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 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 ...

during the 1970s and 1980s but is no longer in common use. Enflurane is a structural

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

of isoflurane. It vaporizes readily, but is a liquid at room temperature.

Physical properties

Pharmacology

The exact mechanism of the action of general anaesthetics has not been delineated. Enflurane acts as a positive allosteric modulator of the GABA_A,

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 ...

, and 5-HT₃ receptors, and as a negative allosteric modulator of the

AMPA α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate Glutamic acid (symbol Glu or E; kn ...

, kainate, and

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

s, as well as of

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...

Side effects

Clinically, enflurane produces a dose-related depression of myocardial contractility with an associated decrease in myocardial oxygen consumption. Between 2% and 5% of the inhaled dose is oxidised in the liver, producing

fluoride Fluoride (). According to this source, is a possible pronunciation in British English. is an Inorganic chemistry, inorganic, Monatomic ion, monatomic Ion#Anions and cations, anion of fluorine, with the chemical formula (also written ), whose ...

ions and difluoromethoxy-difluoroacetic acid. This is significantly higher than the metabolism of its structural isomer isoflurane. Enflurane also lowers the threshold for

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

, and should especially not be used on people with

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

. Like all potent inhalation anaesthetic agents it is a known trigger of malignant hyperthermia. Like the other potent inhalation agents it relaxes the uterus in pregnant women which is associated with more blood loss at delivery or other procedures on the gravid uterus. The obsolete (as an anaesthetic) agent methoxyflurane had a nephrotoxic effect and caused acute kidney injury, usually attributed to the liberation of fluoride ions from its metabolism. Enflurane is similarly metabolised but the liberation of fluoride results in a lower plasma level and enflurane related kidney failure seemed unusual if seen at all.

Occupational safety

The U.S. National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) for exposure to waste anaesthetic gas of 2 ppm (15.1 mg/m³) over a 60-minute period. Symptoms of occupational exposure to enflurane include eye irritation,

central nervous system depression Central nervous system depression (or CNS depression) is a nervous system disorder characterized by a severely impaired physiological state in which patients may exhibit decreased rate of breathing, decreased heart rate, and loss of consciousnes ...

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 ...

, convulsions, and respiratory depression.

References

{{Authority control 5-HT3 agonists AMPA receptor antagonists NMDA receptor antagonists Kainate receptor antagonists General anesthetics Ethers Organochlorides Organofluorides GABAA receptor positive allosteric modulators Nicotinic antagonists Glycine receptor agonists Fluranes Difluoromethoxy compounds