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Understanding Benzodiazephine Use, Abuse, and Detection
Siemens Healthcare Diagnostics, the leading clinical diagnostics company, is committed to providing clinicians with the vital information they need for the accurate diagnosis, treatment and monitoring of patients. Our comprehensive portfolio of performance-driven systems, unmatched menu offering and IT solutions, in conjunction with highly responsive service, is designed to streamline workflow, enhance operational efficiency and support improved patient care. Syva, EMIT, EMIT II, EMIT d.a.u., and all associated marks are trademarks of General Siemens Healthcare Diagnostics Inc. All Drugs other trademarks and brands are the Global Division property of their respective owners. of Abuse Siemens Healthcare Product availability may vary from Diagnostics Inc. country to country and is subject 1717 Deerfield Road to varying regulatory requirements. Deerfield, IL 60015-0778 Please contact your local USA representative for availability. www.siemens.com/diagnostics Siemens Global Headquarters Global Siemens Healthcare Headquarters Siemens AG Understanding Wittelsbacherplatz 2 Siemens AG 80333 Muenchen Healthcare Sector Germany Henkestrasse 127 Benzodiazephine Use, 91052 Erlangen Germany Abuse, and Detection Telephone: +49 9131 84 - 0 www.siemens.com/healthcare www.usa.siemens.com/diagnostics Answers for life. Order No. A91DX-0701526-UC1-4A00 | Printed in USA | © 2009 Siemens Healthcare Diagnostics Inc. Syva has been R1 R2 a leading developer N and manufacturer of AB R3 X N drugs-of-abuse tests R4 for more than 30 years. R2 C Now part of Siemens Healthcare ® Diagnostics, Syva boasts a long and Benzodiazepines have as their basic chemical structure successful track record in drugs-of-abuse a benzene ring fused to a seven-membered diazepine ring. testing, and leads the industry in the All important benzodiazepines contain a 5-aryl substituent ring (ring C) and a 1,4–diazepine ring. -
Analytical Methods for Determination of Benzodiazepines. a Short Review
Cent. Eur. J. Chem. • 12(10) • 2014 • 994-1007 DOI: 10.2478/s11532-014-0551-1 Central European Journal of Chemistry Analytical methods for determination of benzodiazepines. A short review Review Article Paulina Szatkowska1, Marcin Koba1*, Piotr Kośliński1, Jacek Wandas1, Tomasz Bączek2,3 1Department of Toxicology, Faculty of Pharmacy, Collegium Medicum of Nicolaus Copernicus University, 85-089 Bydgoszcz, Poland 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland 3Institute of Health Sciences, Division of Human Anatomy and Physiology, Pomeranian University of Słupsk, 76-200 Słupsk, Poland Received 16 July 2013; Accepted 6 February 2014 Abstract: Benzodiazepines (BDZs) are generally commonly used as anxiolytic and/or hypnotic drugs as a ligand of the GABAA-benzodiazepine receptor. Moreover, some of benzodiazepines are widely used as an anti-depressive and sedative drugs, and also as anti-epileptic drugs and in some cases can be useful as an adjunct treatment in refractory epilepsies or anti-alcoholic therapy. High-performance liquid chromatography (HPLC) methods, thin-layer chromatography (TLC) methods, gas chromatography (GC) methods, capillary electrophoresis (CE) methods and some of spectrophotometric and spectrofluorometric methods were developed and have been extensively applied to the analysis of number of benzodiazepine derivative drugs (BDZs) providing reliable and accurate results. The available chemical methods for the determination of BDZs in biological materials and pharmaceutical formulations are reviewed in this work. Keywords: Analytical methods • Benzodiazepines • Drugs analysis • Pharmaceutical formulations © Versita Sp. z o.o. 1. Introduction and long). For this reason, an application of these drugs became broader allowing their utility to a larger extent, Benzodiazepines have been first introduced into medical and at the same time, problems related to drug abuse practice in the 60s of the last century. -
The Misuse of Benzodiazepines Among High-Risk Opioid Users in Europe
EMBARGO — 7 JUNE 7. 6. 2018 UPDATED 11:30 Central European Time/CET (10:30 Western European Time/WET/Lisbon) Proof - 28 May 2018 not for circulation PERSPECTIVES ON DRUGS The misuse of benzodiazepines among high-risk opioid users in Europe Benzodiazepines are a widely prescribed I Introduction group of medicines with a range of clinical uses that include treating Benzodiazepines have a range of clinical uses and are among the most commonly prescribed medicines globally. anxiety, insomnia and managing alcohol They are useful in the short-term treatment of anxiety and withdrawal. This group of medicines is insomnia, and in managing alcohol withdrawal (Medicines often misused by high-risk opioid users, and Healthcare Products Regulatory Agency, 2015). Like all medicines, benzodiazepines can produce side effects. They and this is associated with considerable may also be misused, which we define as use without a morbidity and mortality. This paper prescription from a medical practitioner or, if prescribed, when describes the impact of benzodiazepines they are used outside accepted medical practice or guidelines. misuse on the health and treatment of While the misuse of benzodiazepines has been identified high-risk opioid users. as a concern for large groups in the general population, for example, among elderly people and women, this analysis focuses specifically on misuse among high-risk opioid users (1), a group of people among whom these medicines have been linked with severe treatment challenges and implicated in considerable numbers of drug-related deaths. It is important to stress that much benzodiazepine prescribing to high-risk drug users is done with legitimate therapeutic aims in mind. -
Proposed Regulation of the State Board of Pharmacy
PROPOSED REGULATION OF THE STATE BOARD OF PHARMACY LCB File No. R150-16 Workshop September 8, 2016 Explanation – Language in blue italics is new; language in red text [omitted material] is language to be omitted, and language in green text indicates prior Board-approved amendments that are in the process of being codified. AUTHORITY: §1, NRS 639.070 A REGULATION relating to controlled substances; adding certain substances to the controlled substances listed in Schedule IV; and providing other matters properly relating thereto. Section 1. NAC 453.540 is hereby amended to read as follows: NAC 453.540 Schedule IV. 1. Schedule IV consists of the drugs and other substances listed in this section, by whatever official, common, usual, chemical or trade name designated. 2. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture or preparation containing any of the following narcotic drugs, including, without limitation, their salts, calculated as the free anhydrous base of alkaloid, is hereby enumerated on schedule IV, in quantities: (a) Not more than 1 milligram of difenoxin and not less than 25 micrograms of atropine sulfate per dosage unit; or (b) Dextropropoxyphene (alpha-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2-propionoxy- butane). 3. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture or preparation which contains any quantity of the following substances, including, without limitation, their salts, isomers and salts of isomers, is hereby enumerated -
124.210 Schedule IV — Substances Included. 1
1 CONTROLLED SUBSTANCES, §124.210 124.210 Schedule IV — substances included. 1. Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. 2. Narcotic drugs. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation containing any of the following narcotic drugs, or their salts calculated as the free anhydrous base or alkaloid, in limited quantities as set forth below: a. Not more than one milligram of difenoxin and not less than twenty-five micrograms of atropine sulfate per dosage unit. b. Dextropropoxyphene (alpha-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2- propionoxybutane). c. 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol, its salts, optical and geometric isomers and salts of these isomers (including tramadol). 3. Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: a. Alprazolam. b. Barbital. c. Bromazepam. d. Camazepam. e. Carisoprodol. f. Chloral betaine. g. Chloral hydrate. h. Chlordiazepoxide. i. Clobazam. j. Clonazepam. k. Clorazepate. l. Clotiazepam. m. Cloxazolam. n. Delorazepam. o. Diazepam. p. Dichloralphenazone. q. Estazolam. r. Ethchlorvynol. s. Ethinamate. t. Ethyl Loflazepate. u. Fludiazepam. v. Flunitrazepam. w. Flurazepam. x. Halazepam. y. Haloxazolam. z. Ketazolam. aa. Loprazolam. ab. Lorazepam. ac. Lormetazepam. ad. Mebutamate. ae. Medazepam. af. Meprobamate. ag. Methohexital. ah. Methylphenobarbital (mephobarbital). -
WO 2015/072853 Al 21 May 2015 (21.05.2015) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/072853 Al 21 May 2015 (21.05.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 45/06 (2006.01) A61K 31/5513 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/045 (2006.01) A61K 31/5517 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/522 (2006.01) A61P 31/22 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 31/551 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/NL20 14/050781 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 13 November 2014 (13.1 1.2014) SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 61/903,433 13 November 2013 (13. -
Benzodiazepines for Anxiety Disorder Treatment When, If Ever, Would I Consider Using Benzodiazepines for Long-Term Treatment of Anxiety Disorders?
UW PACC Psychiatry and Addictions Case Conference UW Medicine | Psychiatry and Behavioral Sciences BENZODIAZEPINES FOR ANXIETY DISORDER TREATMENT WHEN, IF EVER, WOULD I CONSIDER USING BENZODIAZEPINES FOR LONG-TERM TREATMENT OF ANXIETY DISORDERS? DEB COWLEY MD UNIVERSITY OF WASHINGTON 9/24/20 UW PACC ©2020 University of Washington GENERAL DISCLOSURES The University of Washington School of Medicine also gratefully acknowledges receipt of educational grant support for this activity from the Washington State Legislature through the Safety-Net Hospital Assessment, working to expand access to psychiatric services throughout Washington State. UW PACC ©2020 University of Washington GENERAL DISCLOSURES UW PACC is also supported by Coordinated Care of Washington UW PACC ©2020 University of Washington SPEAKER DISCLOSURES • No conflicts of interest relevant to this topic • Medical Director, PAL for Moms – Weekdays 9-5 – Free – 1-877-725-4666 (PAL4MOM) – [email protected] – Funded by Washington State Health Care Authority UW PACC ©2020 University of Washington PLANNER DISCLOSURES The following series planners have no relevant conflicts of interest to disclose: Mark Duncan MD Cameron Casey Barb McCann PhD Betsy Payn Rick Ries MD Diana Roll Kari Stephens PhD Cara Towle MSN RN Anna Ratzliff MD PhD has received book royalties from John Wiley & Sons (publishers). UW PACC ©2020 University of Washington CASE • A 60 yo woman presents with a long history of generalized anxiety disorder. She also has a history of hypertension and sleep apnea (using CPAP). She has taken benzodiazepines for more than 20 years and is currently on alprazolam 1 mg qid. She does not want to change this medication because she says it has been very helpful and “I don’t know what I would do without it.” She knows she needs it because she becomes very anxious before each dose. -
A Review of the Evidence of Use and Harms of Novel Benzodiazepines
ACMD Advisory Council on the Misuse of Drugs Novel Benzodiazepines A review of the evidence of use and harms of Novel Benzodiazepines April 2020 1 Contents 1. Introduction ................................................................................................................................. 4 2. Legal control of benzodiazepines .......................................................................................... 4 3. Benzodiazepine chemistry and pharmacology .................................................................. 6 4. Benzodiazepine misuse............................................................................................................ 7 Benzodiazepine use with opioids ................................................................................................... 9 Social harms of benzodiazepine use .......................................................................................... 10 Suicide ............................................................................................................................................. 11 5. Prevalence and harm summaries of Novel Benzodiazepines ...................................... 11 1. Flualprazolam ......................................................................................................................... 11 2. Norfludiazepam ....................................................................................................................... 13 3. Flunitrazolam .......................................................................................................................... -
Supplementary Material 0114-5916/09/0007-0001/$49.95/0 REVIEW ARTICLE © 2009 Adis Data Information BV
Drug Safety 2009; 32 (7): Supplementary Material 0114-5916/09/0007-0001/$49.95/0 REVIEW ARTICLE © 2009 Adis Data Information BV. All rights reserved. Pharmacokinetic Changes of Psychotropic Drugs in Patients with Liver Disease Implications for Dose Adaptation Chantal Schlatter,† Sabin S. Egger,† Lydia Tchambaz† and Stephan Krähenbühl Division of Clinical Pharmacology & Toxicology, University Hospital, Basel, Switzerland † These authors contributed equally to this work. Supplementary Material This supplementary material contains the table referred to in the full version of this article, which can be found at http://drugsafety.adisonline.com. Note the reference citations and reference list are independent from the published article and reference numbering will differ. 1 Table I. Kinetic data including metabolic pathway, hepatic and dose-dependent adverse effects and dose adjustment recommendations for the use of psychotropic drugs in patients with liver disease b Drug Drug Metabolism Q0 t1/2 [h] PB Vd F [%] Clsys E Hepatic Dose-dependent Studies performed and dosage recom- cat.a [%] [L/kg] [L/h] adverse adverse reactions mendations effects Psychostimulants Am- Lo Deethylation 0.95 2 95 restlessness, dizzi- Studies: No clinical studies available in pa- fepramone of the amine ness, tremor, insom- tients with liver disease. Product information: function, nia, anxiety, delirium, Contraindicated in patients with liver failure. reduction of hallucinations, de- Personal recommendation: Should be the ketone pression, changes in avoided in patients with liver disease. function, libido, pallor or flush- and hy- ing, palpitation, ar- droxylation rhythmia, anginal pain, of the ben- hypertension, circula- zene ring[1-3] tory collapse, exces- sive sweating, dry mouth, anorexia[1] Methyl- Hi Deesterifi- 0.95 2 20 2 30 40 0.7 Case re- nervousness, insom- Studies: No clinical studies available in pa- phenidate cation by ports: nia, headache, dizzi- tients with liver disease. -
Harmonized Tariff Schedule of the United States (2020) Revision 6 Annotated for Statistical Reporting Purposes
Harmonized Tariff Schedule of the United States (2020) Revision 6 Annotated for Statistical Reporting Purposes CHAPTER 29 ORGANIC CHEMICALS VI 29-1 Notes 1. Except where the context otherwise requires, the headings of this chapter apply only to: (a) Separate chemically defined organic compounds, whether or not containing impurities; (b) Mixtures of two or more isomers of the same organic compound (whether or not containing impurities), except mixtures of acyclic hydrocarbon isomers (other than stereoisomers), whether or not saturated (chapter 27); (c) The products of headings 2936 to 2939 or the sugar ethers, sugar acetals and sugar esters, and their salts, of heading 2940, or the products of heading 2941, whether or not chemically defined; (d) Products mentioned in (a), (b) or (c) above dissolved in water; (e) Products mentioned in (a), (b) or (c) above dissolved in other solvents provided that the solution constitutes a normal and necessary method of putting up these products adopted solely for reasons of safety or for transport and that the solvent does not render the product particularly suitable for specific use rather than for general use; (f) The products mentioned in (a), (b), (c), (d) or (e) above with an added stabilizer (including an anticaking agent) necessary for their preservation or transport; (g) The products mentioned in (a), (b), (c), (d), (e) or (f) above with an added antidusting agent or a coloring or odoriferous substance added to facilitate their identification or for safety reasons, provided that the additions do not render the product particularly suitable for specific use rather than for general use; (h) The following products, diluted to standard strengths, for the production of azo dyes: diazonium salts, couplers used for these salts and diazotizable amines and their salts. -
A. Schedule IV Shall Consist Of
1 REVISOR 6800.4240 6800.4240 SCHEDULE IV CONTROLLED SUBSTANCES. The following items are listed in Schedule IV: A. Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this part. B. Narcotic drugs. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation containing any of the following narcotic drugs, or their salts calculated as the free anhydrous base or alkaloid, in limited quantities as follows: (1) Not more than one milligram of difenoxin and not less than 25 micrograms of atropine sulfate per dosage unit. (2) Dextropropoxyphene (alpha-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2- propionoxybutane), for example, Darvon, Darvocet. C. Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts, isomers, and salts of isomers is possible within the specific chemical designation: Statutory Name Some examples of common names, trade names, or names of products which contain a controlled substance (1) Alprazolam Xanax (2) Barbital Barbitone (3) Bromazepam (4) Camazepam (5) Chloral betaine Beta-Chlor (6) Chloral hydrate Noctec, Somnos (7) Chlordiazepoxide Librium, Libritabs (8) Clobazam (9) Clonazepam Clonopin (10) Clorazepate Tranxene (11) Clotiazepam Copyright ©2013 -
(12) Patent Application Publication (10) Pub. No.: US 2010/0184806 A1 Barlow Et Al
US 20100184806A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0184806 A1 Barlow et al. (43) Pub. Date: Jul. 22, 2010 (54) MODULATION OF NEUROGENESIS BY PPAR (60) Provisional application No. 60/826,206, filed on Sep. AGENTS 19, 2006. (75) Inventors: Carrolee Barlow, Del Mar, CA (US); Todd Carter, San Diego, CA Publication Classification (US); Andrew Morse, San Diego, (51) Int. Cl. CA (US); Kai Treuner, San Diego, A6II 3/4433 (2006.01) CA (US); Kym Lorrain, San A6II 3/4439 (2006.01) Diego, CA (US) A6IP 25/00 (2006.01) A6IP 25/28 (2006.01) Correspondence Address: A6IP 25/18 (2006.01) SUGHRUE MION, PLLC A6IP 25/22 (2006.01) 2100 PENNSYLVANIA AVENUE, N.W., SUITE 8OO (52) U.S. Cl. ......................................... 514/337; 514/342 WASHINGTON, DC 20037 (US) (57) ABSTRACT (73) Assignee: BrainCells, Inc., San Diego, CA (US) The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system (21) Appl. No.: 12/690,915 including by stimulating or increasing neurogenesis, neuro proliferation, and/or neurodifferentiation. The disclosure (22) Filed: Jan. 20, 2010 includes compositions and methods based on use of a peroxi some proliferator-activated receptor (PPAR) agent, option Related U.S. Application Data ally in combination with one or more neurogenic agents, to (63) Continuation-in-part of application No. 1 1/857,221, stimulate or increase a neurogenic response and/or to treat a filed on Sep. 18, 2007. nervous system disease or disorder. Patent Application Publication Jul. 22, 2010 Sheet 1 of 9 US 2010/O184806 A1 Figure 1: Human Neurogenesis Assay Ciprofibrate Neuronal Differentiation (TUJ1) 100 8090 Ciprofibrates 10-8.5 10-8.0 10-7.5 10-7.0 10-6.5 10-6.0 10-5.5 10-5.0 10-4.5 Conc(M) Patent Application Publication Jul.