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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 -
Effect of Aminophylline on Diaphragmatic Contractility in the Piglet
003 1-3998/90/2803-0196$02.00/0 PEDIATRIC RESEARCH Vol. 28, No. 3, 1990 Copyright 0 1990 International Pediatric Research Foundation, Inc. Printed in (I.S.A. Effect of Aminophylline on Diaphragmatic Contractility in the Piglet DENNIS E. MAYOCK, THOMAS A. STANDAERT, JON F. WATCHKO, AND DAVID E. WOODRUM1 University of Washington School of Medicine, Department of Pediatrics, Division of Neonatal and Respiratory Diseases, Seattle, Washington 98195 ABSTRACT. Minute ventilation, arterial blood gases, ar- of arterial oxygen > 8 kPa (60 torr) in room air, and a partial terial pH, cardiac output, and transdiaphragmatic force pressure of the arterial carbon dioxide 5 6.7 kPa (50 torr) were generation, both during spontaneous ventilation and in accepted for study. The animals were anesthetized with an i.v. response to phrenic nerve stiwulation during airway occlu- combination of chloralose (30 mg/kg) and urethane (1 50 mg/ sion at end expiration, were measured in nine anesthetized, kg) and studied in the supine position. Subsequent infusions of tracheostomized piglets before and 30 min after parenteral anesthetic were used if the piglet developed jaw clonus. A trache- infusion of 20 mg/kg aminophylline. Serum theophylline ostomy was placed and connected to a two-way nonrebreathing levels averaged 109 f 21 ~mol/L(19.7 f 3.7 ~g/mL)at valve (model 2384, Hans Rudolph, Inc., Kansas City, MO). 30 min postinfusion. No significant changes were noted in Inspiratory flow was detected by a hot-wire anemometer and pH, blood gases, blood Pressure, or ventilatory measures integrated to provide tidal volume. All animals breathed 50% after aminophylline. -
Benzodiazepines
Benzodiazepines Using benzodiazepines in Children and Adolescents Overview Benzodiazepines are group of medications used to treat several different conditions. Some examples of these medications include: lorazepam (Ativan®); clonazepam (Rivotril®); alprazolam (Xanax®) and oxazepam (Serax®). Other benzodiazepine medications are available, but are less commonly used in children and adolescents. What are benzodiazepines used for? Benzodiazepines may be used for the following conditions: • anxiety disorders: generalized anxiety disorder; social anxiety disorder; post-traumatic stress disorder (PTSD); panic attacks/disorder; excessive anxiety prior to surgery • sleep disorders: trouble sleeping (insomnia); waking up suddenly with great fear (night terrors); sleepwalking • seizure disorders (epilepsy) • alcohol withdrawal • treatment of periods of extreme slowing or excessive purposeless motor activity (catatonia) Your doctor may be using this medication for another reason. If you are unclear why this medication is being prescribed, please ask your doctor. How do benzodiazepines work? Benzodiazepines works by affecting the activity of the brain chemical (neurotransmitter) called GABA. By enhancing the action of GABA, benzodiazepines have a calming effect on parts of the brain that are too excitable. This in turn helps to manage anxiety, insomnia, and seizure disorders. How well do benzodiazepines work in children and adolescents? When used to treat anxiety disorders, benzodiazepines decrease symptoms such as nervousness, fear, and excessive worrying. Benzodiazepines may also help with the physical symptoms of anxiety, including fast or strong heart beat, trouble breathing, dizziness, shakiness, sweating, and restlessness. Typically, benzodiazepines are prescribed to manage anxiety symptoms that are uncomfortable, frightening or interfere with daily activities for a short period of time before conventional anti-anxiety treatments like cognitive-behavioural therapy or anti-anxiety takes effect. -
Statement on Safe Use of Propofol 2019
Statement on Safe Use of Propofol Committee of Origin: Ambulatory Surgical Care (Approved by the ASA House of Delegates on October 27, 2004, and amended on October 23, 2019) Because sedation is a continuum, it is not always possible to predict how an individual patient will respond. Due to the potential for rapid, profound changes in sedative/anesthetic depth and the lack of antagonist medications, agents such as propofol require special attention. Even if moderate sedation is intended, patients receiving propofol should receive care consistent with that required for deep sedation. The Society believes that the involvement of an anesthesiologist in the care of every patient undergoing anesthesia is optimal. However, when this is not possible, non-anesthesia personnel who administer propofol should be qualified to rescue* patients whose level of sedation becomes deeper than initially intended and who enter, if briefly, a state of general anesthesia.** • The physician responsible for the use of sedation/anesthesia should have the education and training to manage the potential medical complications of sedation/anesthesia. The physician should be proficient in airway management, have advanced life support skills appropriate for the patient population, and understand the pharmacology of the drugs used. The physician should be physically present throughout the sedation and remain immediately available until the patient is medically discharged from the post procedure recovery area. • The practitioner administering propofol for sedation/anesthesia should, at a minimum, have the education and training to identify and manage the airway and cardiovascular changes which occur in a patient who enters a state of general anesthesia, as well as the ability to assist in the management of complications. -
Aminophylline Catalog Number A1755 Storage
Aminophylline Catalog Number A1755 Storage Temperature –20 °C Replacement for Catalog Number 216895 CAS RN 317-34-0 Storage/Stability Synonyms: theophylline hemiethylenediamine complex; Aminophylline should be kept tightly closed to prevent 3,7-dihydro-1,3-demethyl-1H-purine-2,6-dione CO2 absorption from the atmosphere, which leads to compound with 1,2-ethanediamine (2:1); formation of theophylline and decreased solubility in 1,2 3 (theophylline)2 • ethylenediamine aqueous solutions. Stock solutions should be protected from light and prevented from contact with Product Description metals.2 Molecular Formula: C7H8N4O2 ·1/2 (C2H8N2) Molecular Weight: 210.3 References 1. The Merck Index, 12th ed., Entry# 485. Aminophylline is a xanthine derivative which is a 2. Martindale: The Extra Pharmacopoeia, 31st ed., combination of theophylline and ethylenediamine that is Reynolds, J. E. F., ed., Royal Pharmaceutical more water soluble than theophylline alone. Society (London, England: 1996), pp. 1651-1652. Aminophylline has been widely used as an inhibitor of 3. Data for Biochemical Research, 3rd ed., Dawson, cAMP phosphodiesterase.3 R. M. C., et al., Oxford University Press (New York, NY: 1986), pp. 316-317. Aminophylline has been shown to limit 4. Pelech, S. L., et al., cAMP analogues inhibit phosphatidylcholine biosynthesis in cultured rat phosphatidylcholine biosynthesis in cultured rat hepatocytes.4 It has been used in studies of acute hepatocytes. J. Biol. Chem., 256(16), 8283-8286 hypoxemia in newborn and older guinea pigs.5 The (1981). effect of various xanthine derivatives, including 5. Crisanti, K. C., and Fewell, J. E., Aminophylline aminophylline, on activation of the cystic fibrosis alters the core temperature response to acute transmembrane conductance regulator (CFTR) chloride hypoxemia in newborn and older guinea pigs. -
Rosemary)-Derived Ingredients As Used in Cosmetics
Safety Assessment of Rosmarinus Officinalis (Rosemary)-Derived Ingredients as Used in Cosmetics Status: Tentative Amended Report for Public Comment Release Date: March 28, 2014 Panel Meeting Date: June 9-10, 2014 All interested persons are provided 60 days from the above release date to comment on this safety assessment and to identify additional published data that should be included or provide unpublished data which can be made public and included. Information may be submitted without identifying the source or the trade name of the cosmetic product containing the ingredient. All unpublished data submitted to CIR will be discussed in open meetings, will be available at the CIR office for review by any interested party and may be cited in a peer-reviewed scientific journal. Please submit data, comments, or requests to the CIR Director, Dr. Lillian J. Gill. The 2014 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D.; Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This safety assessment was prepared by Monice M. Fiume, Assistant Director/Senior Scientific Analyst. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200♢ Washington, DC 20036 ♢ ph 202.331.0651 ♢ fax 202.331.0088 ♢ [email protected] TABLE OF CONTENTS Abstract ...................................................................................................................................................................................................................................... -
Intravenous Sedation and Preparing for Your Procedure
Oral and Maxillofacial Surgery Intravenous sedation and preparing for your procedure Information for patients Please ensure that you read this leaflet before you come to hospital for your operation What is sedation? Sedation is a way of using drugs (sedatives) to make you feel relaxed and sleepy during your procedure. We will give you your sedatives through an injection into a vein. Sedation is not a general anaesthetic and you will not be unconscious. You may not remember much of what happens during the procedure and directly afterwards. This is quite normal. Local anaesthetic will be given once you have been sedated. Do not drive, operate machinery or sign important documents for at least 24 hours after your procedure. You must make sure that you have a responsible adult with you who can stay in the department for a couple of hours and take you home by car or taxi. Someone must also stay with you for at least 24 hours after your procedure. Your procedure will be cancelled if you do not bring someone with you who can do this. Preparation for your procedure and what to bring with you • Patients having a procedure under sedation must follow the current fasting guidelines for general anaesthesia. You must not eat or drink for 6 hours before your procedure but you may have water up to 2 hours before. If you do eat or drink after these times your surgery will be cancelled. • Avoid alcohol for 24 hours before your procedure. • Bring with you a list of any medication or drugs you are taking. -
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. -
Moderate Sedation Study Guide 11-17-10
PROCEDURE RELATED SEDATION Outline I Introduction II Definitions: The 5 Levels of Sedation and Anesthesia III Emergency Procedures, Critical Care Areas and Policy Exclusions IV The Pre-Sedation Assessment V NPO: The Timing of Eating and Drinking before Sedation VI Review of Some Agents Used for Sedation VII Orders for Procedure Related Sedation VIII Environmental Requirements and Monitoring During Sedation IX Post-Procedure Monitoring and the PAR Score X Discharge Criteria and Concluding Post-Procedure Monitoring 1 PROCEDURE RELATED SEDATION Lance Brown, MD, MPH I. Introduction The purpose of this tutorial is to familiarize the reader with the Loma Linda University Medical Center Policy M-86 for Procedure Related Sedation. Procedure related sedation is used to make necessary medical procedures as comfortable as possible for patients and to facilitate the performance of necessary medical procedures by health care providers (typically physicians). It is important for health care providers performing procedure related sedation to be familiar with the pharmacologic characteristics of the agents being used, to understand the risk factors for complications related to procedure related sedation, and to individually plan the sedation for each patient. Each health care practitioner privileged to provide procedure related sedation takes responsibility for both the comfort and safety of the patients in their care. II. Definitions At Loma Linda University Medical Center, we have defined five distinct levels of sedation and anesthesia. Familiarity with the definitions of these levels of sedation is important for safely providing procedure related sedation and for complying with the policy of the Medical Center. It must be recognized, however, that sedation occurs along a continuum and that individual patients may have different degrees of sedation for a given dose and route of medication. -
Acute Migraine Treatment
Acute Migraine Treatment Morris Levin, MD Professor of Neurology Director, Headache Center UCSF Department of Neurology San Francisco, CA Mo Levin Disclosures Consulting Royalties Allergan Oxford University Press Supernus Anadem Press Amgen Castle Connolly Med. Publishing Lilly Wiley Blackwell Mo Levin Disclosures Off label uses of medication DHE Antiemetics Zolmitriptan Learning Objectives At the end of the program attendees will be able to 1. List all important options in the acute treatment of migraine 2. Discuss the evidence and guidelines supporting the major migraine acute treatment options 3. Describe potential adverse effects and medication- medication interactions in acute migraine pharmacological treatment Case 27 y/o woman has suffered ever since she can remember from “sick headaches” . Pain is frontal, increases over time and is generally accompanied by nausea and vomiting. She feels depressed. The headache lasts the rest of the day but after sleeping through the night she awakens asymptomatic 1. Diagnosis 2. Severe Headache relief Diagnosis: What do we need to beware of? • Misdiagnosis of primary headache • Secondary causes of headache Red Flags in HA New (recent onset or change in pattern) Effort or Positional Later onset than usual (middle age or later) Meningismus, Febrile AIDS, Cancer or other known Systemic illness - Neurological or psych symptoms or signs Basic principles of Acute Therapy of Headaches • Diagnose properly, including comorbid conditions • Stratify therapy rather than treat in steps • Treat early -
Accurate Measurement, and Validation of Solubility Data † ‡ ‡ § † ‡ Víctor R
Article Cite This: Cryst. Growth Des. 2019, 19, 4101−4108 pubs.acs.org/crystal In the Context of Polymorphism: Accurate Measurement, and Validation of Solubility Data † ‡ ‡ § † ‡ Víctor R. Vazqueź Marrero, , Carmen Piñero Berríos, , Luz De Dios Rodríguez, , ‡ ∥ ‡ § Torsten Stelzer,*, , and Vilmalí Lopez-Mej́ ías*, , † Department of Biology, University of Puerto RicoRío Piedras Campus, San Juan, Puerto Rico 00931, United States ‡ Crystallization Design Institute, Molecular Sciences Research Center, University of Puerto Rico, San Juan, Puerto Rico 00926, United States § Department of Chemistry, University of Puerto RicoRío Piedras Campus, San Juan, Puerto Rico 00931, United States ∥ Department of Pharmaceutical Sciences, University of Puerto RicoMedical Sciences Campus, San Juan, Puerto Rico 00936, United States *S Supporting Information ABSTRACT: Solubility measurements for polymorphic com- pounds are often accompanied by solvent-mediated phase transformations. In this study, solubility measurements from undersaturated solutions are employed to investigate the solubility of the two most stable polymorphs of flufenamic acid (FFA forms I and III), tolfenamic acid (TA forms I and II), and the only known form of niflumic acid (NA). The solubility was measured from 278.15 to 333.15 K in four alcohols of a homologous series (methanol, ethanol, 1- propanol, n-butanol) using the polythermal method. It was established that the solubility of these compounds increases with increasing temperature. The solubility curves of FFA forms I and III intersect at ∼315.15 K (42 °C) in all four solvents, which represents the transition temperature of the enantiotropic pair. In the case of TA, the solubility of form II could not be reliably obtained in any of the solvents because of the fast solvent- mediated phase transformation. -
Download Product Insert (PDF)
PRODUCT INFORMATION Proxyphylline Item No. 20937 CAS Registry No.: 603-00-9 Formal Name: 3,7-dihydro-7-(2-hydroxypropyl)-1,3- N dimethyl-1H-purine-2,6-dione O N Synonym: NSC 163343 C H N O MF: 10 14 4 3 N FW: 238.2 N Purity: ≥98% O UV/Vis.: λmax: 273, 324 nm Supplied as: A crystalline solid OH Storage: -20°C Stability: As supplied, 2 years from the QC date provided on the Certificate of Analysis, when stored properly Laboratory Procedures Proxyphylline is supplied as a crystalline solid. A stock solution may be made by dissolving the proxyphylline in the solvent of choice. Proxyphylline is soluble in organic solvents such as ethanol, DMSO, and dimethyl formamide (DMF), which should be purged with an inert gas. The solubility of proxyphylline in ethanol is approximately 1 mg/ml and approximately 10 mg/ml in DMSO and DMF. Further dilutions of the stock solution into aqueous buffers or isotonic saline should be made prior to performing biological experiments. Ensure that the residual amount of organic solvent is insignificant, since organic solvents may have physiological effects at low concentrations. Organic solvent-free aqueous solutions of proxyphylline can be prepared by directly dissolving the crystalline solid in aqueous buffers. The solubility of proxyphylline in PBS, pH 7.2, is approximately 1 mg/ml. We do not recommend storing the aqueous solution for more than one day. Description Proxyphylline is a methylxanthine derivative that has bronchodilatory actions.1 It has also been reported 2 to have vasodilatory and cardiac stimulatory effects.