National Clearinghouse for Drug Abuse Information Selected Reference Series, Series 4, No
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(Methadone Hydrochloride Oral Concentrate USP) and Methadose
NDA 17-116/S-021 Page 3 Methadose™ Oral Concentrate (methadone hydrochloride oral concentrate USP) and Methadose™ Sugar-Free Oral Concentrate (methadone hydrochloride oral concentrate USP) dye-free, sugar-free, unflavored CII Rx only FOR ORAL USE ONLY Deaths have been reported during initiation of methadone treatment for opioid dependence. In some cases, drug interactions with other drugs, both licit and illicit, have been suspected. However, in other cases, deaths appear to have occurred due to the respiratory or cardiac effects of methadone and too-rapid titration without appreciation for the accumulation of methadone over time. It is critical to understand the pharmacokinetics of methadone and to exercise vigilance during treatment initiation and dose titration (see DOSAGE AND ADMINISTRATION). Patients must also be strongly cautioned against self- medicating with CNS depressants during initiation of methadone treatment. Respiratory depression is the chief hazard associated with methadone hydrochloride administration. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, particularly in the early dosing period. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration. Cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, NDA -
Opioid Receptorsreceptors
OPIOIDOPIOID RECEPTORSRECEPTORS defined or “classical” types of opioid receptor µ,dk and . Alistair Corbett, Sandy McKnight and Graeme Genes encoding for these receptors have been cloned.5, Henderson 6,7,8 More recently, cDNA encoding an “orphan” receptor Dr Alistair Corbett is Lecturer in the School of was identified which has a high degree of homology to Biological and Biomedical Sciences, Glasgow the “classical” opioid receptors; on structural grounds Caledonian University, Cowcaddens Road, this receptor is an opioid receptor and has been named Glasgow G4 0BA, UK. ORL (opioid receptor-like).9 As would be predicted from 1 Dr Sandy McKnight is Associate Director, Parke- their known abilities to couple through pertussis toxin- Davis Neuroscience Research Centre, sensitive G-proteins, all of the cloned opioid receptors Cambridge University Forvie Site, Robinson possess the same general structure of an extracellular Way, Cambridge CB2 2QB, UK. N-terminal region, seven transmembrane domains and Professor Graeme Henderson is Professor of intracellular C-terminal tail structure. There is Pharmacology and Head of Department, pharmacological evidence for subtypes of each Department of Pharmacology, School of Medical receptor and other types of novel, less well- Sciences, University of Bristol, University Walk, characterised opioid receptors,eliz , , , , have also been Bristol BS8 1TD, UK. postulated. Thes -receptor, however, is no longer regarded as an opioid receptor. Introduction Receptor Subtypes Preparations of the opium poppy papaver somniferum m-Receptor subtypes have been used for many hundreds of years to relieve The MOR-1 gene, encoding for one form of them - pain. In 1803, Sertürner isolated a crystalline sample of receptor, shows approximately 50-70% homology to the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the the genes encoding for thedk -(DOR-1), -(KOR-1) and orphan (ORL ) receptors. -
(Butorphanol Tartrate) Nasal Spray
NDA 19-890/S-017 Page 3 ® STADOL (butorphanol tartrate) Injection, USP STADOL NS® (butorphanol tartrate) Nasal Spray DESCRIPTION Butorphanol tartrate is a synthetically derived opioid agonist-antagonist analgesic of the phenanthrene series. The chemical name is (-)-17-(cyclobutylmethyl) morphinan-3, 14-diol [S- (R*,R*)] - 2,3 - dihydroxybutanedioate (1:1) (salt). The molecular formula is C21H29NO2,C4H6O6, which corresponds to a molecular weight of 477.55 and the following structural formula: Butorphanol tartrate is a white crystalline substance. The dose is expressed as the tartrate salt. One milligram of the salt is equivalent to 0.68 mg of the free base. The n-octanol/aqueous buffer partition coefficient of butorphanol is 180:1 at pH 7.5. STADOL (butorphanol tartrate) Injection, USP, is a sterile, parenteral, aqueous solution of butorphanol tartrate for intravenous or intramuscular administration. In addition to 1 or 2 mg of butorphanol tartrate, each mL of solution contains 3.3 mg of citric acid, 6.4 mg sodium citrate, and 6.4 mg sodium chloride, and 0.1 mg benzethonium chloride (in multiple dose vial only) as a preservative. NDA 19-890/S-017 Page 4 STADOL NS (butorphanol tartrate) Nasal Spray is an aqueous solution of butorphanol tartrate for administration as a metered spray to the nasal mucosa. Each bottle of STADOL NS contains 2.5 mL of a 10 mg/mL solution of butorphanol tartrate with sodium chloride, citric acid, and benzethonium chloride in purified water with sodium hydroxide and/or hydrochloric acid added to adjust the pH to 5.0. The pump reservoir must be fully primed (see PATIENT INSTRUCTIONS) prior to initial use. -
Phencyclidine: an Update
Phencyclidine: An Update U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse and Mental Health Administration Phencyclidine: An Update Editor: Doris H. Clouet, Ph.D. Division of Preclinical Research National Institute on Drug Abuse and New York State Division of Substance Abuse Services NIDA Research Monograph 64 1986 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administratlon National Institute on Drug Abuse 5600 Fishers Lane Rockville, Maryland 20657 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, DC 20402 NIDA Research Monographs are prepared by the research divisions of the National lnstitute on Drug Abuse and published by its Office of Science The primary objective of the series is to provide critical reviews of research problem areas and techniques, the content of state-of-the-art conferences, and integrative research reviews. its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community. Editorial Advisors MARTIN W. ADLER, Ph.D. SIDNEY COHEN, M.D. Temple University School of Medicine Los Angeles, California Philadelphia, Pennsylvania SYDNEY ARCHER, Ph.D. MARY L. JACOBSON Rensselaer Polytechnic lnstitute National Federation of Parents for Troy, New York Drug Free Youth RICHARD E. BELLEVILLE, Ph.D. Omaha, Nebraska NB Associates, Health Sciences Rockville, Maryland REESE T. JONES, M.D. KARST J. BESTEMAN Langley Porter Neuropsychiatric lnstitute Alcohol and Drug Problems Association San Francisco, California of North America Washington, D.C. DENISE KANDEL, Ph.D GILBERT J. BOTV N, Ph.D. College of Physicians and Surgeons of Cornell University Medical College Columbia University New York, New York New York, New York JOSEPH V. -
A Review of Prehospital Pain Management
A Review of Prehospital Pain Management Jennifer Farah, MD EMS & Disaster Medicine Fellow University of California, San Diego Outline • Non-medicinal methods (e.g. ice-packs) • NSAIDs and Acetaminophen • Morphine • Fentanyl • Ketamine… the future? Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) • Aspirin, Ibuprofen, Naproxen, Celecoxib • Dose (Ibuprofen): 10mg/kg (max daily 1200mg-3200mg/day) • Onset (oral): 25-30 mins • Peak: 1-2hr • Duration: 4-6hr • Cost: $0.11-0.21 / 200mg tablet Acetaminophen (Tylenol) • Dose: 15mg/kg PO (max daily dose 4000mg/day) • Onset (oral): 15-20 mins • Peak: 1-1.5hr • Duration: 4-6hr • IV: Should be administered as a 15 min infusion • Cost: $0.02-0.36 / 325mg tablet Morphine • Pure opioid agonist selective to μ – receptors • Onset IV: 5 mins • Duration: 4-5 hours • Dose: 2-10mg IV per 70kg (0.1mg/kg) • Controlled substance schedule II • Cost: $0.71 /10mg • Shelf life: 3 years Fentanyl • Pure opioid agonist to μ – receptors • Onset IV: Almost immediate • Duration: 30-60 mins • Dose: 50-100mcg IV or 0.5-1.5mcg/kg • Controlled substance schedule II • Cost: $0.83/ 100μg • Shelf life: 3 years Advantages of Fentanyl • x50-100 more potent than morphine Fentanyl 0.1mg = Morphine 10mg • Quick onset of action • Preserves cardiac stability • Less nausea (not validated) • May cause muscle rigidity (chest wall rigidity) Fleischman R. et al Prehospital Emergency Care 2010 • Retrospective before and after study from morphine to fentanyl in an ALS EMS system in 2007 • 355 patients Morphine, 363 patients Fentanyl • Morphine 2--5 mg IV, repeated q5 mins to a max of 20 mg. • Fentanyl 50μg IV, repeated doses of 25--50μg q3--5 minutes to a max of 200 μg. -
Drugs of Abuseon September Archived 13-10048 No
U.S. DEPARTMENT OF JUSTICE DRUG ENFORCEMENT ADMINISTRATION WWW.DEA.GOV 9, 2014 on September archived 13-10048 No. v. Stewart, in U.S. cited Drugs of2011 Abuse EDITION A DEA RESOURCE GUIDE V. Narcotics WHAT ARE NARCOTICS? Also known as “opioids,” the term "narcotic" comes from the Greek word for “stupor” and originally referred to a variety of substances that dulled the senses and relieved pain. Though some people still refer to all drugs as “narcot- ics,” today “narcotic” refers to opium, opium derivatives, and their semi-synthetic substitutes. A more current term for these drugs, with less uncertainty regarding its meaning, is “opioid.” Examples include the illicit drug heroin and pharmaceutical drugs like OxyContin®, Vicodin®, codeine, morphine, methadone and fentanyl. WHAT IS THEIR ORIGIN? The poppy papaver somniferum is the source for all natural opioids, whereas synthetic opioids are made entirely in a lab and include meperidine, fentanyl, and methadone. Semi-synthetic opioids are synthesized from naturally occurring opium products, such as morphine and codeine, and include heroin, oxycodone, hydrocodone, and hydromorphone. Teens can obtain narcotics from friends, family members, medicine cabinets, pharmacies, nursing 2014 homes, hospitals, hospices, doctors, and the Internet. 9, on September archived 13-10048 No. v. Stewart, in U.S. cited What are common street names? Street names for various narcotics/opioids include: ➔ Hillbilly Heroin, Lean or Purple Drank, OC, Ox, Oxy, Oxycotton, Sippin Syrup What are their forms? Narcotics/opioids come in various forms including: ➔ T ablets, capsules, skin patches, powder, chunks in varying colors (from white to shades of brown and black), liquid form for oral use and injection, syrups, suppositories, lollipops How are they abused? ➔ Narcotics/opioids can be swallowed, smoked, sniffed, or injected. -
Ketamine Homogeneous Enzyme Immunoassay (HEIA™)
Ketamine Homogeneous Enzyme Immunoassay (HEIA™) Exclusively from Immunalysis Formula: C13H16CINO Semi-Quantitative or Qualitative Testing Systematic Name: (RS)- 2- (2- chlorophenyl)- 2- (methylamino)cyclohexanone Accurate and reliable Brand Names: Ketanest®, Ketaset®, Ketalar® Ready to use About Ketamine: Ketamine is an anesthetic agent used in the United States since 1972 for veterinary and pediatric medicine. It is also used in the treatment of depression and postoperative pain management. However, in recent years it has gained popularity as a street drug used at clubs and raves due to its hallucinogenic effects. Administration: Oral; intravenous; intramuscular; insufflation Elimination: Ketamine metabolizes by N-demethylation to Norketamine and further dehydrogenates to Dehydronorketamine. After 72 hours of a single dose, 2.3% of Ketamine is unchanged, 1.6% is Norketamine, 16.2% is Dehydronorketamine, and 80% is hydroxylated derivatives of Ketamine.1,2 Abuse Potential: An overdose can cause unconsciousness and dangerously slowed breathing. 1) R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, Fourth Edition, p. 412-414. 2) K. Moore, J.Skerov, B.Levine, and A.Jacobs, Urine Concentrations of Ketamine and Norketamine Following Illegal Consumption, J.Anal, Toxicol. 25: 583-588 (2001). Ketanest® is a registered trademark of Pfizer, Inc., Ketaset® is a trademark of ZOETIS W LLC., Ketalar® is a trademark of PAR STERILE PRODUCTS, LLC. Tel 909.482.0840 | Toll Free 888.664.8378 | Fax 909.482.0850 ISO13485:2003 www.immunalysis.com CERTIFIED -
Torbugesic® Orbugesic®
In horses, intravenous dosages of butorphanol Repeated administration of butorphanol at 1 mg/kg DOSAGE ranging from 0.05 to 0.4 mg/kg were shown to be (10 times the recommended dose) every four hours The recommended dosage in the horse is 0.1 mg 7. Popio, K.A. et al: “Hemodynamic and Respiratory eff ective in alleviating visceral and superfi cial pain for 48 hours caused constipation in one of two of butorphanol per kilogram of body weight Eff ects of Morphine and Butorphanol,” Clin. for at least 4 hours, as illustrated in the following horses. (0.05 mg/lb) by intravenous injection. This is Pharmacol. Ther. 23: 281–287, 1978. fi gure: equivalent to 5 mL of TORBUGESIC for each 1000 lbs 8. Robertson, J.T. and Muir, W.W.: “Cardiopulmonary Subacute Equine Studies body weight. Eff ects of Butorphanol Tartrate in Horses,” Am. J. Analgesic Eff ects of Butorphanol Given at Horses were found to tolerate butorphanol given The dose may be repeated within 3 to 4 hours Vet. Res. 42: 41–44, 1981. Various Dosages in Horses with Abdominal Pain intravenously at dosages of 0.1, 0.3 and 0.5 mg/kg but treatment should not exceed 48 hours. 9. Kalpravidh, M. et al: “Eff ects of Butorphanol, every 4 hours for 48 hours followed by once daily Pre-clinical model studies and clinical fi eld trials in Flunixin, Levorphanol, Morphine, Pentazocine injections for a total of 21 days. The only detectable horses demonstrate that the analgesic eff ects of and Xylazine in Ponies,” Am. -
Tennessee Drug Statutes Chart
Tennessee Drug Statutes Chart Tennessee Code: Title 39 Criminal Code SCHEDULE I OFFENSES/PENALTIES ENHANCEMENTS/ (*All sentences are for BENEFIT RESTRICTIONS standard offenders. Enhancement/mitigating factors may increase/reduce sentence. See sentencing statutes in appendix) 39-17-405 Criteria 39-17-417(b) (1) High potential for abuse; (2) Manufacture, delivery, No accepted med. Use in US or sale, possession w/ lacks accepted safety for med use intent (p.w.i.) of Schedule I Class B felony: 8-12yrs; <$100,000 39-17-406 Substances 3-17-417(i) Manufacture, (b) Opiates delivery, p.w.i. of heroin (c) Opium derivatives: E.g., (>15g); morphine heroin, codeine compounds, (>15g); hydromorphone morphine compounds, etc. (>5g); LSD (>5g); (d) Hallucinogenic substances: cocaine (>26g); E.g., MDMA, mescaline, DMT, pentazocine & peyote, LSD, psilocybin, synthetic tripelennamine (>5g); THC, etc. PCP (>30g); (e) Depressants: e.g., GHB, barbiturates (>100g); Qualuudes phenmetrazine (>50g); (f) Stimulants: E.g., fenethylline, amphetamine/ BZP methamphetamine (>26g); peyote (>1000g); Other Schedule I or II substances (>200g) Class B felony: 8-12yrs; <$200,000 SCHEDULE II 1 Tennessee Drug Statutes Chart Tennessee Code: Title 39 Criminal Code 39-17-407 Criteria 3-17-417(j) Manufacture, (1) high potential for abuse; (2) delivery, p.w.i. of heroin accepted med use in US w/ severe (>150g); morphine restrictions; and (3) abuse may (>150g); lead to severe psych or phys hydromorphone (>50g); dependence LSD (>50g); cocaine (>300g); pentazocine & tripelennamine (>50g); PCP (>300g); barbiturates (>1000g); phenmetrazine (>500g); amphetamine/ methamphetamine (>300g); peyote (>10000g); Other Schedule I or II substances (>2000g) Class A felony; 15-25yrs; <$500,000 39-17-408 Substances 39-17-417(c)(1) (b) Narcotics derived from Manufacture, delivery, vegetable origin or chemical p.w.i. -
Psycho Pharmacology © by Springer-Verlag 1976
Psychopharmacology 47, 65- 69 (1976) Psycho pharmacology © by Springer-Verlag 1976 Generalization of Morphine and Lysergic Acid Diethylamide (LSD) Stimulus Properties to Narcotic Analgesics I. D. HIRSCHHORN* and J. A. ROSECRANS Department of Pharmacology, Medical College of Virginia, Richmond, Virginia 23298, U.S.A. Abstract. The present investigation sought to deter- Physical dependence is not always associated with drug mine whether the stimulus properties of morphine craving and a high abuse liability. Some narcotic- and lysergic acid diethylamide (LSD) would gener- antagonist analgesics, such as cyclazocine and nalor- alize to several narcotic analgesics which vary in their phine, produce physical dependence with chronic subjective effects. Morphine and saline served as administration, but withdrawal does not result in drug discriminative stimuli for one group of rats in a 2-1ever seeking behavior (Martin et al., 1965; Martin and discrimination task. LSD and saline were discrimina- Gorodetzky, 1965). However, both cyclazocine and tive stimuli for a second group. Depression of one nalorphine have subjective side effects characterized lever in an operant chamber resulted in reinforcement by dysphoria and hallucinations (Haertzen, 1970) following the administration of morphine or LSD which render them unsuitable for therapeutic use. and the opposite lever was reinforced after saline. Pentazocine, a less potent antagonist of morphine After discriminated responding was stable, stimulus than cyclazocine and nalorphine, more closely resem- generalization tests with narcotic analgesics and bles morphine in its pharmacological effects and has antagonists showed that the stimulus properties of a somewhat greater incidence of non-medical use morphine generalized to methadone and meperidine, than antagonists of the nalorphine type (Paddock and partially to pentazocine, all of which produce etal., 1969). -
Update in Anaesthesia
Update in Anaesthesia Pentazocine Karen Henderson Correspondence Email: [email protected] Introduction use with 30 - 40 mg of pentazocine equivalent In 1967 pentazocine became the first opioid to 10 mg morphine. When given by mouth, the agonist-antagonist to be introduced into analgesic action of pentazocine is much weaker clinical practice as an analgesic. It was hoped than morphine and is thought to lie somewhere that pentazocine would prove to be a powerful between that of peripherally acting analgesics analgesic, free of the side-effects of opioid such as paracetamol and weak opioids such as narcotics, particularly avoiding drug dependency. codeine. In practice pentazocine has proved to be less Other actions of pentazocine mirror those of effective than hoped, but it is still used widely in other opioids including respiratory depression, Clinical Overview Articles resource-poor countries. cough suppression, miosis, decreased gastric Chemistry emptying and constipation and increased smooth Pentazocine is a benzmorphan which is muscle tone in the uterus and bladder. However chemically related to morphine. It is a white or in normal use these effects are usually of little cream, odourless, crystalline powder. It consists clinical significance. of a racemic mixture of dextro- (d) and laevo- In contrast to other strong opioid analgesics Summary (l) isomers which is soluble in acidic aqueous however, there is a dose-related systemic This article describes solutions. Pentazocine hydrochloride is used for and pulmonary hypertension, increased left the pharmacology oral use and the lactate form is used for parenteral ventricular end-diastolic pressure and a rise in and rectal administration. and clinical uses of central venous pressure, probably as a result of the opioid agonist- Molecular weight (free base)........................321.9 a rise in plasma catecholamine concentrations. -
ARK™ Ketamine Assay Package Insert
The ARK Ketamine Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed positive analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug test result, particularly when the For Criminal Justice and Forensic Use Only preliminary test result is positive. 3 SUMMARY AND EXPLANATION OF THE TEST Ketamine ((+/-)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone) is a synthetic, non- RK™ Ketamine Assay barbiturate and rapid-acting general anesthetic that is indicated for use in both human and A veterinary surgical procedures.1,2 This ARK Diagnostics, Inc. package insert for the ARK Ketamine Assay must be read prior to use. Package insert instructions must be followed accordingly. The assay provides a simple Ketamine is a Schedule III substance under the United States Controlled Substances Act for and rapid analytical screening procedure for detecting ketamine in urine. Reliability of the its potential for abuse and risk of dependence. Ketamine is structurally and pharmacologically assay results cannot be guaranteed if there are any deviations from the instructions in this similar to phencyclidine (PCP), but is less potent, has a faster onset and shorter duration of package insert. action relative to PCP. Ketamine produces a variety of symptoms including, but not limited to anxiety, dysphoria, disorientation, insomnia, flashbacks, hallucinations, and psychotic episodes.1,3 CUSTOMER SERVICE Following administration in humans, ketamine is N-demethylated by liver microsomal ARK Diagnostics, Inc.