Sevoflurane
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| Systematic (IUPAC) name | |
| 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane | |
| Clinical data | |
| Trade names | Sojourn, Ultane, Sevorane |
| AHFS/Drugs.com | Consumer Drug Information |
| Pregnancy cat. | ? |
| Legal status | POM (UK) ℞-only (US) |
| Routes | inhaled |
| Identifiers | |
| CAS number | 28523-86-6  |
| ATC code | N01AB08 |
| PubChem | CID 5206 |
| DrugBank | DB01236 |
| ChemSpider | 5017 |
| UNII | 38LVP0K73A |
| KEGG | D00547 |
| ChEBI | CHEBI:9130 |
| ChEMBL | CHEMBL1200694  |
| Chemical data | |
| Formula | C4H3F7O |
| Mol. mass | 200.055 g/mol |
| SMILES | eMolecules & PubChem |
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Sevoflurane (1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane), also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology.[citation needed] It is often administered in a mixture of nitrous oxide and oxygen. After desflurane, it is the volatile anesthetic with the fastest onset and offset.[1] Though desflurane has the lowest blood/gas coefficient of the currently used volatile anesthetics, sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.
First reports of sevoflurane appeared in the literature in 1971. The agent was developed by scientists at Baxter Laboratories. It was introduced into clinical practice initially in Japan in 1990. Its name comes from having seven fluorine atoms. The rights for sevoflurane in the US and other countries were held by Abbott Laboratories. It is now available as a generic drug.
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[edit] Metabolism in humans
Sevoflurane forms at least two degradation products, compound A [fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether][2] also called PIFE (pentafluoroisopropenyl fluoromethyl ether) and Compound B [1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane],[3] also called PMFE (pentafluoromethoxy isopropyl fluoromethyl ether) on contact with the soda lime in a rebreathing apparatus, which absorbs exhaled carbon dioxide, especially at higher temperatures and when the soda lime is desiccated. Hydrofluoric acid is formed in the same reaction as compound A. Compound A has been shown to cause renal necrosis in rats. In humans, direct histological evidence of renal toxicity has not been demonstrated, although there is dose-related proteinuria, glycosuria and enzymuria. During low-flow anaesthesia, when the lower fresh gas flow leads to decreased flushing of the circuit and increased temperature of the soda lime, compound A may build up to clinically significant levels, although there have never been any reports of adverse events in humans. As a result, sevoflurane is sometimes administered with a minimum fresh gas flow of 2 liters per minute, making it a relatively expensive choice for maintaining general anesthesia. Only two countries currently maintain mandatory minimum flow rates of 2L/min; Canada and Australia. Recent generic competition in select markets has also significantly lowered the unit cost of sevoflurane, making it more cost effective.
[edit] Animal studies
Sevoflurane has been implicated in neuronal degeneration in infant mice. This activity is thought to occur via blockade of NMDA receptors or hyperactivity of GABA neurotransmission. In one study, the researchers showed exposure of infant mice to inhaled sevoflurane resulted in learning deficits and abnormal social behaviour.[4]
Sevoflurane raises intracranial pressure and can cause respiratory depression.[5]
[edit] Physical properties
| Boiling point: | 58.6 °C | (at 101.325 kPa) | |
| Density: | 1.517–1.522 g/cm³ | (at 20 °C) | |
| MAC : | 1.8 vol % | ||
| Molecular weight: | 200 u | ||
| Vapor pressure: | 157 mmHg (20.9 kPa) | (at 20 °C) | |
| 197 mmHg (26.3 kPa) | (at 25 °C) | ||
| 317 mmHg (42.3 kPa) | (at 36 °C) | ||
| Blood:Gas partition coefficient: | 0.68 | ||
| Oil:Gas partition coefficient: | 47 |
[edit] References
- ^ Sakai EM, Connolly LA, Klauck JA (December 2005). "Inhalation anesthesiology and volatile liquid anesthetics: focus on isoflurane, desflurane, and sevoflurane". Pharmacotherapy 25 (12): 1773–88. doi:10.1592/phco.2005.25.12.1773. PMID 16305297. http://www.atypon-link.com/doi/abs/10.1592/phco.2005.25.12.1773.
- ^ Stabernack CR, Eger EI 2nd, Warnken UH, Förster H, Hanks DK, Ferrell LD (2003). "Sevoflurane degradation by carbon dioxide absorbents may produce more than one nephrotoxic compound in rats". Can J Anaesth 50 (3): 249–52. doi:10.1007/BF03017793. PMID 12620947.
- ^ Schmidt, R.; Roeder, M.; Oeckler, O.; Simon, A.; Schurig, V. (2000). "Separation and absolute configuration of the enantiomers of a degradation product of the new inhalation anesthetic sevoflurane". Chirality 12 (10): 751–5. doi:10.1002/1520-636X(2000)12:10<751::AID-CHIR8>3.0.CO;2-H. PMID 11054834.
- ^ Satomoto M, Satoh Y, Terui K, et al. (March 2009). "Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice". Anesthesiology 110 (3): 628–37. doi:10.1097/ALN.0b013e3181974fa2. PMID 19212262. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0003-3022&volume=110&issue=3&spage=628.
- ^ Sevoflurane. http://anesthesiageneral.com/sevoflurane/.
[edit] Additional reading
- Patel SS, Goa KL (April 1996). "Sevoflurane. A review of its pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia". Drugs 51 (4): 658–700. PMID 8706599. http://adisonline.com/drugs/Abstract/1996/51040/Sevoflurane__A_Review_of_its_Pharmacodynamic_and.9.aspx.
"Erratum". Drugs 52 (2): 253. August 1996. http://adisonline.com/drugs/toc/1996/52020#-832002973. - Wallin, Richard F., Regan, Bernard M., Napoli, Martha D., Stern, Ivan j. (Nov.-Dec. 1975). "Sevoflurane: A New Inhalational Anesthetic Agent". Anesthesia and Analgesia 84 (6): 58-766.
[edit] External links
- "Propofol and Sevoflurane Anesthesia". http://www.priory.com/anaesthesia/propofol_and_sevoflurane.htm.
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