enflurane

{{Infobox drug

| verifiedrevid = 461093677

| IUPAC_name = (RS)-2-chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane

| image = Enflurane.svg

| image_class = skin-invert-image

| image2 = Enflurane-3D-balls.png

| tradename =

| Drugs.com = {{drugs.com|CONS|enflurane}}

| pregnancy_category =

| legal_AU =

| legal_BR = C1

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}

| legal_CA =

| legal_DE =

| legal_NZ =

| legal_UK =

| legal_US =

| legal_EU =

| legal_UN =

| legal_status =

| routes_of_administration =

| bioavailability =

| protein_bound = 97%

| metabolism =

| elimination_half-life =

| IUPHAR_ligand = 7175

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 13838-16-9

| ATC_prefix = N01

| ATC_suffix = AB04

| ATC_supplemental =

| PubChem = 3226

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00228

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 3113

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 91I69L5AY5

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D00543

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 4792

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1257

| C=3 | H=2 | Cl=1 | F=5 | O=1

| smiles = FC(Cl)C(F)(F)OC(F)F

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C3H2ClF5O/c4-1(5)3(8,9)10-2(6)7/h1-2H

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = JPGQOUSTVILISH-UHFFFAOYSA-N

}}

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{{cite book| vauthors = Niedermeyer E, Lopes da Silva FH |title=Electroencephalography: Basic Principles, Clinical Applications, and Related Fields|url=https://books.google.com/books?id=tndqYGPHQdEC&pg=PA1156|year=2005|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-5126-1|page=1156}} but is no longer in common use.{{cite book | vauthors = Hemmings Jr HC, Egan TD |doi=10.1016/C2009-0-41712-4|title=Pharmacology and Physiology for Anesthesia|year=2013|isbn=9781437716795}}

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

Physical properties

class="wikitable"

! 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.{{cite web | vauthors = Perkins B | date = 7 February 2005 | work = Scientific American | url=http://www.scientificamerican.com/article/how-does-anesthesia-work/ | title=How does anesthesia work?}} Enflurane acts as a positive allosteric modulator of the GABA_A,{{cite journal | vauthors = Wakamori M, Ikemoto Y, Akaike N | title = 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 = Journal of Neurophysiology | volume = 66 | issue = 6 | pages = 2014–2021 | date = December 1991 | pmid = 1667416 | doi = 10.1152/jn.1991.66.6.2014 }}{{cite journal | vauthors = Jones MV, Brooks PA, Harrison NL | title = Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics | journal = The Journal of Physiology | volume = 449 | pages = 279–293 | date = April 1992 | pmid = 1326046 | pmc = 1176079 | doi = 10.1113/jphysiol.1992.sp019086 }}{{cite journal | vauthors = Krasowski MD, Harrison NL | title = The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations | journal = British Journal of Pharmacology | volume = 129 | issue = 4 | pages = 731–743 | date = February 2000 | pmid = 10683198 | pmc = 1571881 | doi = 10.1038/sj.bjp.0703087 }}{{cite journal | vauthors = Lin LH, Chen LL, Zirrolli JA, Harris RA | title = General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acidA receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 263 | issue = 2 | pages = 569–578 | date = November 1992 | pmid = 1331405 }} glycine, and 5-HT₃ receptors,{{cite book| vauthors = Perry EK, Ashton H, Young AH |title=Neurochemistry of Consciousness: Neurotransmitters in Mind |url= https://books.google.com/books?id=3o2fCDDoSuUC&pg=PA154 |year=2002|publisher=John Benjamins Publishing|isbn=978-1-58811-124-1|pages=154–}}{{cite book| vauthors = Cote CJ, Lerman J, Anderson BJ |title=A Practice of Anesthesia for Infants and Children: Expert Consult - Online and Print|url=https://books.google.com/books?id=MAXTnQStL0cC&pg=PA499|year=2013|publisher=Elsevier Health Sciences|isbn=978-1-4377-2792-0|pages=499–}} and as a negative allosteric modulator of the AMPA, kainate, and NMDA receptors,{{cite book| vauthors = Barash P, Cullen BF, Stoelting RK, Cahalan M, Stock CM, Ortega R |title=Clinical Anesthesia, 7e: Print + Ebook with Multimedia|url=https://books.google.com/books?id=exygUxEuxnIC&pg=PA116|date=7 February 2013|publisher=Lippincott Williams & Wilkins|isbn=978-1-4698-3027-8|pages=116–}}{{cite journal | vauthors = Lin LH, Chen LL, Harris RA | title = Enflurane inhibits NMDA, AMPA, and kainate-induced currents in Xenopus oocytes expressing mouse and human brain mRNA | journal = FASEB Journal | volume = 7 | issue = 5 | pages = 479–485 | date = March 1993 | pmid = 7681790 | doi = 10.1096/fasebj.7.5.7681790 | doi-access = free | s2cid = 1050582 }} as well as of nicotinic acetylcholine receptors.

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.{{Cite journal |url=https://thinklab.com/discussion/prediction-in-epilepsy/224#6 |title=Enflurane has established ictogenic properties? |date=April 2004 |website=Thinklab |access-date=October 17, 2016 |doi=10.15363/thinklab.d224 |vauthors=Khankhanian P, Himmelstein D |doi-access=free |archive-date=October 18, 2016 |archive-url=https://web.archive.org/web/20161018215613/https://thinklab.com/discussion/prediction-in-epilepsy/224#6 |url-status=dead }} 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.{{cite book | vauthors = Morgan GE, Mikhail MS, Murray MJ, Larson CP | title = Clinical Anesthesiology | location = New York | publisher = Lange Medical Books/McGraw-Hill | date = September 2006 | edition = 3rd | page = 142 }}

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.{{Cite web|title = CDC - NIOSH Pocket Guide to Chemical Hazards - Enflurane|url = https://www.cdc.gov/niosh/npg/npgd0253.html|website = www.cdc.gov|access-date = 2015-10-01}}