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Isoflurane

Systematic (IUPAC) name

(RS)-2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane

OR

(RS)-1-chloro-2,2,2-trifluoroethyl difluoromethyl ether

Clinical data

Trade names Forane

Identifiers

CAS Registry Number 26675-46-7

ATC code N01AB06

PubChem CID: 3763

IUPHAR/BPS 2505

DrugBank DB00753

ChemSpider 3631

UNII CYS9AKD70P

KEGG D00545

ChEBI CHEBI:6015

ChEMBL CHEMBL1256

Chemical data

IsofluraneFrom Wikipedia, the free encyclopedia

Isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane) is a halogenated ether used for inhalationalanesthesia. Together with enflurane and halothane, itreplaced the flammable ethers used in the pioneer days ofsurgery. Its name comes from being a structural isomerof enflurane, hence they have the same empiricalformula. It is a racemic mixture of (R) and (S) opticalisomers. Its use in human medicine is now starting todecline, being replaced with sevoflurane, desflurane, andthe intravenous anaesthetic propofol. Isoflurane is stillfrequently used for veterinary anaesthesia.

Isoflurane is always administered in conjunction with airand/or pure oxygen. Often nitrous oxide is also used.Although its physical properties imply that anaesthesia

can be induced more rapidly than with halothane,[1] itspungency can irritate the respiratory system, negatingthis theoretical advantage conferred by its physicalproperties. It is usually used to maintain a state ofgeneral anesthesia that has been induced with anotherdrug, such as thiopentone or propofol. It vaporizesreadily, but is a liquid at room temperature. It iscompletely nonflammable.

It is on the WHO Model List of Essential Medicines, themost important medications needed in a health

system.[2]

Contents

1 Adverse effects

1.1 Use with the elderly

2 Physical properties

3 Mechanism of action4 References

5 External links

Adverse effects

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Formula C3H2ClF5O

Molecular mass 184.5 g/mol

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Concerns have been raised as to the safety of certaingeneral anesthetics, in particular ketamine andisoflurane in infants and young children due tosignificant neurodegeneration. The risk ofneurodegeneration is increased in combination of theseagents with nitrous oxide and benzodiazepines such asmidazolam. This has led the FDA and other bodies to

take steps to investigate these concerns.[3]

Use with the elderly

Concerns exist with regard to the relationship between administration of isoflurane and postoperative

cognitive dysfunction (POCD), for which the elderly are especially vulnerable.[4] Exposure of culturedhuman cells to isoflurane has been reported to induce apoptosis and accumulation and aggregation ofamyloid beta protein, and may contribute to POCD, but this remains unknown. The study was based on invitro research; further in vivo research is needed to determine the relevance of these findings in clinical

practice and to improve the safety of anesthesia.[5] An animal model has shown anesthesia with isofluraneincreases amyloid pathology in mice models of Alzheimer's disease, and has been shown to induce cognitive

decline in mice.[6] Memory impairment following isoflurane anesthesia in mice can be prevented by pre-

administering the GABA(A)α5 subunit inverse agonist L-655,708.[7] It is not yet known if the drug can helpprevent POCD in humans.

Biophysical studies using state-of-the-art NMR spectroscopy has provided molecular details of how inhaledanesthetics interact with three amino acid residues (G29, A30 and I31) of amyloid beta peptide and induceaggregation. This area is important as "some of the commonly used inhaled anesthetics may cause brain

damage that accelerates the onset of Alzheimer’s disease".[8]

Physical properties

Molecular weight 184.5g/mol

Boiling point (at 1 atm): 48.5 °C

Density (at 25 °C): 1.496 g/mL

MAC : 1.15 vol %

Vapor pressure: 238 mmHg 31.7 kPa (at 20 °C)

295 mmHg 39.3 kPa (at 25 °C)

367 mmHg 48.9 kPa (at 30 °C)

450 mmHg 60.0 kPa (at 35 °C)

Water solubility 13.5 mM (at 25 °C)[9]

Blood:gas partition coefficient: 1.4

Oil:gas partition coefficient: 98

Mechanism of action

SMILES

InChI

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Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated.[10]

Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA,glutamates and glycine receptors, but has different effects on each receptor. It potentiates glycine receptoractivity, which decreases motor function. It inhibits receptor activity in the NMDA glutamate receptorsubtypes. Isoflurane inhibits conduction in activated potassium channels. Isoflurane also affectsintracellular molecules. It activates calcium ATPase by increasing membrane fluidity. It binds to the Dsubunit of ATP synthase and NADH dehydrogenase.

References

External links

Rx Med (http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-

1. Niedermeyer, Ernst; Silva, F. H. Lopes da (2005). Electroencephalography: Basic Principles, ClinicalApplications, and Related Fields (http://books.google.com/books?id=tndqYGPHQdEC&pg=PA1156). LippincottWilliams & Wilkins. p. 1156. ISBN 978-0-7817-5126-1.

2. "WHO Model List of EssentialMedicines" (http://apps.who.int/iris/bitstream/10665/93142/1/EML_18_eng.pdf?ua=1) (PDF). World Health Organization. October 2013. p. 6. Retrieved 22 April 2014.

3. Mellon, RD.; Simone, AF.; Rappaport, BA. (Mar 2007). "Use of anesthetic agents in neonates and young

children." (http://www.anesthesia-analgesia.org/cgi/content/full/104/3/509). Anesth Analg 104 (3): 509–20.doi:10.1213/01.ane.0000255729.96438.b0 (https://dx.doi.org/10.1213%2F01.ane.0000255729.96438.b0).PMID 17312200 (https://www.ncbi.nlm.nih.gov/pubmed/17312200).

4. M. C. Lewis, I. Nevoa, M. A. Paniaguaa, A. Ben-Aric, E. Prettoa, S. Eisdorfera, E. Davidsona, I. Matotc, C.Eisdorfer (2007). "Uncomplicated general anesthesia in the elderly results in cognitive decline: Does cognitive

decline predict morbidity and mortality?". Medical Hypotheses 68 (3): 484–492. doi:10.1016/j.mehy.2006.08.030(https://dx.doi.org/10.1016%2Fj.mehy.2006.08.030). PMID 17141964(https://www.ncbi.nlm.nih.gov/pubmed/17141964).

5. Z. Xie, Y. Dong, U. Maeda, R. D. Moir, W. Xia, D. J. Culley, G. Crosby, R. E. Tanzi (2007). "The InhalationAnesthetic Isoflurane Induces a Vicious Cycle of Apoptosis and Amyloid β-Protein Accumulation". Journal of

Neuroscience 27 (6): 1247–1254. doi:10.1523/JNEUROSCI.5320-06.2007(https://dx.doi.org/10.1523%2FJNEUROSCI.5320-06.2007). PMID 17287498(https://www.ncbi.nlm.nih.gov/pubmed/17287498).

6. S. L. Bianchi, T. Tran, C. Liu, S. Lin, Y. Li, J. M. Keller, R. G. Eckenhoff, M. F. Eckenhoff (2007). "Brain andbehavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics". Neurobiology of Aging

28 (in press): 1002–10. doi:10.1016/j.neurobiolaging.2007.02.009(https://dx.doi.org/10.1016%2Fj.neurobiolaging.2007.02.009). PMID 17346857(https://www.ncbi.nlm.nih.gov/pubmed/17346857).

7. Saab, BJ; Maclean AJ; Kanisek M; Zurek AA; Martin LJ; Roder JC; Orser BA (November 2010). "Short-termmemory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptor inverse

agonist L-655,708.". Anesthesiology 113 (5): 1061–71. doi:10.1097/ALN.0b013e3181f56228(https://dx.doi.org/10.1097%2FALN.0b013e3181f56228). PMID 20966663(https://www.ncbi.nlm.nih.gov/pubmed/20966663).

8. Kuehn, BM. (Apr 2007). "Anesthesia-Alzheimer disease link probed". JAMA 297 (16): 1760.doi:10.1001/jama.297.16.1760 (https://dx.doi.org/10.1001%2Fjama.297.16.1760). PMID 17456811(https://www.ncbi.nlm.nih.gov/pubmed/17456811).

9. The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy. Seto T, MashimoT, Yoshiya I, Kanashiro M, Taniguchi Y. (http://www.ncbi.nlm.nih.gov/pubmed/1391078), retrieved 2014-05-14

10. http://www.scientificamerican.com/article/how-does-anesthesia-work/

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Categories: 5-HT3 agonists Ethers GABAA receptor positive allosteric modulators

General anesthetics Glycine receptor agonists Nicotinic antagonists NMDA receptor antagonists

Organochlorides Organofluorides

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