Halothane: Difference between revisions

{{Short description|General anaesthetic}}

{{Use dmy dates|date=June 2024}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| verifiedrevid = 443852402

| width = 120

| alt =

| width2 = 120

| alt2 =

<!-- Clinical data -->

| pronounce =

| tradename = Fluothane

| Drugs.com = {{drugs.com|pro|halothane}}

| MedlinePlus =

| DailyMedID = Halothane

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration = [[Inhalation]]

| class =

| ATC_prefix = N01

| ATC_suffix = AB01

| ATC_supplemental =

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

| legal_AU_comment =

| legal_BR = C1

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |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=3 August 2023 |access-date=16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = <ref>{{cite web | title=Halothane, USP | website=DailyMed | date=18 September 2013 | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=120083 | access-date=11 February 2022}}</ref><ref name="Fluothane">{{cite web | title=Fluothane: FDA-Approved Drugs | website=U.S. Food and Drug Administration | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=011338 | access-date=12 February 2022}}</ref>

| legal_EU =

| legal_EU_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

| metabolism = [[Liver|Hepatic]] ([[CYP2E1]]<ref name = "DB01159">{{cite web | url = https://go.drugbank.com/drugs/DB01159 | title = Halothane | id = DB01159 | work = DrugBank }}</ref>)

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion = [[Kidney]], [[respiratory]]

<!-- Identifiers -->

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

| CAS_number = 151-67-7

| CAS_supplemental =

| PubChem = 3562

| IUPHAR_ligand = 2401

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

| DrugBank = DB01159

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

| ChEBI = 5615

| NIAID_ChemDB =

| PDB_ligand =

| synonyms =

<!-- Chemical and physical data -->

| IUPAC_name = 2-Bromo-2-chloro-1,1,1-trifluoroethane

| C=2 | H=1 | Br=1 | Cl=1 | F=3

| SMILES = BrC(Cl)C(F)(F)F

| StdInChI_comment =

| density = 1.871

| density_notes = (at 20 °C)

| melting_point = -118

| melting_high =

| melting_notes =

| boiling_point = 50.2

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''Halothane''', sold under the brand name '''Fluothane''' among others, is a [[general anaesthetic]].<ref name=WHO2008/> It can be used to induce or maintain [[anaesthesia]].<ref name=WHO2008/> One of its benefits is that it does not increase the production of [[saliva]], which can be particularly useful in those who are difficult to [[intubate]].<ref name=WHO2008/> It is given by [[inhalation]].<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 978-92-4-154765-9 | author = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | pages=17–8 }}</ref>

<!-- Side effects and mechanism -->

Side effects include an [[Heart arrhythmia|irregular heartbeat]], [[respiratory depression]], and [[hepatotoxicity]].<ref name=WHO2008/> Like all volatile anesthetics, it should not be used in people with a personal or family history of [[malignant hyperthermia]].<ref name=WHO2008/> It appears to be safe in [[porphyria]].<ref name="Porphyrias">{{cite journal | vauthors = James MF, Hift RJ | title = Porphyrias | journal = British Journal of Anaesthesia | volume = 85 | issue = 1 | pages = 143–53 | date = July 2000 | pmid = 10928003 | doi = 10.1093/bja/85.1.143 | doi-access = free | title-link = doi }}</ref> It is unclear whether its usage during [[pregnancy]] is harmful to the fetus, and its use during a [[cesarean section|C-section]] is generally discouraged.<ref name=Pro2005/> Halothane is a [[Chirality (chemistry)|chiral]] molecule that is used as a [[racemic mixture]].<ref name="The Anaesthesia Science Viva Book">{{cite book| vauthors = Bricker S |title=The Anaesthesia Science Viva Book|url=https://books.google.com/books?id=RkhPlWywV_IC&pg=PT161|publisher=Cambridge University Press|date=17 June 2004|isbn=978-0-521-68248-0|via=Google Books|page=161|url-status=live|archive-url=https://web.archive.org/web/20170910175402/https://books.google.com/books?id=RkhPlWywV_IC&pg=PT161|archive-date=10 September 2017}}</ref>

<!-- Society and culture -->

Halothane was discovered in 1951.<ref name=Wal2012>{{cite book| vauthors = Walker SR |title=Trends and Changes in Drug Research and Development|date=2012|publisher=Springer |isbn=978-94-009-2659-2|page=109|url=https://books.google.com/books?id=FB_2CAAAQBAJ&pg=PA109|url-status=live|archive-url=https://web.archive.org/web/20170910151826/https://books.google.com/books?id=FB_2CAAAQBAJ&pg=PA109|archive-date=10 September 2017}}</ref> It was approved for medical use in the United States in 1958.<ref name="Fluothane" /> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> Its use in [[developed countries]] has been mostly replaced by newer anesthetic agents such as [[sevoflurane]].<ref>{{cite book| vauthors=Yentis SM, Hirsch NP, Ip J |title=Anaesthesia and Intensive Care A-Z: An Encyclopedia of Principles and Practice |date=2013 |publisher=Elsevier Health Sciences |isbn=978-0-7020-5375-7 |page=264 |edition=5th |url=https://books.google.com/books?id=Te7TAAAAQBAJ&pg=PA264 |url-status=live |archive-url=https://web.archive.org/web/20170910175402/https://books.google.com/books?id=Te7TAAAAQBAJ&pg=PA264 |archive-date=10 September 2017}}</ref> It is no longer commercially available in the United States.<ref name=Pro2005>{{cite web |title=Halothane — FDA prescribing information, side effects and uses |website=www.drugs.com |url=https://www.drugs.com/pro/halothane.html |access-date=13 December 2016 |date=June 2005 |url-status=live |archive-url=https://web.archive.org/web/20161221003503/https://www.drugs.com/pro/halothane.html |archive-date=21 December 2016}}</ref> Halothane also contributes to [[ozone depletion]].<ref name=Kum2013>{{Cite book |url=https://books.google.com/books?id=1VXUBgAAQBAJ&pg=PA33 |title=Pharmaceuticals in the Environment: Sources, Fate, Effects and Risks| vauthors = Kümmerer K |publisher=Springer |year=2013 |isbn=978-3-662-09259-0 |pages=33}}</ref><ref name=Lan1999>{{cite journal |vauthors=Langbein T, Sonntag H, Trapp D, Hoffmann A, Malms W, Röth EP, Mörs V, Zellner R |title=Volatile anaesthetics and the atmosphere: atmospheric lifetimes and atmospheric effects of halothane, enflurane, isoflurane, desflurane and sevoflurane |journal=British Journal of Anaesthesia |volume=82 |issue=1 |pages=66–73 |date=January 1999 |pmid=10325839 |doi=10.1093/bja/82.1.66 |doi-access=free |title-link=doi}}</ref>

==Medical uses==

[[File:Fluothane packaging 01.jpg|thumb|upright|Packaging of Fluothane brand of halothane]]

It is a potent anesthetic with a [[minimum alveolar concentration]] (MAC) of 0.74%.<ref>{{cite book | vauthors = Lobo SA, Ojeda J, Dua A, Singh K, Lopez J | title = Minimum Alveolar Concentration |date=2022 | url=http://www.ncbi.nlm.nih.gov/books/NBK532974/ |id=NBK532974 | series = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30422569 }}</ref> Its [[blood/gas partition coefficient]] of 2.4 makes it an agent with moderate induction and recovery time.<ref>{{Cite journal | vauthors = Bezuidenhout E |title=The blood–gas partition coefficient |url=https://www.researchgate.net/publication/348461499 |journal=[[Southern African Journal of Anaesthesia and Analgesia]] |volume=1 |issue=3 |pages=3 |issn=2220-1181 |eissn=2220-1173 |date=November 2020 |doi=10.36303/SAJAA.2020.26.6.S3.2528|doi-access=free }}</ref> It is not a good [[analgesic]] and its muscle relaxation effect is moderate.<ref>{{cite web |title=Halothane | work = Anesthesia General |url=http://anesthesiageneral.com/halothane/ |url-status=live |archive-url=https://web.archive.org/web/20110216054455/http://anesthesiageneral.com/halothane/ |archive-date=16 February 2011 |date=31 October 2010 }}</ref>

Halothane is colour-coded red on [[anaesthetic vaporiser]]s.<ref>{{cite journal |vauthors=Subrahmanyam M, Mohan S |title=Safety features in anaesthesia machine |journal=Indian J Anaesth |volume=57 |issue=5 |pages=472–480 |date=September 2013 |pmid=24249880 |pmc=3821264 |doi=10.4103/0019-5049.120143 |doi-access=free}}</ref>

[[File:Halothane container.jpg|thumb|Vaporiser used for halothane]]

==Side effects==

Side effects include [[Heart arrhythmia|irregular heartbeat]], [[respiratory depression]], and [[hepatotoxicity]].<ref name=WHO2008/> It appears to be safe in [[porphyria]].<ref name="Porphyrias"/> It is unclear whether use during [[pregnancy]] is harmful to the baby, and it is not generally recommended for use during a [[cesarean section|C-section]].<ref name=Pro2005/>

In rare cases, repeated exposure to halothane in adults was noted to result in severe [[liver]] injury. This occurred in about one in 10,000 exposures. The resulting syndrome was referred to as halothane [[hepatitis]], immunoallergic in origin,<ref>{{cite book | vauthors = Habibollahi P, Mahboobi N, Esmaeili S, Safari S, Dabbagh A, Alavian SM | title = Halothane | series = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet] | date= January 2018 | pmid=31643481 | url=https://www.ncbi.nlm.nih.gov/books/NBK548151/ |id=NBK548151}}</ref> and is thought to result from the metabolism of halothane to [[trifluoroacetic acid]] via oxidative reactions in the liver. About 20% of inhaled halothane is metabolized by the liver and these products are excreted in the urine. The hepatitis syndrome had a mortality rate of 30% to 70%.<ref>{{cite journal | vauthors = Wark H, Earl J, Chau DD, Overton J | title = Halothane metabolism in children | journal = British Journal of Anaesthesia | volume = 64 | issue = 4 | pages = 474–481 | date = April 1990 | pmid = 2334622 | doi = 10.1093/bja/64.4.474 | doi-access = free }}</ref> Concern for hepatitis resulted in a dramatic reduction in the use of halothane for adults and it was replaced in the 1980s by [[enflurane]] and [[isoflurane]].<ref name = "Gyorfi_1997">{{cite book | vauthors = Gyorfi MJ, Kim PY | title = Halothane Toxicity |date=2022 |url= http://www.ncbi.nlm.nih.gov/books/NBK545281/ |id=NBK545281 |series =StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31424865 }}</ref><ref>{{Cite journal | vauthors = Hankins DC, Kharasch ED |date=9 May 1997 |title=Determination of the halothane metabolites trifluoroacetic acid and bromide in plasma and urine by ion chromatography |journal=Journal of Chromatography B: Biomedical Sciences and Applications |volume=692 |issue=2 |pages=413–8 |doi=10.1016/S0378-4347(96)00527-0 |pmid=9188831 |issn=0378-4347}}</ref> By 2005, the most common volatile anesthetics used were [[isoflurane]], [[sevoflurane]], and [[desflurane]]. Since the risk of halothane hepatitis in children was substantially lower than in adults, halothane continued to be used in pediatrics in the 1990s as it was especially useful for inhalation induction of anesthesia.<ref>{{cite journal | vauthors = Okuno T, Koutsogiannaki S, Hou L, Bu W, Ohto U, Eckenhoff RG, Yokomizo T, Yuki K | title = Volatile anesthetics isoflurane and sevoflurane directly target and attenuate Toll-like receptor 4 system | journal = FASEB Journal | volume = 33 | issue = 12 | pages = 14528–41 | date = December 2019 | pmid = 31675483 | pmc = 6894077 | doi = 10.1096/fj.201901570R | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sakai EM, Connolly LA, Klauck JA | title = Inhalation anesthesiology and volatile liquid anesthetics: focus on isoflurane, desflurane, and sevoflurane | journal = Pharmacotherapy | volume = 25 | issue = 12 | pages = 1773–88 | date = December 2005 | pmid = 16305297 | doi = 10.1592/phco.2005.25.12.1773 | s2cid = 40873242 }}</ref> However, by 2000, sevoflurane, excellent for inhalation induction, had largely replaced the use of halothane in children.<ref>{{cite journal | vauthors = Patel SS, Goa KL | title = Sevoflurane. A review of its pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia | journal = Drugs | volume = 51 | issue = 4 | pages = 658–700 | date = April 1996 | pmid = 8706599 | doi = 10.2165/00003495-199651040-00009 | s2cid = 265731583 }}</ref>

Halothane sensitises the heart to catecholamines, so it is liable to cause cardiac arrhythmia, occasionally fatal, particularly if [[hypercapnia]] has been allowed to develop. This seems to be especially problematic in dental anesthesia.<ref>{{cite journal | vauthors = Paris ST, Cafferkey M, Tarling M, Hancock P, Yate PM, Flynn PJ | title = Comparison of sevoflurane and halothane for outpatient dental anaesthesia in children | journal = British Journal of Anaesthesia | volume = 79 | issue = 3 | pages = 280–4 | date = September 1997 | pmid = 9389840 | doi = 10.1093/bja/79.3.280 | doi-access = free }}</ref>

Like all the potent inhalational anaesthetic agents, it is a potent trigger for [[malignant hyperthermia]].<ref name=WHO2008/> Similarly, in common with the other potent inhalational agents, it relaxes uterine smooth muscle and this may increase blood loss during delivery or termination of pregnancy.<ref>{{cite journal | vauthors = Satuito M, Tom J | title = Potent Inhalational Anesthetics for Dentistry | journal = Anesthesia Progress | volume = 63 | issue = 1 | pages = 42–8; quiz 49 | year = 2016 | pmid = 26866411 | pmc = 4751520 | doi = 10.2344/0003-3006-63.1.42 }}</ref>

=== Occupational safety ===

People can be exposed to halothane in the workplace by breathing it in as waste anaesthetic gas, skin contact, eye contact, or swallowing it.<ref>{{Cite journal |year=1999 |title=Common Name: Halothene |url=https://nj.gov/health/eoh/rtkweb/documents/fs/0969.pdf |journal=Hazardous Substance Fact Sheet |type=PDF |volume=969 |issue=1 |via=[[New Jersey Department of Health|New Jersey Department of Health and Senior Services]]}}</ref> The [[National Institute for Occupational Safety and Health]] (NIOSH) has set a [[recommended exposure limit]] (REL) of 2 ppm (16.2&nbsp;mg/m³) over 60 minutes.<ref>{{Cite web |title =Halothane |work=NIOSH Pocket Guide to Chemical Hazards |url = https://www.cdc.gov/niosh/npg/npgd0310.html|publisher=(NIOSH) National Institute for Occupational Safety and Health, Centers for Disease Control |access-date = 3 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151208104932/http://www.cdc.gov/niosh/npg/npgd0310.html|archive-date = 8 December 2015}}</ref>

==Pharmacology==

The exact mechanism of the action of general anaesthetics [[Theories of general anaesthetic action|has not been delineated]].<ref>{{cite web | vauthors = Perkins B |url=http://www.scientificamerican.com/article/how-does-anesthesia-work/ |title=How does anesthesia work? |publisher=[[Scientific American]] |date=7 February 2005 |access-date=30 June 2016}}</ref> Halothane activates [[GABAA receptor|GABA_A]] and [[glycine receptor]]s.<ref name="HemmingsHopkins2006">{{cite book| vauthors = Hemmings HC, Hopkins PM |title=Foundations of Anesthesia: Basic Sciences for Clinical Practice|url=https://books.google.com/books?id=xaXu1wHmENoC&pg=PA292|year=2006|publisher=Elsevier Health Sciences|isbn=978-0-323-03707-5|pages=292–|url-status=live|archive-url=https://web.archive.org/web/20160430015130/https://books.google.com/books?id=xaXu1wHmENoC&pg=PA292|archive-date=30 April 2016}}</ref><ref name="BarashCullen2013">{{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–|url-status=live|archive-url=https://web.archive.org/web/20160617063751/https://books.google.com/books?id=exygUxEuxnIC&pg=PA116|archive-date=17 June 2016}}</ref> It also acts as an [[NMDA receptor antagonist]],<ref name="BarashCullen2013" /> inhibits [[nicotinic acetylcholine receptor|nACh]] and [[voltage-gated sodium channel]]s,<ref name="HemmingsHopkins2006" /><ref name="SchüttlerSchwilden2008">{{cite book| vauthors = Schüttler J, Schwilden H |title=Modern Anesthetics|url=https://books.google.com/books?id=JpkkWhPbh2QC&pg=PA70|date=8 January 2008|publisher=Springer |isbn=978-3-540-74806-9|pages=70–|url-status=live|archive-url=https://web.archive.org/web/20160501142907/https://books.google.com/books?id=JpkkWhPbh2QC&pg=PA70|archive-date=1 May 2016}}</ref> and activates [[5-HT3 receptor|5-HT₃]] and [[tandem pore domain potassium channel|twin-pore K⁺ channel]]s.<ref name="HemmingsHopkins2006" /><ref name="Bowery2006">{{cite book| vauthors = Bowery NG |title=Allosteric Receptor Modulation in Drug Targeting|url=https://books.google.com/books?id=WRfgvOKfZMcC&pg=PA143|date=19 June 2006|publisher=CRC Press|isbn=978-1-4200-1618-5|pages=143–|url-status=live|archive-url=https://web.archive.org/web/20160510001416/https://books.google.com/books?id=WRfgvOKfZMcC&pg=PA143|archive-date=10 May 2016}}</ref> It does not affect the [[AMPA receptor|AMPA]] or [[kainate receptor]]s.<ref name="BarashCullen2013" />

==Chemical and physical properties==

Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) is a dense, highly volatile, clear, colourless, nonflammable liquid with a chloroform-like sweet odour. It is very slightly soluble in water and miscible with various organic solvents. Halothane can decompose to [[hydrogen fluoride]], [[hydrogen chloride]] and [[hydrogen bromide]] in the presence of light and heat.<ref>Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1761</ref>

|[[Boiling point]]: ||align=right| 50.2&nbsp;°C || (at 101.325 kPa)

|[[Density]]: ||align=right| 1.871 g/cm³|| (at 20&nbsp;°C)

|[[Vapor pressure]]: ||align=right| 244 mmHg (32kPa) || (at 20&nbsp;°C)

| ||align=right|288 mmHg (38kPa) || (at 24&nbsp;°C)

|[[Blood:gas partition coefficient]]: ||align=right|2.3

| Oil:gas partition coefficient: ||align=right|224

Chemically, halothane is an [[alkyl halide]] (not an [[ether]] like many other anesthetics).<ref name = "DB01159" /> The structure has one stereocenter, so (''R'')- and (''S'')-[[optical isomer]]s occur.{{citation needed|date=February 2022}}

The commercial synthesis of halothane starts from [[trichloroethylene]], which is reacted with [[hydrogen fluoride]] in the presence of [[antimony trichloride]] at 130&nbsp;°C to form [[2-chloro-1,1,1-trifluoroethane]]. This is then reacted with [[bromine]] at 450&nbsp;°C to produce halothane.<ref>{{Ref patent3 | country = US | number = 2921098 | status = granted | title = PROCESS FOR THE PREPARATION OF 1,1,1-TRIFLUORO-2-BROMO-2-CHLOROETHANE | pubdate = 30 June 1958 | gdate = January 1960 | pridate= 1954-08-20 | inventor = Suckling et al. | assign1= Imperial Chemical Industries | google_patent_id = 6JpaAAAAEBAJ }}</ref>

==Related substances==

Attempts to find anesthetics with less metabolism led to [[halogenated ether]]s such as [[enflurane]] and [[isoflurane]]. The incidence of [[liver|hepatic]] reactions with these agents is lower. The exact degree of [[hepatotoxic]] potential of enflurane is debated, although it is minimally metabolized. Isoflurane is essentially not metabolized and reports of associated liver injury are quite rare.<ref>{{cite book | vauthors = | title = Halogenated Anesthetics | series = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury | date = January 2018 | pmid = 31644158 | url = https://pubmed.ncbi.nlm.nih.gov/31644158/ | id = NBK548851 }}</ref> Small amounts of [[trifluoroacetic acid]] can be formed from both halothane and isoflurane metabolism and possibly accounts for cross sensitization of patients between these agents.<ref>{{cite journal | vauthors = Ma TG, Ling YH, McClure GD, Tseng MT | title = Effects of trifluoroacetic acid, a halothane metabolite, on C6 glioma cells | journal = Journal of Toxicology and Environmental Health | volume = 31 | issue = 2 | pages = 147–158 | date = October 1990 | pmid = 2213926 | doi = 10.1080/15287399009531444 | bibcode = 1990JTEH...31..147M }}</ref><ref>{{cite journal | vauthors = Biermann JS, Rice SA, Fish KJ, Serra MT | title = Metabolism of halothane in obese Fischer 344 rats | journal = Anesthesiology | volume = 71 | issue = 3 | pages = 431–7 | date = September 1989 | pmid = 2774271 | doi = 10.1097/00000542-198909000-00020 | doi-access = free }}</ref>

The main advantage of the more modern agents is lower blood solubility, resulting in faster induction of and recovery from anaesthesia.<ref>{{cite journal | vauthors = Eger EI | title = The pharmacology of isoflurane | journal = British Journal of Anaesthesia | volume = 56 | pages = 71S–99S | date = 1984 | issue = Suppl 1 | pmid = 6391530 | url = https://pubmed.ncbi.nlm.nih.gov/6391530/ }}</ref>

==History==

[[File:The Fluothane Story.png|thumb|An advertisement for ''Fluothane'', published in various American medical journals between 1961 and 1962.]]

Halothane was first synthesized by [[Charles Suckling|C. W. Suckling]] of [[Imperial Chemical Industries]] in 1951 at the ICI [[Widnes Laboratory]] and was first used clinically by M. Johnstone in [[Manchester]] in 1956. Initially, many pharmacologists and anaesthesiologists had doubts about the safety and efficacy of the new drug. But halothane, which required specialist knowledge and technologies for safe administration, also afforded British anaesthesiologists the opportunity to remake their speciality as a profession during a period, when the newly established [[National Health Service]] needed more specialist consultants.<ref name="Medicating">{{cite journal | vauthors = Mueller LM | title = Medicating Anaesthesiology: Pharmaceutical Change, Specialisation and Healthcare Reform in Post-War Britain | journal = Social History of Medicine | date = March 2021 | volume = 34 | issue = 4 | pages = 1343–65 | doi = 10.1093/shm/hkaa101 }}</ref> In this context, halothane eventually became popular as a nonflammable general anesthetic replacing other [[volatile anesthetic]]s such as [[trichloroethylene]], [[diethyl ether]] and [[cyclopropane]]. In many parts of the world it has been largely replaced by newer agents since the 1980s but is still widely used in developing countries because of its lower cost.<ref>{{cite book | vauthors = Bovill JG | title = Modern Anesthetics | chapter = Inhalation Anaesthesia: From Diethyl Ether to Xenon | series = Handbook of Experimental Pharmacology | issue = 182 | pages = 121–142 | date = 2008 | volume = 182 | pmid = 18175089 | doi = 10.1007/978-3-540-74806-9_6 | isbn = 978-3-540-72813-9 }}</ref>

[[File:Halothane meter.jpg|thumb|A meter for measuring halothane. This was used to measure the amount of halothane as flow of inspired gas during anesthesia.]]

Halothane was given to many millions of people worldwide from its introduction in 1956 through the 1980s.<ref name="NiedermeyerSilva2005">{{cite book| vauthors = Niedermeyer E, 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 |url-status=live |archive-url= https://web.archive.org/web/20160509001417/https://books.google.com/books?id=tndqYGPHQdEC&pg=PA1156|archive-date=9 May 2016}}</ref> Its properties include cardiac depression at high levels, cardiac sensitization to [[catecholamine]]s such as [[norepinephrine]], and potent bronchial relaxation. Its lack of airway irritation made it a common inhalation induction agent in pediatric anesthesia.<ref>{{cite journal | vauthors = Himmel HM | title = Mechanisms involved in cardiac sensitization by volatile anesthetics: general applicability to halogenated hydrocarbons? | journal = Critical Reviews in Toxicology | volume = 38 | issue = 9 | pages = 773–803 | date = 2008 | pmid = 18941968 | doi = 10.1080/10408440802237664 | s2cid = 12906139 }}</ref><ref>{{cite journal | vauthors = Chavez CA, Ski CF, Thompson DR | title = Psychometric properties of the Cardiac Depression Scale: a systematic review | journal = Heart, Lung & Circulation | volume = 23 | issue = 7 | pages = 610–8 | date = July 2014 | pmid = 24709392 | doi = 10.1016/j.hlc.2014.02.020 }}</ref>

Its use in [[developed countries]] has been mostly replaced by newer anesthetic agents such as [[sevoflurane]].<ref>{{cite book| vauthors = Yentis SM, Hirsch NP, Ip J |title=Anaesthesia and Intensive Care A-Z: An Encyclopedia of Principles and Practice|date=2013|publisher=Elsevier Health Sciences |isbn=978-0-7020-5375-7 |page=264|edition=5th |url=https://books.google.com/books?id=Te7TAAAAQBAJ&pg=PA264 |language=en|url-status=live|archive-url= https://web.archive.org/web/20170910175402/https://books.google.com/books?id=Te7TAAAAQBAJ&pg=PA264|archive-date=10 September 2017}}</ref> It is not commercially available in the United States.<ref name=Pro2005/>

==Society and culture==

===Availability===

It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd" /> It is available as a volatile liquid, at 30, 50, 200, and 250 ml per container but in many developed nations is not available having been displaced by newer agents.<ref>{{cite book |title=National formulary of India |edition=4th |location=New Delhi, India |publisher=Indian Pharmacopoeia Commission |date=2011 |page=411}}</ref>

It is the only [[inhalational anesthetic]] containing [[bromine]], which makes it [[radiopaque]].<ref>{{cite book | vauthors = Miller AL, Theodore D, Widrich J | title = Inhalational Anesthetic |date=2022 | url = http://www.ncbi.nlm.nih.gov/books/NBK554540/ |id=NBK554540 | series = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32119427 }}</ref> It is colorless and pleasant-smelling, but unstable in light. It is packaged in dark-colored bottles and contains 0.01% [[thymol]] as a stabilizing agent.<ref name = "Gyorfi_1997" />

===Greenhouse gas===

Owing to the presence of covalently bonded fluorine, halothane absorbs in the [[atmospheric window]] and is therefore a [[greenhouse gas]]. However, it is much less potent than most other [[chlorofluorocarbons]] and [[bromofluorocarbons]] due to its short atmospheric lifetime, estimated at only one year vis-à-vis over 100 years for many [[perfluorocarbons]].<ref name="potential">{{cite journal| vauthors = Hodnebrog Ø, Etminan M, Fuglestvedt JS, Marston G, Myhre G, Nielsen CJ, Shine KP, Wallington TJ |title=Global warming potentials and radiative efficiencies of halocarbons and related compounds: A comprehensive review |journal=Reviews of Geophysics |date=24 April 2013 |volume=51 |issue=2 |pages=300–378| doi = 10.1002/rog.20013 | bibcode = 2013RvGeo..51..300H | url = https://centaur.reading.ac.uk/31338/1/ReviewGWP_2nd_rev_v2.pdf }}</ref> Despite its short lifespan, halothane still has a [[global warming potential]] 47 times that of carbon dioxide, although this is over 100 times smaller than the most abundant fluorinated gases, and about 800 times smaller than the GWP of [[sulfur hexafluoride]] over 500 years.<ref name="Updated">{{cite journal | vauthors = Hodnebrog Ø, Aamaas B, Fuglestvedt JS, Marston G, Myhre G, Nielsen CJ, Sandstad M, Shine KP, Wallington TJ | title = Updated Global Warming Potentials and Radiative Efficiencies of Halocarbons and Other Weak Atmospheric Absorbers | journal = Reviews of Geophysics | volume = 58 | issue = 3 | pages = e2019RG000691 | date = September 2020 | doi = 10.1029/2019RG000691 | pmid = 33015672 | pmc = 7518032 | bibcode = 2020RvGeo..5800691H }}</ref> Halothane is believed to make a negligible contribution to [[global warming]].<ref name="potential"/>

===Ozone depletion===

Halothane is an [[ozone depletion|ozone depleting substance]] with an [[Ozone depletion potential|ODP]] of 1.56 and it is calculated to be responsible for 1% of total stratospheric ozone layer depletion.<ref name=Kum2013/><ref name=Lan1999/>

{{Clear}}

== References ==

{{Reflist}}

{{Navboxes

| title = [[Pharmacodynamics]]

| titlestyle = background:#ccccff

| list1 =

{{GABAA receptor positive modulators}}

{{Glycine receptor modulators}}

{{Ionotropic glutamate receptor modulators}}

{{Nicotinic acetylcholine receptor modulators}}

{{Serotonin receptor modulators}}

}}

{{Portal bar|Medicine}}

{{Authority control}}

[[Category:5-HT3 agonists]]

[[Category:GABAA receptor positive allosteric modulators]]

[[Category:Glycine receptor agonists]]

[[Category:Hepatotoxins]]

[[Category:Nicotinic antagonists]]

[[Category:NMDA receptor antagonists]]

[[Category:Trifluoromethyl compounds]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Withdrawn drugs]]

[[Category:World Health Organization essential medicines]]

[[Category:Ozone depletion]]

[[Category:Racemic mixtures]]