|Systematic (IUPAC) name|
1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
|Mol. mass||184.5 g/mol|
| (what is this?) |
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 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, 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.
Anesthesia gases used globally contribute the equivalent of one million cars to global warming. Isoflurane is a greenhouse gas, with a global warming potential of 1401. One tonne of sevoflurane emitted is equivalent to 1401 tonnes of carbon dioxide in the atmosphere. Taking into account the different amounts typically used in 1 hour of anesthesia (1 minimal alveolar concentration-hour), isoflurane causes 2.2 times the global warming of sevoflurane, but is much less damaging than desflurane, which causes 26.8 times the damage.
|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)|
|Blood:Gas Partition coefficient:||1.4|
|Oil:Gas Partition coefficient:||98|
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.
Concerns have been raised as to the safety of certain general anesthetics, in particular ketamine and isoflurane in neonates and young children due to significant neurodegeneration. The risk of neurodegeneration is increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam. This has led to the FDA and other bodies to take steps to investigate these concerns.
Concerns exist with regard to long-lasting postoperative cognitive decline in the elderly and its association with anesthesia. Exposure of cultured human cells to isoflurane has been reported to induce apoptosis and accumulation and aggregation of amyloid beta protein, and is proposed to be the cause of postoperative cognitive decline (PCD) which has been described as a subtle form of dementia. The elderly are the most vulnerable to PCD. The study, however, was based on in vitro research; further in vivo research is needed to determine the relevance of these findings in clinical practice and to improve the safety of anesthesia. An animal model has shown anesthesia with isoflurane increases amyloid pathology in mice models of Alzheimer's disease, and has been shown to induce cognitive decline in mice.
Biophysical studies using state-of-the-art NMR spectroscopy has provided molecular details 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".