Halothane

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Halothane From Wikipedia, the free encyclopedia

Halothane

Systematic (IUPAC) name 2-Bromo-2-chloro-1,1,1-trifluoroethane

Clinical data AHFS/Drugs.com

Micromedex Detailed Consumer Information

Pregnancy cat.

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Legal status

? Pharmacokinetic data

Metabolism Excretion

Hepatic (CYP2E1[1]) Renal Identifiers

CAS number

151-67-7

ATC code

N01AB01

PubChem

CID 3562

IUPHAR ligand 2401 DrugBank ChemSpider UNII

DB01159 3441 UQT9G45D1P

KEGG

D00542

ChEBI

CHEBI:5615

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ChEMBL

CHEMBL931 Chemical data

Formula

C2HBrClF3

Mol. mass

197.381 g/mol

SMILES

eMolecules & PubChem

InChI[show] (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Its use in developed countries, however, has been almost entirely superseded by newer inhalational anaesthetic agents.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 [hide]  

1 Anesthetic properties 2 Related substances

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3 History

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4 Physical properties

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5 Synthesis

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6 References

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7 Further reading

[edit] 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]

[edit] Related substances

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Chemically, halothane is not an ether; it is an alkyl halide. 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.

[edit] 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. 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.

[edit] Physical properties Boiling point: Density: Molecular Weight: Vapor pressure:

50.2 °C (at 101.325 kPa) 1.868 g/cm³ (at 20 °C) 197.4 u 244 mmHg (at 20 °C) 288 mmHg (at 24 °C)

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MAC: Blood:Gas Partition coefficient: Oil:Gas Partition coefficient:

0.75 vol % 2.5 224

[edit] 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-1,1,1trifluoroethane. This is then reacted with bromine at 450 °C to produce halothane.[4]

[edit] References 1. 2.

^ DrugBank: DB01159 (Halothane) ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. March 2011. Retrieved 2011-08-22.

3. 4.

^ Halothane. ^ Suckling et al.,"PROCESS FOR THE PREPARATION OF 1,1,1-TRIFLUORO2-BROMO-2-CHLOROETHANE", US patent 2921098, granted January 1960 , assigned to Imperial Chemical Industries

[edit] Further reading  

Atkinson, Rushman, Lee. A Synopsis of Anaesthesia. 1987. Eger, Eisenkraft, Weiskopf. The Pharmacology of Inhaled Anesthetics. 2003. [hide]v · d · eAnesthetic: General anesthetics (N01A) Ethers

Inhalation

Diethyl ether • Methoxypropane • Vinyl ether • halogenated ethers (Desflurane • Enflurane • Isoflurane • Methoxyflurane • Sevoflurane)

HaloalkanesChloroform • Halothane# • Trichloroethylene Others

Cyclopropane • Ethylene • Nitrous oxide# • Xenon

Injection BarbituratesHexobarbital • Methohexital • Narcobarbital • Thiopental#

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Opioids

Alfentanil • Anileridine • Fentanyl • Phenoperidine • Remifentanil • Sufentanil

Neuroactive Alfaxalone • Minaxolone steroids Others

Droperidol • Etomidate • Fospropofol • gamma-Hydroxybutyric acid • Ketamine# /Esketamine • Midazolam • Propanidid • Propofol

#

WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III M: CNS

anat(n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco(m/d/e/h/v/s)/cong/tumr, sysi/epon, injr