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Benzodiazepines: Uses and Risks Charlie Reznikoff, MD Hennepin Healthcare
Benzodiazepines: Uses and Risks Charlie Reznikoff, MD Hennepin healthcare 4/22/2020 Overview benzodiazepines • Examples of benzos and benzo like drugs • Indications for benzos • Pharmacology of benzos • Side effects and contraindications • Benzo withdrawal • Benzo tapers 12/06/2018 Sedative/Hypnotics • Benzodiazepines • Alcohol • Z-drugs (Benzo-like sleeping aids) • Barbiturates • GHB • Propofol • Some inhalants • Gabapentin? Pregabalin? 12/06/2018 Examples of benzodiazepines • Midazolam (Versed) • Triazolam (Halcion) • Alprazolam (Xanax) • Lorazepam (Ativan) • Temazepam (Restoril) • Oxazepam (Serax) • Clonazepam (Klonopin) • Diazepam (Valium) • Chlordiazepoxide (Librium) 4/22/2020 Sedatives: gaba stimulating drugs have incomplete “cross tolerance” 12/06/2018 Effects from sedative (Benzo) use • Euphoria/bliss • Suppresses seizures • Amnesia • Muscle relaxation • Clumsiness, visio-spatial impairment • Sleep inducing • Respiratory suppression • Anxiolysis/disinhibition 12/06/2018 Tolerance to benzo effects? • Effects quickly diminish with repeated use (weeks) • Euphoria/bliss • Suppresses seizures • Effects incompletely diminish with repeated use • Amnesia • Muscle relaxation • Clumsiness, visio-spatial impairment • Seep inducing • Durable effects with repeated use • Respiratory suppression • Anxiolysis/disinhibition 12/06/2018 If you understand this pharmacology you can figure out the rest... • Potency • 1 mg diazepam <<< 1 mg alprazolam • Duration of action • Half life differences • Onset of action • Euphoria, clinical utility in acute -
Belviq® (Lorcaserin) Patient Information
Belviq® (lorcaserin) Patient Information Who Is Belviq For? Belviq is a medication for chronic weight management. It is for people with overweight and weight-related conditions or obesity. It is meant to be used together with a lifestyle therapy regimen involving a reduced calorie diet and increased physical activity. How Does Belviq Work? Belviq works in the brain as an appetite suppressant. Who Should Not Take Belviq? Women who are pregnant, nursing, or planning to become pregnant. How Is Belviq Dosed? Belviq® (lorcaserin) Belviq XR® (lorcaserin extended release) Take one 10 mg tablet 2 times each day with Take one 20 mg tablet once daily with or or without food. without food. Is Belviq a Controlled Substance? Belviq is a federally controlled substance because it contains lorcaserin hydrochloride and may be abused or lead to drug dependence. Some states do not allow your doctor to prescribe more than one month at a time. Which Medications Might Not Be Safe to Use with Belviq? Belviq can affect how other medicines work in your body, and other medicines can affect how Belviq works. Tell your doctor about all the medicines and supplements you take, especially those used to treat depression, migraines, or other medical conditions, such as: • Triptans—used to treat migraine headache • Medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium, selective serotonin uptake inhibitors (SSRIs), selective serotonin- norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), or antipsychotics • Cabergoline—used to treat a hormone imbalance involving prolactin • Linezolid—an antibiotic • Tramadol—an opioid pain reliever • Dextromethorphan—an over-the-counter medicine used to treat the common cold or cough • Over-the-counter supplements such as tryptophan or St. -
The Toxicology Panel -17Th Nysam (Virtual) Conference 2021
THE TOXICOLOGY PANEL -17TH NYSAM (VIRTUAL) CONFERENCE 2021 MODERATOR: TIMOTHY J. WIEGAND, MD, FACMT, FAACT, DFASAM JoAn Laes, MD Addiction Medicine Faculty Hennepin County Medical Center, Minneapolis, MN Lewis Nelson, MD, FACMT Chair, Department of Emergency Medicine, Rutgers New Jersey Medical School Jeanmarie Perrone, MD Director of Division of Medical Toxicology & Penn Center PANELISTS for Addiction Medicine and Policy Ross Sullivan, MD Director SUNY Upstate Emergency Bridge Clinic & Medical Director Helio Health, Syracuse, NY Paul Wax, MD, FACMT Executive Director the American College of Medical Toxicology CONFLICT OF NONE OF OUR SPEAKERS HAVE ANY CONFLICTS OF INTEREST INTEREST TO DISCLOSE A 27 year-old M with history of opioid and sedative use disorder had been doing well in an outpatient treatment program with mix of counseling and treatment with buprenorphine/naloxone. CASE 1 He entered the program about 9 months prior after a 28 day combined detoxification/inpatient facility stay where he was transitioned from heroin/fentanyl (“10 bags/day”) to the buprenorphine and “detoxified” from 2-4 mg alprazolam and/or 2-4 mg clonazepam daily. CASE 1 About 9 months into the program he is found sleeping at work by his boss and when awoke he is slurring his speech and has trouble walking. This was a job he’d lost prior to treatment but they had let him back in 3 months after starting in treatment after he demonstrated sobriety –he worked with his father in a recycling plant coordinating large shipments and sometimes picking up materials using heavy equipment and other machinery. He lives with his parents and they are quite upset about the incident but he states, “I wasn’t using I was just tired!” CASE 1 The parents communicate with his counselor and he is brought in for a urine drug test –which initially tests positive for benzodiazepines but the confirmation is negative. -
WHO Expert Committee on Drug Dependence
WHO Technical Report Series 1034 This report presents the recommendations of the forty-third Expert Committee on Drug Dependence (ECDD). The ECDD is responsible for the assessment of psychoactive substances for possible scheduling under the International Drug Control Conventions. The ECDD reviews the therapeutic usefulness, the liability for abuse and dependence, and the public health and social harm of each substance. The ECDD advises the Director-General of WHO to reschedule or to amend the scheduling status of a substance. The Director-General will, as appropriate, communicate the recommendations to the Secretary-General of the United Nations, who will in turn communicate the advice to the Commission on Narcotic Drugs. This report summarizes the findings of the forty-third meeting at which the Committee reviewed 11 psychoactive substances: – 5-Methoxy-N,N-diallyltryptamine (5-MeO-DALT) WHO Expert Committee – 3-Fluorophenmetrazine (3-FPM) – 3-Methoxyphencyclidine (3-MeO-PCP) on Drug Dependence – Diphenidine – 2-Methoxydiphenidine (2-MeO-DIPHENIDINE) Forty-third report – Isotonitazene – MDMB-4en-PINACA – CUMYL-PEGACLONE – Flubromazolam – Clonazolam – Diclazepam The report also contains the critical review documents that informed recommendations made by the ECDD regarding international control of those substances. The World Health Organization was established in 1948 as a specialized agency of the United Nations serving as the directing and coordinating authority for international health matters and public health. One of WHO’s constitutional functions is to provide objective, reliable information and advice in the field of human health, a responsibility that it fulfils in part through its extensive programme of publications. The Organization seeks through its publications to support national health strategies and address the most pressing public health concerns of populations around the world. -
The Melanocortin-4 Receptor As Target for Obesity Treatment: a Systematic Review of Emerging Pharmacological Therapeutic Options
International Journal of Obesity (2014) 38, 163–169 & 2014 Macmillan Publishers Limited All rights reserved 0307-0565/14 www.nature.com/ijo REVIEW The melanocortin-4 receptor as target for obesity treatment: a systematic review of emerging pharmacological therapeutic options L Fani1,3, S Bak1,3, P Delhanty2, EFC van Rossum2 and ELT van den Akker1 Obesity is one of the greatest public health challenges of the 21st century. Obesity is currently responsible for B0.7–2.8% of a country’s health costs worldwide. Treatment is often not effective because weight regulation is complex. Appetite and energy control are regulated in the brain. Melanocortin-4 receptor (MC4R) has a central role in this regulation. MC4R defects lead to a severe clinical phenotype with lack of satiety and early-onset severe obesity. Preclinical research has been carried out to understand the mechanism of MC4R regulation and possible effectors. The objective of this study is to systematically review the literature for emerging pharmacological obesity treatment options. A systematic literature search was performed in PubMed and Embase for articles published until June 2012. The search resulted in 664 papers matching the search terms, of which 15 papers remained after elimination, based on the specific inclusion and exclusion criteria. In these 15 papers, different MC4R agonists were studied in vivo in animal and human studies. Almost all studies are in the preclinical phase. There are currently no effective clinical treatments for MC4R-deficient obese patients, although MC4R agonists are being developed and are entering phase I and II trials. International Journal of Obesity (2014) 38, 163–169; doi:10.1038/ijo.2013.80; published online 18 June 2013 Keywords: MC4R; treatment; pharmacological; drug INTRODUCTION appetite by expressing anorexigenic polypeptides such as Controlling the global epidemic of obesity is one of today’s pro-opiomelanocortin and cocaine- and amphetamine-regulated most important public health challenges. -
CRITERIA for DRUG COVERAGE Solriamfetol (Sunosi)
Criteria-Based Consultation Prescribing Program CRITERIA FOR DRUG COVERAGE Solriamfetol (Sunosi) Notes: * Intolerance excludes adverse drug reactions that are expected, mild in nature, resolve with continued treatment, and do not require medication discontinuation Initiation (new start) criteria: Non-formulary solriamfetol (Sunosi) will be covered on the prescription drug benefit for 12 months when the following criteria are met: • Prescribed by a Sleep Specialist • Prescribed for the treatment of excessive daytime sleepiness due to narcolepsy OR excessive daytime sleepiness due to obstructive sleep apnea (OSA) • Patient is 18 years of age or older • Patient has failed a trial of, or patient has an allergy or intolerance* to: o Modafinil or armodafinil AND o A stimulant medication (ie methylphenidate, dextroamphetamine, amphetamine salt combination, etc.) • OSA only: patient is currently treated for OSA [i.e. use of CPAP, or use of oral appliances (eg mandibular advancement device, tongue retaining devices), or had past OSA surgery] Criteria for current Kaiser Permanente members already taking the medication who have not been reviewed previously: Non-formulary solriamfetol (Sunosi) will be covered on the prescription drug benefit for 24 months when the following criteria are met: • See above New Start criteria Criteria for new members entering Kaiser Permanente already taking the medication who have not been reviewed previously: Non-formulary solriamfetol (Sunosi) will be covered on the prescription drug benefit for 12 months when the -
Flualprazolam Sample Type: Biological Fluid
Flualprazolam Sample Type: Biological Fluid Latest Revision: June 25, 2019 Date of Report: June 25, 2019 1. GENERAL INFORMATION IUPAC Name: 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3- a][1,4]benzodiazepine InChI String: InChI=1S/C17H12ClFN4/c1-10-21-22-16-9-20-17(12-4-2-3-5- 14(12)19)13-8-11(18)6-7-15(13)23(10)16/h2-8H,9H2,1H3 CFR: Not Scheduled (06/2019) CAS# 28910-91-0 Synonyms: 2’-Fluoro Alprazolam, ortho-Fluoro Alprazolam Source: NMS Labs – Toxicology Department 2. CHEMICAL DATA Chemical Molecular Molecular Exact Mass Analyte Formula Weight Ion (M) [M+H]+ Flualprazolam C17H12ClFN4 326.75 326 327.0807 Important Note: All identifications were made based on evaluation of analytical data (LC-QTOF) in comparison to analysis of acquired reference material. Report Prepared By: Alex J. Krotulski, MSFS, and Barry K. Logan, PhD, F-ABFT 3. SAMPLE HISTORY Flualprazolam has been identified in three cases since March 2018. The geographical and demographic breakdown is below: Geographical Location: Pennsylvania (n=2), Indiana (n=1) Biological Sample: Blood (n=3) Date of First: Collection: March 8, 2018 Receipt: March 10, 2018 Date of Most Recent: Collection: June 3, 2019 Receipt: June 7, 2019 Additional NPS: Etizolam (n=2), Clonazolam (n=1), Flubromazolam (n=1) 4. BRIEF DESCRIPTION Flualprazolam is classified as a novel benzodiazepine, although its synthesis and activity have been previously described in the literature.1 Benzodiazepines are central nervous system depressants. Novel benzodiazepines, often pirated from early drug discovery or pharmaceutical studies, have appeared on novel and illicit drug markets in recent years. -
Introduced B.,Byhansen, 16
LB301 LB301 2021 2021 LEGISLATURE OF NEBRASKA ONE HUNDRED SEVENTH LEGISLATURE FIRST SESSION LEGISLATIVE BILL 301 Introduced by Hansen, B., 16. Read first time January 12, 2021 Committee: Judiciary 1 A BILL FOR AN ACT relating to the Uniform Controlled Substances Act; to 2 amend sections 28-401, 28-405, and 28-416, Revised Statutes 3 Cumulative Supplement, 2020; to redefine terms; to change drug 4 schedules and adopt federal drug provisions; to change a penalty 5 provision; and to repeal the original sections. 6 Be it enacted by the people of the State of Nebraska, -1- LB301 LB301 2021 2021 1 Section 1. Section 28-401, Revised Statutes Cumulative Supplement, 2 2020, is amended to read: 3 28-401 As used in the Uniform Controlled Substances Act, unless the 4 context otherwise requires: 5 (1) Administer means to directly apply a controlled substance by 6 injection, inhalation, ingestion, or any other means to the body of a 7 patient or research subject; 8 (2) Agent means an authorized person who acts on behalf of or at the 9 direction of another person but does not include a common or contract 10 carrier, public warehouse keeper, or employee of a carrier or warehouse 11 keeper; 12 (3) Administration means the Drug Enforcement Administration of the 13 United States Department of Justice; 14 (4) Controlled substance means a drug, biological, substance, or 15 immediate precursor in Schedules I through V of section 28-405. 16 Controlled substance does not include distilled spirits, wine, malt 17 beverages, tobacco, hemp, or any nonnarcotic substance if such substance 18 may, under the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. -
Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances Joshua Zolton Seither [email protected]
Florida International University FIU Digital Commons FIU Electronic Theses and Dissertations University Graduate School 4-25-2018 Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances Joshua Zolton Seither [email protected] DOI: 10.25148/etd.FIDC006565 Follow this and additional works at: https://digitalcommons.fiu.edu/etd Part of the Chemistry Commons Recommended Citation Seither, Joshua Zolton, "Application of High Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances" (2018). FIU Electronic Theses and Dissertations. 3823. https://digitalcommons.fiu.edu/etd/3823 This work is brought to you for free and open access by the University Graduate School at FIU Digital Commons. It has been accepted for inclusion in FIU Electronic Theses and Dissertations by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. FLORIDA INTERNATIONAL UNIVERSITY Miami, Florida APPLICATION OF HIGH RESOLUTION MASS SPECTROMETRY FOR THE SCREENING AND CONFIRMATION OF NOVEL PSYCHOACTIVE SUBSTANCES A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in CHEMISTRY by Joshua Zolton Seither 2018 To: Dean Michael R. Heithaus College of Arts, Sciences and Education This dissertation, written by Joshua Zolton Seither, and entitled Application of High- Resolution Mass Spectrometry for the Screening and Confirmation of Novel Psychoactive Substances, having been approved in respect to style and intellectual content, is referred to you for judgment. We have read this dissertation and recommend that it be approved. _______________________________________ Piero Gardinali _______________________________________ Bruce McCord _______________________________________ DeEtta Mills _______________________________________ Stanislaw Wnuk _______________________________________ Anthony DeCaprio, Major Professor Date of Defense: April 25, 2018 The dissertation of Joshua Zolton Seither is approved. -
1 'New/Designer Benzodiazepines'
1 ‘New/Designer Benzodiazepines’: an analysis of the literature and psychonauts’ trip reports 2 Laura Orsolini*1,2,3, John M. Corkery1, Stefania Chiappini1, Amira Guirguis1, Alessandro Vento4,5,6,7, 3 Domenico De Berardis3,8,9, Duccio Papanti1, and Fabrizio Schifano1 4 5 1 Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical 6 Sciences, University of Hertfordshire, Hatfield, AL10 9AB, Herts, UK. 7 2 Neomesia Mental Health, Villa Jolanda Hospital, Jesi, Italy. 8 3 Polyedra, Teramo, Italy. 9 4 NESMOS Department (Neurosciences, Mental Health and Sensory Organs), Sapienza University – Rome, School of 10 Medicine and Psychology; Sant’Andrea Hospital, Rome, Italy 11 5 School of psychology - G. Marconi Telematic University, Rome, Italy 12 6 Addictions Observatory (ODDPSS), Rome, Italy 13 7 Mental Health Department - ASL Roma 2, Rome, Italy 14 8 Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University of “G. D’Annunzio”, Chieti, 15 Italy. 16 9 NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital “G. Mazzini”, ASL 4 17 Teramo, Italy. 18 19 Corresponding author: 20 Laura Orsolini, Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life 21 and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, Herts, UK; Villa Jolanda Hospital, Neomesia 22 Mental Health, Villa Jolanda, Italy; Polyedra, Teramo, Italy; E-mail address: [email protected]. Tel.: (+39) 392 23 3244643. 24 25 Conflicts of Interest 26 The authors declare that this research was conducted in the absence of any commercial or financial relationships 27 that could be construed as a potential conflict of interest. -
Nanotechnology‐Mediated Drug Delivery for the Treatment Of
REVIEW Obesity www.advhealthmat.de Nanotechnology-Mediated Drug Delivery for the Treatment of Obesity and Its Related Comorbidities Yung-Hao Tsou, Bin Wang, William Ho, Bin Hu, Pei Tang, Sydney Sweet, Xue-Qing Zhang,* and Xiaoyang Xu* crisis globally. People with a body mass Obesity is a serious health issue affecting humanity on a global scale. index (BMI, mass in kilograms divided by Recognized by the American Medical Association as a chronic disease, the the square of the height in meters) above −2 [3,4] incidence of obesity continues to grow at an accelerating rate and obesity 30 kg m are considered obese. The American Medical Association has classi- has become one of the major threats to human health. Excessive weight fied obesity as a reversible and preventable gain is tied to metabolic syndrome, which is shown to increase the risk chronic disease, which is accompanied of chronic diseases, such as heart disease and type 2 diabetes, taxing an by a host of related deadly comorbidities already overburdened healthcare system and increasing mortality worldwide. including type 2 diabetes, heart disease, [5] Available treatments such as bariatric surgery and pharmacotherapy are and several types of cancers. Particularly, often accompanied by adverse side effects and poor patient compliance. diabetic disorders and cardiovascular dis- eases are the most common comorbidities Nanotechnology, an emerging technology with a wide range of biomedical associated with obesity. applications, has provided an unprecedented opportunity to improve The causes of obesity are complex and the treatment of many diseases, including obesity. This review provides multivariate. Broadly speaking, behavior an introduction to obesity and obesity-related comorbidities. -
NMS Labs Demo Report
NMS Labs CONFIDENTIAL 200 Welsh Road, Horsham, PA 19044-2208 Phone: (215) 657-4900 Fax: (215) 657-2972 e-mail: [email protected] Robert A. Middleberg, PhD, F-ABFT, DABCC-TC, Laboratory Director Demo Report Patient Name 0570B-POS Report Issued 06/19/2017 08:16 Patient ID 0570B-POS Last Report Issued 04/10/2017 13:19 Chain 17000768 Age Not Given DOB Not Given 88888 Gender Not Given Clinical Example Report Attn: IT Department Workorder 17000768 200 Welsh Road Horsham, PA 19044-2208 Received 04/10/2017 12:42 Sample ID 17000768-001 Collect Dt/Tm Not Given Matrix Blood Source Not Given Patient Name 0570B-POS Patient ID 0570B-POS Container Type Clear vial Approx Vol/Weight Not Given Receipt Notes None Entered Reporting Analysis and Comments Result Units Limit Notes 0570B Designer Benzodiazepines, Blood (Forensic) Analysis by High Performance Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) Bromazepam 50 ng/mL 5.0 Bromazepam is a benzodiazepine drug that is used as a novel psychoactive substance. It is reported to have CNS depressant properties and shares anticonvulsant, muscle relaxant, hypnotic, anxiolytic and sedative effects with other benzodiazepines. It is not approved for use in the United States, but is available in some other countries. Average peak plasma concentrations following a single 3 mg, 6 mg and 12 mg dose were reported to be 10 ng/mL at 8 hours, 83 ng/mL at 2 hours and 130 ng/mL at 1-4 hours after dosing, respectively. Chronic oral administration of 9 mg daily resulted in an steady-state plasma concentrations of 81-150 ng/mL (Average = 120 ng/mL).