Assuntos
Overdose de Drogas/história , Naloxona/história , Antagonistas de Entorpecentes/história , Overdose de Drogas/prevenção & controle , História do Século XX , História do Século XXI , Humanos , Nalorfina/história , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/história , Mudança Social/história , Estados UnidosRESUMO
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 & controleAssuntos
Doença de Alzheimer/história , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Animais , Colinérgicos/história , Colinérgicos/uso terapêutico , Inibidores da Colinesterase/história , Inibidores da Colinesterase/uso terapêutico , História do Século XX , Humanos , Naloxona/história , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/história , Antagonistas de Entorpecentes/uso terapêutico , Fisostigmina/história , Fisostigmina/uso terapêuticoAssuntos
Analgesia/história , Raquianestesia/história , Entorpecentes/história , Animais , História do Século XX , Naloxona/história , Naloxona/farmacologia , Antagonistas de Entorpecentes/história , Antagonistas de Entorpecentes/farmacologia , Entorpecentes/administração & dosagem , Dor/tratamento farmacológico , Dor/história , Dor/fisiopatologia , Ratos , Reflexo/efeitos dos fármacosAssuntos
Naloxona/história , Antagonistas de Entorpecentes/história , Dor Pós-Operatória/história , Efeito Placebo , Endorfinas/antagonistas & inibidores , Endorfinas/história , História do Século XX , Humanos , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Extração Dentária/históriaRESUMO
A historical introduction and review of the chemistry of the agonist-antagonist analgesics is presented. This development of strong analgesics with a lowered abuse potential from nalorphine to the clinically useful agonist-antagonists pentazocine, butorphanol, nalbuphine and buprenorphine is discussed in detail. The discovery of the pure antagonist naloxone and naltrexone is described. The possible use of cyclazocine and later naltrexone in treatment of post-dependent narcotic addicts is also described. Finally, structure-activity relationships are summarized relating changes in N-alkylation to the production of narcotic antagonist activity over all of the structural types of opioids.