Assuntos
Indústria Farmacêutica/história , Marketing/história , Preparações Farmacêuticas/história , Analgésicos Opioides/história , Analgésicos Opioides/uso terapêutico , Antibacterianos/história , História do Século XX , Humanos , Uso Excessivo dos Serviços de Saúde/tendências , Oxicodona/história , Oxicodona/uso terapêutico , Oxitetraciclina/históriaRESUMO
Humankind has used and abused psychoactive drugs for millennia. Formally, a psychoactive drug is any agent that alters cognition and mood. The term "psychotropic drug" is neutral and describes the entire class of substrates, licit and illicit, of interest to governmental drug policy. While these drugs are prescribed for issues ranging from pain management to anxiety, they are also used recreationally. In fact, the current opioid epidemic is the deadliest drug crisis in American history. While the topic is highly politicized with racial, gender, and socioeconomic elements, there is no denying the toll drug mis- and overuse is taking on this country. Overdose, fueled by opioids, is the leading cause of death for Americans under 50 years of age, killing ca. 64,000 people in 2016. From a chemistry standpoint, the question is in what ways, if any, did organic chemists contribute to this problem? In this targeted review, we provide brief historical accounts of the main classes of psychoactive drugs and discuss several foundational total syntheses that ultimately provide the groundwork for producing these molecules in academic, industrial, and clandestine settings.
Assuntos
Estimulantes do Sistema Nervoso Central/síntese química , Alucinógenos/síntese química , Alcaloides Opiáceos/síntese química , Psicotrópicos/síntese química , Anfetaminas/síntese química , Anfetaminas/química , Anfetaminas/história , Benzodiazepinas/síntese química , Benzodiazepinas/química , Benzodiazepinas/história , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/história , Cocaína/síntese química , Cocaína/química , Cocaína/história , Cocaína Crack/síntese química , Cocaína Crack/química , Cocaína Crack/história , Indústria Farmacêutica , Overdose de Drogas/epidemiologia , Tolerância a Medicamentos , Epidemias , Alucinógenos/química , Alucinógenos/história , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , Humanos , N-Metil-3,4-Metilenodioxianfetamina/síntese química , N-Metil-3,4-Metilenodioxianfetamina/química , N-Metil-3,4-Metilenodioxianfetamina/história , Alcaloides Opiáceos/química , Alcaloides Opiáceos/história , Ópio/história , Oxicodona/síntese química , Oxicodona/química , Oxicodona/história , Psicotrópicos/química , Psicotrópicos/história , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Medicamentos Sintéticos/síntese química , Medicamentos Sintéticos/química , Medicamentos Sintéticos/história , Estados Unidos/epidemiologiaAssuntos
Analgésicos Opioides/efeitos adversos , Benzodiazepinas/efeitos adversos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Oxicodona/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Analgésicos Opioides/história , Benzodiazepinas/história , Serviço Hospitalar de Emergência/história , História do Século XX , Humanos , Oxicodona/história , Transtornos Relacionados ao Uso de Substâncias/história , Estados Unidos/epidemiologiaRESUMO
The development and implementation of programs in the U.S. to minimize risks and assess unintended consequences of new medications has been increasingly required by the Food and Drug Administration (FDA) since the mid 1990s. This paper provides four case histories of risk management and post-marketing surveillance programs utilized recently to address problems associated with possible abuse, dependence and diversion. The pharmaceutical sponsors of each of these drugs were invited to present their programs and followed a similar template for their summaries that are included in this article. The drugs and presenting companies were OxyContin, an analgesic marketed by Purdue Pharma L.P., Daytrana and Vyvanse, ADHD medications marketed by Shire Pharmaceuticals, Xyrem for narcolepsy marketed by Jazz Pharmaceuticals, and Subutex and Suboxone for opioid dependence marketed by Reckitt Benckiser Pharmaceuticals Inc. These case histories and subsequent discussions provide invaluable real-world examples and illustrate both the promise of risk management programs in providing a path to market and/or for keeping on the market drugs with serious potential risks. They also illustrate the limitations of such programs in actually controlling unintended consequences, as well as the challenge of finding the right balance of reducing risks without posing undue barriers to patient access. These experiences are highly relevant as the FDA increasingly requires pharmaceutical sponsors to develop and implement the more formalized and enforceable versions of the risk management term Risk Evaluation and Mitigation Strategies (REMS).
Assuntos
Indústria Farmacêutica/métodos , Gestão de Riscos/métodos , Buprenorfina/história , Combinação Buprenorfina e Naloxona , Dextroanfetamina/história , Controle de Medicamentos e Entorpecentes , História do Século XX , História do Século XXI , Humanos , Dimesilato de Lisdexanfetamina , Metilfenidato/história , Naloxona/história , Oxicodona/história , Vigilância de Produtos Comercializados , Oxibato de Sódio/história , Transtornos Relacionados ao Uso de Substâncias/prevenção & controleRESUMO
Oxycodone has been in clinical use since 1917. Parenteral oxycodone was used mainly for the treatment of acute postoperative pain whereas combinations, for example, oxycodone and acetaminophen, were used for moderate pain. Since the introduction of controlled-release oxycodone, it has been used to manage cancer-related pain and chronic non-cancer-related pain problems. Controlled studies have been performed in postoperative pain, cancer pain, osteoarthritis-related pain, and neuropathic pain due to postherpetic neuralgia and diabetic neuropathy. The pharmacodynamic effects of oxycodone are typical of a mu-opioid agonist. Oxycodone closely resembles morphine but it has some distinct differences, particularly in its pharmacokinetic profile. Being an old drug, the basic pharmacology of oxycodone has been a neglected field of research.
Assuntos
Analgésicos Opioides , Oxicodona , Analgésicos Opioides/história , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/uso terapêutico , Animais , Disponibilidade Biológica , Interações Medicamentosas , História do Século XX , Humanos , Falência Hepática/metabolismo , Neoplasias/complicações , Oxicodona/história , Oxicodona/farmacocinética , Oxicodona/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Dor Pós-Operatória/tratamento farmacológico , Insuficiência Renal/metabolismoRESUMO
The German firm E. Merck released in 1928, an injectable mixture of scopolamine, oxycodone, and ephedrine under the name SEE. This drug, renamed Scophedal in 1942 caused deep and prolonged analgesia, sedation, euphoria and amnesia without significant respiratory or circulatory depression. Used extensively by the German and Central European surgeons in the 1930s, Scophedal enjoyed immense popularity with the Wehrmacht's medical officers treating frontline mass casualties during World War II. The use of Scophedal declined after 1945, and its production was discontinued in 1987. Despite the clinical enthusiasm it raised, SEE was never critically investigated. This drug may deserve a rigorous re-evaluation.