Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether) 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 ...
. Developed by
Ross Terrell Ross or ROSS may refer to:
People
* Clan Ross, a Highland Scottish clan
* Ross (name), including a list of people with the surname or given name Ross, as well as the meaning
* Earl of Ross, a peerage of Scotland
Places
* RoSS, the Republic of Sout ...
in 1963, it was first used clinically in 1966. It was increasingly used for inhalational
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), ...
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 formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers.
Iso ...
of
isoflurane
Isoflurane, sold under the brand name Forane among others, is a general anesthetic. 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 w ...
. It vaporizes readily, but is a liquid at room temperature.
Physical properties
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, monatomic anion of fluorine, with the chemical formula (also written ), whose salts are typically white or colorless. Fluoride salts typ ...
ions and difluoromethoxy-difluoroacetic acid. This is significantly higher than the metabolism of its structural isomer
isoflurane
Isoflurane, sold under the brand name Forane among others, is a general anesthetic. 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 w ...
.
Enflurane also lowers the threshold for
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, and should especially not be used on people with
epilepsy
Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
. Like all potent inhalation anaesthetic agents it is a known trigger of
malignant hyperthermia
Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during General anaesthesia, general anesthesia, among those who are susceptible. Symptoms include tetany, muscle rigidity, 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
Methoxyflurane, sold under the brand name Penthrox among others, is an inhaled medication primarily used to reduce pain following trauma. It may also be used for short episodes of pain as a result of medical procedures. Onset of pain relief is ...
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
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
seemed unusual if seen at all.
Pharmacology
The exact mechanism of the action of general anaesthetics
has not been delineated. Enflurane 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
GABAA,
glycine, and
5-HT3 receptors,
and as a
negative allosteric modulator of the
AMPA,
kainate, and
NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
s,
as well as of
nicotinic acetylcholine receptors.
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/m
3) over a 60-minute period. Symptoms of occupational exposure to enflurane include eye irritation,
central nervous system depression,
analgesia,
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), ...
,
convulsions
A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...
, and
respiratory depression
Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...
.
References
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Pharmacodynamics
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...
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, list1 =
{{GABAA receptor positive modulators
{{Glycine receptor modulators
{{Ionotropic glutamate receptor modulators
{{Nicotinic acetylcholine receptor modulators
{{Serotonin receptor modulators
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