Halothane


Halothane
Halothane
Systematic (IUPAC) name
2-Bromo-2-chloro-1,1,1-trifluoroethane
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy cat.  ?
Legal status  ?
Pharmacokinetic data
Metabolism Hepatic (CYP2E1[1])
Excretion Renal
Identifiers
CAS number 151-67-7 YesY
ATC code N01AB01
PubChem CID 3562
IUPHAR ligand 2401
DrugBank DB01159
ChemSpider 3441 YesY
UNII UQT9G45D1P YesY
KEGG D00542 YesY
ChEBI CHEBI:5615 YesY
ChEMBL CHEMBL931 YesY
Chemical data
Formula C2HBrClF3 
Mol. mass 197.381 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Halothane (trademarked as Fluothane) is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and chlorine atoms present in halothane. 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. Halothane is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.[2] Its use in developed countries, however, has been almost entirely superseded by newer inhalational anaesthetic agents.

Contents

Anesthetic properties

It is a potent anesthetic with a minimum alveolar concentration of 0.74. Its blood gas coefficient of 2.4 makes it an agent with moderate induction and recovery time. It is not a good analgesic and its muscle relaxation effect is moderate.[3]

Related substances

Chemically, halothane is not an ether; it is an alkyl halide.[4] The structure has one stereocenter, so there are (R)- and (S)-optical isomers. 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. 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.

History

This halogenated hydrocarbon was first synthesized by C. W. Suckling of Imperial Chemical Industries (ICI) in 1951 and was first used clinically by M. Johnstone in Manchester in 1956. Halothane became popular as a nonflammable general anasthetic replacing other volatile anesthetics such as diethyl ether and cyclopropane. Use of the anesthetic was phased out during the 1980s and 1990s as newer anesthetic agents became popular. Halothane retains some use in veterinary surgery and in the Third World because of its lower cost.

Halothane was given to many millions of adult and pediatric patients worldwide from its introduction in 1956 through the 1980s. 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. Due to its cardiac depressive effect, it was contraindicated in patients with cardiac failure. Halothane was also contraindicated in patients susceptible to cardiac arrhythmias, or in situations related to high catecholamine levels such as pheochromocytoma.

Side effects

Repeated exposure to halothane in adults was noted in rare cases to result in severe liver injury. This occurred in about 1 in 10,000 exposures. The resulting syndrome was referred to as halothane hepatitis, 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%. Concern for hepatitis resulted in a dramatic reduction in the use of halothane for adults. It was replaced in the 1980s by enflurane and isoflurane. By the year 2005 the common volatile anesthetics in use were isoflurane, sevoflurane, and desflurane. Since the risk of halothane hepatitis in children was substantially lower than in adults, halothane saw continued use in pediatrics in the 1990s. However, by the year 2000 sevoflurane had largely replaced the use of halothane in children.

Physical properties

Boiling point: 50.2 °C (at 101.325 kPa)
Density: 1.868 g/cm³ (at 20 °C)
Molecular Weight: 197.4 u
Vapor pressure: 244 mmHg (at 20 °C)
288 mmHg (at 24 °C)
MAC: 0.75 vol %
Blood:Gas Partition coefficient: 2.5
Oil:Gas Partition coefficient: 224

Synthesis

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.[5]

Halothane synth.png

References

  1. ^ DrugBank: DB01159 (Halothane)
  2. ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. March 2011. http://whqlibdoc.who.int/hq/2011/a95053_eng.pdf. Retrieved 2011-08-22. 
  3. ^ Halothane. http://anesthesiageneral.com/halothane/. 
  4. ^ "DrugBank: Halothane (DB01159)". 17 December 2010. http://www.drugbank.ca/drugs/DB01159#taxonomy. 
  5. ^ Suckling et al.,"PROCESS FOR THE PREPARATION OF 1,1,1-TRIFLUORO-2-BROMO-2-CHLOROETHANE", US patent 2921098, granted January 1960 , assigned to Imperial Chemical Industries 

Further reading

  • Atkinson, Rushman, Lee. A Synopsis of Anaesthesia. 1987.
  • Eger, Eisenkraft, Weiskopf. The Pharmacology of Inhaled Anesthetics. 2003.

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Look at other dictionaries:

  • Halothane — Général Nom IUPAC (RS) 2 bromo 2 …   Wikipédia en Français

  • halothane — ● halothane nom masculin Dérivé de l éthane, employé comme anesthésique par inhalation, en particulier chez l enfant …   Encyclopédie Universelle

  • halothane — [hal′ə thān΄] n. [ HALO + (E)TH(ER) + ANE] a nonexplosive liquid, CF3CHBrCl, whose vapor is inhaled to produce general anesthesia …   English World dictionary

  • halothane — /hal euh thayn /, n. Pharm. a colorless liquid, C2HBrClF3, used as an inhalant for general anesthesia. [1955 60; HALO + thane, as in fluothane] * * * ▪ drug also called  2 bromo 2 chloro 1,1,1 trifluoroethane , or  fluothane        nonflammable,… …   Universalium

  • halothane — fluorotanas statusas T sritis chemija apibrėžtis Vaistas. formulė CHBrClCF₃ atitikmenys: angl. halothane rus. фторотан ryšiai: sinonimas – 2 brom 2 chlor 1,1,1 trifluoretanas …   Chemijos terminų aiškinamasis žodynas

  • halothane — noun Etymology: halo + ethane Date: 1957 a potent inhalational anesthetic C2HBrClF3 that is nonexplosive and nonflammable …   New Collegiate Dictionary

  • halothane — (= 2 bromo 2 chloro 1,1,1 trifluorethane) Widely used volatile anaesthetic given by inhalation …   Dictionary of molecular biology

  • halothane — noun The halogenated hydrocarbon 2 bromo 2 chloro 1,1,1 trifluoroethane that is used as an inhalational general anaesthetic …   Wiktionary

  • halothane — A widely used potent nonflammable and nonexplosive inhalation anesthetic, with rapid onset and reversal; side effect s include respiratory and cardiovascular depression, and sensitization to epinephrine induced arrhythmias. Often used in children …   Medical dictionary

  • halothane — n. chemical substance used as a general anesthetic …   English contemporary dictionary