Isoflurane-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 and 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. It is on the WHO Model List of Essential
Medicines, the most important medications needed in a health system.
Adverse effects 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.
= Use with the elderly= Concerns exist with regard to the
relationship between administration of isoflurane and postoperative cognitive
dysfunction, 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 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".
Physical properties Mechanism of action
Similar to many general anesthetics, the exact mechanism of the action has not
been clearly delineated. Isoflurane reduces pain sensitivity 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.
References External links
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