DOCSLIB.ORG

Alternative Opioids to Morphine in Palliative Care: Postgrad Med J: First Published As 10.1136/Pmj.77.908.371 on 1 June 2001

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Alternative Opioids to Morphine in Palliative Care: Postgrad Med J: First Published As 10.1136/Pmj.77.908.371 on 1 June 2001 Postgrad Med J 2001;77:371–378 371 Alternative opioids to morphine in palliative care: Postgrad Med J: first published as 10.1136/pmj.77.908.371 on 1 June 2001. Downloaded from a review of current practice and evidence M Barnett This is a review of current practice of opioid x Nausea/vomiting use in palliative care, conducted from the per- x Urinary retention spective of a practising clinician working in the x Myoclonus increasingly complex area of symptom control. x Paradoxical pain In examining alternative opioids to morphine, x Respiratory depression choice and availability of diVerent drugs reflect For practical purposes, the most important the UK perspective. Some drugs or formula- side eVects are sedation, nausea, and constipa- tions may not be available elsewhere, but the tion. principles discussed may hopefully still be Sedation and nausea occur particularly when applied. starting the drug, usually temporarily, but may The aims of this paper are several-fold: recur with dose increases. Nausea can be (1) To present an overview of available opio- pre-empted by using a centrally acting an- ids. tiemetic. This is not always necessary but (2) To consider factors aVecting possible advisable if the patient is already nauseated or choice of opioid—with particular reference fearful about it. Sedation is usually unavoidable to the palliative care setting. but short lived (48–72 hours) among patients (3) To consider availability and limitations of starting oV on low doses. It may become more current data which may aVect evidence intractable at high dose, and there is some work based decisions. on counteracting this eVect with stimulants,1 (4) To comment on areas of interest for future although not widely practised. clinical trials. Constipation, in contrast, occurs in almost every patient taking opioids and does not lessen Terms of reference with continued use, but can be ameliorated by OPIOID RECEPTORS AND EFFECTS aperients. There are three main classes of opioid receptor: Respiratory depression, while potentially mu, kappa, and delta (table 1), responsible for serious, is rarely clinically significant when diVering opioid eVects. Opioid drugs vary in treating pain (even among patients with their receptor aYnity, thus aVecting their prin- respiratory impairment), as this antagonises Walsgrave Hospital, cipal actions (table 2). The main site of action the depressant eVect. In practice respiratory Coventry and is the mu receptor, but some opioids have more http://pmj.bmj.com/ University of Warwick depression usually occurs in opioid naïve complex activity. patients after acute administration (for exam- Correspondence to: ple, bolus intravenous dose). Tolerance devel- Dr M Barnett, Centre for ops rapidly with repeat doses, so does not pose Primary Health Care SIDE EFFECTS OF OPIOIDS Studies, University of Side eVects are common to all opioids, significant problems for long term pain man- Warwick, Coventry although to diVering degrees. agement. CV4 7AL, UK x Sedation Submitted 8 May 2000 x Hallucinations Cancer pain and choice of opioid on September 30, 2021 by guest. Protected copyright. Accepted 31 October 2000 x Constipation “Cancer pain” can be complex. Causes in- clude: direct tumour infiltration of pain sensi- Table 1 Classes of opioid receptor and response mediated tive structures, injuries resulting from cancer treatment (radiation, chemotherapy, or sur- Receptor Response on activation gery) and vascular occlusion due to tumour or Mu Analgesia, respiratory depression, miosis, euphoria, reduced gastrointestinal mobility treatment eVects. Physiologically, there are Kappa Analgesia, dysphoria, psychotomimetic eVects, miosis, respiratory depression three types of pain: Delta Analgesia (1) Somatic or nociceptive pain (arising from Source: Oxford Textbook of Palliative Medicine. receptors in cutaneous or deep tissues such as bone). Table 2 DiVerences in opioid receptor action Opioid Receptor action Comments Morphine Mu agonist Metabolised in liver to morphine-3 and morphine-6 glucuronides (M3G and M6G). M6G metabolite more potent than morphine Hydromorphone Mu agonist Morphine analogue Fentanyl Mu agonist Oxycodone Mu agonist Pentazocine Kappa agonist; weak mu antagonist Multiple receptor activity: kappa eVects analgesic but also increased psychotomimetic eVects cf mu agonists. Mu receptor antagonism can precipitate withdrawal if given alongside mu agonist Methadone Mixed mu/delta agonist; N-methyl-D-aspartate Multiple receptor activity—may act on complex pain (NMDA) receptor antagonist Buprenorphine Partial mu agonist; kappa antagonist; delta agonist Complex receptor action—has dose ceiling for analgesic eVect and antagonises other opioids Tramadol Opioid plus serotonergic eVects For moderate pain. Tricyclic-like action—may act on neuropathic pain www.postgradmedj.com 372 Barnett Postgrad Med J: first published as 10.1136/pmj.77.908.371 on 1 June 2001. Downloaded from Opioid for moderate to Table 4 Relative potency of commonly used opioids severe pain + non Potency ratio with Duration of opioid +/– adjuvant Analgesic oral morphine action (hours) Codeine 1/10 3–5 Opioid for mild to Pethidine 1/8 2–3 moderate pain + non- Tramadol 1/5 5–6 opioid +/– adjuvant Dipipanone 1⁄2 3–5 Oxycodone 1.5–2 5–6 Dextromoramide 2 2–3 Phenazocine 5 6–8 Methadone 5–10 8–12 Non-opioid Pain persists Hydromorphone 7.5 3–5 +/– adjuvant Buprenorphine 60 6–8 or Fentanyl 150 72 Pain increases persists or Choosing an appropriate opioid increases Several factors influence choice of an appropri- ate opioid. Figure 1 WHO analgesic ladder (adapted from WHO2). x Availability x Drug profile (2) Visceral pain (arising from internal organ x Individual patient factors involvement). x Possible/desirable routes of administration (3) Neuropathic pain (arising from peripheral x Comparative analgesic eVects or central nervous systems). x Comparative adverse eVects Most pain can be controlled by pharmaco- x Other potential therapeutic eVects logical means, but it is essential to choose the right drugs for the individual. To help simplify AVAILABILITY approaches to pain control, the World Health In the UK, there is a wide range of opioids Organisation (WHO) developed a three step available (table 3). The initial choice of weak, analgesic ladder (fig 1). The fundamental prin- moderate, or strong opioid is determined after ciples are that: careful assessment of the individual patient. It (1) Inadequate pain control at one level cannot be emphasised enough that pain is requires a move to the next level, not to an multifactorial and that successful treatment alternative drug of the same eYcacy. depends on comprehensive evaluation. (2) Continuous pain requires continuous anal- For the purposes of this review, I will focus gesia. discussion on strong opioids. The steps are simple: DRUG PROFILE (1) Treatment of mild pain is initiated with In palliation, the aim is to administer eVective non-opioid analgesics (for example, para- analgesics with a half life of several hours so that cetamol). pain can be quickly controlled. Once dose http://pmj.bmj.com/ (2) Moderate pain that is not controlled requirements have stabilised, modified release by non-opioids should be treated by a formulations are extremely helpful, allowing weak opioid (alone or in combination longer dose intervals but maintaining flexibility with a non-opioid, for example, co- to make dose alterations without risk of proxamol: paracetamol and dextropo- accumulation. Thus potency and duration of poxyphene). action are major determining factors. Morphine (3) Severe pain should be treated by strong provides the gold standard: in unmodified form opioids. its four hour clinical duration of action allows on September 30, 2021 by guest. Protected copyright. At all levels adjuvant drugs can be added for regular review of pain control. Once stable, sus- specific indications: non-steroidal anti- tained release formulations reduce dose fre- inflammatory drugs (NSAIDs) for bone pain; quency to once or twice daily. Breakthrough anticonvulsants or tricyclics for neuropathic pain is controlled with extra doses of the pain. This is, however, a large subject in its unmodified drug (calculated as 1/6 of the total own right, and will not be dealt with further 24 hour opioid dose requirement). Drugs with a here. very short half life (for example, pethidine) are unsuitable, because of the need for more frequent repeat dosing, which is both inconven- Table 3 A selection of opioids in common use in the UK (from the British National Formulary) ient and can cause build-up of toxic metabolites. Drugs with inherently long half lives (for exam- (1) Weak opioids (2) Moderate and strong opioids ple, methadone), are useful for long term main- Dextropopoxyphene Buprenorphine (Temgesic) tenance, but can be diYcult to titrate safely in Codeine Dextromoramide (Palfium) unstable pain. Table 4 illustrates the relative Dihydrocodeine Diamorphine potency of various opioids compared with oral Dipipanone (Diconal) Fentanyl morphine, and also their duration of action. Hydromorphone (Palladone) Methadone PATIENT FACTORS Morphine Oxycodone Biomedical Pentazocine (Fortral) These include age related changes in metabolism Pethidine and concurrent medical conditions. In palliative Phenazocine (Narphen) care, many patients are both elderly and have Tramadol concurrent medical conditions, both of which www.postgradmedj.com Alternative opioids to morphine in palliative care 373 Table 5 Important clinical drug interactions with opioids Postgrad Med J: first published as 10.1136/pmj.77.908.371
Load more

Recommended publications
  • Best Bets from the Manchester Royal Infirmary Edited by K Mackway-Jones
    247 BEST EVIDENCE TOPIC REPORTS Emerg Med J: first published as 10.1136/emj.19.3.248 on 1 May 2002. Downloaded from Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary Edited by K Mackway-Jones Clinical scenario Best evidence topic reports (BETs) summarise the evidence A 23 year old woman attends an emergency department hav- pertaining to particular clinical questions. They are not ing taken sixty 500 mg paracetamol tablets. Her four hour systematic reviews, but rather contain the best (highest paracetamol levels are above the treatment line. She does not level) evidence that can be practically obtained by busy want to be treated with intravenous therapy. You wonder practising clinicians. The search strategies used to find the whether oral antidote is as effective. best evidence are reported in detail in order to allow clinicians to update searches whenever necessary. The BETs published below were first reported at the Critical Three part question Appraisal Journal Club at the Manchester Royal Infirmary.1 In [patients who need an antidote for paracetamol overdose] Each BET has been constructed in the four stages that have is [intravenous therapy better than oral therapy] at [prevent- been described elsewhere.2 The BETs shown here together ing liver damage and death]? with those published previously and those currently under construction can be seen at http://www.bestbets.org.3 Six Search strategy BETs are included in this issue of the journal. Medline 1966 to 12/01 using the OVID interface. [exp acetyl-
    [Show full text]
  • Recommended Methods for the Identification and Analysis of Fentanyl and Its Analogues in Biological Specimens
    Recommended methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES Laboratory and Scientific Section UNITED NATIONS OFFICE ON DRUGS AND CRIME Vienna Recommended Methods for the Identification and Analysis of Fentanyl and its Analogues in Biological Specimens MANUAL FOR USE BY NATIONAL DRUG ANALYSIS LABORATORIES UNITED NATIONS Vienna, 2017 Note Operating and experimental conditions are reproduced from the original reference materials, including unpublished methods, validated and used in selected national laboratories as per the list of references. A number of alternative conditions and substitution of named commercial products may provide comparable results in many cases. However, any modification has to be validated before it is integrated into laboratory routines. ST/NAR/53 Original language: English © United Nations, November 2017. All rights reserved. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. Mention of names of firms and commercial products does not imply the endorse- ment of the United Nations. This publication has not been formally edited. Publishing production: English, Publishing and Library Section, United Nations Office at Vienna. Acknowledgements The Laboratory and Scientific Section of the UNODC (LSS, headed by Dr. Justice Tettey) wishes to express its appreciation and thanks to Dr. Barry Logan, Center for Forensic Science Research and Education, at the Fredric Rieders Family Founda- tion and NMS Labs, United States; Amanda L.A.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2004/0024006 A1 Simon (43) Pub
    US 2004.0024006A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0024006 A1 Simon (43) Pub. Date: Feb. 5, 2004 (54) OPIOID PHARMACEUTICAL May 30, 1997, now abandoned, and which is a COMPOSITIONS continuation-in-part of application No. 08/643,775, filed on May 6, 1996, now abandoned. (76) Inventor: David Lew Simon, Mansfield Center, CT (US) Publication Classification Correspondence Address: (51) Int. Cl. ................................................ A61K 31/485 David L. Simon (52) U.S. Cl. .............................................................. 514/282 P.O. Box 618 100 Cemetery Road (57) ABSTRACT Mansfield Center, CT 06250 (US) The invention is directed in part to dosage forms comprising a combination of an analgesically effective amount of an (21) Appl. No.: 10/628,089 opioid agonist analgesic and a neutral receptor binding agent or a partial mu-opioid agonist, the neutral receptor binding (22) Filed: Jul. 25, 2003 agent or partial mu-opioid agonist being included in a ratio Related U.S. Application Data to the opioid agonist analgesic to provide a combination product which is analgesically effective when the combina (63) Continuation-in-part of application No. 10/306,657, tion is administered as prescribed, but which is leSS analge filed on Nov. 27, 2002, which is a continuation-in-part Sically effective or less rewarding when administered in of application No. 09/922,873, filed on Aug. 6, 2001, excess of prescription. Preferably, the combination product now Pat. No. 6,569,866, which is a continuation-in affects an opioid dependent individual differently from an part of application No. 09/152,834, filed on Sep.
    [Show full text]
  • Outline for Controlled Substances Program
    Environmental Health and Safety Controlled Substances Program Date of Issuance: Review Date: 10/1/2019 (no changes) 10/01/2018 Revision Number: Initial Prepared by: EH&S Table of Contents HEADINGS Introduction Applicability Responsibilities Registration Requirements Authorized Use Ordering/Purchasing Administering and Dispensing Inventory Procedures (Continuing Records) Security Disposal FORMS: Registering or renewing a DEA or state license (CMU) Controlled Substances Authorized users list (CMU) Employee questionnaire for those with access to controlled substances (CMU) Record of Form 222 use (Order form) (CMU) Records of Controlled Substance Purchases (CMU) Record of Controlled Substance Administering and dispensing (CMU) Controlled Substance Physical Inventory (CMU) DEA Registration of Persons doing research or analysis (Form 225) DEA Registration of Dispensers (Form 224) DEA Registration Instructional (Form 224 and 226 to renew) DEA Report of loss or theft (Form 106) DEA Report of drugs surrendered (From 41) DEA SCHEDULES: Schedule I Schedule II Schedule III Schedule IV Schedule V INTRODUCTION State and Federal regulations have been promulgated concerning the use and handling of US Department of Justice Drug Enforcement Administration (DEA) controlled substances. These regulations are in place to address materials which are or have the potential to be addictive or habit forming. These substances have been categorized into “schedules” that have been created by the DEA to reflect their level of concern. The “Carnegie Mellon University DEA Controlled Substances Program” is intended to ensure that Carnegie Mellon University is in compliance with our regulatory requirements. Required activities under the DEA include: 1. Registration of your work with the DEA and with Carnegie Mellon’s Department of Environmental Health and Safety (EH&S).
    [Show full text]
  • The Prevention and Treatment of Drug Misuse in Britain
    If you have issues viewing or accessing this file contact us at NCJRS.gov. .. " FW The prevention and treatment of drug misuse in Britain "I Issued by Rererence Division BRITISH INFORMATION SERVICES All Agency of the British Government 845 THIRD AVENUE, NEW YORK, N.Y. ]0022 This material is prepared, edited, issued or circulated by British Information Servic(!s, 845 Third Avenue, New York, N. Y.l0022, which is registered under the Foreign Agents Registration Act as an agent of the Brilish Government. This material is filed with the Department of Justice where the required registration statement is available for public inspection. Registration does not indicate approval 0/ the contents of this material by the United States Government. PRINTED IN ENGLAND BY TRADE UNION LABOR BY COLUNS AND WILSON LTD., ANDOVER The prevention and treatment of drug misuse in Britain Prepared by REFERENCE DIVISION CENTRhL OFFICE OF INFORMATION, LONDON Oclo~'er 1978 Quote No RS94S/78 CLASSIFICATION 4(c) N.B.-This pamphlet is i//tellded to be used for referellce purposes alld may be freely used ill preparing articles, speeches, broadcasts, elc. No acknowledgment is necessary. Please Ilote the date ofpreparation. Tire text gives general gUidance only, and should 1I0t be treated as an authoritative statement of the law. Pamphlets ill this series may be obtained from the Tllformation Office at tlte British Embassy, Consulate or High Commission in tile inquirer's Co/lIltl'Y of residellce. CONTENTS Page INTRODUCTION 1 BACKGROUND .. 3 PREVENTING DRUG MISUSE 8 The Law 8 Health Education 17 TREATMENT AND REHABILITATION .. 20 Narcotic Drug Misuse and the Role of the Clinics 20 Treating Other Forms of Drug Misuse 26 Rehabilitation 26 INFORMATION AND RESEARCH ., 29 APPENDICES 1.
    [Show full text]
  • Prescription of Controlled Drugs to Addicts
    1876 BRITISH MEDICAL JOURNAL VOLUME 286 11 JUNE 1983 Br Med J (Clin Res Ed): first published as 10.1136/bmj.286.6381.1876 on 11 June 1983. Downloaded from For Debate . P Unacceptable face of private practice: prescription of controlled drugs to addicts THOMAS BEWLEY, A HAMID GHODSE Abstract practitioners. In the past three years, however, the pattern has shown a pronounced change (table), large numbers of addicts Self administered questionnaires completed by 69 out again having drugs prescribed for them by private general of 100 consecutive drug addicts two attending drug practitioners. These drugs are no longer heroin and cocaine dependence clinics that some suggested private general but other controlled drugs which are not included in the practitioners were easily persuaded to prescribe con- licensing regulations. trolled drugs. These drugs were usually methadone, dipipanone-cyclizine (Diconal), and methylphenidate (Ritalin). Numbers of new narcotic addicts notified to New narcotic addicts notified to Home Office the Home Office confirmed the practice, which may lead Source of notification to a severe spread of addiction, as occurred in the 1960s with heroin and cocaine. Year Hospital treatment Prison medical General medical Total centret officert practitionert If the General Medical Council or a tribunal set up 1972 480 250 80 800 in accordance with the Misuse of Drugs Act 1971 cannot 1973 430 230 150 807 stop then the 1974 380 240 250 870 the practice, present licensing system 1975 390 270 260 922 should be extended to include all controlled drugs. 1976 400 290 290 984 1977 450 290 370 1109 1978 590 240 520 1347 1979 610 270 720 1597 1980 570 240 790 1600 Introduction 1981* 760 320 1220 2300 Prescribing drugs of addiction to addicts is accepted medical Provisional.
    [Show full text]
  • NIDA Drug Supply Program Catalog, 25Th Edition
    RESEARCH RESOURCES DRUG SUPPLY PROGRAM CATALOG 25TH EDITION MAY 2016 CHEMISTRY AND PHARMACEUTICS BRANCH DIVISION OF THERAPEUTICS AND MEDICAL CONSEQUENCES NATIONAL INSTITUTE ON DRUG ABUSE NATIONAL INSTITUTES OF HEALTH DEPARTMENT OF HEALTH AND HUMAN SERVICES 6001 EXECUTIVE BOULEVARD ROCKVILLE, MARYLAND 20852 160524 On the cover: CPK rendering of nalfurafine. TABLE OF CONTENTS A. Introduction ................................................................................................1 B. NIDA Drug Supply Program (DSP) Ordering Guidelines ..........................3 C. Drug Request Checklist .............................................................................8 D. Sample DEA Order Form 222 ....................................................................9 E. Supply & Analysis of Standard Solutions of Δ9-THC ..............................10 F. Alternate Sources for Peptides ...............................................................11 G. Instructions for Analytical Services .........................................................12 H. X-Ray Diffraction Analysis of Compounds .............................................13 I. Nicotine Research Cigarettes Drug Supply Program .............................16 J. Ordering Guidelines for Nicotine Research Cigarettes (NRCs)..............18 K. Ordering Guidelines for Marijuana and Marijuana Cigarettes ................21 L. Important Addresses, Telephone & Fax Numbers ..................................24 M. Available Drugs, Compounds, and Dosage Forms ..............................25
    [Show full text]
  • Narcotic Drugs Stupefiants Estupefacientes
    E/INCB/1993/21Supp.6 INTERNATIONAL NARCOTICS CONTROL BOARD - VIENNA SUPPLEMENT No. 6 TO NARCOTIC DRUGS ESTIMATED WORLD REQUIREMENTS FOR 1994 STATISTICS FOR 1992 ESTIMATES UPDATED AS OF 30 JUNE 1994 ORGANE INTERNATIONAL DE CONTROLE DES STUPEFIANTS - VIENNE SUPPLEMENT N° 6 A r STUPEFIANTS EVALUATIONS DES BESOINS DU MONDE POUR 1994 STATISTIQUES POUR 1992 EVALUATIONS A JOUR AU 30 JUlN 1994 JUNTA INTERNACIONAL DE FISCALlZACION DE ESTUPEFACIENTES - VIENA SUPLEMENTO N.o 6 A ESTUPEFACIENTES PREVISIONES DE LAS NECESIDADES MUNDIALES PARA 1994 ESTADfsTICAS PARA 1992 PREVISIONES ACTUALlZADAS AL 30 DE JUNIO DE 1994 ~If..~~ ~ ~-tR UNITED NATIONS - NATIONS UNIES - NACIONES UNIDAS 1994 The updating of Table A is carried out by means of 12 monthly supplements. In order to facilitate the task of the exporting countries, the 12 supplements now report all the totals of the estimates and not only the amended data. In this way, each supplement cancels and replaces the published table in its entirety. In order to accelerate the transmission of the supplements to the competent national authorities, the 12 supplements will appear in English. Reading of these 12 supplements in French and Spanish may be facilitated by consulting the indexes of countries and territories and of narcotic drugs appearing in the annual publication. La mise El jour du tableau A s'effectue au moyen de douze supplements mensuels. Afin de faciliter la tache des pays exportateurs, les douze supplements contiennent tous les totaux des evaluations et non pas seulement les chiffres qui ont ete modifies. De celte maniere, chaque supplement annule et remplace entierement le tableau publie.
    [Show full text]
  • Prescribing Information Dipipanone 10Mg and Cyclizine 30Mg Tablets (Dipipanone Hydrochloride and Cyclizine Hydrochloride)
    Prescribing Information Dipipanone 10mg and Cyclizine 30mg Tablets (dipipanone hydrochloride and cyclizine hydrochloride) Presentation: Each tablet contains 10mg dipipanone hydrochloride Pregnancy and lactation: Not recommended during pregnancy and and 30mg cyclizine hydrochloride. lactation. Indication: For the management of moderate to severe pain in medical Undesirable effects: Respiratory depression, mental clouding, and surgical conditions in which morphine may be indicated. Cyclizine drowsiness, sedation, confusion, mood changes, euphoria, dysphoria, is effective in preventing nausea and vomiting associated with the psychosis, restlessness, miosis, raised intracranial pressure, administration of narcotic analgesics. constipation, nausea, vomiting, sweating, facial flushing, hypotension, Dosage and administration: For oral use. urticarial, rashes; difficulty with micturition; biliary and renal tract Adults: An initial dose of one tablet every 6 hours can be given which spasm, vertigo, dryness of the mouth/nose/throat, blurred vision, can be increased by half tablet every half hour in severe intractable tachycardia, urinary retention, restlessness, nervousness, insomnia, pain. The dose should not exceed 12 tablets in 24 hours. and auditory/visual hallucinations. Elderly: There is no specific information on the use in elderly patients. (Please refer to the Summary of Product Characteristics for detailed Children: Rarely indicated in children and dosage guidelines cannot information) be stated. Overdose: The signs of overdosage include respiratory depression, Contraindications: Hypersensitivity to dipipanone or cyclizine, pin-point pupils, hypotension, circulatory failure and deepening coma. respiratory depression (especially in the presence of cyanosis and Mydriasis may replace miosis as asphyxia intervenes. Drowsiness, excessive bronchial secretions), bronchial asthma, acute alcoholism, floppiness, miosis and apnoea have been reported in children, as head injury and raised intracranial pressure, patients receiving current have convulsions.
    [Show full text]
  • Disposal Systems of Transdermal Delivery Devices to Prevent Misuse of the Active Agents Contained Therein
    (19) & (11) EP 1 837 023 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 26.09.2007 Bulletin 2007/39 A61K 31/485 (2006.01) A61K 9/70 (2006.01) A61K 31/445 (2006.01) B09B 3/00 (2006.01) (2006.01) (21) Application number: 07003694.2 A61F 13/00 (22) Date of filing: 10.06.2003 (84) Designated Contracting States: (72) Inventors: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR • Baker, Carl J. HU IE IT LI LU MC NL PT RO SE SI SK TR Middletown, NY 10941-5004 (US) Designated Extension States: • Shevchuck, Ihor AL LT LV MK Yonkers, NY 10710 (US) (30) Priority: 10.06.2002 US 387800 P (74) Representative: Maiwald Patentanwalts GmbH Elisenhof, (62) Document number(s) of the earlier application(s) in Elisenstrasse 3 accordance with Art. 76 EPC: 80335 München (DE) 03757468.8 / 1 513 532 Remarks: (71) Applicant: EURO-CELTIQUE S.A. This application was filed on 22 - 02 - 2007 as a 2330 Luxembourg (LU) divisional application to the application mentioned under INID code 62. (54) Disposal systems of transdermal delivery devices to prevent misuse of the active agents contained therein (57) The present invention relates to a transdermal at least one deactivating agent to chemically alter, to de- delivery device disposal system for disposing of a grade, and/or to deactivate the active component (s) con- transdermal delivery device containing at least one phar- tained in the transdermal delivery device, such as an opi- maceutically active component. The disposal system oid antagonist or an opioid agonist deactivating agent so contains
    [Show full text]
  • 1 Animals Used in These Published Studies on CES Clark, Nancy, Mills
    Animals Used in these Published Studies on CES Clark, Nancy, Mills, Daniel, Marchant, Jeremy. Evaluation of the potential efficacy of the Alpha-Stim SCS in the Horse. DeMontfort University Equestrian Centre and Field Station, Caythorpe, Lincolnshire, United Kingdom. 2002. (Publication in process) After completing a successful pilot study of the stress reduction effects of the Alpha- Stim SCS in a 6 horse pilot study, a double-blind study was completed with 8 thoroughbred horses (2 fillies, 3 mares, 3 geldings) at the De Montfort University Equestiran Centre and Field Station at Caythorpe, Lincolnshire, United Kingdom. Alpha-Stim AS-Trode brand self adhesive electrodes were attached to shaved areas on each side of the neck beneath the collar. Alpha-Stim SCS devices were set to provide 0.5 Hz biphasic stimulation at 200 microamperes, or sham stimulation. Heart rate measurements (HR) were provided by an attached Polar Horse Trainer transmitter belt and a Polar Vantage receiver. Observers blind to the treatment condition recorded duration of behaviors of body locomotion, head motion, ear position, oral behavior and the state of the lower lip at 15 second intervals for 15 seconds duration. Four trials were carried out each day for a total of 8 days (4 testing days per week). The frequency of each behavior was calculated and divided by the total number of observations for statistical analysis. The time standing alert decreased significantly from trial 1 to trial 4 (p<0.05). The time spent standing alert also continued to decrease after the stimulation had stopped, suggesting an ongoing effect of CES following the period of actual stimulation.
    [Show full text]
  • Dependence on Dextromoramide
    88 14 January 1967 Anticoagulant Therapy-Biggs and Denson BMEDIsALHJOURNA commercial preparations are very insensitive. When the first area also obviously has great advantages (Poller, 1964). The reference preparation is available it would be an advance for a introduction of a reference preparation with an internationally Br Med J: first published as 10.1136/bmj.1.5532.88 on 14 January 1967. Downloaded from minimum acceptable sensitivity to be established by standards recognized scale and a simple method of adjusting various tech- institutions. Such a concept would encourage the preparation niques to the scale would round off this work. The calibration of satisfactory commercial preparations. scale of commercial preparations could be adjusted to the scale, preparations made individually in clinical laboratories could be x x similarly calibrated. Moreover, attention to sensitivity to the coumarin defect would undoubtedly improve the reliability of control. 30 A single scale properly applied at different centres would ensure safety and uniform dosage for a patient moving from z a one place to another and would greatly improve the standard LU of clinical trials carried out at more than one centre. 10 0 I Summary a The control of anticoagulant therapy by the one-stage pro- thrombin time suffers from the fact that the results of this test are reported differently at different centres. Thus clinical trials with a standard objective of treatment are difficult to organize 0 and a patient cannot travel from one centre to another with any assurance that the level of therapy will remain constant. A method of standardizing the test has been devised so that all may use the same scale of measurement adjusted in each 0 10 20 30 TEST METHOD PERCENTAGE case to fit the preferred thromboplastin.
    [Show full text]