ENa 69 mV). Fast inactivation curves were fitted 10; D-glucose 5; pH 7.30 with NaOH. Studies were con- to a Boltzmann equation of the form I/I ϭ 1/(1 ϩ e(V ducted at room temperature (24 Ϯ 1°C) using conven- max 1/2in 18 – V)/k), where I/I max is normalized current, I max is maximum tional whole cell patch-clamp techniques. Patch elec- current, V is voltage of half maximal inactivation, and k is trodes (tip diameter Ͻ 1 ␮m) were made from borosilicate 1/2in slope factor. INa current decay was analyzed by fitting the glass capillaries (Drummond Scientific, Broomall, PA) using decay phase of the current trace between 90% and 10% of a micropipette puller (P-97; Sutter Instruments, Novato, ϭ maximal INa to the monoexponential equation INa A· CA) and fire polished (Narishige Microforge, Kyoto, Japan). Ϫ ␶ ϩ exp( t/ in) C, where A is maximal INa amplitude, C is
Load more

Recommended publications
  • Classification of Medicinal Drugs and Driving: Co-Ordination and Synthesis Report
    Project No. TREN-05-FP6TR-S07.61320-518404-DRUID DRUID Driving under the Influence of Drugs, Alcohol and Medicines Integrated Project 1.6. Sustainable Development, Global Change and Ecosystem 1.6.2: Sustainable Surface Transport 6th Framework Programme Deliverable 4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Due date of deliverable: 21.07.2011 Actual submission date: 21.07.2011 Revision date: 21.07.2011 Start date of project: 15.10.2006 Duration: 48 months Organisation name of lead contractor for this deliverable: UVA Revision 0.0 Project co-funded by the European Commission within the Sixth Framework Programme (2002-2006) Dissemination Level PU Public PP Restricted to other programme participants (including the Commission x Services) RE Restricted to a group specified by the consortium (including the Commission Services) CO Confidential, only for members of the consortium (including the Commission Services) DRUID 6th Framework Programme Deliverable D.4.4.1 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Page 1 of 243 Classification of medicinal drugs and driving: Co-ordination and synthesis report. Authors Trinidad Gómez-Talegón, Inmaculada Fierro, M. Carmen Del Río, F. Javier Álvarez (UVa, University of Valladolid, Spain) Partners - Silvia Ravera, Susana Monteiro, Han de Gier (RUGPha, University of Groningen, the Netherlands) - Gertrude Van der Linden, Sara-Ann Legrand, Kristof Pil, Alain Verstraete (UGent, Ghent University, Belgium) - Michel Mallaret, Charles Mercier-Guyon, Isabelle Mercier-Guyon (UGren, University of Grenoble, Centre Regional de Pharmacovigilance, France) - Katerina Touliou (CERT-HIT, Centre for Research and Technology Hellas, Greece) - Michael Hei βing (BASt, Bundesanstalt für Straßenwesen, Germany).
    [Show full text]
  • Properties and Units in Clinical Pharmacology and Toxicology
    Pure Appl. Chem., Vol. 72, No. 3, pp. 479–552, 2000. © 2000 IUPAC INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY AND LABORATORY MEDICINE SCIENTIFIC DIVISION COMMITTEE ON NOMENCLATURE, PROPERTIES, AND UNITS (C-NPU)# and INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY CHEMISTRY AND HUMAN HEALTH DIVISION CLINICAL CHEMISTRY SECTION COMMISSION ON NOMENCLATURE, PROPERTIES, AND UNITS (C-NPU)§ PROPERTIES AND UNITS IN THE CLINICAL LABORATORY SCIENCES PART XII. PROPERTIES AND UNITS IN CLINICAL PHARMACOLOGY AND TOXICOLOGY (Technical Report) (IFCC–IUPAC 1999) Prepared for publication by HENRIK OLESEN1, DAVID COWAN2, RAFAEL DE LA TORRE3 , IVAN BRUUNSHUUS1, MORTEN ROHDE1, and DESMOND KENNY4 1Office of Laboratory Informatics, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark; 2Drug Control Centre, London University, King’s College, London, UK; 3IMIM, Dr. Aiguader 80, Barcelona, Spain; 4Dept. of Clinical Biochemistry, Our Lady’s Hospital for Sick Children, Crumlin, Dublin 12, Ireland #§The combined Memberships of the Committee and the Commission (C-NPU) during the preparation of this report (1994–1996) were as follows: Chairman: H. Olesen (Denmark, 1989–1995); D. Kenny (Ireland, 1996); Members: X. Fuentes-Arderiu (Spain, 1991–1997); J. G. Hill (Canada, 1987–1997); D. Kenny (Ireland, 1994–1997); H. Olesen (Denmark, 1985–1995); P. L. Storring (UK, 1989–1995); P. Soares de Araujo (Brazil, 1994–1997); R. Dybkær (Denmark, 1996–1997); C. McDonald (USA, 1996–1997). Please forward comments to: H. Olesen, Office of Laboratory Informatics 76-6-1, Copenhagen University Hospital (Rigshospitalet), 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. E-mail: [email protected] Republication or reproduction of this report or its storage and/or dissemination by electronic means is permitted without the need for formal IUPAC permission on condition that an acknowledgment, with full reference to the source, along with use of the copyright symbol ©, the name IUPAC, and the year of publication, are prominently visible.
    [Show full text]
  • Title 16. Crimes and Offenses Chapter 13. Controlled Substances Article 1
    TITLE 16. CRIMES AND OFFENSES CHAPTER 13. CONTROLLED SUBSTANCES ARTICLE 1. GENERAL PROVISIONS § 16-13-1. Drug related objects (a) As used in this Code section, the term: (1) "Controlled substance" shall have the same meaning as defined in Article 2 of this chapter, relating to controlled substances. For the purposes of this Code section, the term "controlled substance" shall include marijuana as defined by paragraph (16) of Code Section 16-13-21. (2) "Dangerous drug" shall have the same meaning as defined in Article 3 of this chapter, relating to dangerous drugs. (3) "Drug related object" means any machine, instrument, tool, equipment, contrivance, or device which an average person would reasonably conclude is intended to be used for one or more of the following purposes: (A) To introduce into the human body any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (B) To enhance the effect on the human body of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; (C) To conceal any quantity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state; or (D) To test the strength, effectiveness, or purity of any dangerous drug or controlled substance under circumstances in violation of the laws of this state. (4) "Knowingly" means having general knowledge that a machine, instrument, tool, item of equipment, contrivance, or device is a drug related object or having reasonable grounds to believe that any such object is or may, to an average person, appear to be a drug related object.
    [Show full text]
  • Local Anesthetics
    Local Anesthetics Introduction and History Cocaine is a naturally occurring compound indigenous to the Andes Mountains, West Indies, and Java. It was the first anesthetic to be discovered and is the only naturally occurring local anesthetic; all others are synthetically derived. Cocaine was introduced into Europe in the 1800s following its isolation from coca beans. Sigmund Freud, the noted Austrian psychoanalyst, used cocaine on his patients and became addicted through self-experimentation. In the latter half of the 1800s, interest in the drug became widespread, and many of cocaine's pharmacologic actions and adverse effects were elucidated during this time. In the 1880s, Koller introduced cocaine to the field of ophthalmology, and Hall introduced it to dentistry Overwiev Local anesthetics (LAs) are drugs that block the sensation of pain in the region where they are administered. LAs act by reversibly blocking the sodium channels of nerve fibers, thereby inhibiting the conduction of nerve impulses. Nerve fibers which carry pain sensation have the smallest diameter and are the first to be blocked by LAs. Loss of motor function and sensation of touch and pressure follow, depending on the duration of action and dose of the LA used. LAs can be infiltrated into skin/subcutaneous tissues to achieve local anesthesia or into the epidural/subarachnoid space to achieve regional anesthesia (e.g., spinal anesthesia, epidural anesthesia, etc.). Some LAs (lidocaine, prilocaine, tetracaine) are effective on topical application and are used before minor invasive procedures (venipuncture, bladder catheterization, endoscopy/laryngoscopy). LAs are divided into two groups based on their chemical structure. The amide group (lidocaine, prilocaine, mepivacaine, etc.) is safer and, hence, more commonly used in clinical practice.
    [Show full text]
  • A Comprehensive Guide Ram Roth Elizabeth A.M. Frost Clifford Gevirtz
    The Role of Anesthesiology in Global Health A Comprehensive Guide Ram Roth Elizabeth A.M. Frost Cli ord Gevirtz Editors Carrie L.H. Atcheson Associate Editor 123 The Role of Anesthesiology in Global Health Ram Roth • Elizabeth A.M. Frost Clifford Gevirtz Editors Carrie L.H. Atcheson Associate Editor The Role of Anesthesiology in Global Health A Comprehensive Guide Editors Ram Roth Elizabeth A.M. Frost Department of Anesthesiology Department of Anesthesiology Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai New York , NY , USA New York , NY , USA Clifford Gevirtz Department of Anesthesiology LSU Health Sciences Center New Orleans , LA , USA Associate Editor Carrie L.H. Atcheson Oregon Anesthesiology Group Department of Anesthesiology Adventist Medical Center Portland , OR , USA ISBN 978-3-319-09422-9 ISBN 978-3-319-09423-6 (eBook) DOI 10.1007/978-3-319-09423-6 Springer Cham Heidelberg New York Dordrecht London Library of Congress Control Number: 2014956567 © Springer International Publishing Switzerland 2015 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work.
    [Show full text]
  • Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
    MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01
    [Show full text]
  • Drug and Medication Classification Schedule
    KENTUCKY HORSE RACING COMMISSION UNIFORM DRUG, MEDICATION, AND SUBSTANCE CLASSIFICATION SCHEDULE KHRC 8-020-1 (11/2018) Class A drugs, medications, and substances are those (1) that have the highest potential to influence performance in the equine athlete, regardless of their approval by the United States Food and Drug Administration, or (2) that lack approval by the United States Food and Drug Administration but have pharmacologic effects similar to certain Class B drugs, medications, or substances that are approved by the United States Food and Drug Administration. Acecarbromal Bolasterone Cimaterol Divalproex Fluanisone Acetophenazine Boldione Citalopram Dixyrazine Fludiazepam Adinazolam Brimondine Cllibucaine Donepezil Flunitrazepam Alcuronium Bromazepam Clobazam Dopamine Fluopromazine Alfentanil Bromfenac Clocapramine Doxacurium Fluoresone Almotriptan Bromisovalum Clomethiazole Doxapram Fluoxetine Alphaprodine Bromocriptine Clomipramine Doxazosin Flupenthixol Alpidem Bromperidol Clonazepam Doxefazepam Flupirtine Alprazolam Brotizolam Clorazepate Doxepin Flurazepam Alprenolol Bufexamac Clormecaine Droperidol Fluspirilene Althesin Bupivacaine Clostebol Duloxetine Flutoprazepam Aminorex Buprenorphine Clothiapine Eletriptan Fluvoxamine Amisulpride Buspirone Clotiazepam Enalapril Formebolone Amitriptyline Bupropion Cloxazolam Enciprazine Fosinopril Amobarbital Butabartital Clozapine Endorphins Furzabol Amoxapine Butacaine Cobratoxin Enkephalins Galantamine Amperozide Butalbital Cocaine Ephedrine Gallamine Amphetamine Butanilicaine Codeine
    [Show full text]
  • A Brief History Behind the Most Used Local Anesthetics
    Tetrahedron xxx (xxxx) xxx Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet Tetrahedron report XXX A brief history behind the most used local anesthetics * Marco M. Bezerra, Raquel A.C. Leao,~ Leandro S.M. Miranda, Rodrigo O.M.A. de Souza Biocatalysis and Organic Synthesis Group, Chemistry Institute, Federal University of Rio de Janeiro, 21941-909, Brazil article info abstract Article history: The chemistry behind the discovery of local anesthetics is a beautiful way of understanding the devel- Received 13 April 2020 opment and improvement of medicinal/organic chemistry protocols towards the synthesis of biologically Received in revised form active molecules. Here in we present a brief history based on the chemistry development of the most 16 September 2020 used local anesthetics trying to draw a line between the first achievements obtained by the use of Accepted 18 September 2020 cocaine until the synthesis of the mepivacaine analogs nowadays. Available online xxx © 2020 Elsevier Ltd. All rights reserved. Keywords: Anesthetics Medicinal chemistry Organic synthesis Mepivacaíne Contents 1. Introduction . ............................. 00 1.1. Pain and anesthesia . ............................................... 00 1.2. Ancient techniques to achieve anesthesia . ............................... 00 1.3. The objective of this work . .......................................... 00 2. Cocaine .............................................................................................. ............................
    [Show full text]
  • Lidocaine: a Local Anesthetic, Its Adverse Effects and Management
    medicina Review Lidocaine: A Local Anesthetic, Its Adverse Effects and Management Entaz Bahar and Hyonok Yoon * Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gyeongsang National University, Jinju 52828, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-55-772-2422 Abstract: The most widely used medications in dentistry are local anesthetics (LA), especially lidocaine, and the number of recorded adverse allergic responses, particularly of hazardous responses, is quite low. However, allergic reactions can range from moderate to life-threatening, requiring rapid diagnosis and treatment. This article serves as a review to provide information on LA, their adverse reactions, causes, and management. Keywords: local anesthetics; lidocaine; adverse allergic responses 1. Introduction A local anesthetic (LA) is a medicine that is used to numb a small part of the body temporarily before performing a minor surgery like skin biopsy. Before a dental operation, such as tooth extraction, LA may be given to the patient. LA do not cause humans to fall asleep, unlike general anesthesia. They are usually distinguished by their chemical structure, specifically the linkage between the compound’s common components, such as Citation: Bahar, E.; Yoon, H. amide and esters [1]. The vast majority of the regularly used dental LA are amides, for Lidocaine: A Local Anesthetic, Its example, lidocaine, mepivacaine, bupivacaine, etidocaine, prilocaine, and articaine [2]. The Adverse Effects and Management. maximum recommended dose of LA may vary based on the nation, gender, age, weight, Medicina 2021, 57, 782. https:// and medical condition of the patient. The gathering of information from several sources, doi.org/10.3390/medicina57080782 Table1 shows the acceptable maximum doses of LA with or without vasoconstrictor [ 3–5].
    [Show full text]
  • Prescription Medications, Drugs, Herbs & Chemicals Associated With
    Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus American Tinnitus Association Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form, or by any means, without the prior written permission of the American Tinnitus Association. ©2013 American Tinnitus Association Prescription Medications, Drugs, Herbs & Chemicals Associated with Tinnitus American Tinnitus Association This document is to be utilized as a conversation tool with your health care provider and is by no means a “complete” listing. Anyone reading this list of ototoxic drugs is strongly advised NOT to discontinue taking any prescribed medication without first contacting the prescribing physician. Just because a drug is listed does not mean that you will automatically get tinnitus, or exacerbate exisiting tinnitus, if you take it. A few will, but many will not. Whether or not you eperience tinnitus after taking one of the listed drugs or herbals, or after being exposed to one of the listed chemicals, depends on many factors ‐ such as your own body chemistry, your sensitivity to drugs, the dose you take, or the length of time you take the drug. It is important to note that there may be drugs NOT listed here that could still cause tinnitus. Although this list is one of the most complete listings of drugs associated with tinnitus, no list of this kind can ever be totally complete – therefore use it as a guide and resource, but do not take it as the final word. The drug brand name is italicized and is followed by the generic drug name in bold.
    [Show full text]
  • Effective Postoperative Pain Prevention Through Administration of Bupivacaine and Diclofenac Tapio Hyrkas, MD, DDS,* Pekka Ylipaavalniemi, DDS, Phd,* Valle J
    Anesth Prog 41:6-10 1994 SCIENTIFIC REPORT Effective Postoperative Pain Prevention through Administration of Bupivacaine and Diclofenac Tapio Hyrkas, MD, DDS,* Pekka Ylipaavalniemi, DDS, PhD,* Valle J. Oikarinen, MD, DDS, PhD, FDSRCS (Eng.),* and Ilari Paakkari, MD, PhDt *Department of Oral and Maxillofacial Surgery and tDepartment of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland The efficacies of bupivacaine and lidocaine long-acting local anesthetics have given encouraging re- together with a preoperatively administered sults; investigators have demonstrated significant pain re- single-dose oral combination of normal- and duction with bupivacaine2- and etidocaine.5,7 In most sustained-release preparations of diclofenac in studies there was no antiinflammatory premedica- preventing postoperative pain after third molar tion,2,3 57 but one reported effective pain reduction by removal were compared in a double-blind combining a low dose of diflunisal with bupivacaine,4 and crossover study. Bilaterally impacted lower third another used flurbiprofen with etidocaine.8 Preoperative molars were removed in two sessions. Each administration of nonsteroidal antiinflammatory drugs patient was given one type of local anesthetic on (NSAIDs) is not a routine in many studies, perhaps due to one session and the other in the second. Pain fear of complications like alveolitis and postoperative was recorded using a visual analog scale. When bleeding. We have shown that when lidocaine is used for the diclofenac combination (150 mg) was given local anesthesia, oral pretreatment with the NSAID di- before the operation, postoperative analgesia was clofenac combination of fast-acting and sustained-release better with bupivacaine plus diclofenac than with formulations resulted in a very low level of postoperative lidocaine plus diclofenac.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]