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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 -
Test Update Immediate Action Notification
Effective Date: Monday, April 27, 2020 Test Updates Immediate Action In our continuing effort to provide you with the highest quality toxicology laboratory services available, we have compiled important changes regarding a number of tests we perform. Listed below are the types of changes that may be included in this notification, effective Monday, April 27, 2020 Test Changes - Tests that have had changes to the method/ CPT code, units of measurement, scope of analysis, reference comments, or specimen requirements. Discontinued Tests - Tests being discontinued with alternate testing suggestions. Please use this information to update your computer systems/records. These changes are important to ensure standardization of our mutual laboratory databases. If you have any questions about the information contained in this notification, please call our Client Support Department at (866) 522-2206. Thank you for your continued support of NMS Labs and your assistance in implementing these changes. The CPT Codes provided in this document are based on AMA guidelines and are for informational purposes only. NMS Labs does not assume responsibility for billing errors due to reliance on the CPT Codes listed in this document. NMS Labs 200 Welsh Rd. Horsham, PA 19044-2208 [email protected] Page 1 of 6 Effective Date: Monday, April 27, 2020 Test Updates Test Test Name Test Method / Specimen Stability Scope Units Reference Discontinue Code Name CPT Code Req. Comments Designer Benzodiazepines (Qualitative), 0570U • Urine (Forensic) Designer Benzodiazepines Confirmation 52487U • (Qualitative), Urine Designer Benzodiazepines Confirmation, 52487B • Blood Designer Benzodiazepines Confirmation, 52487SP • Serum/Plasma Designer Benzodiazepines, Blood 0570B • (Forensic) Designer Benzodiazepines, 0570SP • Serum/Plasma (Forensic) NMS Labs 200 Welsh Rd. -
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. -
Table 6.12: Deaths from Poisoning, by Sex and Cause, Scotland, 2016
Table 6.12: Deaths from poisoning, by sex and cause, Scotland, 2016 ICD code(s), cause of death and substance(s) 1 Both Males Females ALL DEATHS FROM POISONING 2 1130 766 364 ACCIDENTS 850 607 243 X40 - X49 Accidental poisoning by and exposure to … X40 - Nonopioid analgesics, antipyretics and antirheumatics Paracetamol 2 1 1 Paracetamol, Cocaine, Amphetamine || 1 0 1 X41 - Antiepileptic, sedative-hypnotic, antiparkinsonism and psychotropic drugs, not elsewhere classified Alprazolam, MDMA, Cocaine || Cannabis, Alcohol 1 1 0 Alprazolam, Methadone || Pregabalin, Tramadol, Gabapentin, Cannabis 1 1 0 Alprazolam, Morphine, Heroin, Dihydrocodeine, Buprenorphine || Alcohol 1 1 0 Alprazolam, Oxycodone, Alcohol || Paracetamol 1 0 1 Amitriptyline, Cocaine, Etizolam || Paracetamol, Codeine, Hydrocodone, Alcohol 1 1 0 Amitriptyline, Dihydrocodeine || Diazepam, Paracetamol, Verapamil, Alcohol 1 1 0 Amitriptyline, Fluoxetine, Alcohol 1 0 1 Amitriptyline, Methadone, Diazepam || 1 1 0 Amitriptyline, Methadone, Morphine, Etizolam || Gabapentin, Cannabis, Alcohol 1 1 0 Amitriptyline, Venlafaxine 1 0 1 Amphetamine 1 1 0 Amphetamine || 1 1 0 Amphetamine || Alcohol 1 1 0 Amphetamine || Chlorpromazine 1 1 0 Amphetamine || Fluoxetine 1 1 0 Amphetamine, Dihydrocodeine, Alcohol || Procyclidine, Tramadol, Duloxetine, Haloperidol 1 0 1 Amphetamine, MDMA || Diclazepam, Cannabis, Alcohol 1 1 0 Amphetamine, Methadone || 1 1 0 Amphetamine, Oxycodone, Gabapentin, Zopiclone, Diazepam || Paracetamol, Alcohol 1 0 1 Amphetamine, Tramadol || Mirtazapine, Alcohol 1 1 0 Benzodiazepine -
Benzodiazepine Group ELISA Kit
Benzodiazepine Group ELISA Kit Benzodiazepine Background Since their introduction in the 1960s, benzodiazepines have been widely prescribed for the treatment of anxiety, insomnia, muscle spasms, alcohol withdrawal, and seizure-prevention as they are depressants of the central nervous system. Despite the fact that they are highly effective for their intended use, benzodiazepines are prescribed with caution as they can be highly addictive. In fact, researchers at NIDA (National Institute on Drug Abuse) have shown that addiction for benzodiazepines is similar to that of opioids, cannabinoids, and GHB. Common street names of benzodiazepines include “Benzos” and “Downers”. The five most encountered benzodiazepines on the illicit market are alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin), diazepam (Valium), and temazepam (Restori). The method of abuse is typically oral or snorted in crushed form. The DEA notes a particularly high rate of abuse among heroin and cocaine abusers. Designer benzodiazepines are currently offered in online shops selling “research chemicals”, providing drug abusers an alternative to prescription-only benzodiazepines. Data defining pharmacokinetic parameters, drug metabolisms, and detectability in biological fluids is limited. This lack of information presents a challenge to forensic laboratories. Changes in national narcotics laws in many countries led to the control of (phenazepam and etizolam), which were marketed by pharmaceutical companies in some countries. With the control of phenazepam and etizolam, clandestine laboratories have begun researching and manufacturing alternative benzodiazepines as legal substitutes. Delorazepam, diclazepam, pyrazolam, and flubromazepam have emerged as compounds in this class of drugs. References Drug Enforcement Administration, Office of Diversion Control. “Benzodiazepines.” http://www.deadiversion.usdoj.gov/drugs_concern/benzo_1. -
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. -
Drug Names That Are Too Close for Comfort
MEDICATION SAFETY Drug Names That Are Too Close for Comfort and therefore at risk of “seeing” prescriptions for the newer product clobazam as the more familiar clonazePAM. Use TWO IDENtifieRS at THE POS Within the span of a couple of days, the Institute for Safe Medication Practices received two more reports of wrong patient errors at the point-of-sale. Both were submitted by the parents of the patients involved. In one event, a teenager, who Look- and sound-alike similarity between the official names was supposed to receive methylphenidate for Attention Deficit clobazam (ONFI) and clonazePAM (KLONOPIN) has led Hyperactivity Disorder (ADHD), was given a cardiac drug to several reports expressing concern that patients may in- intended for a different patient. The mother who was picking advertently receive the wrong medication in either hospital up the prescription for her son caught the error because or outpatient settings. The drugs share similar indications, the pharmacist mentioned that “this will help with the chest although they have 10-fold strength difference in available pains.” Of course, this means that the other patient was given dosage forms. Clobazam was approved by Food and Drug the methylphenidate instead of the cardiac drug. It turned out Administration in October 2011 for adjunctive treatment of that the teenager and the other patient had the same name. Lennox-Gaustaut seizures and other epileptic syndromes. Lennox-Gaustaut is a form of childhood-onset epilepsy In the second case, a patient was dispensed amLODIPine, a characterized by frequent seizures and different seizure calcium channel blocker, instead of the anticonvulsant gab- types, often accompanied by developmental delay and apentin. -
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. -
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. -
CAS Number Index
2334 CAS Number Index CAS # Page Name CAS # Page Name CAS # Page Name 50-00-0 905 Formaldehyde 56-81-5 967 Glycerol 61-90-5 1135 Leucine 50-02-2 596 Dexamethasone 56-85-9 963 Glutamine 62-44-2 1640 Phenacetin 50-06-6 1654 Phenobarbital 57-00-1 514 Creatine 62-46-4 1166 α-Lipoic acid 50-11-3 1288 Metharbital 57-22-7 2229 Vincristine 62-53-3 131 Aniline 50-12-4 1245 Mephenytoin 57-24-9 1950 Strychnine 62-73-7 626 Dichlorvos 50-23-7 1017 Hydrocortisone 57-27-2 1428 Morphine 63-05-8 127 Androstenedione 50-24-8 1739 Prednisolone 57-41-0 1672 Phenytoin 63-25-2 335 Carbaryl 50-29-3 569 DDT 57-42-1 1239 Meperidine 63-75-2 142 Arecoline 50-33-9 1666 Phenylbutazone 57-43-2 108 Amobarbital 64-04-0 1648 Phenethylamine 50-34-0 1770 Propantheline bromide 57-44-3 191 Barbital 64-13-1 1308 p-Methoxyamphetamine 50-35-1 2054 Thalidomide 57-47-6 1683 Physostigmine 64-17-5 784 Ethanol 50-36-2 497 Cocaine 57-53-4 1249 Meprobamate 64-18-6 909 Formic acid 50-37-3 1197 Lysergic acid diethylamide 57-55-6 1782 Propylene glycol 64-77-7 2104 Tolbutamide 50-44-2 1253 6-Mercaptopurine 57-66-9 1751 Probenecid 64-86-8 506 Colchicine 50-47-5 589 Desipramine 57-74-9 398 Chlordane 65-23-6 1802 Pyridoxine 50-48-6 103 Amitriptyline 57-92-1 1947 Streptomycin 65-29-2 931 Gallamine 50-49-7 1053 Imipramine 57-94-3 2179 Tubocurarine chloride 65-45-2 1888 Salicylamide 50-52-2 2071 Thioridazine 57-96-5 1966 Sulfinpyrazone 65-49-6 98 p-Aminosalicylic acid 50-53-3 426 Chlorpromazine 58-00-4 138 Apomorphine 66-76-2 632 Dicumarol 50-55-5 1841 Reserpine 58-05-9 1136 Leucovorin 66-79-5 -
Indicators of Drug Or Alcohol Abuse Or Misuse
New Trends in Substance Abuse 2018 Lynn Riemer Ron Holmes, MD 720-480-0291 720-630-5430 [email protected] [email protected] www.actondrugs.org Facebook/ACTonDrugs Indicators of Drug or Alcohol Abuse or Misuse: Behavioral Physical - Abnormal behavior - Breath or body odor - Exaggerated behavior - Lack of coordination - Boisterous or argumentative - Uncoordinated & unsteady gait - Withdrawn - Unnecessary use of arms or supports for balance - Avoidance - Sweating and/or dry mouth - Changing emotions & erratic behavior - Change in appearance Speech Performance - Slurred or slow speech - Inability to concentrate - Nonsensical patterns - Fatigue & lack of motivation - Confusion - Slowed reactions - Impaired driving ability The physiologic factors predisposing to addiction Nearly every addictive drug targets the brain’s reward system by flooding the circuit with the neurotransmitter, dopamine. Neurotransmitters are necessary to transfer impulses from one brain cell to another. The brain adapts to the overwhelming surges in dopamine by ultimately producing less dopamine and by reducing the number of dopamine receptors in the reward circuit. As a result, two important physiologic adaptations occur: (1) the addict’s ability to enjoy the things that previously brought pleasure is impaired because of decreased dopamine, and (2) higher and higher doses of the abused drug are needed to achieve the same “high” that occurred when the drug was first used. This compels the addict to increase drug consumption to increase dopamine production leading to physiologic addiction with more and more intense cravings for the drug. The effects of addiction on the brain Nearly all substances of abuse affect the activity of neurotransmitters that play an important role in connecting one brain cell to another. -
S1 Table. List of Medications Analyzed in Present Study Drug
S1 Table. List of medications analyzed in present study Drug class Drugs Propofol, ketamine, etomidate, Barbiturate (1) (thiopental) Benzodiazepines (28) (midazolam, lorazepam, clonazepam, diazepam, chlordiazepoxide, oxazepam, potassium Sedatives clorazepate, bromazepam, clobazam, alprazolam, pinazepam, (32 drugs) nordazepam, fludiazepam, ethyl loflazepate, etizolam, clotiazepam, tofisopam, flurazepam, flunitrazepam, estazolam, triazolam, lormetazepam, temazepam, brotizolam, quazepam, loprazolam, zopiclone, zolpidem) Fentanyl, alfentanil, sufentanil, remifentanil, morphine, Opioid analgesics hydromorphone, nicomorphine, oxycodone, tramadol, (10 drugs) pethidine Acetaminophen, Non-steroidal anti-inflammatory drugs (36) (celecoxib, polmacoxib, etoricoxib, nimesulide, aceclofenac, acemetacin, amfenac, cinnoxicam, dexibuprofen, diclofenac, emorfazone, Non-opioid analgesics etodolac, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, (44 drugs) ketoprofen, ketorolac, lornoxicam, loxoprofen, mefenamiate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, pranoprofen, proglumetacin, sulindac, talniflumate, tenoxicam, tiaprofenic acid, zaltoprofen, morniflumate, pelubiprofen, indomethacin), Anticonvulsants (7) (gabapentin, pregabalin, lamotrigine, levetiracetam, carbamazepine, valproic acid, lacosamide) Vecuronium, rocuronium bromide, cisatracurium, atracurium, Neuromuscular hexafluronium, pipecuronium bromide, doxacurium chloride, blocking agents fazadinium bromide, mivacurium chloride, (12 drugs) pancuronium, gallamine, succinylcholine