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Methoxyflurane (INN), formerly marketed as Penthrane by Abbott Laboratories, is a halogenated ether that was in clinical use as a volatile inhalational anesthetic from its introduction by Joseph F. Artusio ''et al'' in 1960 until the late 1970s. It was first synthesized in the late 1940s by William T. Miller and his team of chemists following their involvement in the Manhattan Project.〔 Methoxyflurane is an extremely potent and highly lipid-soluble anesthetic agent, characterized by very slow induction (onset of action) and emergence (offset or dissipation) times. It is non-flammable, has relatively mild hemodynamic effects, and it does not predispose the heart to rhythm disturbances. It is, however, a significant respiratory depressant. Methoxyflurane has powerful analgesic (pain-relieving) properties at well below full anesthetic doses. It was utilized in self-administration devices for obstetric analgesia, in a manner that foreshadowed the patient-controlled analgesia infusion pumps of today. The biodegradation of methoxyflurane produces inorganic fluoride and dichloroacetic acid (DCAA). The combined effects of these two compounds may be responsible for the toxicity of methoxyflurane to some of the major organs of the human body. Methoxyflurane was determined to be nephrotoxic (damaging to the kidneys) in a dose-dependent response and hepatotoxic (damaging to the liver) at anesthetic doses in 1973, and the drug was abandoned as a general anesthetic in the late 1970s.〔Mazze, Richard I. M.D. Methoxyflurane Revisited: Tale of an Anesthetic from Cradle to Grave. Anesthesiology, October 2006; Vol 105(4), pp 843–846〕 In 1999, the manufacturer discontinued distribution of methoxyflurane in the United States and Canada, and on September 6, 2005, the Food and Drug Administration determined that it should be withdrawn from the market for safety concerns.〔 It is however still used in Australia as an emergency analgesic for the initial management of pain due to acute trauma, as well as for brief painful procedures such as changing of wound dressings or for transport of injured people. ==Medical use== Methoxyflurane has been extensively used since the 1970s in Australia as an emergency analgesic for short-term use, mostly by the Australian and New Zealand Defence Forces,〔 and the Australian ambulance services.〔〔〔 The drug is currently only available from one manufacturer (Medical Developments International, Melbourne, Victoria, Australia). It is self-administered to children and adults using the Penthrox inhaler, a hand-held inhaler device, known as "the green whistle".〔〔〔〔 A non-opioid alternative to morphine, it is also easier to use than nitrous oxide.〔 As of 2010, methoxyflurane was listed under the Pharmaceutical Benefits Scheme for the initial management of pain due to acute trauma, as well as for brief painful procedures such as changing of wound dressings or for patient transport.〔 A portable, disposable, single-use inhaler device (the Penthrox inhaler), along with a single 3 milliliter brown glass vial of methoxyflurane is provided in doctor's kits that allows conscious hemodynamically stable patients (including children over the age of 5 years) to self-administer the drug, under supervision.〔 The device is often referred to as the "green whistle", due to its appearance.〔 Each 3 milliliter dose lasts approximately 30 minutes.〔 Pain relief begins after 6–8 breaths and continues for several minutes after stopping inhalation.〔 The maximum recommended dose is 6 milliliters per day or 15 milliliters per week because of the risk of cumulative dose-related nephrotoxicity, and it should not be used on consecutive days.〔 Despite the potential for renal impairment when used at anesthetic doses, no significant adverse effects have been reported in the literature when it is used at the lower doses (up to 6 milliliters) used for producing analgesia and sedation.〔〔〔 Due to the risk of organ (especially renal) toxicity, methoxyflurane is contraindicated in patients with pre-existing kidney disease or diabetes mellitus, and is not recommended to be administered in conjunction with tetracyclines or other potentially nephrotoxic or enzyme-inducing drugs.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Methoxyflurane」の詳細全文を読む スポンサード リンク
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