Halothane

In a study on halothane-induced hepatitis in the United States the incidence of fatal massive hepatic necrosis from any cause was 7.1 in 10,000 after multiple administrations of halothane and only 2.4 in 10,000 after multiple administrations of non-halothane anesthetics. However, this increased risk appeared to be more than offset by higher mortality for other reasons in the non-halothane group. The general enthusiasm for halothane is reflected by the fact that it is now used for more than 70% of all anesthetic procedures in the United Kingdom (Davies and Holmes 1972). 

Minor alterations in hepatic dysfunction also occur more commonly after halothane administration than other general anesthetics now in common use (Wright et al. 1975). Nonetheless, when jaundice occurs after halothane use, the prognosis is serious. In a review by Little in 1968 the mortality rate was calculated to be 35% in the 400 patients who had developed this complication. When death occurs, it is usually due to hepatic failure with coma. Obesity, early onset of jaundice after anesthesia, and associated blood coagulation abnormalities are more likely to be associated with a fatal outcome. If recovery occurs, it is almost always complete. In 

Synonyms 2 -Bromo-2 -chloro-1,1)1 -trifluo-roethane bromochlorotrifluoroethane Fluo-thane 

Toxicology. Halothane causes central nervous system depression, affects the cardiovascular system, and occasionally causes hepatitis. 

Halothane is used as a clinical anesthetic, and all levels of central nervous system depression can be expected, including amnesia, analgesia, anesthesia, and respiratory depression. Levels ranging from 5000 to 3 0,000 ppm can induce anesthesia, whereas 5000-15,000ppm can maintain it. A 30-minute exposure to 4000 ppm caused amnesia and impairment of manual dexterity, whereas similar exposure to 1000 ppm did not alter the outcome on various psychomotor tests.  

Levels of halothane associated with anesthesia may also reduce cardiac output by 20-50%. Tachyarrhythmias may occur in the presence of halothane.  

Hepatitis occasionally occurs in patients after clinical anesthesia. Typically, 2-5 days after anesthesia, a fever develops, accompanied by anorexia, nausea, and vomiting. There may be a progression to hepatic failure, and death occurs in about 50% of these patients. The incidence of the syndrome is 1 in 10,000 anesthetic administrations, and it is seen most often after repeated administration of halothane over a short period of time. 

Nomiya, B. and Ogawa, H. U.S. Patent 3,322,813 May 30, 1967 assigned to Meiji Seika Kaisha, Ltd., Japan 

Therapeutic Function Inhalation anesthetic Chemical Name 2-bromo-2-chloro-1,1,1-trifluoroethane Common Name — 

This condensate was washed with dilute caustic soda solution and dried over calcium chloride. The exit gases from this condenser were scrubbed with water and dilute caustic soda solution, dried and passed to a condenser cooled with a mixture of solid carbon dioxide and trichloroethylene which caused the unchanged 1,1,1-trifluoro-2-chloroethane to condense. This second condensate was then combined with the first and the mixture was fractionally distilled. 

Suckling, C.W. and Raventos, J. U.S. Patent 2,849,502 August 26, 1958 assigned to Imperial Chemical Industries Limited, England 

Halothan Hoechst Halovis Narco tan Rhodialothan Somnothane 

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Inhalation Anesthetics. Examples of highly duorinated halocarbons and ethers are halothane [151-67-7], duroxene [406-90-6], endurane... 

Halothane. Halothane or Fluothane, 2-bromo-2-chloro-l,l,l-trifluoroethane [151 -67-7] is a colorless Hquid with a pleasant odor. Its lower flammability limit, 4.8% in 70% N2O/30% O2, renders it essentially nonflammable. It has a vapor pressure of 32.5 kPa (244 mm Hg) at 20 °C and is stable to soda lime. However, it is photochemicaHy reactive. 

Fluoride produced from the biodegradation of halothane or the other agents has Htde effect on normal kidney function (59). Halothane usage has been declining because of the potential Hver effects, although the agent is used where inhalation induction is desired, especially in pediatrics. 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

Sevoflurane. Sevoflurane, l,l,l,3,3,3-hexafluoro-2-propyl fluromethyl ether [28523-86-6] is nonpungent, suggesting use in induction of anesthesia. The blood/gas partition coefficient is less than other marketed products (Table 1) yet similar to nitrous oxide, suggesting fast onset and recovery. In animal studies, recovery was faster for sevoflurane than for isoflurane, enflurane, or halothane (76). Sevoflurane is stable to light, oxygen, and metals (28). However, the agent does degrade in soda lime (77). 

Subcommittee on the National Halothane Study of the Committee on Anesthesia, National Academy of Sciences—National Research Council,/. 

Parent substances and metaboHtes may be stored in tissues, such as fat, from which they continue to be released following cessation of exposure to the parent material. In this way, potentially toxic levels of a material or metaboHte may be maintained in the body. However, the relationship between uptake and release, and the quantitative aspects of partitioning, may be complex and vary between different materials. For example, volatile lipophilic materials are generally more rapidly cleared than nonvolatile substances, and the half-Hves may differ by orders of magnitude. This is exemplified by comparing halothane and DDT (see Anesthetics Insectcontholtechnology). 

In veterinary medicine, the Hst of inhalation anesthetics generally includes only two agents, halothane [151 -67-7] and methoxyflurane [76-38-0]. Although ether (ethyl ether) is used extensively in experimental work with laboratory animals, the risks associated with its use and the advantages of halothane and methoxyflurane have removed ether from general use by the practitioner. 

Halothane and methoxyflurane are volatile and are used in a vaporizer and deflvered to the animal via an oxygen carrier. Both agents can be dehvered with nitrous oxide [14522-82-8], a mild anesthetic that when combined with halothane or methoxyflurane can induce anesthesia faster than... 

Glycol monoethyl ether, see 2-Ethoxyethanol Guthion, see Azinphosmethyl Halothane Heptane (n-heptane)... 

The toxic effect depends both on lipid and blood solubility. I his will be illustrated with an example of anesthetic gases. The solubility of dinitrous oxide (N2O) in blood is very small therefore, it very quickly saturates in the blood, and its effect on the central nervous system is quick, but because N,0 is not highly lipid soluble, it does not cause deep anesthesia. Halothane and diethyl ether, in contrast, are very lipid soluble, and their solubility in the blood is also high. Thus, their saturation in the blood takes place slowly. For the same reason, the increase of tissue concentration is a slow process. On the other hand, the depression of the central nervous system may become deep, and may even cause death. During the elimination phase, the same processes occur in reverse order. N2O is rapidly eliminated whereas the elimination of halothane and diethyl ether is slow. In addition, only a small part of halothane and diethyl ether are eliminated via the lungs. They require first biotransformation and then elimination of the metabolites through the kidneys into the... 

A nonconventional synthesis of the known inhalation anaesthetic, 2-bromo-2 chloro-l,l,l-trifluoroethane (Halothane), based on the reaction of ethyl 1,2 di bromo-1,2-dicliloroethyl ether with anhydrous hydrogen fluoride and sulfur tetrafluoride, has been patented The reaction presumably involves cleavage of the ether linkage, followed by fluorination of the intermediate bromochloroacetyl halide with sulfur tetrafluoride, ethyl halides are the by-products [2] (equation 2)... 

Dozens of compounds have been used in in vivo fluonne NMR and MRI studies, chosen more for their commercial availability and established biochemistry than for ease of fluonne signal detection [244] Among the more common of these are halothane and other fluormated anesthetics [245, 246], fluorodeoxyglucose [242 243], and perfluormated synthetic blood substitutes, such as Fluosol [246], a mixture of perfluorotnpropylamine and perfluorodecahn Results have been Imut-ed by chemical shift effects (multiple signals spread over a wide spectral range) and long acquisition times... 

Halothane remams the leading anesthetic m many parts of the world However, It IS beheved to cause a fuhmnant hepatitis in rare, susceptible mdividuals, especially after repeated use within short intervals It was believed, but now disputed, that this hepatitis resulted from toxic metabohtes [2] (Actually, the major metabolite is tnfluoroacebc acid, which as a salt in body fluids, is benign ) As rare as the hepatitis cases were (1 m 20 000), they frequently resulted m malpractice suits, especially in the United States This problem led to a search for more ideal nonflammable anesthetics that are also metabohzed to a lesser extent [i]... 

An isomer of enflurane named isoflurane (l-chloro-2,2,2-tnfluoroethyl difluoromethyl ether) does not produce uncontrolled movements, is nonflammable, and IS metabolized to an even lesser extent than enflurane [7] As of this wntmg, isoflurane is the fastest growing anesthebc m more economically developed coun tries, but because of cost, it has not overtaken halothane in the rest of the world... 

Fazidinium bromide Fenoterol hydrobromide Folic acid Halothane Ifenprodil tartrate Ketamine HCI Mema ntine Metaproterenol Norfenefrine Oxaflozane HCI Phendimetrazine tartrate Phentermine HCI Procarbazine HCI Promegestone Pyrovalerone HCI Sulfacytine Sulfalene Trioxsalen N-8romoacetamide Fluazacort... 

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