Isoflurane

Isoflurane
Names
Trade namesForane, others
IUPAC name
  • (RS)-2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane
    OR
    (RS)-1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • C
Routes of
use		inhalation
Defined daily dosenot established[1]
External links
AHFS/Drugs.comFDA Professional Drug Information
Chemical and physical data
FormulaC3H2ClF5O
Molar mass184.49 g·mol−1
3D model (JSmol)
SMILES
  • FC(F)(F)C(Cl)OC(F)F
InChI
  • InChI=1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2H checkY
  • Key:PIWKPBJCKXDKJR-UHFFFAOYSA-N checkY

Isoflurane, sold under the trade name Forane among others, is a general anesthetic.[2] It can be used to start or maintain anesthesia, however other medications are often used to start anesthesia rather than isoflurane, due to airway irritation with isoflurane.[3][4] Isoflurane is given via inhalation.[2]

Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an irregular heartbeat.[3] Serious side effects can include malignant hyperthermia or high blood potassium.[2] It should not be used in people with a history of malignant hyperthermia in either themselves or their family members.[3] It is unknown if its use during pregnancy is safe for the fetus, but use during a cesarean section appears to be safe.[2][3] Isoflurane is a halogenated ether.[5]

Isoflurane was approved for medical use in the United States in 1979.[2] It is on the World Health Organization's List of Essential Medicines.[6] The wholesale cost of isoflurane in the developing world is about US$17.24–170.40 per 250 ml bottle.[7]

Medical uses

Isoflurane is always administered in conjunction with air or pure oxygen. Often, nitrous oxide is also used. Although its physical properties imply that anaesthesia can be induced more rapidly than with halothane,[8] 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 that has been induced by another drug, such as thiopentone or propofol.

Dosage

The defined daily dose is not established[1]

Side 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.[9] Whether these concerns occur in humans is unclear.[9]

Elderly

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 weight184.5g/mol
Boiling point (at 1 atm):48.5 °C
Density (at 25 °C):1.496 g/mL
MAC :1.15 vol %
Vapor pressure:238 mmHg31.7 kPa(at 20 °C)
295 mmHg39.3 kPa(at 25 °C)
367 mmHg48.9 kPa(at 30 °C)
450 mmHg60.0 kPa(at 35 °C)
Water solubility13.5 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 . 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. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 22 January 2021. Retrieved 20 September 2020.
  2. 1 2 3 4 5 "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.
  3. 1 2 3 4 "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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. ↑ "Isoflurane". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.
  8. ↑ Niedermeyer, Ernst; da Silva, F. H. Lopes (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.
  9. 1 2 Mellon RD, Simone AF, Rappaport BA (March 2007). "Use of anesthetic agents in neonates and young children". Anesthesia and Analgesia. 104 (3): 509–20. doi:10.1213/01.ane.0000255729.96438.b0. PMID 17312200. Archived from the original on 2009-03-09.
  10. ↑ Kuehn BM (April 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 (January 1992). "The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy". Journal of Pharmaceutical and Biomedical Analysis. 10 (1): 1–7. doi:10.1016/0731-7085(92)80003-6. PMID 1391078.
  12. ↑ "How does anesthesia work?". Scientific American. February 7, 2005. Archived from the original on May 29, 2016.
  13. ↑ Jones MV, Brooks PA, Harrison NL (April 1992). "Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics". The Journal of Physiology. 449: 279–93. doi:10.1113/jphysiol.1992.sp019086. PMC 1176079. PMID 1326046.
  14. ↑ Jenkins A, Franks NP, Lieb WR (February 1999). "Effects of temperature and volatile anesthetics on GABA(A) receptors". Anesthesiology. 90 (2): 484–91. doi:10.1097/00000542-199902000-00024. PMID 9952156.
  15. ↑ Lin LH, Chen LL, Zirrolli JA, Harris RA (November 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): 569–78. PMID 1331405.
  16. ↑ Krasowski MD, Harrison NL (February 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): 731–43. doi:10.1038/sj.bjp.0703087. PMC 1571881. PMID 10683198.
  17. ↑ Grasshoff C, Antkowiak B (November 2006). "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): 687–94. doi:10.1093/bja/ael239. PMID 16973644. Archived (PDF) from the original on 2017-09-10.
  18. ↑ Buljubasic N, Rusch NJ, Marijic J, Kampine JP, Bosnjak ZJ (June 1992). "Effects of halothane and isoflurane on calcium and potassium channel currents in canine coronary arterial cells". Anesthesiology. 76 (6): 990–8. doi:10.1097/00000542-199206000-00020. PMID 1318010.
  19. ↑ Weis F, Beiras-Fernandez A, Hauer D, Hornuss C, Sodian R, Kreth S, et al. (August 2010). "Effect of anaesthesia and cardiopulmonary bypass on blood endocannabinoid concentrations during cardiac surgery". British Journal of Anaesthesia. 105 (2): 139–44. doi:10.1093/bja/aeq117. PMID 20525978. Archived from the original on 2021-08-28. Retrieved 2016-12-19.
  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. Bibcode:2015GeoRL..42.1606V. doi:10.1002/2014GL062785. Archived from the original on 2021-05-20. Retrieved 2019-09-24.
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