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Isoflurane

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Isoflurane
Clinical data
Trade namesForane, others
AHFS/Drugs.comFDA Professional Drug Information
Pregnancy
category
  • C
Routes of
administration		inhalation
ATC code
Identifiers
  • (RS)-2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane
    OR
    (RS)-1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.043.528 Edit this at Wikidata
Chemical and physical data
FormulaC3H2ClF5O
Molar mass184.5 g/mol g·mol−1
3D model (JSmol)
  • FC(F)(F)C(Cl)OC(F)F
  • InChI=1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2H checkY
  • Key:PIWKPBJCKXDKJR-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Isoflurane, sold under the trade name Forane among others, is a general anesthetic.[1] It can be used to start or maintain anesthesia.[1] Often another medication is used to start anesthesia due to airway irritation with isoflurane.[2][3] It is used by inhalation.[1]

Side effects include a decreased ability to breathe (respiratory depression), low blood pressure, and irregular heartbeat.[2] Serious side effects may include malignant hyperthermia and high blood potassium.[1] It should not be used in people with a history of malignant hyperthermia in either themselves or their family members.[2] It is unknown if use during pregnancy is safe for the baby, but use during a cesarean section appears to be safe.[1][2] Isoflurane is in the halogenated ether family of medication.[4]

Isoflurane was approved for medical use in the United States in 1979.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[5] The wholesale cost in the developing world is about 17.24 to 170.40 USD per 250 ml bottle.[6]

Medical uses

Isoflurane is always administered in conjunction with air and/or pure oxygen. Often nitrous oxide is also used. Although its physical properties imply that anaesthesia can be induced more rapidly than with halothane,[7] its pungency can irritate the respiratory system, negating any possible advantage conferred by its physical properties. It is usually used to maintain a state of general anesthesia which has been induced with another drug, such as thiopentone or propofol.

Adverse effects

Animal studies have raised safety concerns of certain general anesthetics, in particular ketamine and isoflurane, in young children. The risk of neurodegeneration was increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam.[8] Whether these concerns occur in humans is unclear.[8]

Elderly

Concerns exist with regard to the relationship between administration of isoflurane and postoperative cognitive dysfunction (POCD), for which the elderly are especially vulnerable.[9]

Biophysical studies using NMR spectroscopy has provided molecular details of how inhaled anesthetics interact with three amino acid residues (G29, A30 and I31) of amyloid beta peptide and induce aggregation. This area is important as "some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimer’s disease".[10]

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)[11]
Blood:gas partition coefficient: 1.4
Oil:gas partition coefficient: 98

It is a racemic mixture of (R)- and (S)-optical isomers. It vaporizes readily, but is a liquid at room temperature. It does not burn.

Mechanism of action

Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated.[12] Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamate and glycine receptors, but has different effects on each receptor. Isoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors.[13][14][15][16] It potentiates glycine receptor activity, which decreases motor function.[17] It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels.[18] Isoflurane also affects intracellular molecules. It activates calcium ATPase by increasing membrane fluidity[citation needed] . It binds to the D subunit of ATP synthase and NADH dehydrogenase.

General anaesthesia with isoflurane reduces plasma endocannabinoid AEA concentrations, and this could be a consequence of stress reduction after loss of consciousness.[19]

History

Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula.

Environment

The average lifetime of isoflurane in the atmosphere is 3.2 years, its global warming potential is 510 and the yearly emissions add up to 880 tons.[20]

Other animals

Isoflurane is frequently used for veterinary anaesthesia.

See also

References

  1. ^ a b c d e f "Isoflurane - FDA prescribing information, side effects and uses". www.drugs.com. March 2015. Archived from the original on 21 December 2016. Retrieved 13 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  2. ^ a b c d "Isoflurane (inhalation anaesthetic) - Summary of Product Characteristics (SPC) - (eMC)". www.medicines.org.uk. 11 January 2016. Archived from the original on 20 December 2016. Retrieved 13 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  3. ^ Kliegman, Robert M.; Stanton, Bonita M. D.; Geme, Joseph St; Schor, Nina F. (2015). Nelson Textbook of Pediatrics (20 ed.). Elsevier Health Sciences. p. 420. ISBN 9780323263528. Archived from the original on 2016-12-20. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  4. ^ Aglio, Linda S.; Lekowski, Robert W.; Urman, Richard D. (2015). Essential Clinical Anesthesia Review: Keywords, Questions and Answers for the Boards. Cambridge University Press. p. 115. ISBN 9781107681309. Archived from the original on 2016-12-20. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  5. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived from the original (PDF) on 13 December 2016. Retrieved 8 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  6. ^ "Isoflurane". International Drug Price Indicator Guide. Retrieved 8 December 2016.
  7. ^ Niedermeyer, Ernst; Silva, F. H. Lopes da (2005). Electroencephalography: Basic Principles, Clinical Applications, and Related Fields. Lippincott Williams & Wilkins. p. 1156. ISBN 978-0-7817-5126-1. Archived from the original on 2016-05-09. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  8. ^ a b Mellon, RD.; Simone, AF.; Rappaport, BA. (Mar 2007). "Use of anesthetic agents in neonates and young children". Anesth Analg. 104 (3): 509–20. doi:10.1213/01.ane.0000255729.96438.b0. PMID 17312200. Archived from the original on 2009-03-09. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  9. ^ 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. PMID 17141964.
  10. ^ Kuehn, BM. (Apr 2007). "Anesthesia-Alzheimer disease link probed". JAMA. 297 (16): 1760. doi:10.1001/jama.297.16.1760. PMID 17456811.
  11. ^ Seto, T; Mashimo, T; Yoshiya, I; Kanashiro, M; Taniguchi, Y (1992), "The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy", J Pharm Biomed Anal, 10 (1): 1–7, PMID 1391078
  12. ^ "How does anesthesia work?". Scientific American. February 7, 2005. Archived from the original on May 29, 2016. {{cite web}}: Italic or bold markup not allowed in: |publisher= (help); Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  13. ^ M. V. Jones, P. A. Brooks & N. L. Harrison (1992). "Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics". The Journal of Physiology. 449: 279–293. PMC 1176079. PMID 1326046.
  14. ^ A. Jenkins, N. P. Franks & W. R. Lieb (1999). "Effects of temperature and volatile anesthetics on GABA(A) receptors". Anesthesiology. 90 (2): 484–491. PMID 9952156.
  15. ^ L. H. Lin, L. L. Chen, J. A. Zirrolli & R. A. Harris (1992). "General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acidA receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium". The Journal of Pharmacology and Experimental Therapeutics. 263 (2): 569–578. PMID 1331405.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ M. D. Krasowski & N. L. Harrison (2000). "The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations". British Journal of Pharmacology. 129 (4): 731–743. doi:10.1038/sj.bjp.0703087. PMC 1571881. PMID 10683198.
  17. ^ Grasshoff, C.; Antkowiak, B. (2006-09-13). "Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats" (PDF). British Journal of Anaesthesia. 97 (5): 687–694. doi:10.1093/bja/ael239. ISSN 0007-0912. PMID 16973644. Archived from the original (PDF) on 2017-09-10. {{cite journal}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  18. ^ Buljubasic, N.; Rusch, NJ.; Marijic, J; Kampine; ZJ, Bosnjak (1992). "Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells". Anaesthesiology. 96 (6): 990–998. PMID 1318010.
  19. ^ Weis, F.; Beiras-Fernandez, A.; Hauer, D.; Hornuss, C.; Sodian, R.; Kreth, S.; Briegel, J.; Schelling, G. (2010-08-01). "Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery". British Journal of Anaesthesia. 105 (2): 139–144. doi:10.1093/bja/aeq117. ISSN 0007-0912. PMID 20525978.
  20. ^ Martin K. Vollmer; Tae Siek Rhee; Matt Rigby; Doris Hofstetter; Matthias Hill; Fabian Schoenenberger; Stefan Reimann (2015). "Modern inhalation anesthetics: Potent greenhouse gases in the global atmosphere". Geophysical Research Letters. 42 (5): 1606–1611. doi:10.1002/2014GL062785.

External links

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