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gas partition coefficient of 2 4 makes it an agent with moderate induction and recovery time 15 it is not a good analgesic and its muscle relaxation effect is moderate 16 halothane is colour coded red on anaesthetic vaporisers 17 vaporiser used for halothane side effects edit side effects include irregular heartbeat respiratory depression and hepatotoxicity 5 it appears to be safe in porphyria 7 it is unclear whether use during pregnancy is harmful to the baby and it is not generally recommended for use during a c section 8 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 18 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 19 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 20 21 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 22 23 however by 2000 sevoflurane excellent for inhalation induction had largely replaced the use of halothane in children 24 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 25 like all the potent inhalational anaesthetic agents it is a potent trigger for malignant hyperthermia 5 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 26 occupational safety edit people can be exposed to halothane in the workplace by breathing it in as waste anaesthetic gas skin contact eye contact or swallowing it 27 the national institute for occupational safety and health niosh has set a recommended exposure limit rel of 2 ppm 16 2 mg m 3 over 60 minutes 28 pharmacology edit the exact mechanism of the action of general anaesthetics has not been delineated 29 halothane activates gaba a and glycine receptors 30 31 it also acts as an nmda receptor antagonist 31 inhibits nach and voltage gated sodium channels 30 32 and activates 5 ht 3 and twin pore k channels 30 33 it does not affect the ampa or kainate receptors 31 chemical and physical properties edit halothane 2 bromo 2 chloro 1 1 1 trifluoroethane is a very dense clear colourless nonflammable liquid with a chloroform like sweet odour it is highly volatile having a vapor pressure of 32 5 kpa at 20 c 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 34 chemically halothane is an alkyl halide not an ether like many other anesthetics 4 the structure has one stereocenter so r and s optical isomers occur citation needed synthesis edit the commercial synthesis of halothane starts from trichloroethylene which is reacted with hydrogen fluoride in the presence of antimony trichloride at 130 c to form 2 chloro 1 1 1 trifluoroethane this is then reacted with bromine at 450 c to produce halothane 35 related substances edit attempts to find anesthetics with less metabolism led to halogenated ethers such as enflurane and isoflurane the incidence of 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 36 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 37 38 the main advantage of the more modern agents is lower blood solubility resulting in faster induction of and recovery from anaesthesia 39 history edit an advertisement for fluothane published in various american medical journals between 1961 and 1962 halothane was first synthesized by 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 40 in this context halothane eventually became popular as a nonflammable general anesthetic replacing other volatile anesthetics 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 41 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 42 its properties include cardiac depression at high levels cardiac sensitization to catecholamines such as norepinephrine and potent bronchial relaxation its lack of airway irritation made it a common inhalation induction agent in pediatric anesthesia 43 44 its use in developed countries has been mostly replaced by newer anesthetic agents such as sevoflurane 45 it is not commercially available in the united states 8 society and culture edit availability edit halothane 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 46 a major producer of halothane for anesthetic purposes piramal pharma ceased production of halothane at the end of 2023 which has led to dwindling supplies 47 48 it is the only inhalational anesthetic containing bromine which makes it radiopaque 49 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 20 greenhouse gas edit 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 50 despite its short lifespan halothane still has a global warming potential 50 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 51 halothane is believed to make a negligible contribution to global warming 50 ozone depletion edit halothane is an ozone depleting substance with an odp of 1 56 and it is calculated to be responsible for 1 of total stratospheric ozone layer depletion 12 13 unlike most ozone depleting substances it is not governed under the montreal protocol 52 references edit anvisa 31 march 2023 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 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inhalation anaesthesia fr...