Isoflurane, sold under the brand name Forane among others, is a halogenated ether used as a

general anesthetic General anaesthetics (or anesthetics) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of aware ...

. It can be used to start or maintain

anesthesia Anesthesia (American English) or anaesthesia (British English) is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prev ...

; however, other medications are often used to start anesthesia, due to airway irritation with isoflurane. Isoflurane is given via

inhalation Inhalation (or inspiration) happens when air or other gases enter the lungs. Inhalation of air Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...

. Isoflurane was approved for medical use in the United States in 1979. It is on the World Health Organization's List of Essential Medicines.

Medical uses

Isoflurane is always administered in conjunction with

air An atmosphere () is a layer of gases that envelop an astronomical object, held in place by the gravity of the object. A planet retains an atmosphere when the gravity is great and the temperature of the atmosphere is low. A stellar atmosph ...

or pure

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

. Often,

nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or factitious air, among others, is a chemical compound, an Nitrogen oxide, oxide of nitrogen with the Chemical formula, formula . At room te ...

is also used. Although its physical properties imply that anaesthesia can be induced more rapidly than with

halothane Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful ...

, its pungency can irritate the respiratory system, negating any possible advantage conferred by its physical properties. Thus, it is mostly used in general anesthesia as a maintenance agent after induction of general anesthesia with an intravenous agent such as

thiopentone Sodium thiopental, also known as Sodium Pentothal (a trademark of Abbott Laboratories), thiopental, thiopentone, or Trapanal (also a trademark), is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog ...

or propofol.

Mechanism of action

Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated. Isoflurane reduces pain sensitivity (

analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...

) and relaxes muscles. Isoflurane likely binds to

GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

and

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

receptors, but has different effects on each receptor. Isoflurane acts as a positive allosteric modulator of the GABA_A receptor in electrophysiology studies of neurons and recombinant receptors. 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 inhibits

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

calcium ATPases (PMCAs) which affects membrane fluidity by hindering the flow of (

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

ions) out across the membrane, this in turn affects

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

depolarization In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

. It binds to the D subunit of ATP synthase and

NADH dehydrogenase NADH dehydrogenase is an enzyme that converts nicotinamide adenine dinucleotide (NAD) from its reduced form (NADH) to its oxidized form (NAD+). Members of the NADH dehydrogenase family and analogues are commonly systematically named using the f ...

. General anaesthesia with isoflurane reduces plasma endocannabinoid AEA concentrations, and this could be a consequence of stress reduction after loss of consciousness.

Adverse effects

Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an irregular heartbeat. Isoflurane can cause a sudden decrease in blood pressure due to dose-dependent peripheral vasodilation. This may be specially marked in hypovolemic patients. Serious side effects can include malignant hyperthermia or high blood potassium. It should not be used in patients with a history of malignant hyperthermia in either themselves or their family members. It is unknown if its use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

is safe for the fetus, but use during a cesarean section appears to be safe. Animal studies have raised safety concerns of certain general anesthetics, in particular

ketamine Ketamine is a cyclohexanone-derived general anesthetic and NMDA receptor antagonist with analgesic and hallucinogenic properties, used medically for anesthesia, depression, and pain management. Ketamine exists as its S- (esketamine) a ...

and isoflurane, in young children. The risk of

neurodegeneration A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their cell death, death. Neurodegenerative diseases include amyotrophic lateral sc ...

was increased in combination of these agents with nitrous oxide and

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat co ...

such as

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia, premedication before surgical anesthesia, and procedural sedation, and to treat psychomotor agitation, severe agitation. It induces ...

. Whether these concerns occur in humans is unclear.

Elderly

Biophysical studies using 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".

Anesthetic Physical properties

Isoflurane has a

Minimum alveolar concentration Minimum alveolar concentration or MAC is the concentration, often expressed as a percentage by volume, of a vapour in the alveoli of the lungs that is needed to prevent movement (motor response) in 50% of subjects in response to surgical (pain) sti ...

(MAC) of 1.15 vol %. The blood/gas partition coefficient is 1.4, and the oil/gas partition coefficient is 98. Its vapor pressure at is . It is administered as a

racemic mixture In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

of (''R'')- and (''S'')-optical isomers. It is non-

combustible A combustible material is a material that can burn (i.e., sustain a flame) in air under certain conditions. A material is flammable if it ignites easily at ambient temperatures. In other words, a combustible material ignites with some effort a ...

but can give off irritable and

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

fumes when exposed to flame.

History

Together with

enflurane Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether) is a halogenated ether. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s but ...

and

, Isoflurane began to replace the flammable ethers used in the pioneer days of

surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...

; this shift began in the 1940s to the 1950s. Its name comes from being a

structural isomer In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a compound is a compound that contains the same number and type of atoms, but with a different connectivity (i.e. arrangement of bonds) between them. The ...

of enflurane, hence they have the same empirical formula.

Environment

The average lifetime of isoflurane in the atmosphere is 3.2 years, its

global warming potential Global warming potential (GWP) is a measure of how much heat a greenhouse gas traps in the atmosphere over a specific time period, relative to carbon dioxide (). It is expressed as a multiple of warming caused by the same mass of carbon dioxide ( ...

is 510 (times greater than carbon dioxide) and yearly emissions as of 2015 were 880 tons.

Veterinary use

Isoflurane is frequently used for veterinary anaesthesia.

References

External links

* - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether * - 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether as an anesthetic agent {{Portal bar, Medicine 5-HT3 receptor positive allosteric modulators Ethers GABAA receptor positive allosteric modulators General anesthetics Glycine receptor agonists Nicotinic antagonists NMDA receptor antagonists Organochlorides Organofluorides World Health Organization essential medicines Fluranes Wikipedia medicine articles ready to translate Trifluoromethyl compounds Difluoromethoxy compounds