Isoflurane

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Isoflurane
Isoflurane.svg
Isoflurane-3D-vdW.png
Clinical data
Trade names Forane, others
AHFS/Drugs.com FDA Professional Drug Information
License data
Pregnancy
category
Routes of
administration 		Inhalation
ATC code
Legal status
Legal status
Pharmacokinetic data
Onset of action 1.14±0.35 min to 50% steady-state. [5]
Elimination half-life ~10 minutes [5]
Identifiers
  • 2-chloro-2-difluoromethoxy-1,1,1-trifluoroethane
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.043.528 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C3H2ClF5O
Molar mass 184.49 g·mol−1
3D model (JSmol)
Density 1.496 g/cm3 [6]
Boiling point 48.5 °C (119.3 °F) [6]
Solubility in water 13.5 mM (at 25 °C (77 °F)) [7]
  • FC(F)(F)C(Cl)OC(F)F
  • InChI=1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2H Yes check.svgY
  • Key:PIWKPBJCKXDKJR-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Isoflurane, sold under the brand name Forane among others, is a halogenated ether used as a general anesthetic. [4] [8] It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia, due to airway irritation with isoflurane. [3] [9] Isoflurane is given via inhalation. [4]

Contents

Isoflurane was approved for medical use in the United States in 1979. [4] [10] It is on the World Health Organization's List of Essential Medicines. [11] [12]

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, [13] its pungency can irritate the respiratory system, negating any possible advantage conferred by its physical properties. Thus, it is mostly used in general anesthesia as a maintenance agent after induction of general anesthesia with an intravenous agent such as thiopentone or propofol. [14] [15] [16]

Mechanism of action

Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated. [17] 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. [18] [19] [20] [21] It potentiates glycine receptor activity, which decreases motor function. [22] It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels. [23] Isoflurane also affects intracellular molecules. It inhibits plasma membrane calcium ATPases (PMCAs) which affects membrane fluidity by hindering the flow of Ca2+ (calcium ions) out across the membrane, this in turn affects neuron depolarization. [24] 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. [25]

Adverse effects

Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an irregular heartbeat. [3] Isoflurane can cause a sudden decrease in blood pressure due to dose-dependent peripheral vasodilation. This may be specially marked in hypovolemic patients. [16]

Serious side effects can include malignant hyperthermia or high blood potassium. [4] It should not be used in patients 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. [3] [4]

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. [26] Whether these concerns occur in humans is unclear. [26]

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. [27] This area is important as "some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimer's disease". [28]

Anesthetic Physical properties

Isoflurane has a Minimum alveolar concentration (MAC) of 1.15 vol %. The blood/gas partition coefficient is 1.4, and the oil/gas partition coefficient is 98.[ citation needed ] Its vapor pressure at 20 °C (68 °F) is 31.7 kilopascals (238 mmHg). [6]

It is administered as a racemic mixture of (R)- and (S)-optical isomers. [29] It is non-combustible but can give off irritable and toxic fumes when exposed to flame. [6]

History

Together with enflurane and halothane, Isoflurane began to replace the flammable ethers used in the pioneer days of surgery; this shift began in the 1940s to the 1950s. [30] Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula. [31]

Environment

The average lifetime of isoflurane in the atmosphere is 3.2 years, its global warming potential is 510 (times greater than carbon dioxide) and yearly emissions as of 2015 were 880 tons. [32] [ needs update ]

Veterinary use

Isoflurane is frequently used for veterinary anaesthesia. [33] [34]

References

  1. ↑ "Isoflurane Use During Pregnancy". Drugs.com. 2 September 2020. Retrieved 9 September 2020.
  2. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. 1 2 3 4 5 "Isoflurane 100% Inhalation Vapour, Liquid - Summary of Product Characteristics (SmPC)". (emc). 29 October 2019. Retrieved 9 September 2020.
  4. 1 2 3 4 5 6 "Forane- isoflurane inhalant". DailyMed. Retrieved 11 February 2022.
  5. 1 2 Freiermuth D, Mets B, Bolliger D, Reuthebuch O, Doebele T, Scholz M, et al. (December 2016). "Sevoflurane and Isoflurane-Pharmacokinetics, Hemodynamic Stability, and Cardioprotective Effects During Cardiopulmonary Bypass". Journal of Cardiothoracic and Vascular Anesthesia. 30 (6): 1494–1501. doi:10.1053/j.jvca.2016.07.011. PMID   27692704.
  6. 1 2 3 4 "Isoflurane". PubChem. U.S. National Library of Medicine. Retrieved 2022-04-07.
  7. ↑ 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.
  8. ↑ Aglio LS, Lekowski RW, Urman RD (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.
  9. ↑ Kliegman R, Stanton B, St Geme J, Schor NF (2015). Nelson Textbook of Pediatrics (20 ed.). Elsevier Health Sciences. p. 420. ISBN   9780323263528. Archived from the original on 2016-12-20.
  10. ↑ "Forane: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 11 February 2022.
  11. ↑ 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.
  12. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  13. ↑ Niedermeyer E, da Silva FH (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.
  14. ↑ Pauca AL, Dripps RD (July 1973). "Clinical experience with isoflurane (Forane): preliminary communication". British Journal of Anaesthesia. 45 (7): 697–703. doi: 10.1093/bja/45.7.697 . PMID   4730162.
  15. ↑ Chen Z (August 2004). "The effects of isoflurane and propofol on intraoperative neurophysiological monitoring during spinal surgery". Journal of Clinical Monitoring and Computing. 18 (4): 303–308. doi:10.1007/s10877-005-5097-5. PMID   15779842. S2CID   195331061.
  16. 1 2 Hawkley TF, Preston M, Maani CV (2022). "Isoflurane". StatPearls. PMID   30422552.
  17. ↑ "How does anesthesia work?". Scientific American . February 7, 2005. Archived from the original on May 29, 2016.
  18. ↑ 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: 279–293. doi:10.1113/jphysiol.1992.sp019086. PMC   1176079 . PMID   1326046.
  19. ↑ Jenkins A, Franks NP, Lieb WR (February 1999). "Effects of temperature and volatile anesthetics on GABA(A) receptors". Anesthesiology. 90 (2): 484–491. doi: 10.1097/00000542-199902000-00024 . PMID   9952156.
  20. ↑ 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): 569–578. doi:10.1016/S0022-3565(25)10387-X. PMID   1331405.
  21. ↑ 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): 731–743. doi:10.1038/sj.bjp.0703087. PMC   1571881 . PMID   10683198.
  22. ↑ 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". British Journal of Anaesthesia. 97 (5): 687–694. doi: 10.1093/bja/ael239 . PMID   16973644. S2CID   14269792.
  23. ↑ 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): 990–998. doi: 10.1097/00000542-199206000-00020 . PMID   1318010.
  24. ↑ Franks JJ, Horn JL, Janicki PK, Singh G (January 1995). "Halothane, isoflurane, xenon, and nitrous oxide inhibit calcium ATPase pump activity in rat brain synaptic plasma membranes". Anesthesiology. 82 (1): 108–117. doi: 10.1097/00000542-199501000-00015 . PMID   7832292. S2CID   26993898.
  25. ↑ 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): 139–144. doi: 10.1093/bja/aeq117 . PMID   20525978.
  26. 1 2 Mellon RD, Simone AF, Rappaport BA (March 2007). "Use of anesthetic agents in neonates and young children". Anesthesia and Analgesia. 104 (3): 509–520. doi: 10.1213/01.ane.0000255729.96438.b0 . PMID   17312200. S2CID   43818997. Archived from the original on 2009-03-09.
  27. ↑ Mandal, et al. (April 2009). "Isoflurane and desflurane at clinically relevant concentrations induce amyloid b-peptide oligomerization: An NMR study". Biochemical and Biophysical Research Communications. 379 (3): 716–720. Bibcode:2009BBRC..379..716M. doi:10.1016/j.bbrc.2008.12.092. PMID   19116131.
  28. ↑ Kuehn BM (April 2007). "Anesthesia-Alzheimer disease link probed". JAMA. 297 (16): 1760. doi:10.1001/jama.297.16.1760. PMID   17456811.
  29. ↑ Bu W, Pereira LM, Eckenhoff RG, Yuki K (2014-05-06). "Stereoselectivity of isoflurane in adhesion molecule leukocyte function-associated antigen-1". PLOS ONE. 9 (5): e96649. Bibcode:2014PLoSO...996649B. doi: 10.1371/journal.pone.0096649 . PMC   4011845 . PMID   24801074.
  30. ↑ Terrell RC (March 2008). "The invention and development of enflurane, isoflurane, sevoflurane, and desflurane". Anesthesiology. 108 (3): 531–533. doi: 10.1097/ALN.0b013e31816499cc . PMID   18292690.
  31. ↑ Calvey TN (August 1995). "Isomerism and anaesthetic drugs". Acta Anaesthesiologica Scandinavica. Supplementum. 106: 83–90. doi:10.1111/j.1399-6576.1995.tb04316.x. PMID   8533553. S2CID   24183480.
  32. ↑ Vollmer MK, Rhee TS, Rigby M, Hofstetter D, Hill M, Schoenenberger F, et al. (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 .
  33. ↑ Ludders JW (March 1992). "Advantages and guidelines for using isoflurane". The Veterinary Clinics of North America. Small Animal Practice. 22 (2): 328–331. doi: 10.1016/s0195-5616(92)50626-x . PMID   1585568.
  34. ↑ "Isoflurane-Vet 100% w/w Inhalation vapour, liquid". www.noahcompendium.co.uk. Retrieved 2022-04-07.
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