DOCSLIB.ORG

Sodium Channels and Nociception – the Effects of Local Anesthetics

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Sodium Channels and Nociception – the Effects of Local Anesthetics PERIODICUM BIOLOGORUM UDC 57:61 VOL. 111, No 2, 215–218, 2009 CODEN PDBIAD ISSN 0031-5362 Overview Sodium channels and nociception – the effects of local anesthetics Abstract INES DRENJAN^EVI]-PERI]1 IVANA HAR[ANJI DRENJAN^EVI]3 Background and Purpose: Pain is an unpleasant warning sensation of DUBRAVKA IVI]1,3 imminent damage of the tissue or organ, and is a very frequent reason for 1,2 KATARINA [AKI]-ZDRAV^EVI] patients to seek the physician's help. The aim of this paper is to give an over- view on the role of voltage gated sodium channels in nociception and to 1University Josip Juraj Strossmayer, School of Medicine highlight the mechanisms of the action of local anesthetics in inhibiting Department of Physiology and Immunology conduction of ion currents, thus affecting the sense of pain. J. Huttlera 4, 31000 Osijek Materials and Methods: A comprehensive search of the literature with 2Clinical Hospital Center Rebro ili key words: voltage gated sodium channels (VGSC), nociception, local anes- Rebro University Hospital thetics, a, b- subunit isoforms in Medline was conducted. Dept of Anaesthesiology, Reanimatology and Intensive Care Unit Results: VGSC isoforms Nav1.7, Nav1.8, Nav1.9 are highly expressed in Kispati}eva 12, 10000 Zagreb nociceptive neurons and associated with neuropathic pain syndrome. Hu- 3 man studies demonstrated that point mutations of these isoforms, particu- Clinical Hospital Osijek larly Nav1.7 underlie insensitivity or hypersensitivity to pain. The sodium Dept of Anesthesiology, Reanimatology and Intensive Care Unit channel blockers are anesthetics of choice for local analgesia and anesthesia. J. Huttlera 4, 31000 Osijek However, currently available drugs are not considered selective enough and have relatively narrow therapeutic windows, which can limit their useful- Correspondence: ness. Isoform – selective pharmacological blockers or gene therapy ap- Ines Drenjan~evi}-Peri} proaches targeted at down-regulating specific isoforms could show in- University Josip Juraj Strossmayer, School of Medicine creased therapeutic efficacy for treating pain. Department of Physiology and Immunology Conclusions: Due to restrictive appearance of isoforms Nav1.7 and J. Huttlera 4, 31000 Osijek E-mail: [email protected] Nav1.8 in nociceptive neurons, drugs targeting these isoforms would be of great interest, especially in treatment of neuropathic pain syndrome. Key words: voltage-gated sodium channels, nociception, local anaesthetics, a, b- subunit isoforms ain is an unpleasant warning sensation of imminent damage of the Ptissue or organ, and is a very frequent reason for patients seeking the physician's help. Peripheral neurons – nociceptors relay information about noxious stimuli in the periphery to the central nervous system. Activation of both central and peripheral neurons contributes to increased sense of pain. Nociception and altered pain sensitivity occurs due to changing of the activity of ion channels, mainly voltage-gated sodium channels (1). These channels are crucial in clinically relevant analgesics, such as lidocaine (1). Sodium channels are composed of a-subunit, the primary func- tional unit of voltage-gated sodium channel, which could be associated b b b b b Received March 7, 2009. with four different -subunits ( 1, 2, 3 and 4)–(2,3). It is likely that b-subunits play a role in stabilization of the a-subunits in the mem- Ines Drenjan~evi}-Peri} et al. Sodium channels and nociception – the effects of local anesthetics brane and/or localization of the a-subunits to specific of Nav1.8 in human neuropathic pain (CUMMINS 2007). membrane domains (3). In addition several other acces- Studies on transgenic mice indicate the Nav1.9 channel, sory proteins such as calmodulin (4) or annexin II (5) along with Nav1.7 and Nav1.8, may be an important that have been identified may be important modulators contributor to inflammatory pain, but may not be crucial of voltage-gated sodium channels. to neuropathic pain associated with nerve injury (17, Nine distinct voltage-gated sodium channel a-sub- 18). The modulation of a tetrodotoxin (TTX) – resistant units (Nav1.1-1.9) have been cloned from mammals (6). voltage-gated sodium current (such as via Nav1.8) may The predominant sodium channel isoforms in nocicep- underlie inflammation-induced sensitization of nocicep- tive neurons are Nav1.7, Nav1.8, and Nav1.9. (7). Addi- tion of high-threshold primary afferent neurons (19). tionally,Nav1.1, Nav1.3, and Nav1.6, are the very impor- Modulation of TTX-R currents is an endogenous mech- tant voltage-gated sodium channels expressed in anism used to control neuronal excitability, and therapeu- peripheral sensory neurons (1). The role of Nav1.3 tic intervention blocking that current could be effective channels in pain is controversial. Nav1.3 is expressed in in treatment of hyperalgesia and pain (19). For example, a developing neurons, and down-regulated in mature neu- study by Gold et al. showed that u-opioid receptor ago- rons (8), but are re-expressed in a condition of neuropathic nist blocked PGE2-induced modulation of the current. pain and inflammation (9), contributing to the overall Furthermore, because of the restricted distribution of sodium current and the neuronal hyperexcitability ob- TTX-R Na1 currents and the observation that a decrease served in dorsal root ganglion (DRG) sensory neurons in the expression of these currents has little impact on following nerve injury or inflammation. Nav1.6 is the low threshold mechanical transduction, targeting these predominant voltage-gated sodium channel located in currents may lead to the development of a pharmaco- the nodes of Ranvier in both peripheral and central ner- therapy for the treatment of hyperalgesia with fewer side vous system myelinated neurons (10), The role of Nav1.6, effects than currently available drugs (19). if any, in nociception and pain sensations is not clear. Several different types of sodium channel isoforms are Similarly, Nav1.1, although it is expressed in central and preferentially expressed in the peripheral sensory neu- peripheral neurons, has no clear place in nociception. rons, and some of them can be regulated by inflamma- Several recent studies have demonstrated that com- tion or axonal injury (1). For example, Nav1.7 are up- plete loss of function of one specific voltage gated sodium regulated in chronic inflammation (20, 21), suggesting channel, which expresses Nav1.7 isoform, results in com- their role in increased pain sensations associated with in- plete insensitivity to pain (11, 12). On the other hand, flammation. It is known that calmodulin (CaM) can subtle, but significant changes in gating properties of so- modulate Nav1.4 (skeletal muscle) and Nav1.6 (neuro- dium channels caused by point mutations of Nav1.7, can nal) current amplitudes and properties (4). However, a result in increased pain sensations and contribute to the (new) recent study demonstrated that inhibition of so- development of chronic pain syndrome, such as the fa- dium current caused by the CaM inhibitor trifloupera- miliar painful inherited neuropathy, inherited erythro- zine (TFP) is largely independent of the inhibition of melalgia (13, 14). At least 9 distinct point mutations in CaM interaction with Nav subunit of voltage gated so- SCN9A altering the amino acid sequence of Nav1.7 dium channels, but can be attributed to direct interaction channels (13, 14). Mutations in the Nav1.7 channels are of the drug with the sodium channels in a state-depend- identified cause significant hyperpolarizing shifts in the ent manner. The ability of TFP to block Nav1.7 at low channel V1/2 of activation as well as larger ramp currents doses could make it a potential therapeutic regimen for (13, 15). Other Nav1.7 point mutations underlie a sec- regional anesthesia and pain management that would be ond autosomal dominant chronic pain disorder, paroxys- more potent than traditional local anesthetics (7). mal extreme pain disorder (PEPD), characterized by severe The almost exclusive expression patterns of the volt- burning rectal, ocular and submandibular pain sensation age – gated sodium channels that are associated with (16). pain makes them very attractive targets for the develop- Another isoform of voltage-gated sodium channels, ment of novel analgesics. Sodium channels are subject to Nav1.8, is almost exclusively expressed in nociceptive extensive modulation in various pathophysiological con- neurons, and is important in normal pain function. Nav1.8 ditions, such as inflammation or nerve injury as well as is a tetrodotoxin resistant (TTX-R) sodium channel and pharmacologically induced by drugs. For example, te- is highly expressed in small-diameter sensory neurons. trodotoxin (TTX) can block these channels with a high Nav1.8 plays a role in inflammatory pain and the onset degree of selectivity. TTX and other toxins were invalu- of neuropathic pain (1). Nav1.8 also plays a role in hy- able tools in uncovering the functional properties of so- perexcitability in inherited erythromelalgia, together with dium channels and their roles in electro-excitability. Other Nav1.7 isoform (1). More than 50% of C fibers and 10% substances that interact with sodium channels, such as of A fibers express Nav1.8 channels. The expression and local anesthetics (LA), class I antiarrhythmic drugs and biophysical properties of Nav1.8 channels can be modu- anticonvulsants, are now commonly used to treat pain, lated by ongoing nociceptive input (17). Because of the epilepsy, ataxias and other pathophysiological conditions exclusive expression of Nav1.8, a selective Nav1.8 chan- (22, 23). LAs are very effective in preventing the sense of nel inhibitor would be useful in treating inflammatory nociception, by blocking sodium currents through volt- pain and should be able to provide solid data on the role age-gated sodium channels, thus inhibiting the conduc- 216 Period biol, Vol 111, No 2, 2009. Sodium channels and nociception – the effects of local anesthetics Ines Drenjan~evi}-Peri} et al. tion of action potentials in excitable tissues, specifically REFERENCES neural tissues.
Load more

Recommended publications
  • Chapter 11 Local Anesthetics
    Chapter LOCAL ANESTHETICS 11 Kenneth Drasner HISTORY MECHANISMS OF ACTION AND FACTORS ocal anesthesia can be defined as loss of sensation in AFFECTING BLOCK L a discrete region of the body caused by disruption of Nerve Conduction impulse generation or propagation. Local anesthesia can Anesthetic Effect and the Active Form of the be produced by various chemical and physical means. Local Anesthetic However, in routine clinical practice, local anesthesia is Sodium Ion Channel State, Anesthetic produced by a narrow class of compounds, and recovery Binding, and Use-Dependent Block is normally spontaneous, predictable, and complete. Critical Role of pH Lipid Solubility Differential Local Anesthetic Blockade Spread of Local Anesthesia after Injection HISTORY PHARMACOKINETICS Cocaine’s systemic toxicity, its irritant properties when Local Anesthetic Vasoactivity placed topically or around nerves, and its substantial Metabolism potential for physical and psychological dependence gene- Vasoconstrictors rated interest in identification of an alternative local 1 ADVERSE EFFECTS anesthetic. Because cocaine was known to be a benzoic Systemic Toxicity acid ester (Fig. 11-1), developmental strategies focused Allergic Reactions on this class of chemical compounds. Although benzo- caine was identified before the turn of the century, its SPECIFIC LOCAL ANESTHETICS poor water solubility restricted its use to topical anesthe- Amino-Esters sia, for which it still finds some limited application in Amino-Amide Local Anesthetics modern clinical practice. The
    [Show full text]
  • Pharmacology for Regional Anaesthesia
    Sign up to receive ATOTW weekly - email [email protected] PHARMACOLOGY FOR REGIONAL ANAESTHESIA ANAESTHESIA TUTORIAL OF THE WEEK 49 26TH MARCH 2007 Dr J. Hyndman Questions 1) List the factors that determine the duration of a local anaesthetic nerve block. 2) How much more potent is bupivocaine when compared to lidocaine? 3) How does the addition of epinephrine increase the duration of a nerve block? 4) What is the maximum recommended dose of: a) Plain lidocaine? b) Lidocaine with epinephrine 1:200 000? 5) What is the recommended dose of a) Clonidine to be added to local anaesthetic solution? b) Sodium bicarbonate? In this section, I will discuss the pharmacology of local anaesthetic agents and then describe the various additives used with these agents. I will also briefly cover the pharmacology of the other drugs commonly used in regional anaesthesia practice. A great number of drugs are used in regional anaesthesia. I am sure no two anaesthetists use exactly the same combinations of drugs. I will emphasise the drugs I use in my own practice but the reader may select a different range of drugs according to his experience and drug availability. The important point is to use the drugs you are familiar with. For the purposes of this discussion, I am going to concentrate on the following drugs: Local anaesthetic agents Lidocaine Prilocaine Bupivacaine Levobupivacaine Ropivacaine Local anaesthetic additives Epinephrine Clonidine Felypressin Sodium bicarbonate Commonly used drugs Midazolam/Temazepam Fentanyl Ephedrine Phenylephrine Atropine Propofol ATOTW 49 Pharmacology for regional anaesthesia 29/03/2007 Page 1 of 6 Sign up to receive ATOTW weekly - email [email protected] Ketamine EMLA cream Ametop gel Naloxone Flumazenil PHARMACOLOGY OF LOCAL ANAESTHETIC DRUGS History In 1860, cocaine was extracted from the leaves of the Erythroxylon coca bush.
    [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]
  • Comparison of Levobupivacaine and Lidocaine for Post-Operative Analgesia Following Tympanoplasty
    Jemds.com Original Research Article Comparison of Levobupivacaine and Lidocaine for Post-Operative Analgesia Following Tympanoplasty Anagha Yogesh Rajguru1, Mannuru Khaleel Basha2, Yarlagadda Lakshmi Sravya3, Tripti Rai4, Naman Pincha5, Kaenat Ahmed6, Sanket Chandrasekhar Prabhune7 1, 2, 3, 4, 5, 6, 7 Department of Otorhinolaryngology, Krishna Institute of Medical Sciences, Deemed to Be University, Karad, Maharashtra, India. ABSTRACT BACKGROUND A pure s-enantiomer of bupivacaine known as levobupivacaine, is now considered a Corresponding Author: safer alternative for regional anaesthesia than a racemic solution, bupivacaine since Mannuru Khaleel Basha. it is as efficacious as bupivacaine, but with better pharmacokinetics. Levobupivacaine Department of ENT, Krishna Institute of is clinically tolerated well in cases requiring regional anaesthesia with both bolus Medical Sciences University, Karad- 415110, Maharashtra, India. administration and post-operative infusion. There are very few incidence of Adverse E-mail: [email protected] Drug Reactions (ADR) if administration is monitored appropriately as most ADRs are due to mistakes causing systemic exposure of drug. Hypersensitivity reaction to drug DOI: 10.14260/jemds/2020/664 1 or pharmacological effects of anaesthesia though rare can also cause ADRs. Lidocaine (Xylocaine), is available commonly in a 0.5 % or 1 % solution, though How to Cite This Article: several more concentrations are available. It is the most commonly used infiltrative Rajguru AY, Basha MK, Sravya YL, et al. amide anaesthetic. Higher concentrations show no difference in pharmacodynamics Comparison of levobupivacaine and but may increase the risk of toxicity.2 The duration of action may be increased by lidocaine for post-operative analgesia addition of epinephrine. It can be added in concentrations of 1:100,000 or 1:200,000.
    [Show full text]
  • Local Anesthetics in Cosmetic Dermatology
    COSMETIC DERMATOLOGY Local Anesthetics in Cosmetic Dermatology Peter W. Hashim, MD, MHS; John K. Nia, MD; Mark Taliercio, BS; Gary Goldenberg, MD PRACTICE POINTS • The proper delivery of local anesthesia is integral to successful cosmetic interventions. • Regional nerve blocks can provide effective analgesia while reducing the number of injections and preserving the architecture of the cosmetic field. copy Local anesthetics play an important role in cos- LOCAL ANESTHETICS metic dermatology. Techniques using topical and The sensation of pain is carried to the central ner- regional anesthesia provide numerous pain man- vousnot system by unmyelinated C nerve fibers. Local agement options for laser and injection treatments. anesthetics (LAs) act by blocking fast voltage-gated In this article, we review strategies to maximize sodium channels in the cell membrane of the nerve, patient comfort during cosmetic interventions. thereby inhibiting downstream propagation of an Cutis. 2017;99:393-397.Doaction potential and the transmission of painful stimuli.1 The chemical structure of LAs is funda- mental to their mechanism of action and metabo- ocal anesthesia is a central component of suc- lism. Local anesthetics contain a lipophilic aromatic cessful interventions in cosmetic dermatol- group, an intermediate chain, and a hydrophilic Logy. The number of anesthetic medications amine group. Broadly, agents are classified as amides and administration techniques has grown in recent or esters depending on the chemical group attached years as outpatient cosmetic procedures continue to the intermediate chain.2 Amides (eg, lidocaine, to expand. Pain is a commonCUTIS barrier to cosmetic bupivacaine, articaine, mepivacaine, prilocaine, procedures, and alleviating the fear of painful inter- levobupivacaine) are metabolized by the hepatic sys- ventions is critical to patient satisfaction and future tem; esters (eg, procaine, proparacaine, benzocaine, visits.
    [Show full text]
  • Treatment for Acute Pain: an Evidence Map Technical Brief Number 33
    Technical Brief Number 33 R Treatment for Acute Pain: An Evidence Map Technical Brief Number 33 Treatment for Acute Pain: An Evidence Map Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov Contract No. 290-2015-0000-81 Prepared by: Minnesota Evidence-based Practice Center Minneapolis, MN Investigators: Michelle Brasure, Ph.D., M.S.P.H., M.L.I.S. Victoria A. Nelson, M.Sc. Shellina Scheiner, PharmD, B.C.G.P. Mary L. Forte, Ph.D., D.C. Mary Butler, Ph.D., M.B.A. Sanket Nagarkar, D.D.S., M.P.H. Jayati Saha, Ph.D. Timothy J. Wilt, M.D., M.P.H. AHRQ Publication No. 19(20)-EHC022-EF October 2019 Key Messages Purpose of review The purpose of this evidence map is to provide a high-level overview of the current guidelines and systematic reviews on pharmacologic and nonpharmacologic treatments for acute pain. We map the evidence for several acute pain conditions including postoperative pain, dental pain, neck pain, back pain, renal colic, acute migraine, and sickle cell crisis. Improved understanding of the interventions studied for each of these acute pain conditions will provide insight on which topics are ready for comprehensive comparative effectiveness review. Key messages • Few systematic reviews provide a comprehensive rigorous assessment of all potential interventions, including nondrug interventions, to treat pain attributable to each acute pain condition. Acute pain conditions that may need a comprehensive systematic review or overview of systematic reviews include postoperative postdischarge pain, acute back pain, acute neck pain, renal colic, and acute migraine.
    [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]
  • 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]
  • Anesthetic Agents: General and Local Anesthetics T IMOTHY J
    Chapter 16 Anesthetic Agents: General and Local Anesthetics T IMOTHY J. MAHER Drugs Covered in This Chapter Inhaled general anesthetics • Propofol • Levobupivacaine • Ether • Fospropofol • Lidocaine • Halothane • Thiopental • Prilocaine • Desflurane Local anesthetics • Procaine • Ropivacaine • Enflurane • Articaine • Tetracaine • Isoflurane • Benzocaine • Methoxyflurane • Bupivacaine • Sevoflurane • Chloroprocaine • Nitrous oxide • Cocaine Intravenous general anesthetics • Dibucaine • Etomidate • Dyclonine • Ketamine • Mepivacaine Abbreviations BTX, batrachotoxin GABA, g-aminobutyric acid NO, nitric oxide CNS, central nervous system HBr, hydrobromic acid NMDA, N-methyl-D-aspartate COCl2, phosgene HCl, hydrochloric acid PABA, p-aminobenzoic acid EEG, electroencephalograph MAC, minimum alveolar concentration PCP, phencyclidine EMLA, Eutectic Mixture of a Local Na/K-ATPase, sodium-potassium STX, saxitoxin Anesthetic adenosine triphosphatase TTX, tetrodotoxin 508 LLemke_Chap16.inddemke_Chap16.indd 550808 112/9/20112/9/2011 44:14:08:14:08 AAMM CHAPTER 16 / ANESTHETIC AGENTS: GENERAL AND LOCAL ANESTHETICS 509 SCENARIO Paul Arpino, R.Ph. CDL is a 70-year-old obese man scheduled for carpal tunnel sur- During the preoperative assessment before the scheduled day of gery. A review of his medical file indicates a history of obstruc- surgery, the team discovers that CDL has an undefined allergy tive sleep apnea and benign prostatic hypertrophy (BPH). CDL to procaine (Novocain) and that he experienced severe blistering sleeps with a continuous positive pressure airway device and his after a dental procedure many years ago and was told he cannot BPH is treated with tamsulosin, 0.4 mg daily. Given that patients receive “drugs like Novocain again.” with sleep apnea are at high risk for respiratory depression, the clinical team decides that a peripheral nerve block would be a (The reader is directed to the clinical solution and chemical analy- better alternative to both neuraxial and general anesthesia.
    [Show full text]
  • Uia-14-LEVOBUPIVACAINE.Pdf
    Update in Anaesthesia 23 LEVOBUPIVACAINE A long acting local anaesthetic, with less cardiac and neurotoxicity Manuel Galindo Arias, MD, Professor of Anesthesiology Fundacion Univarsitaria San Martin, Bogota, Colombia Introduction The property of isomerism occurs when two or more compounds An intermediate chain have the same molecular composition, but a different structure An amino group which often results in different properties. There are two types of The benzene ring is very soluble in lipids. isomerism - structural and stereoisomersim. Structural isomerism means that the compounds have the same molecular formula, but a different chemical structure. This may Carbon chain linkage result in the compounds having similar actions like the anaesthetic volatile agents isoflurane and enflurane or different actions like R2 promazine and promethazine. N Stereoisomerism describes those compounds which have the R3 same molecular formula and chemical structure, but the atoms are Aromatic head Amino tail orientated in a different direction. There are two isomers, each a lipophilic hydrophilic mirror image of the other, called enantiomers. They are also called optical isomers because they rotate the plane of polarised light Figure 1. The three components of a local anaesthetic - benzene either to the right referred to as +, dextro, d or D isomer, or to the ring (aromatic head), intermediate chain (carbon chain linkage), left referred to as -, laevo (levo), l or L isomer. More recently this amino tail (tertiary amine) classification has been replaced by the R-/S- notation, which describes the arrangement of the molecules around the chiral The intermediate portion, a bridge between the other two, can centre (R is for rectus the Latin for right, and S for sinister, left).
    [Show full text]
  • Sodium Channel Na Channels; Na+ Channels
    Sodium Channel Na channels; Na+ channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change (Voltage-gated, voltage-sensitive, or voltage-dependent sodium channel also called VGSCs or Nav channel) or a binding of a substance (a ligand) to the channel (ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. Voltage-gated Na+ channels can exist in any of three distinct states: deactivated (closed), activated (open), or inactivated (closed). Ligand-gated sodium channels are activated by binding of a ligand instead of a change in membrane potential. www.MedChemExpress.com 1 Sodium Channel Inhibitors, Agonists, Antagonists, Activators & Modulators (+)-Kavain (-)-Sparteine sulfate pentahydrate Cat. No.: HY-B1671 ((-)-Lupinidine sulfate pentahydrate) Cat. No.: HY-B1304 (+)-Kavain, a main kavalactone extracted from Piper (-)-Sparteine sulfate pentahydrate ((-)-Lupinidine methysticum, has anticonvulsive properties, sulfate pentahydrate) is a class 1a antiarrhythmic attenuating vascular smooth muscle contraction agent and a sodium channel blocker. It is an through interactions with voltage-dependent Na+ alkaloid, can chelate the bivalents calcium and and Ca2+ channels. magnesium. Purity: 99.98% Purity: ≥98.0% Clinical Data: Launched Clinical Data: Launched Size: 10 mM × 1 mL, 5 mg, 10 mg Size: 10 mM × 1 mL, 50 mg (Rac)-AMG8379 20(S)-Ginsenoside Rg3 ((Rac)-AMG8380) Cat. No.: HY-108425B (20(S)-Propanaxadiol; S-ginsenoside Rg3) Cat.
    [Show full text]
  • Rational Design, Synthesis, and In-Silico Evaluation of Homologous Local Anesthetic Compounds As TASK-1 Channel Blockers †
    Proceeding Paper Rational Design, Synthesis, and In-Silico Evaluation of Homologous Local Anesthetic Compounds as TASK-1 Channel Blockers † Lorena Camargo-Ayala 1, Luis Prent-Peñaloza 2, Mauricio Bedoya 3, Margarita Gutiérrez 2,* and Wendy González 3,4,* 1 Doctorate in Sciences Mention in Research and Development of Bioactive Products, Institute of Chemistry of Natural Resources, Organic Synthesis Laboratory and Biological Activity (LSO-Act-Bio), University of Talca, Casilla 747, Talca 3460000, Chile; [email protected] 2 Organic Synthesis Laboratory and Biological Activity (LSO-Act-Bio), Institute of Chemistry of Natural Resources, University of Talca, Casilla 747, Talca 3460000, Chile; [email protected] 3 Center for Bioinformatics and Molecular Simulations (CBSM), Universidad de Talca, Casilla 747, Talca 3460000, Chile; [email protected] 4 Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD). Universidad de Talca, Casilla 747, Talca 3460000, Chile * Correspondence: [email protected] (M.G.); [email protected] (W.G.) † Presented at the 24th International Electronic Conference on Synthetic Organic Chemistry, 15 November–15 December 2020; Available online: https://ecsoc-24.sciforum.net/. Abstract: Advances in different technological and scientific fields have led to the development of tools that allow the design of drugs in a rational way, using defined therapeutic targets, and through Citation: Camargo-Ayala, L.; simulations that offer a molecular view of the ligand–receptor interactions, giving precise infor-
    [Show full text]