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; however, other medications are often used to start anesthesia rather than isoflurane, due to airway irritation with isoflurane. Isoflurane is given via inhalation. Side effects of isoflurane include a decreased ability to breathe (respiratory depression),

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

, and an irregular heartbeat. Serious side effects can include

malignant hyperthermia Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complica ...

high blood potassium Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...

. 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 develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

is safe for the fetus, but use during a

cesarean section Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or ...

appears to be safe. Isoflurane is a halogenated ether. Isoflurane was approved for medical use in the United States in 1979. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

Isoflurane is always administered in conjunction with

air The atmosphere of Earth is the layer of gases, known collectively as air, retained by Earth's gravity that surrounds the planet and forms its planetary atmosphere. The atmosphere of Earth protects life on Earth by creating pressure allowing f ...

or pure

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...

. Often,

nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has ...

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 p ...

or propofol.

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 Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ...

and isoflurane, in young children. The risk of neurodegeneration was increased in combination of these agents with nitrous oxide and benzodiazepines such as

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of ...

. Whether these concerns occur in humans is unclear.

Elderly

Biophysical studies using

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...

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 of (''R'')- and (''S'')-optical isomers. Isoflurane has a melting point of 48 - 48.5° Celsius (118 - 119°

Fahrenheit The Fahrenheit scale () is a temperature scale based on one proposed in 1724 by the physicist Daniel Gabriel Fahrenheit (1686–1736). It uses the degree Fahrenheit (symbol: °F) as the unit. Several accounts of how he originally defined hi ...

) and a boiling point of 48.5 - 49 °C (119 - 120 °F). It is non-

combustible A combustible material is something that can burn (i.e., ''combust'') in air. A combustible material is flammable if it ignites easily at ambient temperatures. In other words, a combustible material ignites with some effort and a flammable mat ...

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 subs ...

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 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 professional ...

) and relaxes muscles. Isoflurane likely binds to GABA, glutamate 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 ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...

receptors, but has different effects on each receptor. Isoflurane acts as a

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

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 ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...

glutamate receptor subtypes. Isoflurane inhibits conduction in activated

potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of c ...

s. Isoflurane also affects intracellular molecules. It inhibits plasma membrane

calcium ATPase Ca2+ ATPase is a form of P-ATPase that transfers calcium after a muscle has contracted. The two kinds of calcium ATPase are: *Plasma membrane Ca2+ ATPase (PMCA) *Sarcoplasmic reticulum Ca2+ ATPase (SERCA) Plasma membrane Ca2+ ATPase (PMCA) P ...

s (PMCAs) which affects membrane fluidity by hindering the flow of Ca²⁺ (

calcium Calcium is a chemical element with the 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 t ...

ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

s) out across the membrane, this in turn affects

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

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

. 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 for ...

. General anaesthesia with isoflurane reduces plasma

endocannabinoid Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

AEA concentrations, and this could be a consequence of stress reduction after

loss of consciousness Loss may refer to: Arts, entertainment, and media Music * ''Loss'' (Bass Communion album) (2006) * ''Loss'' (Mull Historical Society album) (2001) *"Loss", a song by God Is an Astronaut from their self-titled album (2008) * Losses "(Lil Tjay son ...

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 In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be ...

used in the pioneer days of surgery; this shift began in the 1940s to the 1950s. Its name comes from being a structural isomer of enflurane, hence they have the same

empirical formula In chemistry, the empirical formula of a chemical compound is the simplest whole number ratio of atoms present in a compound. A simple example of this concept is that the empirical formula of sulfur monoxide, or SO, would simply be SO, as is the ...

Environment

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

global warming potential Global warming potential (GWP) is the heat absorbed by any greenhouse gas in the atmosphere, as a multiple of the heat that would be absorbed by the same mass of carbon dioxide (). GWP is 1 for . For other gases it depends on the gas and the time ...

is 510 and the yearly emissions add up to 880 tons.

Veterinary use

Isoflurane is frequently used for

veterinary anaesthesia Veterinary anesthesia is anesthesia performed on non-human animals by a veterinarian or a Registered Veterinary Technician. Anesthesia is used for a wider range of circumstances in animals than in people, due to animals' inability to cooperate with ...

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