DOCSLIB.ORG

Cleveland Clinic Laboratories

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cleveland Clinic Laboratories Cleveland Clinic Laboratories Technical Brief Quantitative Urine Pain Management Drug Screening with HPLC-MS/MS Background Information enzymatic hydrolysis is much milder, but needs longer incubation time to achieve sufficient (>80%) hydrolysis Pain management drugs are among the most prescribed efficiency.7 medications, and they are also the most abused class of prescription drugs.1-2 Therefore, many states including Ohio Cleveland Clinic Laboratories offer an HPLC-MS/MS method have enacted laws governing the prescription of pain for quantitative screening of 11 pain management drugs and management drugs. Patients enrolled in pain management five other commonly abused drugs in urine.8 In this method, programs need to be monitored for compliance, which total drug concentration is measured after enzymatic hydroly- means appropriate use of prescribed drugs and abstinence sis. This assay also includes an adulteration test using urine from non-prescribed drugs. test strips to ensure specimen quality. In addition to pain management, this test can also be used for monitoring Urine is the most commonly used specimen in monitoring patient compliance in rehabilitation programs. pain management and illicit drug use. A single urine specimen can be tested for a number of drugs. Immunoassay (IA) can The high sensitivity of this method is capable of detecting be used as a screening method, but it lacks specificity and drug manufacturing impurities. As an example, codeine is a sensitivity. For example, most immunoassay tests cannot known manufacturing impurity in morphine (~0.04%) and distinguish various opiate drugs and cannot detect oxymor- can be detected by this method.9 3-4 phone at all. In addition, immunoassay is only semi- Clinical Information quantitative and clinicians in some cases need quantitative assessment of urine drug concentrations.3 For example, the This test detects the following 11 pain management drugs morphine-to-codeine ratio can help identify heroine abusers.5 in urine: High performance liquid chromatography tandem mass Morphine Hydromorphone spectrometry (HPLC-MS/MS) offers high resolving power, Codeine Methadone and metabolite high selectivity and wide dynamic range, all of which enable Dihydrocodeine Fentanyl and metabolite simultaneous quantification of a broad spectrum of drugs Oxycodone Tramadol and metabolite present in biological matrices.3 In clinical laboratories, Oxymorphone Buprenorphine and metabolite HPLC-MS/MS can be used as a confirmation method in Hydrocodone conjunction with a prior immunoassay-based screening method, Also included are five commonly abused drugs that are not or it can be used as a stand-alone screening method offering prescribed for pain management: quantitative results with high confidence. Amphetamine Heroin metabolite Some drugs/metabolites (e.g. morphine, codeine and THCA) Methamphetamine Marijuana metabolite are present in urine as both free and glucuronide conjugates. Cocaine metabolite The conjugation rate varies significantly. In order to have In most cases, both parent drug and metabolite are quantified. consistent results, conjugated drugs are usually converted to Tetrahydrocannabinol (THC, the main active component of free drugs prior to HPLC-MS/MS analysis. Chemical hydrolysis marijuana), cocaine and heroin have rather short half-lives and is very efficient but may result in unwanted reactions. For therefore only the stable metabolites are analyzed. As a result, example, acid hydrolysis will convert heroin and its metabolite, a total of 20 analytes are measured in this test (Table 1). 6-monoacetylmorphine (6-MAM), to morphine.6 In contrast, 03.25.11 (rev 02.11.13) This test can assist clinicians to determine patient compliance. Detailed data interpretations for each analyte are listed below: Presence of prescribed drugs/metabolites and absence of Morphine: Morphine may arise from morphine-containing non-prescribed drugs/metabolites indicate patient compliance. drugs, poppy seeds or by metabolism of codeine and heroin. Test results are for medical purposes only. Morphine is metabolized to hydromorphone. Interpretation Codeine: Codeine is not a recognized metabolite of other Table 1 lists the lower limit of quantification (LLOQ) and opiates and its presence indicates use of a codeine-containing higher limit of quantification (HLOQ) for each analyte in the drug. Codeine is metabolized to morphine. Other minor Pain Panel. A result greater than the LLOQ for a parent drug metabolites include hydrocodone, hydromorphone and and/or metabolite indicates use of the drug. dihydrocodeine. Use of heroin is indicated when 1) both codeine and morphine are detected in urine; 2) morphine Table 1. Analytical Measurement Ranges concentration is >10,000 ng/mL; and 3) morphine-to-codeine ratio is above 2. Analyte LLOQ HLOQ (ng/ml) (ng/ml) Dihydrocodeine: The presence of dihydrocodeine may arise from dihydrocodeine-containing drugs or from the metabolism Morphine 5 5365 of hydrocodone. Dihydrocodeine is also metabolized to Codeine 11 5484 hydrocodone. Dihydrocodeine 5 5184 Oxycodone: Oxycodone is not a recognized metabolite of Oxycodone 5 4719 other opiates and its presence indicates use of an oxycodone- Oxymorphone 5 4581 containing drug. Oxycodone is metabolized to oxymorphone. Hydrocodone 8 5270 Oxymorphone: Oxymorphone may arise from oxymorphone- containing drugs or by metabolism of oxycodone. Hydromorphone 5 4980 Hydrocodone: Hydrocodone may arise from hydrocodone- Methadone 16 4897 containing drugs or by metabolism of dihydrocodeine. EDDP 6 4178 Hydrocodone is metabolized to hydromorphone and Fentanyl 6 5971 dihydrocodeine. Norfentanyl 6 5514 Hydromorphone: Hydromorphone may arise from hydro- Tramadol 25 5208 morphone-containing drugs or by metabolism of morphine and hydrocodone. O-desmethyl Tramadol 20 5000 Amphetamine: Amphetamine may arise from amphetamine- Buprenorphine 20 5000 containing drugs (eg. Adderall and Benzedrine) or by metabo- Norbuprenorphine 20 4300 lism of methamphetamine. Clobenzorex, famprofazone, Amphetamine 5 5365 fenethylline, fenproporex and mefenorex contain amphetamine pro-drugs that can be metabolized to amphetamine. Selegiline Methamphetamine 8 5339 is metabolized to both amphetamine and methamphetamine. Benzoylecgonine 24 5410 Methamphetamine: Methamphetamine may arise from 6-Acetylmorphine 5 4800 methamphetamine-containing drugs or metabolism of THCA 21 5008 selegiline, which is metabolized to both methamphetamine and amphetamine. Over-the-counter inhalers for nasal The level of drugs/metabolites in urine is affected by dose, decongestion may cause positive methamphetamine results. metabolic rate, sample collection time relative to the drug Methamphetamine is metabolized to amphetamine. use and hydration status. Benzoylecgonine: Benzoylecgonine is a metabolite of cocaine. Presence of benzoylecgonine indicates use of cocaine. Methadone: Presence of methadone indicates use of a Table 2. Adulteration test results methadone-containing drug. Methadone is metabolized to Urine Test Strip Results Clinical Interpretation EDDP (2-ethylidene-1,5-dimethyl1-3,3-diphenylpyrrolidine). Urine methadone levels vary widely depending on metabolism Creatinine 10 - 20 mg/dL and Dilution and urine pH. However, urine EDDP levels are less affected specific gravity < 1.003 by pH and are preferable for assessing compliance with Creatinine <10 mg/dL and specific Substitution methadone therapy. The absence of EDDP and presence of gravity < 1.003 or >1.020 methadone in a urine specimen very likely indicate adulteration Presence of oxidant and/or Adulteration by direct addition of methadone to the urine specimen. pH<3 or pH>10 EDDP: EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyr- rolidine) is a metabolite of methadone, and its presence indicates use of a methadone-containing drug. Methodology Fentanyl: Presence of fentanyl indicates use of a fentanyl- 1) Isotope-labeled internal standards are added to each containing drug. Fentanyl is metabolized to norfentanyl. urine sample. Norfentanyl: Norfentanyl is a metabolite of fentanyl, and its 2) All samples are subjected to enzymatic hydrolysis presence indicates use of a fentanyl-containing drug. (16-24 hours) to convert glucuronide conjugates to free drugs. Hydrolysis efficiency is >90% for all drugs. Tramadol: Presence of tramadol indicates use of a tramadol- containing drug (Ultram). Tramadol is metabolized to 3) After hydrolysis, samples are analyzed by turbulent O-Desmethyltramadol. flow online extraction and HPLC-MS/MS in the multiple reaction monitoring mode. O-Desmethyltramadol: O-Desmethyltramadol is an active metabolite of Tramadol and its presence indicates use of a 4) Analyte concentration is calculated based on analyte to tramadol-containing drug (Ultram). internal standard peak area ratio with the use of a calibration curve. THCA: Tetrahydrocannabinol carboxylic acid (THCA) is a metabolite of delta-9-tetrahydrocannabinol, which is the 5) A specimen quality test is included with this testing that main active component of marijuana. Presence of THCA measures creatinine concentration, specific gravity, pH indicates use of marijuana. and presence of oxidant. 6-MAM: 6-MAM (6-monoacetylmorphine, also known as References 6-acetylmorphine) is a unique metabolite of heroin. Presence 1. P Compton, P Athanasos, Nurs Clin North Am 2003. of 6-MAM indicates use of heroin. 6-MAM is further 38, 525. metabolized to morphine and absence of 6-MAM does not 2. L Manchikanti, KA Cash, KS Damron, R Manchukonda, rule out the use of heroin. V
Load more

Recommended publications
  • Opioid Powders Page: 1 of 9
    Federal Employee Program® 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.70.64 Section: Prescription Drugs Effective Date: April 1, 2020 Subsection: Analgesics and Anesthetics Original Policy Date: October 20, 2017 Subject: Opioid Powders Page: 1 of 9 Last Review Date: March 13, 2020 Opioid Powders Description Buprenorphine Powder, Butorphanol Powder, Codeine Powder, Hydrocodone Powder, Hydromorphone Powder, Levorphanol Powder, Meperidine Powder, Methadone Powder, Morphine Powder, Oxycodone Powder, Oxymorphone Powder Background Pharmacy compounding is an ancient practice in which pharmacists combine, mix or alter ingredients to create unique medications that meet specific needs of individual patients. Some examples of the need for compounding products would be: the dosage formulation must be changed to allow a person with dysphagia (trouble swallowing) to have a liquid formulation of a commercially available tablet only product, or to obtain the exact strength needed of the active ingredient, to avoid ingredients that a particular patient has an allergy to, or simply to add flavoring to medication to make it more palatable. Buprenorphine, butorphanol, codeine, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxycodone, and oxymorphone powders are opioid drugs that are used for pain control. The intent of the criteria is to provide coverage consistent with product labeling, FDA guidance, standards of medical practice, evidence-based drug information, and/or published guidelines. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death (1-15). Regulatory Status 5.70.64 Section: Prescription Drugs Effective Date: April 1, 2020 Subsection: Analgesics and Anesthetics Original Policy Date: October 20, 2017 Subject: Opioid Powders Page: 2 of 9 FDA-approved indications: 1.
    [Show full text]
  • Hydromorphone
    Hydromorphone WHAT IS HYDROMORPHONE? sedation, and reduced anxiety. It may also cause Hydromorphone belongs to a class of drugs mental clouding, changes in mood, nervousness, called “opioids,” which includes morphine. It and restlessness. It works centrally (in the has an analgesic potency of two to eight times brain) to reduce pain and suppress cough. greater than that of morphine and has a rapid Hydromorphone use is associated with both onset of action. physiological and psychological dependence. WHAT IS ITS ORIGIN? What is its effect on the body? Hydromorphone is legally manufactured and Hydromorphone may cause: distributed in the United States. However, • Constipation, pupillary constriction, urinary retention, users can obtain hydromorphone from nausea, vomiting, respiratory depression, dizziness, forged prescriptions, “doctor-shopping,” impaired coordination, loss of appetite, rash, slow or theft from pharmacies, and from friends and rapid heartbeat, and changes in blood pressure acquaintances. What are its overdose effects? What are the street names? Acute overdose of hydromorphone can produce: Common street names include: Severe respiratory depression, drowsiness • D, Dillies, Dust, Footballs, Juice, and Smack progressing to stupor or coma, lack of skeletal muscle tone, cold and clammy skin, constricted What does it look like? pupils, and reduction in blood pressure and heart Hydromorphone comes in: rate • Tablets, capsules, oral solutions, and injectable Severe overdose may result in death due to formulations respiratory depression. How is it abused? Which drugs cause similar effects? Users may abuse hydromorphone tablets by Drugs that have similar effects include: ingesting them. Injectable solutions, as well as • Heroin, morphine, hydrocodone, fentanyl, and tablets that have been crushed and dissolved oxycodone in a solution may be injected as a substitute for heroin.
    [Show full text]
  • Pre - PA Allowance Age 12 Years of Age Or Older – Ultracet (Tramadol and Acetaminophen) and Codeine/APAP Products
    OPIOID IR COMBO DRUGS Apadaz* (benzhydrocodone-acetaminophen), Codeine-acetaminophen, Dvorah* (dihydrocodeine-caffeine-acetaminophen*), Hydrocodone-acetaminophen, Hydrocodone- acetaminophen solution 10-325mg*, Hydrocodone-ibuprofen, Nalocet* (oxycodone- acetaminophen*), Oxycodone-acetaminophen, Oxycodone-aspirin, Oxycodone-ibuprofen, Primlev*/Prolate* (oxycodone-acetaminophen*), Tramadol-acetaminophen, Trezix (dihydrocodeine-caffeine-acetaminophen) *Prior authorization for certain non-covered formulations applies only to formulary exceptions Pre - PA Allowance Age 12 years of age or older – Ultracet (tramadol and acetaminophen) and Codeine/APAP products Quantity Patients 18 years or older will be able to fill the Pre-PA Allowance after they have filled an initial 7 day supply of IR opioid therapy or if they have been on IR or ER opioid therapy in the last 180 days Patients age 17 and under will require a PA after they have filled a 3 day supply of the Pre- PA Allowance Patients with opioid addiction treatment or methadone in the last 30 days will not be eligible for Pre-PA Allowance Immediate Release Tablets or Capsules ≤ 50 MME/day Medication Strength Quantity Limit Codeine/APAP soln 120-12 mg/5 mL Hydrocodone/APAP soln 7.5/325 mg/15 mL 5400 mL per 90 days Hydrocodone/APAP elixir 10/300 mg/15 mL Oxycodone/APAP soln 5-325 mg/5 mL 3000 mL per 90 days Hydrocodone/ibuprofen 5/200 mg, 7.5/200 mg, 10/200 mg 270 units per 90 days Oxycodone/ibuprofen 5/400 mg Oxycodone/APAP 10/325 mg Codeine/APAP 60/300 mg Hydrocodone/APAP 7.5/300 mg, 7.5/325
    [Show full text]
  • 1 Impact of Opioid Agonists on Mental Health in Substitution
    Impact of opioid agonists on mental health in substitution treatment for opioid use disorder: A systematic review and Bayesian network meta-analysis of randomized clinical trials Supplementary Table 1_ Specific search strategy for each database The following general combination of search terms, Boolean operators, and search fields were used where “*” means that any extension of that word would be considered: Title field [opium OR opiate* OR opioid OR heroin OR medication assisted OR substitution treatment OR maintenance treatment OR methadone OR levomethadone OR buprenorphine OR suboxone OR (morphine AND slow) OR diamorphine OR diacetylmorphine OR dihydrocodeine OR hydromorphone OR opium tincture OR tincture of opium OR methadol OR methadyl OR levomethadyl] AND Title/Abstract field [trial* OR random* OR placebo] AND All fields [depress* OR anxiety OR mental] Wherever this exact combination was not possible, a more inclusive version of the search strategy was considered. Database Search Strategy Ovid for EBM Reviews - Cochrane Central Register of (opium or opiate$ or opioid or heroin or medication Controlled Trials August 2018; Embase 1974 to assisted or substitution treatment or maintenance September 07, 2018; MEDLINE(R) and Epub Ahead treatment or methadone or levomethadone or of Print, In-Process & Other Non-Indexed Citations buprenorphine or suboxone or (morphine and slow) or and Daily 1946 to September 07, 2018 diamorphine or diacetylmorphine or dihydrocodeine or hydromorphone or opium tincture or tincture of opium or methadol or methadyl
    [Show full text]
  • The Inhibition of Enkephalin Catabolism by Dual Enkephalinase Inhibitor: a Novel Possible Therapeutic Approach for Opioid Use Disorders
    Alvarez-Perez Beltran (Orcid ID: 0000-0001-8033-3136) Maldonado Rafael (Orcid ID: 0000-0002-4359-8773) THE INHIBITION OF ENKEPHALIN CATABOLISM BY DUAL ENKEPHALINASE INHIBITOR: A NOVEL POSSIBLE THERAPEUTIC APPROACH FOR OPIOID USE DISORDERS ALVAREZ-PEREZ Beltran1*, PORAS Hervé 2*, MALDONADO Rafael1 1 Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona Biomedical Research Park, c/Dr Aiguader 88, 08003 Barcelona, Spain, 2 Pharmaleads, Paris BioPark, 11 Rue Watt, 75013 Paris, France *Both authors participated equally to the manuscript Correspondence: Rafael Maldonado, Laboratori de Neurofarmacologia, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona (PRBB), c/Dr. Aiguader, 88, 08003 Barcelona, Spain. E-mail: [email protected] ABSTRACT Despite the increasing impact of opioid use disorders on society, there is a disturbing lack of effective medications for their clinical management. An interesting innovative strategy to treat these disorders consists in the protection of endogenous opioid peptides to activate opioid receptors, avoiding the classical opioid-like side effects. Dual Enkephalinase Inhibitors (DENKIs) physiologically activate the endogenous opioid system by inhibiting the enzymes responsible for the breakdown of enkephalins, protecting endogenous enkephalins, increasing their half-lives and physiological actions. The activation of opioid receptors by the increased enkephalin levels, and their well-demonstrated safety, suggest that DENKIs could represent a novel analgesic therapy and a possible effective treatment for acute opioid withdrawal, as well as a promising alternative to opioid substitution therapy minimizing side effects. This new pharmacological class of compounds could bring effective and safe medications avoiding the This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record.
    [Show full text]
  • Hydromorphone and Morphine Are Not the Same Drug!
    HYDROmorphone and Morphine are not the same drug! HYDROmorphone and morphine are deemed high risk/high alert medications. An Independent Double Check (IDC) must be done to avoid errors when administering all high risk drugs. Please refer to Clinical Practice Standard 1-20-6-3-260. HYDROmorphone and morphine need to knows: HYDROmorphone is 5 times more potent than morphine! (e.g., 1 mg of HYDROmorphone PO is equivalent to 5 mg of morphine PO) When administered via the subcutaneous route, these drugs are twice as strong! Therefore when converting between oral and subcutaneous routes half the dose. (10 mg of oral morphine = 5 mg of subcutaneous morphine) HYDROmorphone and morphine: The name game. Both drugs are used in the management of moderate to severe pain. HYDROmorphone and morphine come in different brand names and formulations. HYDROmorphone = Dilaudid (Injectable), Jurnista (SR), HYDROmorph Contin (SR) Morphine = Morphine Sulphate (Injectable), MS-IR, M.O.S. (Liquid/Tablet/SR), M-Eslon (SR), Statex (Liquid/Tablet/Supp.), Doloral (Liquid), MS Contin (SR), Kadian (SR) (SR=Slow Release CAP) *As per NH, use the generic names (NOT THE BRAND NAME), of these drugs in your documentation. Common side effects: 3 ‘B’s of opioid prescribing: Common: Nausea, Vomiting, Constipation, Sedation, Syncope, Xerostomia (Dry Mouth), If your client is on an opioid: Delirium, Restlessness, Urinary Retention. Do they have a Breakthrough? Less Common: Respiratory Depression, Do they have something for Barfing? Opioid-Induced Neurotoxicity, Myoclonus, Do they have something for their Bowels? Pruritis (itching). Opioid induced neurotoxicity: What does it look like? Opioid induced neurotoxicity is the result of a build up of toxic opioid metabolites in the blood stream.
    [Show full text]
  • List of Narcotic Substances Circulation of Which Is Restricted in Uzbekistan
    List of narcotic substances circulation of which is restricted in Uzbekistan 1. 2C-B(4-bromo-2,5-dimethoxyphenethylamine) 2. 3-methylfentanyl 3. 3-methylthiofentanyl 4. 3-Monoacetylmorphine 5. 4-methylaminorex 6. 6- Monoacetylmorphine 7. Acetorphine 8. Acetyl Dihydrocodeine 9. Acetyl-alfametilfentanil 10. Acetylated opium 11. Acetylcodeine 12. Acetylmethadol 13. Alfametadol 14. Alfatsetilmetadol 15. all fungi that contain Psilocine and Psilocybine 16. Allylprodine 17. Alpha Methylfentanyl 18. Alpha Metiltiofentanil 19. Alphaprodine 20. Anileridin 21. Benzethidine 22. Benzylmorphine 23. Betacetylmethadol 24. Betahydroxyfentanyl 25. Betameprodine 26. Betamethadol 27. Betaprodine 28. Bezitramide 29. Cannabis oil (hashish oil) 30. Cannabis, marihuana 31. Cathine ((+)-norpseudoephedrine) 32. Cathinone (l-alpha-aminopropiofenon) 33. Clonitazene 34. Cocaine 35. Codoxime 36. d- Methadone 37. DB [L-(3,4 - methylenedioxyphenyl) -2 butanamine] 38. Desmethylprodine; MPPP (1-methyl-4-phenyl-4-propionoxypiperidine) 39. Desomorphine 40. DET (N,N-diethyltryptamine) 41. Dexamphetamine 42. Diampromide 43. Diethyl phosphate 44. Diethylthiambutene 45. Dihydromorphine 46. Dimenoxadol 47. Dimepheptanol 48. Dimethylthiambutene 49. Dioxaphetyl butyrate 50. Diphenoxine 51. Dipipanone 52. DMA (2,5-dimethoxyamphetamine) 53. DMGP (dimetilgeptilpiran) 54. DMT (dimethyltryptamine) 55. DOB (d, L-2,5-dimethoxy-4-bromo-amphetamine) 56. DOC (d, L-2,5-dimethoxy-4-chloro-amphetamine) 57. DOET (2,5-dimethoxy-4-ethylamphetamine) 58. Drotebanol 59. Ecgonine 60. Ephedrone 61. Ethylmethylthiambutene 62. Eticyclidine 63. Etonitazene 64. Etorphine 65. Etoxeridine 66. Etryptamine 67. Furethidine 68. Hashish (Anasha, cannabis resin) 69. Heroin (Diacetylmorphine) 70. Hydrocodone 71. Hydrocodone phosphate 72. Hydromorphinol 73. Hydromorphone 74. Isomethadone 75. Ketobemidone 76. Khat 77. L- Methadone 78. Levomethorphan 79. Levomoramide 80. Levophenacylmorphan 81. Levorphanol 82. Lysergic acid and its preparations, that include d-Lysergide (LSD, LSD-25) 83.
    [Show full text]
  • Effects of Medication-Assisted Treatment (MAT) on Functional Outcomes Among Patients with Opioid Use Disorder (OUD)
    NATIONAL DEFENSE RESEARCH INSTITUTE Effects of Medication- Assisted Treatment (MAT) for Opioid Use Disorder on Functional Outcomes A Systematic Review Margaret A. Maglione, Laura Raaen, Christine Chen, Gulrez Shah Azhar, Nima Shahidinia, Mimi Shen, Ervant J. Maksabedian Hernandez, Roberta M. Shanman, Susanne Hempel Prepared for the Office of the Secretary of Defense Approved for public release; distribution unlimited For more information on this publication, visit www.rand.org/t/RR2108 Published by the RAND Corporation, Santa Monica, Calif. © Copyright 2018 RAND Corporation R® is a registered trademark. Limited Print and Electronic Distribution Rights This document and trademark(s) contained herein are protected by law. This representation of RAND intellectual property is provided for noncommercial use only. Unauthorized posting of this publication online is prohibited. Permission is given to duplicate this document for personal use only, as long as it is unaltered and complete. Permission is required from RAND to reproduce, or reuse in another form, any of its research documents for commercial use. For information on reprint and linking permissions, please visit www.rand.org/pubs/permissions. The RAND Corporation is a research organization that develops solutions to public policy challenges to help make communities throughout the world safer and more secure, healthier and more prosperous. RAND is nonprofit, nonpartisan, and committed to the public interest. RAND’s publications do not necessarily reflect the opinions of its research clients and sponsors. Support RAND Make a tax-deductible charitable contribution at www.rand.org/giving/contribute www.rand.org Preface Over the past two decades, the U.S. Department of Defense (DoD) has invested unparalleled resources into developing effective treatments for military-related psychological health conditions.
    [Show full text]
  • Opioid-Containing Cough and Cold Products - Assessing the Potential Risk of Opioid Use Disorder and Related Harms in Children and Adolescents
    Summary Safety Review –Opioid-containing cough and cold products - Assessing the potential risk of opioid use disorder and related harms in children and adolescents Product: Cough and cold products containing opioids (including codeine, hydrocodone or normethadone) Potential Safety Issue: Opioid use disorders and related harms in children and adolescents Key Messages • The growing number of overdoses and harms caused by opioids is a major public health concern in Canada. Cough and cold products containing opioids (including codeine, hydrocodone or normethadone) are authorized for sale in Canada to treat cough and cold symptoms in adults and children. • Health Canada reviewed the risk of opioid use disorder and related harms from these products after the United States Food and Drug Administration (US FDA) advised against using these products in children and adolescents in 2018. Health Canada’s safety review found limited evidence to link opioid-containing cough and cold products with opioid use disorders and related harms in children and adolescents. • These products are linked to other known harms (i.e., breathing problems), and there is limited evidence to support the effectiveness of these products in children and adolescents. There are other products available in Canada to help relieve the symptoms of cough and cold in children. • Therefore, Health Canada, as a precautionary measure, is advising Canadians against the use of these products among children and adolescents under 18 years of age. Health Canada will notify the manufacturers to update the product safety information of opioid- containing cough and cold products to limit the recommended age of use (indication) to adults only, 18 years of age and older.
    [Show full text]
  • List of Narcotic Drugs Under International Control
    International Narcotics Control Board Yellow List Annex to Forms A, B and C 59th edition, July 2020 LIST OF NARCOTIC DRUGS UNDER INTERNATIONAL CONTROL Prepared by the INTERNATIONAL NARCOTICS CONTROL BOARD* Vienna International Centre P.O. Box 500 A-1400 Vienna, Austria Internet address: http://www.incb.org/ in accordance with the Single Convention on Narcotic Drugs, 1961** Protocol of 25 March 1972 amending the Single Convention on Narcotic Drugs, 1961 * On 2 March 1968, this organ took over the functions of the Permanent Central Narcotics Board and the Drug Supervisory Body, r etaining the same secretariat and offices. ** Subsequently referred to as “1961 Convention”. V.20-03697 (E) *2003697* Purpose The Yellow List contains the current list of narcotic drugs under international control and additional relevant information. It has been prepared by the International Narcotics Control Board to assist Governments in completing the annual statistical reports on narcotic drugs (Form C), the quarterly statistics of imports and exports of narcotic drugs (Form A) and the estimates of annual requirements for narcotic drugs (Form B) as well as related questionnaires. The Yellow List is divided into four parts: Part 1 provides a list of narcotic drugs under international control in the form of tables and is subdivided into three sections: (1) the first section includes the narcotic drugs listed in Schedule I of the 1961 Convention as well as intermediate opiate raw materials; (2) the second section includes the narcotic drugs listed in Schedule II of the 1961 Convention; and (3) the third section includes the narcotic drugs listed in Schedule IV of the 1961 Convention.
    [Show full text]
  • Narcotic Drugs Stupefiants Estupefacientes
    E/INCB/1993/21Supp.6 INTERNATIONAL NARCOTICS CONTROL BOARD - VIENNA SUPPLEMENT No. 6 TO NARCOTIC DRUGS ESTIMATED WORLD REQUIREMENTS FOR 1994 STATISTICS FOR 1992 ESTIMATES UPDATED AS OF 30 JUNE 1994 ORGANE INTERNATIONAL DE CONTROLE DES STUPEFIANTS - VIENNE SUPPLEMENT N° 6 A r STUPEFIANTS EVALUATIONS DES BESOINS DU MONDE POUR 1994 STATISTIQUES POUR 1992 EVALUATIONS A JOUR AU 30 JUlN 1994 JUNTA INTERNACIONAL DE FISCALlZACION DE ESTUPEFACIENTES - VIENA SUPLEMENTO N.o 6 A ESTUPEFACIENTES PREVISIONES DE LAS NECESIDADES MUNDIALES PARA 1994 ESTADfsTICAS PARA 1992 PREVISIONES ACTUALlZADAS AL 30 DE JUNIO DE 1994 ~If..~~ ~ ~-tR UNITED NATIONS - NATIONS UNIES - NACIONES UNIDAS 1994 The updating of Table A is carried out by means of 12 monthly supplements. In order to facilitate the task of the exporting countries, the 12 supplements now report all the totals of the estimates and not only the amended data. In this way, each supplement cancels and replaces the published table in its entirety. In order to accelerate the transmission of the supplements to the competent national authorities, the 12 supplements will appear in English. Reading of these 12 supplements in French and Spanish may be facilitated by consulting the indexes of countries and territories and of narcotic drugs appearing in the annual publication. La mise El jour du tableau A s'effectue au moyen de douze supplements mensuels. Afin de faciliter la tache des pays exportateurs, les douze supplements contiennent tous les totaux des evaluations et non pas seulement les chiffres qui ont ete modifies. De celte maniere, chaque supplement annule et remplace entierement le tableau publie.
    [Show full text]
  • Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity
    pharmaceutics Review Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity Junzhi Yang 1, Bianca G. Reilly 2, Thomas P. Davis 1,2 and Patrick T. Ronaldson 1,2,* 1 Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1295 N. Martin St., P.O. Box 210207, Tucson, AZ 85721, USA; [email protected] (J.Y.); [email protected] (T.P.D.) 2 Department of Pharmacology, College of Medicine, University of Arizona, 1501 N. Campbell Ave, P.O. Box 245050, Tucson, AZ 85724-5050, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-520-626-2173 Received: 19 September 2018; Accepted: 16 October 2018; Published: 18 October 2018 Abstract: Opioids are highly effective analgesics that have a serious potential for adverse drug reactions and for development of addiction and tolerance. Since the use of opioids has escalated in recent years, it is increasingly important to understand biological mechanisms that can increase the probability of opioid-associated adverse events occurring in patient populations. This is emphasized by the current opioid epidemic in the United States where opioid analgesics are frequently abused and misused. It has been established that the effectiveness of opioids is maximized when these drugs readily access opioid receptors in the central nervous system (CNS). Indeed, opioid delivery to the brain is significantly influenced by the blood-brain barrier (BBB). In particular, ATP-binding cassette (ABC) transporters that are endogenously expressed at the BBB are critical determinants of CNS opioid penetration. In this review, we will discuss current knowledge on the transport of opioid analgesic drugs by ABC transporters at the BBB.
    [Show full text]