Enflurane

Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether) is a halogenated ether. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s[2] but is no longer in common use.[3]

Enflurane
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding97%
Identifiers
  • (RS)-2-chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.034.126
Chemical and physical data
FormulaC3H2ClF5O
Molar mass184.49 g·mol−1
3D model (JSmol)
  • FC(Cl)C(F)(F)OC(F)F
  • InChI=1S/C3H2ClF5O/c4-1(5)3(8,9)10-2(6)7/h1-2H checkY
  • Key:JPGQOUSTVILISH-UHFFFAOYSA-N checkY
  (verify)

Enflurane is a structural isomer of isoflurane. It vaporizes readily, but is a liquid at room temperature.

Physical properties
Property Value
Boiling point at 1 atm 56.5 °C
MAC 1.68
Vapor pressure at 20 °C 22.9 kPa (172 mm Hg)
Blood:gas partition coefficient 1.9
Oil:gas partition coefficient 98

Pharmacology

The exact mechanism of the action of general anaesthetics has not been delineated.[4] Enflurane acts as a positive allosteric modulator of the GABAA,[5][6][7][8] glycine, and 5-HT3 receptors,[9][10] and as a negative allosteric modulator of the AMPA, kainate, and NMDA receptors,[10][11][12] as well as of nicotinic acetylcholine receptors.[9]

Side effects

Clinically, enflurane produces a dose-related depression of myocardial contractility with an associated decrease in myocardial oxygen consumption. Between 2% and 5% of the inhaled dose is oxidised in the liver, producing fluoride ions and difluoromethoxy-difluoroacetic acid. This is significantly higher than the metabolism of its structural isomer isoflurane.

Enflurane also lowers the threshold for seizures, and should especially not be used on people with epilepsy.[13] Like all potent inhalation anaesthetic agents it is a known trigger of malignant hyperthermia.

Like the other potent inhalation agents it relaxes the uterus in pregnant women which is associated with more blood loss at delivery or other procedures on the gravid uterus.

The obsolete (as an anaesthetic) agent methoxyflurane had a nephrotoxic effect and caused acute kidney injury, usually attributed to the liberation of fluoride ions from its metabolism. Enflurane is similarly metabolised but the liberation of fluoride results in a lower plasma level and enflurane related kidney failure seemed unusual if seen at all.[14]

Occupational safety

The U.S. National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) for exposure to waste anaesthetic gas of 2 ppm (15.1 mg/m3) over a 60-minute period. Symptoms of occupational exposure to enflurane include eye irritation, central nervous system depression, analgesia, anesthesia, convulsions, and respiratory depression.[15]

References
  1. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. Niedermeyer E, Lopes da Silva FH (2005). Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. Lippincott Williams & Wilkins. p. 1156. ISBN 978-0-7817-5126-1.
  3. Hemmings Jr HC, Egan TD (2013). Pharmacology and Physiology for Anesthesia. doi:10.1016/C2009-0-41712-4. ISBN 9781437716795.
  4. Perkins B (7 February 2005). "How does anesthesia work?". Scientific American.
  5. Wakamori M, Ikemoto Y, Akaike N (December 1991). "Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat". Journal of Neurophysiology. 66 (6): 2014–2021. doi:10.1152/jn.1991.66.6.2014. PMID 1667416.
  6. Jones MV, Brooks PA, Harrison NL (April 1992). "Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics". The Journal of Physiology. 449: 279–293. doi:10.1113/jphysiol.1992.sp019086. PMC 1176079. PMID 1326046.
  7. Krasowski MD, Harrison NL (February 2000). "The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations". British Journal of Pharmacology. 129 (4): 731–743. doi:10.1038/sj.bjp.0703087. PMC 1571881. PMID 10683198.
  8. Lin LH, Chen LL, Zirrolli JA, Harris RA (November 1992). "General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acidA receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium". The Journal of Pharmacology and Experimental Therapeutics. 263 (2): 569–578. PMID 1331405.
  9. Perry EK, Ashton H, Young AH (2002). Neurochemistry of Consciousness: Neurotransmitters in Mind. John Benjamins Publishing. pp. 154–. ISBN 978-1-58811-124-1.
  10. Cote CJ, Lerman J, Anderson BJ (2013). A Practice of Anesthesia for Infants and Children: Expert Consult - Online and Print. Elsevier Health Sciences. pp. 499–. ISBN 978-1-4377-2792-0.
  11. Barash P, Cullen BF, Stoelting RK, Cahalan M, Stock CM, Ortega R (7 February 2013). Clinical Anesthesia, 7e: Print + Ebook with Multimedia. Lippincott Williams & Wilkins. pp. 116–. ISBN 978-1-4698-3027-8.
  12. Lin LH, Chen LL, Harris RA (March 1993). "Enflurane inhibits NMDA, AMPA, and kainate-induced currents in Xenopus oocytes expressing mouse and human brain mRNA". FASEB Journal. 7 (5): 479–485. doi:10.1096/fasebj.7.5.7681790. PMID 7681790. S2CID 1050582.
  13. Khankhanian P, Himmelstein D (April 2004). "Enflurane has established ictogenic properties?". Thinklab. doi:10.15363/thinklab.d224. Retrieved October 17, 2016.
  14. Morgan GE, Mikhail MS, Murray MJ, Larson CP (September 2006). Clinical Anesthesiology (3rd ed.). New York: Lange Medical Books/McGraw-Hill. p. 142.
  15. "CDC - NIOSH Pocket Guide to Chemical Hazards - Enflurane". www.cdc.gov. Retrieved 2015-10-01.
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