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 no longer in common use.
Enflurane is a structural
isomer of
isoflurane. It vaporizes readily, but is a liquid at room temperature.
Physical properties
Side effects
Clinically, enflurane produces a dose-related depression of
myocardial
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
contractility
Contractility refers to the ability for self-contraction, especially of the muscles or similar active biological tissue
*Contractile ring in cytokinesis
*Contractile vacuole
*Muscle contraction
**Myocardial contractility
*See contractile cell for ...
with an associated decrease in myocardial oxygen consumption. Between 2% and 5% of the inhaled dose is oxidised in the liver, producing
fluoride ions and difluoromethoxy-difluoroacetic acid. This is significantly higher than the metabolism of its structural isomer
isoflurane.
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 synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
, 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 electrica ...
. 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 anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complica ...
.
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
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are c ...
, 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
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 ...
, and
5-HT3 receptors,
and as a
negative 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 t ...
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.
There are several types of glutamatergic ...
,
kainate
Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervo ...
, and
NMDA receptors,
as well as of
nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
s.
Occupational safety
The U.S.
National Institute for Occupational Safety and Health
The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...
(NIOSH) has set a
recommended exposure limit
A recommended exposure limit (REL) is an occupational exposure limit that has been recommended by the United States National Institute for Occupational Safety and Health. The REL is a level that NIOSH believes would be protective of worker safet ...
(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
Central nervous system (CNS) depression is a physiological state that can result in a decreased rate of breathing, decreased heart rate, and loss of consciousness possibly leading to coma or death.
It is the result of inhibited or suppressed brai ...
,
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 ...
,
anesthesia,
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.
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 ...
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{{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