DOCSLIB.ORG

The New Relaxants: Are They Worth It? David 1L Bevan MB MRCP FRCA

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The New Relaxants: Are They Worth It? David 1L Bevan MB MRCP FRCA R88 REFRESHER COURSE OUTLINE The new relaxants: are they worth it? David 1L Bevan MB MRCP FRCA UCH of the current neuromuscular and seems to be nearly as rapid as succinylcholine s drug development prOgrams are con- (Table II). The quick onset of succinylcholine is relat- cerned with the search for a replace- ed to its prompt metabolism and plasma clearance. M ment for the rapid onset, short When metabolism is impaired, i.e. in the presence of duration succinylcholine. This has led to re-evaluation atypical cholinesterase, the onset is also slower. 4 and re-definition of muscle relaxants by the FDA Similarly, the onset of action of mivacurium is consid- according to their onset and duration of action in a erably increased in the presence of atypical plasma dose of 2 x ED9s (Table I). ~ It is unlikely that any neu- cholineseterase, s romuscular blocking drug will be introduced into clin- After iv administration of NMBDs, peak plasma ical practice unless it is almost free of cardiovascular concentrations are achieved almost immediately. activity. The purpose of this presentation is to describe However, when subparalyzing doses are given, maxi- factors leading to the development of new drugs and mum block may not be achieved for 5-7 min. This to review the pharmacology of the recently introduced delay has led to the concept that the neuromuscular intermediate-acting neuromuscular blocking drugs - junction lies within a compartment (effect compart- rocuronium, mivacurium, cisatracurium and rapacuro- ment) separate from plasma or central compartment, nium. One of the problems in the development of the where drug effect is related to concentration. Access "Ideal Relaxant" is cost. An attempt will be made to from the central compartment to this effect compart- put the price of muscle relaxants into perspective. ment is controlled by a rate constant, k o.6 Onset of action is inversely proportional to k~o - drugs with Onset of Action higher kr have a more rapid onset (Table III). 7 Onset depends on the arrival at the receptor of suffi- The time to maximal block is almost independent cient molecules either to produce depolarization of of dose if < 100% block is attained. In doses producing the endplate (depolarizing NMBDs) or to prevent total paralysis, the latter is achieved before the maxi- acetylcholine from reaching enough receptors to cause mal effect at the junction. The time to disappearance neuromuscular transmission (non-depolarizing of twitch decreases with increasing dose. Clinicians NMBDs). Speed of onset is affected mainly by the rate using non-depolarizing drugs to facilitate tracheal of delivery of the drug to the junction. It is modified intubation may use larger doses than necessary to by drug potency and its metabolism. The onset of accelerate the production of good/excellent intubat- non-depolarizing relaxants is inversely proportional to ing conditions. their potency. 2 Thus, of the five recently introduced relaxants - doxacurium, mivacurium, pipecuronium, Pharmacology of the new drugs rocuronium, cisatracurium, the most potent, dox- acurium (EDs0 0.015 mg-kgq) has the slowest onset Rocuronium (10 - 15 min) and the least potent, roccuronium Rocuronium was developed from a series of monoqua- (EDs0 0.15 mg.kg-Z), the most rapid (1.5 - 2.5 min) ternary aminosteroids because of its rapid onset of TABLE I FDA definitions of neuromuscular blocking drugs according to onset and clinical duration (time to T,s) after 2 x ED9s dose (After FDA, 1995q) ONSET- rain CLINICAL DURATION- rain Ultra-rapid Rapid Inter-mediate Slow Ultra-short Short Inter-mediate Long <1 1 - 2 2 - 4 ~ 4 < 4 4- 20 20-50 >50 From the Department of Anesthesia, Vancouver Hospital & Health Sciences Centre, 910 West 10th Avenue, Vancouver, B.C. V5Z 4E3 Canada. CAN J ANESTH 1999 / 46:5 / pp R88-R94 Bevan: THE NEW RELAXANTS R89 action and absence of cardiovascular side effects in ani- tram (57.4%), cis-trans (36.2%) and cis-cis (6.4%) of mals. In humans, it is about one sixth as potent as which the last is pharmacologically inactive. It is a vecuronium and has a more rapid onset of action, potent, non- depolarizing relaxant (ED9s: 60-80 although this is slower than after succinylcholine.8 }ag.kg-1 in adults 12 and 90-100/ag.kg -1 in children, is Nevertheless, tracheal intubating conditions 60 sec after (Table II). The onset of action is not as rapid as suc- rocuronium (0.6 mg.kg-1 [2 x ED9s]) were similar to cinylcholine but recovery is quick due to metabolism those produced by succinylcholine (1 mg.kg-1 x by plasma cholinesterase. The rate of recovery is twice EDgs]). 9 Optimal intubating conditions after rocuronl- as rapid as that from vecuronium or atracufium and is um, as for other neuromuscular relaxants, occur before similar whether administered by bolus or by continu- maximal block is obtained in the peripheral thumb mus- ous infusion to maintain the neuromuscular block. des probably because the laryngeal muscles have an ear- Recovery is so rapid that acceleration by anti- lier onset of effect, l~ When given in large doses, 1.2 cholinesterases is very small so that routine reversal mg.kg-1, intubation conditions 30 sec after administra- may not be necessary. However, if patients are trans- tion were similar to those after 1.5 mg.kg-1 succinyl- ferred to PACU soon after the end of surgery, they choline although the clinical duration was prolonged to may exhibit residual weakness if reversal agents are 46 min. n Apart from its more rapid onset of action, the avoided, i4 Edrophonium is preferred to neostigmine pharmacodynamic behaviour of rocuronium is similar as the latter inhibits plasma cholinesterase and may to vecuronium in duration, recovery and reversal. It is prolong the block. Recovery is considerably pro- potentiated by inhalational anesthetics and the onset longed (> six hours) in patients with atypical plasma and duration of action are prolonged in the elderly. cholinesterase 27 even after small test doses of 0.014 Rocuronium is excreted in the urine and its elimination mg.kg-i,s and the infusion rate required to maintain is decreased in patients with renal failure. constant block is correlated with the plasma cholinesterase activity. Mivacurium is rapidly cleared Mivacurium from the plasma but more slowly in patients undergo- Mivacurium is a bisquaternary benzylisoquinoline ing hepatic transplantation due to the decreased plas- compound consisting of three stereoisomers: trans- ma cholinesterase synthesis. Mivacurium is potentiated by isoflurane and by enflurane. If mivac- urium is given rapidly, over 10-15 sec, it is followed by TABLE II Typicalneuromuscular activity of non-depolarizing a brief, < 5 min, decrease in systolic blood pressure, blocking drugs. cutaneous erythema and histamine release. Is Usually, Potency (ED9s), Onset to maximum effect,25-75% Recovery. the hypotension is mild but in some patients may be Index (RI), and time to 25% T l recovery(Tg0) after 2 x EDgs severe enough to require treatment with vasopressors. dose in adults. EDgs lag.kg-l Onset 25-75% Cisatracurium Recovery Recovery 25% T 1 Atracurium consists of 10 stereoisomers: cisatracurium MAn index - min min Rapacuronium 750 1 - 1.5 10- 15 12 - 20 is one and comprises approximately 15% of the mix- dTC 500 5 - 6 25 - 35 70 90 rare. It is approximately four times as potent as Atracurium 200 5 - 6 10 - 15 25 35 atracurium (Table II) and has been developed because Cisatracurium 50 7 - 8 8 - 9 25 3O it does not release histamine. There are no clinical car- Doxacurium 25 10- 14 30- 50 80 100 diovascular effects in doses exceeding the clinical range Metocurine 280 4 - 6 30 - 40 8O 9O Mivacurium 80 - 150 2 - 3 10 - 15 15 20 and it does not produce cutaneous flushing. 16 It has a Pancuronium 60 4 - 5 25 - 30 50 60 slightly slower onset than atracurium, probably a result Pipecuronium 60 5 - 6 30 - 40 80 90 of its increased potency, but a slightly more rapid Rocuronium 300 2 - 3 10 - 15 25 35 recovery. It is metabolized, like atracurium, by Vecuronium 80 4 - 5 10 - 15 25 35 Hoffmann clearance. However, only 23% of the elimi- nation is organ dependent compared with 61% for atracurium. Cisatracurium, like atracuri ,um, demon- TABLE III Relationship between onset of action and kco.Q strates considerable synergism with aminosteroids such keo (min -~) as rocuronium. 17 Cisatracurium has few advantages adductor pollicis laryngeal adductors over atracurium other than the absence of cardiovascu- Rapacuronium 0.41 0.63 lar effects and histamine release. Its current popularity Rocuronium 0.17 0.26 in North America is more a reflection of attractive pric- Vecuronium 0.12 0.18 ing than superior pharmacological activity. R90 CANADIAN JOURNAL OF ANESTHESIA TABLE IV Intubation 90 sec after succinylcholine or mivacuriumw Increasing the dose of any non-depolarizing relaxant Intubation TOF accelerates the appearance of maximum block and @ 90 sec count acceptable intubating conditions but at the price of Excellent Good 0 4 considerable delay in recovery. Succinylcholine 1 mg.kg-l: dTc 50 pg.kg-1 - 3 min 97 81 10 53 43 Divided doses - ~priming" ~timing" Mivacurium 0.25 mg.kg-1 divided: Although onset can be accelerated with small "prim- 0.15 & 0.1 mg.kg-1 @30 sec 91 51 38 2 88 ing" doses of non-depolarizing relaxant three minutes before the main dose, the effect is small. Priming car- ties the risk of aspiration and difficulty in swallowing, and visual disturbances are uncomfortable for the patient. The practice has largely been superseded by Rapaeuronium the introduction of rocuronium. The latest in the aminosteroid series of neuromuscular Attempts to make use of the rapid recovery of relaxants is rapacuronium and it is currently undergo- mivacurium have included administration of 0.15 and ing pre-clinical evaluation.
Load more

Recommended publications
  • (12) United States Patent (10) Patent N0.: US 8,343,962 B2 Kisak Et Al
    US008343962B2 (12) United States Patent (10) Patent N0.: US 8,343,962 B2 Kisak et al. (45) Date of Patent: *Jan. 1, 2013 (54) TOPICAL FORMULATION (58) Field of Classi?cation Search ............. .. 514/226.5, 514/334, 420, 557, 567 (75) Inventors: Edward T. Kisak, San Diego, CA (US); See application ?le fOr Complete Search history. John M. NeWsam, La Jolla, CA (US); _ Dominic King-Smith, San Diego, CA (56) References C‘ted (US); Pankaj Karande, Troy, NY (US); Samir Mitragotri, Goleta, CA (US) US' PATENT DOCUMENTS 5,602,183 A 2/1997 Martin et al. (73) Assignee: NuvoResearchOntano (CA) Inc., Mississagua, 6,328,979 2B1 12/2001 Yamashita et a1. 7,001,592 B1 2/2006 Traynor et a1. ( * ) Notice: Subject to any disclaimer, the term of this 7,795,309 B2 9/2010 Kisak eta1~ patent is extended or adjusted under 35 2002/0064524 A1 5/2002 Cevc U.S.C. 154(b) by 212 days. FOREIGN PATENT DOCUMENTS This patent is subject to a terminal dis- W0 WO 2005/009510 2/2005 claimer- OTHER PUBLICATIONS (21) APPI' NO‘, 12/848,792 International Search Report issued on Aug. 8, 2008 in application No. PCT/lB2007/0l983 (corresponding to US 7,795,309). _ Notice ofAlloWance issued on Apr. 29, 2010 by the Examiner in US. (22) Med Aug- 2’ 2010 Appl. No. 12/281,561 (US 7,795,309). _ _ _ Of?ce Action issued on Dec. 30, 2009 by the Examiner in US. Appl. (65) Prior Publication Data No, 12/281,561 (Us 7,795,309), Us 2011/0028460 A1 Feb‘ 3’ 2011 Primary Examiner * Raymond Henley, 111 Related U 5 Application Data (74) Attorney, Agent, or Firm * Foley & Lardner LLP (63) Continuation-in-part of application No.
    [Show full text]
  • Factors That Affect the Onset of Action of Non-Depolarizing Neuromuscular
    Review Article pISSN 2005-6419 • eISSN 2005-7563 KJA Factors that affect the onset Korean Journal of Anesthesiology of action of non-depolarizing neuromuscular blocking agents Yong Byum Kim1, Tae-Yun Sung2, and Hong Seuk Yang3 Department of Anesthesiology and Pain Medicine, 1Gil Medical Center, Gachon University College of Medicine, Incheon, 2Konyang University Hospital, Konyang University College of Medicine, Daejeon, 3Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric an- esthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neu- romuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcho- line (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractil- ity, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue.
    [Show full text]
  • The New Neuromuscular Blocking Agents: Do They Offer Any Advantages?
    British Journal of Anaesthesia 87 (6): 912±25 (2001) REVIEW ARTICLE The new neuromuscular blocking agents: do they offer any advantages? E. W. Moore* and J. M. Hunter² University Department of Anaesthesia, University Clinical Department, The Duncan Building, Daulby Street, Liverpool L69 3GA, UK *Corresponding author Br J Anaesth 2001; 87: 912±25 Keywords: neuromuscular block, aminosteroids; neuromuscular block, benzylisoquinoliniums; neuromuscular block, tropinyl diesters; neuromuscular block, tetrahydroisoquinolinium chlorofumarates The introduction of neuromuscular blocking drugs in 1942 animal and human studies. The bis-quaternary ammonium marked a new era in anaesthetic and surgical practice. The salt of bistropinyl diester G-1-64 is the most studied of the anaesthetist was enabled to provide respiratory support tropinyl diester group51 although investigations in humans during long and complex surgery whilst the surgeon was have yet to be reported (Fig. 3). allowed access to body cavities without voluntary or re¯ex muscle movement. In recent years, a generation of anaesthetists trained since atracurium and vecuronium GW280430A became available in 1982, have taken for granted the The structure of this mixed-tetrahydroisoquinolinium speed of onset, shorter and more predictable duration of chlorofumarate is given in Figure 2. The similarity in action, and lack of cardiovascular side-effects that these structure to mivacurium is demonstrated. The presence of drugs have in comparison with their predecessors.56 58 59 three methyl groups between the quaternary nitrogen and The latest generation of neuromuscular blocking drugs aims oxygen atom at each end of the carbon chain suggests that, to provide even greater advantages: as rapid an onset and similar to mivacurium, this compound will not undergo offset as succinylcholine; disposition independent of organ Hofmann degradation.
    [Show full text]
  • Compounds and Bulk Powders
    UnitedHealthcare Pharmacy Clinical Pharmacy Programs Program Number 2021 P 1014-13 Program Prior Authorization/Notification Medication Compounds and Bulk Powders P&T Approval Date 1/2012, 02/2013, 04/2013, 07/2013, 10/2013, 11/2013, 2/2014, 4/2014, 10/2014, 4/2015, 7/2015, 4/2016, 10/2016, 10/2017, 10/2018, 10/2019, 5/2020, 1/2021 Effective Date 4/1/2021; Oxford only: 4/1/2021 1. Background: Compounded medications can provide a unique route of delivery for certain patient- specific conditions and administration requirements. Compounded medications should be produced for a single individual and not produced on a large scale. A dollar threshold may be used to identify compounds which require Notification and must meet the criteria below in order to be covered. Drugs included in the compound must be a covered product. Claims for patients under the age of 6 will process automatically for First-Lansoprazole, First-Omeprazole, and Omeprazole + Syrspend SF compounding kits. 2. Coverage Criteriaa: A. Authorization for compounds and bulk powders will be approved based on all of the following criteria (includes bulk powders requested as a single ingredient such as bulk powder formulations of cholestyramine or nystatin when the powder formulation requested is not the commercially available FDA approved product): 1. The requested drug component is a covered medication -AND- 2. The requested drug component is to be administered for an FDA-approved indication -AND- 3. If a drug included in the compound requires prior authorization and/or step therapy, all drug specific clinical criteria must also be met -AND- 4.
    [Show full text]
  • Compounds and Bulk Powders
    Clinical Pharmacy Program Guidelines for Compounds and Bulk Powders Program Prior Authorization Medication Compounds and Bulk Powders Markets in Scope Arizona, Hawaii, Maryland, Nevada, New Jersey, New York, New York EPP, Pennsylvania- CHIP, Rhode Island, California, South Carolina Issue Date 7/2013 Pharmacy and 5/2020 Therapeutics Approval Date Effective Date 7/2020 1. Background: Compounded medications can provide a unique route of delivery for certain patient-specific conditions and administration requirements. Compounded medications should be produced for a single individual and not produced on a large scale. A dollar threshold may be used to identify compounds which require prior authorization and must meet the criteria below in order to be approved. Drugs included in the compound must be a covered product. 2. Coverage Criteria: A. Authorization for compounds and bulk powders will be approved based on all of the following criteria (includes bulk powders requested as a single ingredient when the powder formulation requested is not the commercially available FDA approved product): 1. The requested drug component is a covered medication -AND- 2. One of the following: a. The requested drug component is to be administered for an FDA- approved indication -OR- b. The use of this drug is supported by information from the appropriate compendia of current literature* -AND- Confidential and Proprietary, © 2020 UnitedHealthcare Services, Inc. 3. If a drug included in the compound requires prior authorization and/or step therapy, all drug specific clinical criteria must also be met -AND- 4. If the drug component is no longer available commercially it must not have been withdrawn for safety reasons -AND- 5.
    [Show full text]
  • RAPLON (Rapacuronium Bromide) for Injection, Administered at 25% Recovery of Control T1
    ™ RAPLON (rapacuronium bromide) for Injection Organon Inc. West Orange, NJ 07052 5310167 8/99 14 ReferenceRevision ID: 12867722 1 THIS DRUG SHOULD BE ADMINISTERED BY ADEQUATELY-TRAINED INDIVIDUALS FAMILIAR WITH ITS ACTIONS, CHARACTERISTICS AND HAZARDS. DESCRIPTION RAPLON™ (rapacuronium bromide) for Injection is a nondepolarizing neuromuscular blocking agent. Its chemical name is 1-[(2β,3α,5α,16β,17β)-3-(Acetyloxy)-17-(1-oxopropoxy)-2-(1­ piperidinyl)androstan-16-yl]-1-(2-propenyl) piperidinium bromide. The chemical formula of the bromide salt is C37H61BrN2O4 with a molecular weight of 677.78. The structural formula is: O O N+ H N H H O H – O Br ReferenceRevision ID: 12867722 2 RAPLON™ is a synthetic steroid molecule with a mono-quaternary structure in the form of a bromide salt. This chemical structure has a basic steroid framework similar to other neuromuscular blocking agents like vecuronium, pancuronium, rocuronium, and pipecuronium. Rapacuronium bromide is distinguished as being a propenyl bromide ammonium salt with a 17-hydroxy propionate carboxyester that has the same basic steroid backbone as the rest of the family of steroid neuromuscular blockers. RAPLON™ is supplied as a sterile, nonpyrogenic lyophilized cake in 5 mL and 10 mL vials. Each 5 mL vial contains 100 mg of rapacuronium bromide base, 35.8 mg of citric acid anhydrous, 7.5 mg of sodium phosphate dibasic anhydrous, 137.5 mg of mannitol, and sodium hydroxide and/or phosphoric acid to buffer and adjust the pH. When the 5 mL vial is reconstituted to a volume of 5 mL with sterile water for injection or bacteriostatic water for injection, an isotonic preparation for intravenous injection is obtained at a pH of 4.0 with a concentration of 20 mg of rapacuronium bromide base per mL.
    [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]
  • Methylnaltrexone Bromide
    含溴药物品种资料汇编 药智数据 编纂 简要说明： 本资料汇编由正文 100 页，附件 112 页构成。正文部分汇总了全部含溴药物， 包括曾经研究过、曾经上市应用、目前尚在应用以及目前尚在研的含溴药物，计 259 种。对于其中 15 种重点药物，在附件部分给出其合成方法、研发背景、药理、 药代、安全性、临床试验等方面详细的研究结果。 著录体例： 1，【别 名】，包括药物的试验编号、商标名称及其英文异名； 2，【名称来源】，指的是 WHO DI 网站上公布的推荐 INN 表和建议 INN 表， 例如，pINN-073,1995 rINN-036,1996 表示该 INN 名称来自于 1995 年的推荐 INN 第 73 表和 1996 年的建议 INN 第 36 表。 3，【中文 CADN】，指的是经国家药典委员会确定的中国药品通用名称，名 后注(97)，表示该名称见于《中国药品通用名称》（1997 年版）；名后注(GB4)， 表示该名称见于《国家药品标准工作手册》（第四版）。 4，【建议 CADN】，指的是第 3 条中所述两书均未收录，由《药智数据》根据 INN 和 CADN 命名规律而自拟的药品中文译名。 【英文 INN】acebrochol 【别 名】acebrocol 【名称来源】pINN-001,1953 rINN-001,1955 【中文 CADN】醋溴考尔 (97) 【建议 CADN】 【化学表述】Cholestan-3-ol, 5,6-dibromo-, acetate, (3β,5α,6β)- 【CA 登记号】[514-50-1] 【分 子 式】C29H48Br2O2 【结 构 式】 【品种类别】神经系统>催眠镇静药>其它 【英文 INN】azamethonium bromide 【别 名】 【名称来源】pINN-001,1953 rINN-001,1955 【中文 CADN】阿扎溴铵(GB4) 【建议 CADN】 【化学表述】3-methyl-3-azapentane-1,5-bis(ethyl dimethyl ammonium) bromide 【CA 登记号】[306-53-6] 【分 子 式】C13H33Br2N3 【结 构 式】 【品种类别】心血管系统>抗高血压药>双季铵盐类 【英文 INN】benzpyrinium bromide 【别 名】 【名称来源】pINN-001,1953 rINN-001,1955 【中文 CADN】苄吡溴铵(GB4) 【建议 CADN】 【化学表述】Pyridinium, 1-benzyl-3-(dimethylcarbamyloxy)-, bromide 【CA 登记号】[587-46-2] 【分 子 式】C15H17BrN2O2 【结 构 式】 【品种类别】拟胆碱药 英文 INN】bibrocathol 【别 名】Noviform 【名称来源】pINN-001,1953 rINN-001,1955 【中文 CADN】铋溴酚(97) 【建议 CADN】 【化学表述】4,5,6,7-Tetrabromo-2-hydroxy-1,3,2-Benzodioxabismole 【CA 登记号】[6915-57-7] 【分 子 式】C6HBiBr4O3 【结 构 式】 【品种类别】眼科用药>消毒防腐药>其它 【英文 INN】carbromal 【别 名】 【名称来源】pINN-001,1953 rINN-001,1955 【中文 CADN】卡溴脲(97) 【建议 CADN】 【化学表述】Butanamide, N-(aminocarbonyl)-2-bromo-2-ethyl- 【CA 登记号】[77-65-6]
    [Show full text]
  • Clinical Pharmacology of Rocuronium Bromid Clinical
    CLINICAL PHARMACOLOGY OF ROCURONIUM BROMIDE Jerrold H. Levy, MD Professor of Anesthesiology Emory University School of Medicine Division of Cardiothoracic Anesthesiology and Critical Care Emory Healthcare Atlanta, Georgia HISTORICAL PERSPECTIVES OF NEUROMUSCULAR BLOCKING AGENTS INTRODUCTION OF NEW DRUGS 1494 - 1942 Curare 1947 - 1951 Succinylcholine chloride, Gallamine, Metocurine, Decamethonium 1960’s Alcuronium 1970’s Pancuronium bromide, Fazadinium 1980’s Vecuronium bromide, Atracurium besylate 1990 Pipecuronium bromide 1991 Doxacurium chloride 1992 Mivacurium chloride 1994 Rocuronium bromide 1999 Rapacuronium bromide STRUCTURAL CLASSES OF NONDEPOL.ARIZING RELAXANTS • Steroids: Rocuronium bromide, Vecuronium bromide, Pancuronium bromide, Pipecuronium bromide • Naturally occurring benzylisoquinolones: curare, metocurine • Benzylisoquinoliniums: Atracurium besylate, Mivacurium chloride, Doxacurium chloride THE IDEAL RELAXANT • Nondepolarizing • Rapid onset • Dose-dependent duration • No side-effects • Elimination independent of organ function • No active or toxic metabolites ONSET OF PARALYSIS IS AFFECTED BY: • Dose (relative to ED95) • Potency (number of molecules) • Keo (chemistry/blood flow) • Clearance • Age PHARMACODYNAMICS OF ROCURONIUM BROMIDE ONSET OF ROCURONIUM BROMIDE Onset: rapid to intermediate (dose dependent) TRACHEAL INTUBATION Pre-Medication Meperidine 1 mg/kg Atropine 0.01 mg/kg Induction Propofol to 2.5 mg/kg Alfentanil to 0.25 mg/kg Rocuronium bromide 0.6 mg/kg OR Succinylcholine chloride 1 mg/kg Intubation 60 sec.
    [Show full text]
  • Chapter 13 – Pharmacology of Muscle Relaxants and Their Antagonists Mohamed Naguib, Cynthia A
    Chapter 13 – Pharmacology of Muscle Relaxants and Their Antagonists Mohamed Naguib, Cynthia A. Lien HISTORY AND CLINICAL USE In 1942 Griffith and Johnson[1] suggested that d-tubocurarine (dTc) is a safe drug to use during surgery to provide skeletal muscle relaxation. One year later, Cullen[2] described its use in 131 patients who had received general anesthesia for their surgery. In 1954, Beecher and Todd[3] reported a sixfold increase in mortality in patients receiving dTc versus those who had not received a relaxant. The increased mortality was due to a general lack of understanding of the pharmacology of neuromuscular blockers and their antagonism. The impact of residual neuromuscular blockade postoperatively was not appreciated, guidelines for monitoring muscle strength had not been established, and the importance of pharmacologically antagonizing residual blockade was not understood. Since then, the understanding of neuromuscular blocker pharmacology has improved, and relaxants have become an important component of many anesthetics and have facilitated the growth of surgery into new areas with the use of innovative techniques.[4] Succinylcholine, introduced by Thesleff[5] and by Foldes and colleagues in 1952,[4] changed anesthetic practice drastically. Its rapid onset of effect and ultrashort duration of action allowed for rapid tracheal intubation. In 1967, Baird and Reid first reported on clinical administration of the synthetic aminosteroid pancuronium.[6] Though similar to dTc, in terms of its duration of action, this compound had an improved cardiovascular side effect profile. It lacked ganglionic-blocking and histamine-releasing properties and was mildly vagolytic. The resulting increases in heart rate and blood pressure were considered significant improvements over its predecessors.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,969,508 B2 Dugger, III (45) Date of Patent: Nov
    USOO6969.508B2 (12) United States Patent (10) Patent No.: US 6,969,508 B2 Dugger, III (45) Date of Patent: Nov. 29, 2005 (54) BUCCAL POLAR AND NON-POLAR SPRAY 6,071,539 A 6/2000 Robinson et al. ........... 424/466 OR CAPSULE CONTAINING DRUGS FOR 6,110,486 A 8/2000 Dugger, III ................. 424/435 TREATING PAIN 6,299,900 B1 10/2001 Reed et al. 6,458.842 B1 10/2002 Dickinson et al. (75) Inventor: Hy A. Dugger, III, Flemington, NJ 6,706.2556,676.931 B2 3/20041/2004 Dugger,Dickinson III. et al. ( ) 2003/0077227 A1 4/2003 Dugger 2003/0082107 A1 5/2003 Dugger (73) Assignee: NovalDel Pharma, Inc., Flemington, NJ 2003/0211047 A1 * 11/2003 Dugger, III .................. 424/45 (US) 2004/0120895 A1 * 6/2004 Dugger, III .................. 424/44 2004/0141923 A1 7/2004 Mohammed (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 FOREIGN PATENT DOCUMENTS U.S.C. 154(b) by 0 days. DE 3.338978 5/1984 DE 3246081 6/1984 (21) Appl. No.: 10/726,625 DE 4OOO7705 9/1991 DE 40382O3 6/1992 (22) Filed: Dec. 4, 2003 DE 41.12303 10/1992 (65) Prior PublicationO O Data EPDE O1404344132176 5/19854/1993 US 2004/0120896 A1 Jun. 24, 2004 EP O213 108 3/1987 EP O315960 5/1989 Related U.S. Application Data EP O3867OO 3/1990 EP 0471161. 2/1992 (60) Division- - - of application No. 10/230,059, filed on Aug. 29, EP O656206 A1 * 6/1992 2002, which is a continuation-in-part of application No.
    [Show full text]
  • Managing Drug Shortages: Seven Years' Experience at One Health
    REPORTS Managing drug shortages REPORTS Managing drug shortages: Seven years’ experience at one health system ERIN R. FOX AND LINDA S. TYLER rug shortages have substantially affected patient care over the Abstract: A health system’s experience in therapeutic categories were central ner- past few years. While shortages monitoring drug shortages since 1996 vous system agents (24%) and serums, D within the organization and since 2001 on a toxoids, and vaccines (17%). Of the 119 have no single cause, manufacturing national level is described. shortages in 2001, 70 (59%) were still on- problems, regulatory actions, busi- Since January 1996, the Drug Informa- going as of the end of June 2002. The most ness decisions, and inventory prac- tion Service (DIS) at the University of Utah common potential safety problems were tices all contribute to the phenome- Hospitals and Clinics (UUHSC) has system- that clinicians might be unfamiliar with the non. Determining the true frequency atically prepared written bulletins to affect- alternative agent (54%) and that the alter- of drug shortages is difficult, in part ed practitioners when drug shortages native’s dosage requirement was different because “drug shortage” means dif- occurred. The DIS began providing infor- (50%). Over half of the shortages were cost ferent things depending on one’s mation on a national level to the American neutral, but the assessment did not include Society of Health-System Pharmacists in substantial potential indirect costs. perspective. Most health care organi- January 2001. Detailed information on drug shortages zations consider a drug shortage to A total of 224 drug shortages were collected by a health system’s drug infor- be a supply issue that affects how the tracked from January 1996 to June 2002.
    [Show full text]