Isoflurane

Isoflurane
Clinical data
Trade names Forane
ATC code N01AB06 (WHO)
Identifiers
CAS Number 26675-46-7 YesY
PubChem (CID) 3763
IUPHAR/BPS 2505
DrugBank DB00753 N
ChemSpider 3631 YesY
UNII CYS9AKD70P YesY
KEGG D00545 YesY
ChEBI CHEBI:6015 YesY
ChEMBL CHEMBL1256 YesY
ECHA InfoCard 100.043.528
Chemical and physical data
Formula C3H2ClF5O
Molar mass 184.5 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Isoflurane is a halogenated ether used for inhalational anesthesia. 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. It is a racemic mixture of (R)- and (S)-optical isomers. Its use in human medicine is now starting to decline, being replaced with sevoflurane, desflurane, and the intravenous anaesthetic propofol. Isoflurane is still frequently used for veterinary anaesthesia.

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,[1] its pungency can irritate the respiratory system, negating this theoretical advantage conferred by its physical properties. It is usually used to maintain a state of general anesthesia that has been induced with another drug, such as thiopentone or propofol. It vaporizes readily, but is a liquid at room temperature. It is completely nonflammable.

It is on the WHO Model List of Essential Medicines, the most important medications needed in a health system.[2]

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.[3] Whether these concerns occur in humans is unclear.[3]

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]

Biophysical studies using state-of-the-art 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".[5]

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)[6]
Blood:gas partition coefficient: 1.4
Oil:gas partition coefficient: 98

Mechanism of action

Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated.[7] Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamate and glycine receptors, but has different effects on each receptor. It potentiates glycine receptor activity, which decreases motor function. It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels. 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.

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.[8]

References

  1. ↑ 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.
  2. ↑ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. p. 6. Retrieved 22 April 2014.
  3. 1 2 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.
  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. PMID 17141964.
  5. ↑ Kuehn, BM. (Apr 2007). "Anesthesia-Alzheimer disease link probed". JAMA. 297 (16): 1760. doi:10.1001/jama.297.16.1760. PMID 17456811.
  6. ↑ The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR spectroscopy. Seto T, Mashimo T, Yoshiya I, Kanashiro M, Taniguchi Y., PMID 1391078
  7. ↑ "How does anesthesia work?". Scientific American. February 7, 2005.
  8. ↑ 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. doi:10.1002/2014GL062785.
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