Opioid Tolerance in Methadone Maintenance Treatment: Comparison
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Opioid-Induced Hyperalgesia in Humans Molecular Mechanisms and Clinical Considerations
SPECIAL TOPIC SERIES Opioid-induced Hyperalgesia in Humans Molecular Mechanisms and Clinical Considerations Larry F. Chu, MD, MS (BCHM), MS (Epidemiology),* Martin S. Angst, MD,* and David Clark, MD, PhD*w treatment of acute and cancer-related pain. However, Abstract: Opioid-induced hyperalgesia (OIH) is most broadly recent evidence suggests that opioid medications may also defined as a state of nociceptive sensitization caused by exposure be useful for the treatment of chronic noncancer pain, at to opioids. The state is characterized by a paradoxical response least in the short term.3–14 whereby a patient receiving opioids for the treatment of pain Perhaps because of this new evidence, opioid may actually become more sensitive to certain painful stimuli. medications have been increasingly prescribed by primary The type of pain experienced may or may not be different from care physicians and other patient care providers for the original underlying painful condition. Although the precise chronic painful conditions.15,16 Indeed, opioids are molecular mechanism is not yet understood, it is generally among the most common medications prescribed by thought to result from neuroplastic changes in the peripheral physicians in the United States17 and accounted for 235 and central nervous systems that lead to sensitization of million prescriptions in the year 2004.18 pronociceptive pathways. OIH seems to be a distinct, definable, One of the principal factors that differentiate the use and characteristic phenomenon that may explain loss of opioid of opioids for the treatment of pain concerns the duration efficacy in some cases. Clinicians should suspect expression of of intended use. -
Clinical and Pharmacokinetic Evaluation of S
Casoni et al. Acta Veterinaria Scandinavica (2015) 57:21 DOI 10.1186/s13028-015-0112-4 RESEARCH Open Access Clinical and pharmacokinetic evaluation of S-ketamine for intravenous general anaesthesia in horses undergoing field castration Daniela Casoni1*, Claudia Spadavecchia1, Beat Wampfler2, Wolfgang Thormann3 and Olivier L Levionnois1 Abstract Background: Intravenous anaesthetic drugs are the primary means for producing general anaesthesia in equine practice. The ideal drug for intravenous anaesthesia has high reliability and pharmacokinetic properties indicating short elimination and lack of accumulation when administered for prolonged periods. Induction of general anaesthesia with racemic ketamine preceded by profound sedation has already an established place in the equine field anaesthesia. Due to potential advantages over racemic ketamine, S-ketamine has been employed in horses to induce general anaesthesia, but its optimal dose remains under investigation. The objective of this study was to evaluate whether 2.5 mg/kg S-ketamine could be used as a single intravenous bolus to provide short-term surgical anaesthesia in colts undergoing surgical castration, and to report its pharmacokinetic profile. Results: After premedication with romifidine and L-methadone, the combination of S-ketamine and diazepam allowed reaching surgical anaesthesia in the 28 colts. Induction of anaesthesia as well as recovery were good to excellent in the majority (n = 22 and 24, respectively) of the colts. Seven horses required additional administration of S-ketamine to prolong the duration of surgical anaesthesia. Redosing did not compromise recovery quality. Plasma concentration of S-ketamine decreased rapidly after administration, following a two-compartmental model, leading to the hypothesis of a consistent unchanged elimination of the parent compound into the urine beside its conversion to S-norketamine. -
Opioid-Induced Hyperalgesia a Qualitative Systematic Review Martin S
Anesthesiology 2006; 104:570–87 © 2006 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Opioid-induced Hyperalgesia A Qualitative Systematic Review Martin S. Angst, M.D.,* J. David Clark, M.D., Ph.D.† Opioids are the cornerstone therapy for the treatment of an all-inclusive and current overview of a topic that may moderate to severe pain. Although common concerns regard- be difficult to grasp as a whole because new evidence ing the use of opioids include the potential for detrimental side accumulates quickly and in quite distinct research fields. effects, physical dependence, and addiction, accumulating evi- dence suggests that opioids may yet cause another problem, As such, a comprehensive review may serve as a source often referred to as opioid-induced hyperalgesia. Somewhat document. However, a systematic review also uses a paradoxically, opioid therapy aiming at alleviating pain may framework for presenting information, and such a frame- Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/104/3/570/360792/0000542-200603000-00025.pdf by guest on 01 October 2021 render patients more sensitive to pain and potentially may work may facilitate and clarify future communication by aggravate their preexisting pain. This review provides a com- clearly delineating various entities or aspects of OIH. prehensive summary of basic and clinical research concerning opioid-induced hyperalgesia, suggests a framework for organiz- Finally, a systematic review aims at defining the status ing pertinent information, delineates the status quo of our quo of our knowledge concerning OIH, a necessary task knowledge, identifies potential clinical implications, and dis- to guide future research efforts and to identify potential cusses future research directions. -
RMP Levopidon
VI.2 Elements for a public summary VI.2.1 Overview of disease epidemiology Levomethadone is indicated as substitution therapy for maintenance of opioid dependence in adults in conjunction with appropriate medical, social and psychosocial care. Opioid users entering specialist treatment are on average 33 years old, with female patients being younger in most countries. Across Europe, male opioid clients outnumber their female counterparts by a ratio of about three to one. The great majority of opioid clients report having started to use the drug before the age of 30, with almost half (46 %) of all opioid clients having done so before the age of 20. In general, opioid users report higher levels of homelessness and unemployment and lower levels of education than primary users of other drugs, and they are usually concentrated in urban areas. Source: EMCDDA (European Monitoring Centre for Drugs and Drug Addiction) 2012 Annual report on the state of the drugs problem in Europe http://www.emcdda.europa.eu/publications/annual-report/2012 VI.2.2 Summary of treatment benefits Levomethadone reduces withdrawal symptoms in people addicted to heroin or other narcotic drugs without causing the “high” associated with the drug addiction. Levomethadone treatment is an integral part of detoxification and maintenance programs in case of opioid addiction. There are several relevant objectives of levomethadone maintenance therapy: to suppress signs and symptoms of opioid withdrawal, to extinguish opioid-drug craving, and to block the reinforcing effects of illicit opioids. Each of these objectives is accomplished in phases, rather than at once, relying on the administration of adequate levomethadone doses to achieve and sustain optimum blood levels. -
Nitrous Oxide in Emergency Medicine Í O’ Sullivan, J Benger
214 ANALGESIA Emerg Med J: first published as 10.1136/emj.20.3.214 on 1 May 2003. Downloaded from Nitrous oxide in emergency medicine Í O’ Sullivan, J Benger ............................................................................................................................. Emerg Med J 2003;20:214–217 Safe and predictable analgesia is required for the identify these zones as there is considerable vari- potentially painful or uncomfortable procedures often ation between people. He also emphasised the importance of the patient’s pre-existing beliefs. If undertaken in an emergency department. The volunteers expect to fall asleep while inhaling characteristics of an ideal analgesic agent are safety, 30% N2O then a high proportion do so. An appro- predictability, non-invasive delivery, freedom from side priate physical and psychological environment increases the actions of N2O and may allow lower effects, simplicity of use, and a rapid onset and offset. doses to be more effective. Unlike many other Newer approaches have threatened the widespread use anaesthetic agents, N2O exhibits an acute toler- of nitrous oxide, but despite its long history this simple ance effect, whereby its potency is greater at induction than after a period of “accommoda- gas still has much to offer. tion”. .......................................................................... MECHANISM OF ACTION “I am sure the air in heaven must be this Some writers have suggested that N2O, like wonder-working gas of delight”. volatile anaesthetics, causes non-specific central nervous system depression. Others, such as 4 Robert Southey, Poet (1774 to 1843) Gillman, propose that N2O acts specifically by interacting with the endogenous opioid system. HISTORY N2O is known to act preferentially on areas of the Nitrous oxide (N2O) is the oldest known anaes- brain and spinal cord that are rich in morphine thetic agent. -
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. -
What Are the Treatments for Heroin Addiction?
How is heroin linked to prescription drug abuse? See page 3. from the director: Research Report Series Heroin is a highly addictive opioid drug, and its use has repercussions that extend far beyond the individual user. The medical and social consequences of drug use—such as hepatitis, HIV/AIDS, fetal effects, crime, violence, and disruptions in family, workplace, and educational environments—have a devastating impact on society and cost billions of dollars each year. Although heroin use in the general population is rather low, the numbers of people starting to use heroin have been steadily rising since 2007.1 This may be due in part to a shift from abuse of prescription pain relievers to heroin as a readily available, cheaper alternative2-5 and the misperception that highly pure heroin is safer than less pure forms because it does not need to be injected. Like many other chronic diseases, addiction can be treated. Medications HEROIN are available to treat heroin addiction while reducing drug cravings and withdrawal symptoms, improving the odds of achieving abstinence. There are now a variety of medications that can be tailored to a person’s recovery needs while taking into account co-occurring What is heroin and health conditions. Medication combined with behavioral therapy is particularly how is it used? effective, offering hope to individuals who suffer from addiction and for those around them. eroin is an illegal, highly addictive drug processed from morphine, a naturally occurring substance extracted from the seed pod of certain varieties The National Institute on Drug Abuse (NIDA) has developed this publication to Hof poppy plants. -
HPLC Enantioseparation of Tramadol and Its Metabolites: Method Validation and Application to Environmental Samples
HPLC enantioseparation of Tramadol and its metabolites: method validation and application to environmental samples Cátia Sofia Rodrigues Silva Master in Quality Control Faculty of Pharmacy of University of Porto 2016 Separação enantiomérica por HPLC do Tramadol e seus metabolitos: validação do método e aplicação em amostras ambientais Cátia Sofia Rodrigues Silva Dissertação do 2º Ciclo de Estudos Conducente ao Grau de Mestre em Controlo de Qualidade – especialização em Ambiente Trabalho realizado sob a orientação do Professor Doutor Carlos Manuel Magalhães Afonso e Professora Doutora Maria Elizabeth Tiritan 2016 De acordo com a legislação em vigor, não é permitida a reprodução de qualquer parte desta dissertação/tese HPLC enantioseparation of tramadol and metabolites: method validation and application to environmental samples ACKNOWLEDGEMENTS I would like to thank to Prof. Dr. Carlos Afonso, my supervisor, and Prof.ª Dr.ª Maria Elizabeth Tiritan, my co-supervision, for all the support, patience and dedication during the realization of this seminar and the experimental work. Your unconditional support was very important to me and it was certainly a privilege to work with you and acquire all knowledge you have given to me. To Prof.ª Dr.ª Cláudia Ribeiro, to Master Alexandra Maia, PhD Student, and to Master Virgínia Gonçalves, Superior technical of IINFACTS, I would like to thank for all the support that given me in experimental work, over this year, and for all the attention and availability in the laboratory’s work. To my parents, my family and my friends which have a lot of patience for me and make me laugh in the certain time. -
The Effects of the Morphine Analogue Levorphanol on Leukocytes: Metabolic Effects at Rest and During Phagocytosis
The effects of the morphine analogue levorphanol on leukocytes: Metabolic effects at rest and during phagocytosis Nancy Wurster, … , Penelope Pettis, Sharon Lebow J Clin Invest. 1971;50(5):1091-1099. https://doi.org/10.1172/JCI106580. Studies on bacteria have suggested that morphine-like drugs have effects on the cell membrane. To determine the effect of this class of drugs on a mammalian cell, we selected the rabbit peritoneal exudate granulocyte, which undergoes striking membrane changes during phagocytosis. We examined the effect in vitro of the morphine analogue, levorphanol on phagocytosis and metabolism by granulocytes incubated with and without polystyrene particles or live Escherichia coli. Levorphanol (1 or 2 mmoles/liter) decreased: (a) acylation of lysolecithin or lysophosphatidylethanolamine in the medium (which is stimulated about two-fold during phagocytosis) both at rest (40%) and during phagocytosis (60%); (b) uptake of latex particles and Escherichia coli, as judged by electron microscopy; (c) killing of live Escherichia coli (10-fold); (d) 14 14 + CO2 production from glucose-1- C during phagocytosis by at least 80%; (e) K content of granulocytes (35%); (f) oxidation of linoleate-1-14C by 50%, and its incorporation into triglyceride by more than 80%. However, levorphanol stimulated 2 to 3-fold the incorporation of linoleate-1-14C or palmitate-1-14C into several phospholipids. Glucose uptake, lactate production, and adenosine triphosphate (ATP) content are not affected by the drug. Thus, levorphanol does not appear to exert its effects through generalized metabolic suppression. Removal of levorphanol by twice resuspending the granulocytes completely reverses all inhibition. In line with observations on bacteria, it appears that the complex effects of levorphanol on […] Find the latest version: https://jci.me/106580/pdf The Effects of the Morphine Analogue Levorphanol on Leukocytes METABOLIC EFFECTS AT REST AND DURING PHAGOCYTOSIS NANcY WuRsTE, PETER ELSBACH, ERIc J. -
Package Leaflet: Information for the User Levomethadone Molteni 5 Mg
Package leaflet: Information for the user Levomethadone Molteni 5 mg/ml oral solution Levomethadone hydrochloride Read all of this leaflet carefully before you start taking this medicine - because it contains important information for you. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or pharmacist. This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What Levomethadone Molteni is and what it is used for 2. What you need to know before you take Levomethadone Molteni 3. How to take Levomethadone Molteni 4. Possible side effects 5. How to store Levomethadone Molteni 6. Contents of the pack and other information 1. What Levomethadone Molteni is and what it is used for Levomethadone Molteni contains the active substance levomethadone hydrochloride. It belongs to a group of medicines which act on your nervous system. Levomethadone Molteni is used to treat adults who are addicted to drugs called ‘opioids’ or ‘narcotic analgesics’ - such as heroin and morphine. It acts as a substitute for the addictive drugs. 2. What you need to know before you take Levomethadone Molteni Do not take Levomethadone Molteni if: you are allergic to levomethadone or any of the other ingredients of this medicine (listed in section 6) you are taking medicines for depression called ‘MAOIs’ (monoamine oxidase inhibitors) or have taken them in the last 2 weeks (see ‘Other medicines and Levomethadone Molteni’) you are taking medicines to treat addiction or strong painkillers (see ‘Other medicines and Levomethadone Molteni’) you have severe breathing or lung problems you are not addicted to opioid drugs. -
The Main Tea Eta a El Mattitauli Mali Malta
THE MAIN TEA ETA USA 20180169172A1EL MATTITAULI MALI MALTA ( 19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2018 /0169172 A1 Kariman (43 ) Pub . Date : Jun . 21 , 2018 ( 54 ) COMPOUND AND METHOD FOR A61K 31/ 437 ( 2006 .01 ) REDUCING APPETITE , FATIGUE AND PAIN A61K 9 / 48 (2006 .01 ) (52 ) U . S . CI. (71 ) Applicant : Alexander Kariman , Rockville , MD CPC . .. .. .. .. A61K 36 / 74 (2013 .01 ) ; A61K 9 / 4825 (US ) (2013 . 01 ) ; A61K 31/ 437 ( 2013 . 01 ) ; A61K ( 72 ) Inventor: Alexander Kariman , Rockville , MD 31/ 4375 (2013 .01 ) (US ) ( 57 ) ABSTRACT The disclosed invention generally relates to pharmaceutical (21 ) Appl . No. : 15 /898 , 232 and nutraceutical compounds and methods for reducing appetite , muscle fatigue and spasticity , enhancing athletic ( 22 ) Filed : Feb . 16 , 2018 performance , and treating pain associated with cancer, trauma , medical procedure , and neurological diseases and Publication Classification disorders in subjects in need thereof. The disclosed inven ( 51 ) Int. Ci. tion further relates to Kratom compounds where said com A61K 36 / 74 ( 2006 .01 ) pound contains at least some pharmacologically inactive A61K 31/ 4375 ( 2006 .01 ) component. pronuPatent Applicationolan Publication manu saJun . decor21, 2018 deSheet les 1 of 5 US 2018 /0169172 A1 reta Mitragynine 7 -OM - nitragynine *** * *momoda W . 00 . Paynantheine Speciogynine **** * * * ! 1000 co Speclociliatine Corynartheidine Figure 1 Patent Application Publication Jun . 21, 2018 Sheet 2 of 5 US 2018 /0169172 A1 -
Methadone and Levomethadone: Risks and Costs Analyses
METHADONE AND LEVOMETHADONE: PS-096, N07 RISKS AND COSTS ANALYSES Nora Pittet1, Isabella De Giorgi Salamun2, Olivier Simon3,4, Mohamed Hachaichi3, Eric Bergeron3, Mélanie Allaz2,3, Antoine Wildhaber3, Jacques Besson3, Farshid Sadeghipour1,2 1Section of pharmaceutical Sciences, University of Geneva, University of Lausanne; 2Pharmacy Service; 3Community Psychiatry, Lausanne University Hospital CHUV, Lausanne; 4Addiction Medicine College of Romandia COROMA, Switzerland . Background Conclusions • Racemic methadone oral solution 10mg/mL is the gold • This study allows the identification and quantification standard in the Opioid Agonist Treatment (OAT). of the main risks related to methadone and • Since recently, a levomethadone solution 5mg/mL is available levomethadone in our hospital. in Switzerland and will decrease the cardiac toxicity. • IM have been proposed taking into account the • However, the risk of errors and confusion in prescriptions, clinical and pharmacoeconomic aspects. preparation and administration seems to be significant and the • A cost-benefit analysis would be a perspective for a costs would be probably higher than the racemic solution. better assessment of the impact of levomethadone on Objectives morbidity/ mortality and the costs involved. • To analyse the risks of different dosage forms and Table 1: The 25 most critical FM products formulation from the prescription to the N° FM Who? CI administration of methadone and levomethadone in the 1 Error during hospital-outpatient transfer CHUV 343 2 Error of unit conversion AATC 336 Ambulatory Addiction Treatment Centre (AATC) and the 3 No double-check (or done by the patient only) CHUV 336 General Psychiatry. 4 Ambulatory-Hospital transmission by oral CHUV 294 5 Confusion between methadone and levomethadone bottles CHUV 294 • To assess the associated costs for the entire hospital.