Isoflurane, sold under the brand name Forane among others, is a

general anesthetic General anaesthetics (or anesthetics, see spelling differences) 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 ...

. It can be used to start or maintain

anesthesia Anesthesia 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 prevention of pain), paralysis (muscle relaxation), ...

; however, other medications are often used to start anesthesia rather than isoflurane, 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 ...

. Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an

irregular heartbeat Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

. 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 is safe for the fetus, but use during a cesarean section appears to be safe. Isoflurane is a

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 (substituted) alkyl groups. A good example of an ether is t ...

. 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 or pure oxygen. Often, nitrous oxide 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 i ...

, 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 of pe ...

propofol Propofol, marketed as Diprivan, among other names, is a short-acting medication that results in a decreased level of consciousness and a lack of memory for events. Its uses include the starting and maintenance of general anesthesia, sedation f ...

Adverse effects

Isoflurane can cause a sudden decrease in blood pressure due to dose-dependent peripheral vasodilation. This may be specially marked in hypovolemic patients. Animal studies have raised safety concerns of certain general anesthetics, in particular ketamine and isoflurane, in young children. The risk of

neurodegeneration A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

was increased in combination of these agents with nitrous oxide and

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, i ...

such as midazolam. 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".

Physical properties

It is administered as a

racemic mixture In chemistry, a racemic mixture, or racemate (), is one that has equal amounts 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 racemates. ...

of (''R'')- and (''S'')-optical isomers. Isoflurane has a melting point of 48 - 48.5°

Celsius The degree Celsius is the unit of temperature on the Celsius scale (originally known as the centigrade scale outside Sweden), one of two temperature scales used in the International System of Units (SI), the other being the Kelvin scale. The ...

(118 - 119° Fahrenheit) and a boiling point of 48.5 - 49 °C (119 - 120 °F). It is non- combustible but can give off irritable and toxic fumes when exposed to flame.

Mechanism of action

Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated. Isoflurane reduces pain sensitivity ( analgesia) and relaxes muscles. Isoflurane likely binds to GABA,

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

and glycine 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 (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

calcium ATPases (PMCAs) which affects membrane fluidity by hindering the flow of Ca²⁺ ( calcium ions) out across the membrane, this in turn affects neuron depolarization. It binds to the D subunit of

ATP synthase ATP synthase is a protein that catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate (Pi). It is classified under ligases as it changes ADP by the formation ...

and NADH dehydrogenase. General anaesthesia with isoflurane reduces plasma endocannabinoid AEA concentrations, and this could be a consequence of

stress reduction Stress management is a wide spectrum of techniques and psychotherapies aimed at controlling a person's level of stress, especially chronic stress, usually for the purpose of and for the motive of improving everyday functioning. Stress produces num ...

after loss of consciousness.

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 is ...

and

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

surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...

; 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 chemical compound, compound is another compound whose molecule has the same number of atoms of each element, but with logically distinct chemical bond, b ...

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 is 510 and the yearly emissions add up to 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 agonists 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