Hsrs Alcohol and Other Drug Abuse Module
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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. -
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). -
Drugs of Abuse: Benzodiazepines
Drugs of Abuse: Benzodiazepines What are Benzodiazepines? Benzodiazepines are central nervous system depressants that produce sedation, induce sleep, relieve anxiety and muscle spasms, and prevent seizures. What is their origin? Benzodiazepines are only legally available through prescription. Many abusers maintain their drug supply by getting prescriptions from several doctors, forging prescriptions, or buying them illicitly. Alprazolam and diazepam are the two most frequently encountered benzodiazepines on the illicit market. Benzodiazepines are What are common street names? depressants legally available Common street names include Benzos and Downers. through prescription. Abuse is associated with What do they look like? adolescents and young The most common benzodiazepines are the prescription drugs ® ® ® ® ® adults who take the drug Valium , Xanax , Halcion , Ativan , and Klonopin . Tolerance can orally or crush it up and develop, although at variable rates and to different degrees. short it to get high. Shorter-acting benzodiazepines used to manage insomnia include estazolam (ProSom®), flurazepam (Dalmane®), temazepam (Restoril®), Benzodiazepines slow down and triazolam (Halcion®). Midazolam (Versed®), a short-acting the central nervous system. benzodiazepine, is utilized for sedation, anxiety, and amnesia in critical Overdose effects include care settings and prior to anesthesia. It is available in the United States shallow respiration, clammy as an injectable preparation and as a syrup (primarily for pediatric skin, dilated pupils, weak patients). and rapid pulse, coma, and possible death. Benzodiazepines with a longer duration of action are utilized to treat insomnia in patients with daytime anxiety. These benzodiazepines include alprazolam (Xanax®), chlordiazepoxide (Librium®), clorazepate (Tranxene®), diazepam (Valium®), halazepam (Paxipam®), lorzepam (Ativan®), oxazepam (Serax®), prazepam (Centrax®), and quazepam (Doral®). -
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 .......................................................................................................................... -
Benzodiazepines Addiction & Treatment
Benzodiazepines Addiction & Treatment Benzodiazepines are often used therapeutically to produce sedation, induce sleep, relieve anxiety and muscle spasms, and to prevent seizures. Benzodiazepines act as hypnotics in high doses, anxiolytics in moderate doses, and sedatives in low doses. Benzodiazepines effect the central nervous system functions and are classified as depressants. They are more commonly referred to as “benzos” or “benzies” and are ingestible in pill form or injected. Benzodiazepines can be found in many medications, including, but not limited to: Xanax (alprazolam), Valium (diazepam), Librium (chlordiazepoxide), Tranxene (clorazepate), Paxipam (Halazepam), Centrax (prazepam), Klonopin/Clonopin (Clonazepam), Serax (oxazepam), Restoril (temazepam), ProSom (estazolam), Dalmane (flurazepam) *Rohypnol (Flunitrazepam) is a benzodiazepine not manufactured or legally marketed in the United States; however it is often smuggled in by traffickers. This drug is often referred to as a “roofie” and is known as both a “party drug” and a “date rape” drug. It often is found to be popular among younger users. Effects of Benzodiazepines Benzodiazepine use can lead to amnesia, hostility, irritability, vivid or disturbing dreams, as well as tolerance and physical dependence. Use with alcohol or another depressant can lead to death, and often benzodiazepine abuse is particularly high among heroin and cocaine abusers. Lasting/Long-Term Effects Benzodiazepines target the emotional response system (limbic) of the brain, rather than the entire central nervous system. This leads to fewer long term effects than other drugs; however continued use can lead to physical and psychological dependence as well as addiction. Due to a tolerance developed to benzodiazepines, users must increase their doses in order to achieve the desired effects. -
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 -
Anxiety Disorders, Insomnia, PTSD, OCD
2/3/2020 Anxiety Disorders, Insomnia, PTSD, OCD Steven L. Dubovsky, M.D. 1 2/3/2020 Basic Benzodiazepine Structure R1 R2 N C R7 C R3 C=N R4 R2′ Benzodiazepine R1 R2 R3 R7 R2′ Alprazolam Fused triazolo ring -H -Cl -H Chlordiazepoxide - -NHCH3 -H -Cl -H Clonazepam -H =O -H NO2 -Cl Diazepam -CH3 =O -H -Cl -H 2 2/3/2020 GABA-Benzodiazepine Receptor Complex GABA BZD Cl- 3 2/3/2020 Benzodiazepine Action GABA Cl- + + BZD - Cl- Inverse agonist Flumazenil • Benzodiazepine receptor antagonist R1 R2 • Therapeutic uses: C N – Benzodiazepine overdose R3 C R7 N C – Reversal of conscious sedation R4 = – Reversal of hepatic encephalopathy symptoms R2′ – Facilitation of benzodiazepine withdrawal • Can provoke withdrawal and induce anxiety 4 2/3/2020 BZD Receptor Subtypes • Type 1: Limbic system, locus coeruleus – Anxiolytic • Type 2: Cortex, pyramidal cells – Muscle relaxation, anticonvulsant, CNS depression, sedation, psychomotor impairment • Type 3: Mitochondria, periphery – Dependence, withdrawal BZD Features • Potency – High potency: Midazolam (Versed), alprazolam (Xanax), triazolam (Halcion) – Low potency: Chlordiazepoxide (Librium), flurazepam (Dalmane) • Lipid solubility – High solubility: Alprazolam, diazepam (Valium) – Low solubility: Lorazepam (Ativan), chlordiazepoxide (Librium) • Elimination half-life – Long half-life: Diazepam, chlordiazepoxide – Short half-life: Alprazolam, midazolam 5 2/3/2020 Potency • High potency – Smaller dose to produce same effect – More receptor occupancy – More intense withdrawal • Low potency – Higher doses used -
Safe and Unsafe Medications
SAFE AND UNSAFE MEDICATIONS UNSAFE MEDICATIONS Anesthesia Agents Requiring Caution in Duchenne The following anesthetic agents are NOT SAFE in Duchenne Please refer to parentprojectmd.org/anesthesia for more information. Depolarizing Muscle Relaxants Trigger Rhabdomyolysis: succinylcholine (suxamethonium) Inhaled General Anesthetics (avoid if possible): Examples: desflurane, enflurane, halothane, isoflurane, sevoflurane, xenon SAFE MEDICATIONS All of the following medications are considered to be safe to give to people with Duchenne with close monitoring Anesthesia/Pain Barbiturates/Intravenous Anesthetics diazepam, etomidate, ketamine, methohexital, midazolam, propofol, thiopental Inhaled Non-Volatile General Anesthetic nitrous oxide (“laughing gas”) Local Anesthetics amethocaine, articaine, benzocaine (caution re: methemoglobinemia risk), bupivacaine, etidocaine, lidocaine, levobupivacaine, mepivacaine, procaine, prilocaine, ropivacaine Narcotics (opioids) alfentanil, fentanyl, hydromorphone, meperidine, methadone, methylmorphine, morphine, naloxone, oxycodone, remifentanil, sufentanil Muscle Relaxants atracurium, cisatracurium, doxacurium, d-tubocurarine, metocurine, mivacurium, pancuronium, pipecuronium, rocuronium, vecuronium 1 Behavioral and Psychiatric Medications ADD (with or without hyperactivity) – Short-Acting Stimulants: Obtain baseline ECG before use. Examples: dexmethylphenidate, dextroamphetamine and amphetamine, dextroamphetamine, methylphenidate – Long-Acting Stimulants: Examples: amphetamine sulfate, dextroamphetamine, -
Use and Abuse of Benzodiazepines*
A rticles in the Update series Les articles de la rubrique give a concise, authoritative. Le point fournissent un and up-to-date wurvev of the bhilan concis et fiable de la present position in the se- I .ituation actuelle dans le lected fields, and, over a domaine considere. Des ex- ,/t a e period of years, will cover perts couvriront ainsi .vucl- man v different aspe ts of cessivement de nombreux the biomedical sciences aspects des sciences bio- L e p ointt atid public health. .Mo.st oJf mdicales et de la sante the articles will be writ- publique. La plupart de ces ten, by invitation. bv ic- articles auront donc ete A/nowledged experts on the rediges stir demande par les subject. specialistes les plus autorises. Bulletin ofthe World Health Organization, 61 (4): 551 - 562 (1983) © World Health Organization 1983 Use and abuse of benzodiazepines* WHO REVIEW GROUP Benzodiazepines are widely used for the treatment of anxiety, insomnia, and certain neuromuscular and convulsive disorders. However, their widespread avail- ability has given rise to fears that they are over-prescribed. The problem is compounded by the fact that there is no universal agreement among medical prac- titioners as to the clinical indications warranting the use of these drugs. Although most industrialized countries exercise control over the sale and manufacture of benzodiazepines, many developing countries do not have sufficient control of these drugs. As a result, information on drug utilization and associated problems is diffi- cult to obtain and there is a lack ofcomparative data on drug consumption in differ- ent countries. -
Chlordiazepoxide Oral Capsules for Treatment of Acute Alcohol Withdrawal Is to Be Reviewed for Use Within: Primary Care Secondary Care
New Medicines Committee Briefing March 2016 Chlordiazepoxide oral capsules for treatment of acute alcohol withdrawal is to be reviewed for use within: Primary Care Secondary Care Summary: Chlordiazepoxide is an anxiolytic with a UK marketing authorisation for use in the management of acute alcohol withdrawal. Anxiolytics listed in the Joint Formulary for treatment of alcohol withdrawal include diazepam, escitalopram, lorazepam and propranolol. Chlordiazepoxide would provide an alternative to diazepam and lorazepam for patients who fail to respond to first line treatments. Chlordiazepoxide is more expensive than generic diazepam (Note: Diazepam 10mg ≡ Chlordiazepoxide 25mg) Chlordiazepoxide would provide a long acting alternative to the short acting agents when preventing withdrawal seizures. Chlordiazepoxide would contribute to a smoother withdrawal with fewer rebound symptoms. Chlordiazepoxide is less likely to be abused compared to rapid acting agents (diazepam and lorazepam). Chlordiazepoxide is a schedule 4 controlled drug (CD Benz POM). Page 1 of 14 Formulary application Consultant submitting application: Ediela Iliescu (Consultant Substance Misuse Pschyiatrist) (North Staffordshire Combined Healthcare Trust) Clinical Director supporting application: Derrett Watts (Consultant addiction Psychiatrist) (North Staffordshire, Combined Healthcare Trust) The application is a request for chlordiazepoxide to be considered for inclusion in the North Staffordshire Joint Formulary for the treatment of alcohol withdrawal. In support, the applicant states that chlordiazepoxide is well suited for the treatment of alcohol withdrawal and can be used as an alternative to diazepam. Dr Iliescu states that it is difficult to quantify the exact number of patients that commence detoxification in the community. However, based on the figures provided by One Recovery in South Staffordshire (Stafford, Tamworth, Burton and Cannock), it is estimated that approximately 500 hundred patients per year commence treatment for alcohol detoxification in the community. -
Benzodiazepine Assay
2 SUmmARy Benzodiazepines are sedative-hypnotic drugs that are structurally similar and include widely used drugs such as chlordiazepoxide, diazepam, and oxazepam. The different benzodiazepines are absorbed at different rates, and the timing of their psychoactive effects varies with the absorption rate. Benzodiazepines are usually taken orally and are metabolized in the liver. Some benzodiazepine metabolites are pharmacologically active.2 Benzodiazepines potentiate the effect Benzodiazepine Assay of other central nervous system depressants, such as ethyl alcohol.3 The Emit® II Plus Benzodiazepine Assay, an enzyme immunoassay technique, tests for benzodiazepines and their metabolites in human urine. Positive results for specimens containing September 2010 9F052.4D_E other compounds structurally unrelated to benzodiazepines have not been observed. The cutoff levels for distinguishing positive from negative specimens are 200 ng/mL and 300 ng/mL. Methods historically used for detecting benzodiazepines in biological fluids include gas chromatography with electron-capture4 or flame-ionization detection,5 high-performance liquid chromatography,6 thin-layer chromatography,7 fluorescence-TLC densitometry,8 enzyme immunoassay,9 and radioimmunoassay.10 While confirmation techniques other than GC/MS may be adequate for some drugs of abuse, GC/MS is generally accepted as a vigorous confirmation technique for all drugs, since it provides the best level of confidence in the result.1 Catalog Quantity/ 3 mEThODOLOgy Number Product Description Volume OSR9F229 Emit® II Plus Benzodiazepine Assay The Emit® II Plus Benzodiazepine Assay is a homogeneous enzyme immunoassay technique used for the analysis of specific compounds in human urine.11 The assay is based on competition OSR9F618 R1 (Antibody/Substrate Reagent 1) 2 x 31 mL between drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites.