Subject(s)
Anesthesia, Intravenous , Anesthetics, Intravenous , Thiopental , Alfaxalone Alfadolone Mixture/chemistry , Alfaxalone Alfadolone Mixture/history , Alfaxalone Alfadolone Mixture/pharmacology , Anesthesia, Intravenous/history , Anesthesiology , Anesthetics, Intravenous/chemistry , Anesthetics, Intravenous/history , Anesthetics, Intravenous/pharmacology , Barbiturates/history , Child , History, 20th Century , Humans , Ketamine/history , Ketamine/pharmacology , Pediatrics , Propofol/history , Propofol/pharmacology , Sodium Oxybate/chemistry , Sodium Oxybate/history , Sodium Oxybate/pharmacology , Structure-Activity Relationship , Thiopental/chemistry , Thiopental/history , Thiopental/pharmacologyABSTRACT
Alcohol has been the most important knockout drug in history and literature and continues to play an essential role up to now. Blunt force to the head in the form of a knockout punch is another mechanism leading to a transient loss of consciousness. Diethyl ether and chloroform are among the classical knockout substances. Although they have meanwhile been replaced by modern sedatives and hypnotics, their use is still observed in isolated cases.
Subject(s)
Alcoholic Beverages/history , Anesthetics/history , Chloroform/history , Ether/history , Illicit Drugs/history , Medicine in the Arts , Paintings/history , Sodium Oxybate/history , Unconsciousness/history , History, 16th Century , History, 17th Century , History, 18th Century , History, 19th Century , History, 20th Century , History, Ancient , HumansABSTRACT
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).
Subject(s)
Drug Industry/methods , Risk Management/methods , Buprenorphine/history , Buprenorphine, Naloxone Drug Combination , Dextroamphetamine/history , Drug and Narcotic Control , History, 20th Century , History, 21st Century , Humans , Lisdexamfetamine Dimesylate , Methylphenidate/history , Naloxone/history , Oxycodone/history , Product Surveillance, Postmarketing , Sodium Oxybate/history , Substance-Related Disorders/prevention & controlABSTRACT
The discovery of gamma-hydroxybutyrate (GHB) over 40 years ago led to its immediate use as a general anesthetic agent. Subsequent research demonstrated that GHB is an endogenous compound in the mammalian brain and current research suggests that GHB is a probable neurotransmitter. In the United States, reports of anabolic effects lead to its misuse among body builders during the 1980's while the intoxicating properties of the drug lead to its popularization as a substance of abuse during the 1990's. GHB became associated with reports of drug-facilitated sexual assault and cases of physical dependence and withdrawal. Efforts to ban GHB caused increased use of GHB analogues and pro-drugs. Against this backdrop, GHB was being developed for the treatment of narcolepsy, leading to the approval of Xyrem (sodium oxybate) oral solution in 2002 for the treatment of cataplexy in patients with narcolepsy. A risk management program permits the safe handling and distribution of the approved product, minimizes the risk for diversion, provides professional and patient education about the risks and benefits of sodium oxybate, and includes physician and patient registries. Post-marketing surveillance indicates sodium oxybate has an acceptable safety profile and presents minimal risk for the development of physical dependence.
Subject(s)
Anesthetics, Intravenous/pharmacology , Drug Design , Sodium Oxybate/pharmacology , Anesthetics, Intravenous/adverse effects , Anesthetics, Intravenous/history , Clinical Trials as Topic , History, 20th Century , Humans , Product Surveillance, Postmarketing , Risk Management/methods , Sodium Oxybate/adverse effects , Sodium Oxybate/history , Substance-Related DisordersABSTRACT
Newer drugs of abuse, such as MDMA, GHB, GBL, 1,4-BD and ketamine, are frequently used in the settings of raves and are often promoted on the internet. The popularity of these agents is increasing; therefore, emergency physicians should become familiar with the clinical presentations and management of the toxicity induced by these agents.
