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.
Concerns have been raised as to the safety of certain general anesthetics, in particular ketamine and isoflurane in infants 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 the FDA and other bodies to take steps to investigate these concerns.
Concerns exist with regard to the relationship between administration of isoflurane and postoperative cognitive dysfunction (POCD), for which the elderly are especially vulnerable. Exposure of cultured human cells to isoflurane has been reported to induce apoptosis and accumulation and aggregation of amyloid beta protein, and may contribute to POCD, but this remains unknown. The study 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. Memory impairment following isoflurane anesthesia in mice can be prevented by pre-administering the GABA(A)α5 subunit inverse agonist L-655,708. It is not yet known if the drug can help prevent POCD in humans.
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".
Similar to many general anesthetics, how isoflurane works remains incompletely understood. Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamates 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.
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