Isoflurane
Encyclopedia
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
, 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.
, glutamates and glycine
receptors, but has different effects on each receptor. It inhibits glycine receptor activity, which decreases motor function. It increases receptor activity in the NMDA
glutamate receptor subtype. Isoflurane inhibits conduction in activated potassium channel
s. 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
.
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.
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".
Halogenated ether
A halogenated ether is a subcategory of a larger group of chemicals known as ethers. An ether is an organic chemical that contains an ether group — an oxygen atom connected to two alkyl groups...
used for inhalational anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
. Together with enflurane
Enflurane
Enflurane is a halogenated ether that was commonly used for inhalational anesthesia during the 1970s and 1980s. Developed by Ross Terrell in 1963, it was first used clinically in 1966....
and halothane
Halothane
Halothane is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and...
, it replaced the flammable ethers
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
used in the pioneer days of surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
. 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
Sevoflurane
Sevoflurane , also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology...
, desflurane
Desflurane
Desflurane is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane and isoflurane, it is a racemic mixture of and optical isomers...
and the intravenous anaesthetic propofol
Propofol
Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
. Isoflurane is still frequently used for veterinary anaesthesia.
Isoflurane is always administered in conjunction with air and/or pure oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
. Often nitrous oxide
Nitrous oxide
Nitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...
is also used. Although its physical properties imply that anaesthesia can be induced more rapidly than with halothane
Halothane
Halothane is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and...
, 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
Propofol
Propofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
. It vaporizes readily, but is a liquid at room temperature. It is completely nonflammable.
Physical properties
| Molecular weight | 184.5g/mol | ||
| Boiling point Boiling point The boiling point of an element or a substance is the temperature at which the vapor pressure of the liquid equals the environmental pressure surrounding the liquid.... (at 1 atm Atmosphere (unit) The standard atmosphere is an international reference pressure defined as 101325 Pa and formerly used as unit of pressure. For practical purposes it has been replaced by the bar which is 105 Pa... ): |
48.5 °C | ||
| Density Density The mass density or density of a material is defined as its mass per unit volume. The symbol most often used for density is ρ . In some cases , density is also defined as its weight per unit volume; although, this quantity is more properly called specific weight... (at 25 °C): |
1.496 g/mL | ||
| MAC Minimum alveolar concentration Minimum alveolar concentration or MAC is a concept used to compare the strengths, or potency, of anaesthetic vapours; in simple terms, it is defined as the concentration of the vapour in the lungs that is needed to prevent movement in 50% of subjects in response to surgical stimulus... : |
1.15 vol % | ||
| Vapor pressure Vapor pressure Vapor pressure or equilibrium vapor pressure is the pressure of a vapor in thermodynamic equilibrium with its condensed phases in a closed system. All liquids have a tendency to evaporate, and some solids can sublimate into a gaseous form... : |
238 mmHg Torr The torr is a non-SI unit of pressure with the ratio of 760 to 1 standard atmosphere, chosen to be roughly equal to the fluid pressure exerted by a millimetre of mercury, i.e., a pressure of 1 torr is approximately equal to 1 mmHg... |
31.7 kPa Pascal (unit) The pascal is the SI derived unit of pressure, internal pressure, stress, Young's modulus and tensile strength, named after the French mathematician, physicist, inventor, writer, and philosopher Blaise Pascal. It is a measure of force per unit area, defined as one newton per square metre... |
(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 Solubility Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on... |
Insoluble | ||
| Blood:Gas Partition coefficient: | 1.4 | ||
| Oil:Gas Partition coefficient: | 98 |
Mechanism of action
Similar to many general anesthetics, how isoflurane works remains incompletely understood. Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABAGabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
, glutamates and glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
receptors, but has different effects on each receptor. It inhibits glycine receptor activity, which decreases motor function. It increases receptor activity in the NMDA
NMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...
glutamate receptor subtype. Isoflurane inhibits conduction in activated potassium channel
Potassium channel
In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...
s. Isoflurane also affects intracellular molecules. It activates calcium ATPase
Calcium ATPase
Calcium ATPase is a form of P-ATPase that transfers calcium after a muscle has contracted. The calcium ATPase are:*Plasma membrane Ca2+ ATPase *Sarcoplasmic reticulum Ca2+ ATPase - Plasma membrane Ca2+ ATPase :...
by increasing membrane fluidity. It binds to the D subunit of ATP synthase
ATP synthase
right|thumb|300px|Molecular model of ATP synthase by X-ray diffraction methodATP synthase is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate . ATP is the most commonly used "energy currency" of cells from most organisms...
and NADH dehydrogenase
NADH dehydrogenase
NADH dehydrogenase is an enzyme located in the inner mitochondrial membrane that catalyzes the transfer of electrons from NADH to coenzyme Q...
.
Toxicity
Concerns have been raised as to the safety of certain general anesthetics, in particular ketamineKetamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
and isoflurane in neonates and young children due to significant neurodegeneration
Neurodegeneration
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...
. The risk of neurodegeneration is increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam
Midazolam
Midazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...
. This has led to the FDA and other bodies to take steps to investigate these concerns.
Elderly
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 apoptosisApoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
and accumulation and aggregation of amyloid beta
Amyloid beta
Amyloid beta is a peptide of 36–43 amino acids that is processed from the Amyloid precursor protein. While it is most commonly known in association with Alzheimer's disease, it does not exist specifically to cause disease...
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
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
research; further in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
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".