Isoflurane

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Isoflurane
Isoflurane.svg
Isoflurane-3D-vdW.png
Clinical data
Trade names Forane, others
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Pregnancy
category
Routes of
administration
Inhalation
ATC code
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Legal status
Identifiers
  • (RS)-2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane
    OR
    (RS)-1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
CAS Number
PubChem CID
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DrugBank
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ECHA InfoCard 100.043.528 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C3H2ClF5O
Molar mass 184.49 g·mol−1
3D model (JSmol)
  • FC(F)(F)C(Cl)OC(F)F
  • InChI=1S/C3H2ClF5O/c4-1(3(7,8)9)10-2(5)6/h1-2H Yes check.svgY
  • Key:PIWKPBJCKXDKJR-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Isoflurane, sold under the brand name Forane among others, is a general anesthetic. [4] It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia, due to airway irritation with isoflurane. [3] [5] Isoflurane is given via inhalation. [4]

Contents

Side effects of isoflurane include a decreased ability to breathe (respiratory depression), low blood pressure, and an irregular heartbeat. [3] Serious side effects can include malignant hyperthermia or high blood potassium. [4] It should not be used in patients with a history of malignant hyperthermia in either themselves or their family members. [3] It is unknown if its use during pregnancy is safe for the fetus, but use during a cesarean section appears to be safe. [3] [4] Isoflurane is a halogenated ether. [6]

Isoflurane was approved for medical use in the United States in 1979. [4] [7] It is on the World Health Organization's List of Essential Medicines. [8] [9]

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, [10] 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 or propofol. [11] [12] [13]

Mechanism of action

Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated. [14] Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamate and glycine receptors, but has different effects on each receptor. Isoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors. [15] [16] [17] [18] It potentiates glycine receptor activity, which decreases motor function. [19] It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels. [20] Isoflurane also affects intracellular molecules. It inhibits plasma membrane 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. [21] [22] It binds to the D subunit of ATP synthase and NADH dehydrogenase.

General anaesthesia with isoflurane reduces plasma endocannabinoid AEA concentrations, and this could be a consequence of stress reduction after loss of consciousness. [23]

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. [13]

Animal studies have raised safety concerns of certain general anesthetics, in particular ketamine and isoflurane, in young children. The risk of neurodegeneration was increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam. [24] Whether these concerns occur in humans is unclear. [24]

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. [25] This area is important as "some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimer's disease". [26]

Physical properties

Molecular weight 184.5g/mol [27]
Boiling point (at 1 atm):48.5 °C [27]
Density (at 25 °C):1.496 g/mL [27]
MAC  :1.15 vol %
Vapor pressure:238 mmHg 31.7 kPa (at 20 °C)
295 mmHg39.3 kPa(at 25 °C)
367 mmHg48.9 kPa(at 30 °C)
450 mmHg60.0 kPa(at 35 °C) [27]
Water solubility 13.5 mM(at 25 °C) [28]
Blood:gas partition coefficient:1.4
Oil:gas partition coefficient:98

It is administered as a racemic mixture of (R)- and (S)-optical isomers. [29] Isoflurane has a boiling point of 48.5–49 °C (119.3–120.2 °F). [27] It is non-combustible but can give off irritable and toxic fumes when exposed to flame. [27]

History

Together with enflurane and halothane, Isoflurane began to replace the flammable ethers used in the pioneer days of surgery; this shift began in the 1940s to the 1950s. [30] Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula. [31]

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. [32]

Veterinary use

Isoflurane is frequently used for veterinary anaesthesia. [33] [34]

Related Research Articles

General anaesthetics 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 that causes lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. General anaesthetics do not act as analgesics and should also not be confused with sedatives. General anaesthetics are a structurally diverse group of compounds whose mechanisms encompass multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.

<span class="mw-page-title-main">Halothane</span> General anaesthetic

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 in those who are difficult to intubate. It is given by inhalation.

<span class="mw-page-title-main">Sevoflurane</span> Inhalational anaesthetic

Sevoflurane, sold under the brand name Sevorane, among others, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflurane, it is the volatile anesthetic with the fastest onset. While its offset may be faster than agents other than desflurane in a few circumstances, its offset is more often similar to that of the much older agent isoflurane. While sevoflurane is only half as soluble as isoflurane in blood, the tissue blood partition coefficients of isoflurane and sevoflurane are quite similar. For example, in the muscle group: isoflurane 2.62 vs. sevoflurane 2.57. In the fat group: isoflurane 52 vs. sevoflurane 50. As a result, the longer the case, the more similar will be the emergence times for sevoflurane and isoflurane.

<span class="mw-page-title-main">Cyclopropane</span> Chemical compound

Cyclopropane is the cycloalkane with the molecular formula (CH2)3, consisting of three methylene groups (CH2) linked to each other to form a triangular ring. The small size of the ring creates substantial ring strain in the structure. Cyclopropane itself is mainly of theoretical interest but many of its derivatives - cyclopropanes - are of commercial or biological significance.

<span class="mw-page-title-main">Propofol</span> Intravenous medication used in anesthesia

Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was approved under the brand name Diprivan. Numerous generic versions have since been released. Intravenous administration is used to induce unconsciousness after which anesthesia may be maintained using a combination of medications. It is manufactured as part of a sterile injectable emulsion formulation using soybean oil and lecithin, giving it a white milky coloration.

<span class="mw-page-title-main">Theories of general anaesthetic action</span> How drugs induce reversible suppression of consciousness

A general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthetist/anesthesiologist to induce or maintain general anaesthesia to facilitate surgery.

<span class="mw-page-title-main">Anaesthetic machine</span> Medical device to supply a mix of life-support and anaesthetic gases

An anaesthetic machine or anesthesia machine is a medical device used to generate and mix a fresh gas flow of medical gases and inhalational anaesthetic agents for the purpose of inducing and maintaining anaesthesia.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<span class="mw-page-title-main">Desflurane</span> Chemical compound

Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane, and isoflurane, it is a racemic mixture of (R) and (S) optical isomers (enantiomers). Together with sevoflurane, it is gradually replacing isoflurane for human use, except in economically undeveloped areas, where its high cost precludes its use. It has the most rapid onset and offset of the volatile anesthetic drugs used for general anesthesia due to its low solubility in blood.

<span class="mw-page-title-main">Malignant hyperthermia</span> Medical condition

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. Complications can include muscle breakdown and high blood potassium. Most people who are susceptible to MH are generally unaffected when not exposed to triggering agents.

<span class="mw-page-title-main">Chloralose</span> Chemical compound

Chloralose is an avicide, and a rodenticide used to kill mice in temperatures below 15 °C. It is also widely used in neuroscience and veterinary medicine as an anesthetic and sedative. Either alone or in combination, such as with urethane, it is used for long-lasting, but light anesthesia.

<span class="mw-page-title-main">Enflurane</span> Chemical compound

Enflurane 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.

<span class="mw-page-title-main">Inhalational anesthetic</span> Volatile or gaseous anesthetic compound delivered by inhalation

An inhalational anesthetic is a chemical compound possessing general anesthetic properties that is delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporiser and an anesthetic delivery system. Agents of significant contemporary clinical interest include volatile anesthetic agents such as isoflurane, sevoflurane and desflurane, as well as certain anesthetic gases such as nitrous oxide and xenon.

<span class="mw-page-title-main">Halogenated ether</span> Subcategory of ether used in anesthesiology

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 the solvent diethyl ether. What differentiates a halogenated ether from other types of ethers is the substitution (halogenation) of one or more hydrogen atoms with a halogen atom. Halogen atoms include fluorine, chlorine, bromine, and iodine.

Minimum alveolar concentration or MAC is the concentration, often expressed as a percentage by volume, of a vapour in the alveoli of the lungs that is needed to prevent movement in 50% of subjects in response to surgical (pain) stimulus. MAC is used to compare the strengths, or potency, of anaesthetic vapours. The concept of MAC was first introduced in 1965.

<span class="mw-page-title-main">Methoxyflurane</span> Chemical compound

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 rapid and of a short duration. Use is only recommended with direct medical supervision.

<span class="mw-page-title-main">Flurothyl</span> Chemical compound

Flurothyl (Indoklon) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether, but having the opposite effects, acting as a stimulant and convulsant. A clear and stable liquid, it has a mild ethereal odor whose vapors are non-flammable. It is excreted from the body by the lungs in an unchanged state.

Emergence delirium is a condition in which emergence from general anesthesia is accompanied by psychomotor agitation. Some see a relation to pavor nocturnus while others see a relation to the excitement stage of anesthesia.

Blood–gas partition coefficient, also known as Ostwald coefficient for blood–gas, is a term used in pharmacology to describe the solubility of inhaled general anesthetics in blood. According to Henry's law, the ratio of the concentration in blood to the concentration in gas that is in contact with that blood, when the partial pressure in both compartments is equal, is nearly constant at sufficiently low concentrations. The partition coefficient is defined as this ratio and, therefore, has no units. The concentration of the anesthetic in blood includes the portion that is undissolved in plasma and the portion that is dissolved. The more soluble the inhaled anesthetic is in blood compared to in air, the more it binds to plasma proteins in the blood and the higher the blood–gas partition coefficient.

Nicholas Peter Franks FRS FRSB has been Professor of Biophysics and Anaesthetics at Imperial College London since 1993. His research focuses on how general anaesthetics act at the cell and molecular levels as well as with neuronal networks. Franks holds patents on use of xenon gas as a neuroprotectant and has published research on the use of the anesthetic properties of xenon.

References

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