World Library  
Flag as Inappropriate
Email this Article
 

Halothane

Halothane
Systematic (IUPAC) name
2-Bromo-2-chloro-1,1,1-trifluoroethane
Clinical data
AHFS/Drugs.com
Pharmacokinetic data
Metabolism Hepatic (CYP2E1[1])
Excretion Renal, Respiratory
Identifiers
CAS Registry Number  YesY
ATC code N01
PubChem CID:
IUPHAR/BPS
DrugBank  YesY
ChemSpider  YesY
UNII  YesY
KEGG  YesY
ChEBI  YesY
ChEMBL  YesY
Chemical data
Formula C2HBrClF3
Molecular mass 197.381 g/mol
 YesY   

Halothane (trademarked as Fluothane) is a general anesthetic that is inhaled. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic containing bromine. 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. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[2] Its use in developed countries has been mostly superseded by newer agents such as sevoflurane, isoflurane, and desflurane. As of 2014 it cost about 22 to 52 USD for a 250 ml bottle.[3]

Contents

  • Medical uses 1
  • Side effects 2
  • Pharmacology 3
  • Chemical and physical properties 4
  • Synthesis 5
  • Related substances 6
  • History 7
  • Availability 8
  • References 9
  • Further reading 10

Medical uses

Packaging of ICI Fluothane (their trade name for halothane)

It is a potent anesthetic with a MAC of 0.74%. Its blood/gas partition 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.[4]

Side effects

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, 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 and it was replaced in the 1980s by enflurane and isoflurane. 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 anaesthesia . However, by 2000, sevoflurane, excellent for inhalation induction, had largely replaced the use of halothane in children.

Halothane sensitises the heart to catecholamines, so it is liable to cause cardiac arrhythmias, occasionally fatal, particularly if hypercapnia has been allowed to develop. This seems to be especially problematic in dental anaesthesia.

Like all the potent inhalational anaesthetic agents, it is a potent trigger for malignant hyperthermia. 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.

Pharmacology

Halothane activates GABAA and glycine receptors.[5][6] It also acts as an NMDA receptor antagonist,[6] inhibits nACh and voltage-gated sodium channels,[7][5] and activates 5-HT3 and twin-pore K+ channels.[8][5] It does not affect the AMPA or kainate receptors.[6]

Chemical and 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 (32kPa) (at 20°C)
288 mmHg (38kPa) (at 24°C)
MAC: 0.75 vol %
Blood:gas partition coefficient: 2.3
Oil:gas partition coefficient: 224

Chemically, halothane is an alkyl halide (not an ether like many other anesthetics).[9] The structure has one stereocenter, so (R)- and (S)-optical isomers occur.

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.[10]

Related substances

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.

The main advantage of the more modern agents is lower blood solubility, resulting in faster induction of and recovery from anaesthesia.

History

Halothane was first synthesized by C. W. Suckling of Imperial Chemical Industries in 1951 in Widnes and was first used clinically by M. Johnstone in Manchester in 1956. It became popular as a nonflammable general anasthetic 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 and in veterinary surgery because of its lower cost.

A meter for measuring halothane. This was used to measure the amount of halothane a flow of inspired gas during anesthesia.

Halothane was given to many millions of adult and pediatric patients worldwide from its introduction in 1956 through the 1980s.[11] 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.

Availability

It is available as a volatile liquid, at 30, 50, 200, and 250 ml per container[12] but in many first world nations is not available having been displaced by newer agents.

References

  1. ^ DrugBank: DB01159 (Halothane)
  2. ^
  3. ^
  4. ^
  5. ^ a b c
  6. ^ a b c
  7. ^
  8. ^
  9. ^
  10. ^ 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 
  11. ^
  12. ^ National formulary of India, 4th Ed. New Delhi, India, Indian Pharmacopoeia commission; 2011: 411

Further reading

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


This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.