New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 2): Identification of Nephrotoxic Metabolites

@article{Kharasch2006NewII,
  title={New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 2): Identification of Nephrotoxic Metabolites},
  author={Evan D. Kharasch and Jesara L Schroeder and H. Denny Liggitt and Dustin Ensign and Dale Whittington},
  journal={Anesthesiology},
  year={2006},
  volume={105},
  pages={737-745}
}
Background: Methoxyflurane nephrotoxicity results from its metabolism, which occurs by both dechlorination (to methoxydifluoroacetic acid [MDFA]) and O-demethylation (to fluoride and dichloroacetic acid [DCAA]). Inorganic fluoride can be toxic, but it remains unknown why other anesthetics, commensurately increasing systemic fluoride concentrations, are not toxic. Fluoride is one of many methoxyflurane metabolites and may itself cause toxicity and/or reflect formation of other toxic metabolite(s… 
New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 1): Identification of the Nephrotoxic Metabolic Pathway
TLDR
F fluoride from methoxyflurane anesthesia derives from O-demethylation, which may have implications for interpreting anesthetic defluorination, volatile anesthetic use, and methods to evaluate anesthetic toxicity.
Methoxyflurane revisited: tale of an anesthetic from cradle to grave.
  • R. Mazze
  • Medicine, Biology
    Anesthesiology
  • 2006
TLDR
Evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction is suggested and a proposed metabolic pathway to support this hypothesis is presented.
Adverse Drug Reactions With Halogenated Anesthetics
  • E. Kharasch
  • Medicine, Biology
    Clinical pharmacology and therapeutics
  • 2008
TLDR
This review focuses on adverse organ effects (hepatic, renal, and others) that are attributable to anesthetic metabolism and/or degradation that are associated with halogenated volatile anesthetics.
The role of inhaled methoxyflurane in acute pain management
TLDR
Given the limitations of currently available analgesic agents in the prehospital and emergency department settings, the ease of use and portability of methoxyflurane combined with its rapid onset of effective pain relief and favorable safety profile make it a useful nonopioid option for pain management.
CLASSIC PAPERS REVISITED
TLDR
Evidence is presented to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction and a proposed metabolic pathway to support this hypothesis is presented.
Methoxyflurane: a review with emphasis on its role in dental practice.
TLDR
Methoxyflurane has become attractive for use in dental practice, likely due to its effectiveness as an analgesic and its additional sedative qualities, and its acceptance is controversial as its use in dentistry is largely elective.
Efficacy and safety of inhaled low-dose methoxyflurane for acute paediatric pain: A systematic review
TLDR
In inhaled methoxyflurane has potential to provide easy to administer, needle-free analgesia with a rapid onset and good safety profile for paediatric acute moderate-to-severe pain.
Methoxyflurane: A Review in Trauma Pain
TLDR
Inhaled methoxyflurane may offer advantages over other analgesics administered via the intravenous, intramuscular or intranasal routes in terms of its non-invasive self-administration, ease of use and/or rapid onset of action.
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References

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New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 1): Identification of the Nephrotoxic Metabolic Pathway
TLDR
F fluoride from methoxyflurane anesthesia derives from O-demethylation, which may have implications for interpreting anesthetic defluorination, volatile anesthetic use, and methods to evaluate anesthetic toxicity.
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TLDR
The use of methoxyflurane in clinical anesthesia should be restricted to situations where it offers specific advantages and where dosages less than 2.5 MAC hours can be attained.
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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