Isoflurane


Isoflurane

drugbox
IUPAC_name = 2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane






CAS_number = 26675-46-7
ATC_prefix = N01
ATC_suffix = AB06
ATC_supplemental =
PubChem = 3763
DrugBank = APRD00212
C=3 | H=2 | Cl=1 | F=5 | O=1
molecular_weight = 184.5 g/mol
bioavailability =
protein_bound =
metabolism =
elimination_half-life =
pregnancy_category =
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Isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane) 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 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 means that anaesthesia can be induced more rapidly than with halothane, 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 non-flammable.

A major advantage of isoflurane is that the patent covering its use has expired, therefore it is very economical to use.

Physical properties

Mechanism of action

Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. The mechanism by which general anesthetics produce the anesthetic state is not clearly understood but likely involves interactions with multiple receptor sites to interfere with synaptic transmission. Isoflurane binds to GABA receptors, glutamate receptors and glycine receptors, and also inhibits conduction in activated potassium channels. Glycine inhibition helps to inhibit motor function, while bonding to glutamate receptors mimics the effects of NMDA. It activates calcium ATPase through an increase in membrane fluidity, and binds to the D subunit of ATP synthase and NADH dehydrogenase. In addition, a number of general anesthetics attenuate gap junction communication, which could contribute to anesthetic action.

Possible link to cognitive decline

Isoflurane exposure has been shown to induce cognitive decline in mice. [cite journal
title=Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics
author= S. L. Bianchi, T. Tran, C. Liu, S. Lin, Y. Li, J. M. Keller, R. G. Eckenhoff, M. F. Eckenhoff
journal=Neurobiology of Aging
volume=28
issue=in press
pages=in press
year=2007
doi= 10.1016/j.neurobiolaging.2007.02.009
] Exposure of cultured human cells to isoflurane has been reported to induce apoptosis and accumulation and aggregation of amyloid beta protein. [cite journal
title=The Inhalation Anesthetic Isoflurane Induces a Vicious Cycle of Apoptosis and Amyloid β-Protein Accumulation
author= Z. Xie, Y. Dong, U. Maeda, R. D. Moir, W. Xia, D. J. Culley, G. Crosby, R. E. Tanzi
journal=Journal of Neuroscience
volume=27
issue=6
pages=1247–1254
year=2007
doi= 10.1523/JNEUROSCI.5320-06.2007
pmid=17287498
] Further research will be required to establish whether or not clinical exposure to isoflurane leads to dementia (Alzheimer's disease). [cite journal
title=Uncomplicated general anesthesia in the elderly results in cognitive decline: Does cognitive decline predict morbidity and mortality?
author= M. C. Lewis, I. Nevoa, M. A. Paniaguaa, A. Ben-Aric, E. Prettoa, S. Eisdorfera, E. Davidsona, I. Matotc, C. Eisdorfer
journal=Medical Hypotheses
volume=68
issue=3
pages=484–492
year=2007
doi= 10.1016/j.mehy.2006.08.030
] [cite news
url=http://www.healthfinder.gov/news/newsstory.asp?docID=600964
title=Anesthetic Linked to Alzheimer's Risk
date=15 January 2007
publisher= HealthDay News
accessdate=2007-08-08
first=Steven
last=Reinberg
]

References

External links

* [http://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/CPS-%20Monographs/CPS-%20(General%20Monographs-%20F)/FORANE.html Rx Med]


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