Description
Sevoflurane is a rapidly acting, potent inhalation anesthetic with rapid uptake and
and elimination. While somewhat less potent than halothane, sevoflurane does not
induce arrhythmias and reportedly has no effect on renal function.
Description
Sevoflurane is a halogenated ether with anesthetic properties. It enhances the activity of GABA
A and glycine receptors and inhibits the activity of nicotinic acetylcholine receptors (nAChRs) and glutamate receptors. Sevoflurane enhances the responses of α
2β
1 subunit-containing GABA
A and α
1 subunit-containing glycine receptors at submaximal agonist concentrations in HEK293 cells (EC
50s = 0.45 and 0.36 mM, respectively). Sevoflurane (360 μM) also increases the amplitude of GABA
A receptor responses to GABA stimulation for receptors with an α
1β
2γ
2 subunit composition. It inhibits binding of the high affinity nicotinic agonist epibatidine to nAChRs in mouse brain membranes (IC
50 = 0.77 mM). Formulations containing sevoflurane have been used in the induction and maintenance of general anesthesia.
Chemical Properties
Clear, colourless, volatile liquid.
Uses
1,1,1,3,3,3-Hexafluoro-2-(fluoromethoxy)propane is an volatile anesthetic which inhibited activation of inflammatory neutrophil and granulocyte in human blood during simulated extracorporeal circulati
on.
Uses
Fluoromethyl 1,1,1,3,3,3-hexafluoroisopropyl ether is a volatile anesthetic, which inhibits the activation of inflammatory neutrophil and granulocyte in human blood during simulated extracorporeal circulation. It also serves as an antibacterial and used as an inhalational anaesthetic for induction and maintenance of general anesthesia. Further, it finds application in anesthesia of children and infants to make them asleep for surgery. In addition to this, it is used in veterinary medicine.
Definition
ChEBI: An ether compound having fluoromethyl and 1,1,1,3,3,3-hexafluoroisopropyl as the two alkyl groups.
Manufacturing Process
164 g (2.31 mole) of chlorine is slowly bubbled into a flask containing 370 g
(2.03 mole) of methyl 1,1,1,3,3,3-hexafluoroisopropyl ether illuminated with a
250 watt incandescent lamp, starting at room temperature. The product is
washed with a potassium carbonate solution until neutral, dried over MgSO4
and vacuum distilled to yield 304 g (1.5 mole) of chloromethyl 1,1,1,3,3,3-
hexafluoroisopropyl ether (chloromethyl 1,1,1,3,3,3-hexafluoro-2-propyl
ether), boiling point 78°C.
A solution of chloromethyl 1,1,1,3,3,3-hexafluoro-2-propyl ether (754 g, 3.49
moles) in dry tetrahydrothiophene 1,1-dioxide (203 g, 3,49 moles) were stirred
and heated to 130°C in a creased flask fitted with a fractional distillation
assembly. A distillate (200 ml), b748 56.0° to 62°C, was collected during 5 h.
Then the reaction mixture was cooled to room temperature, dry potassium
fluoride (100 g, 1.74 moles) was added, and the cycle of operations was
repeated 3 times at temperatures between 138° to 185°C to give distillates
(100 ml, 100 ml and 50 ml), b746 58° to 61°C, 55.5° to 57°C, and 54.2° to
55.9°C, respectively. From this portionwise addition of potassium fluoride (503
g, 8.7 moles) there was obtained distillates totalling 672 g, b746 54.2° to
62.0°C, which by GLC analysis was about 92% fluoromethyl and 6.8%
chloromethyl 1,1,1,3,3,3-hexafluoro-2-propyl ether.
Fractional distillation of 659 g gave a forerun (46 g), b745 53.5° to 57.0°C,
and then 99.6% pure fluoromethyl 1,1,1,3,3,3-hexafluoro-2-propyl ether (505
g), b745 57.0° to 57.7°C.
brand name
Ultane (Abbott);Sevofrane.
Therapeutic Function
Anesthetic
Biological Functions
Sevoflurane (Ultane) is the most recently introduced inhalation
anesthetic. It has low tissue and blood solubility,
which allows for rapid induction and emergence and
makes it useful for outpatient and ambulatory procedures.
It has the advantage of not being pungent, a characteristic
that permits a smooth inhalation induction,
and is particularly useful in pediatric anesthesia.
Hypotension is produced by sevoflurane as systemic
vasodilation occurs and cardiac output decreases. Since
it does not directly produce tachycardia, it is a useful alternative
to consider in patients with myocardial ischemia.
However, a concern for reflex-induced tachycardia
remains.
Sevoflurane undergoes hepatic biotransformation
(about 3% of the inhaled dose), and it is somewhat degraded
by conventional CO
2 absorbents. The degradation
product from the absorbent has been reported to
be nephrotoxic, although the report is controversial and
not substantiated by more recent studies. Sevoflurane’s
actions on skeletal muscle and on vascular regulation
within the CNS are similar to those described for the
other halogenated hydrocarbon anesthetics.
General Description
Sevoflurane is a volatile, nonpungent, nonflammable, andnonexplosive liquid with a boiling point of 58.6°C. Theblood:gas partition coefficient is 0.65, the oil:gas partitioncoefficient is 50, and the MAC is 2.1%. Sevoflurane reactswith desiccated carbon dioxide adsorbents, to produce compounds(A and B) with known toxicity . The typeof CO
2 absorbent used, the temperature of the absorbent,and the duration of exposure can influence the degree towhich sevoflurane breaks down. The major breakdownproduct, compound A, pentafluoroisopropenyl fluoromethylether, (PIFE, C
4H
2F
6O) has been studied extensively.Compound A is nephrotoxic in rats and nonhuman primatesand remains a theoretical risk to humans. As discussedpreviously under the stability of inhaled anesthetics,sevoflurane breakdown by CO
2 absorbents generates heatand has resulted in sporadic operating room fires.
Clinical Use
Sevoflurane has been shown to cause epileptic changeson EEGs and case reports of seizures during surgery, especiallyin children, have been reported.
Veterinary Drugs and Treatments
Sevoflurane may be useful in a variety of species when rapid induction
and/or rapid recoveries are desired with an inhalational
anesthetic.
References
[1] JASON A CAMPAGNA Stuart A F Keith W Miller. Mechanisms of actions of inhaled anesthetics.[J]. New England Journal of Medicine, 2003, 348 21: 2110-2124. DOI:
10.1056/nejmra021261[2] MATTHEW D KRASOWSKI Neil L H. The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations[J]. British Journal of Pharmacology, 2009, 129 4: 731-743. DOI:
10.1038/sj.bjp.0703087[3] KOICHI NISHIKAWA Neil L H. The actions of sevoflurane and desflurane on the gamma-aminobutyric acid receptor type A: effects of TM2 mutations in the alpha and beta subunits.[J]. Anesthesiology, 2003, 99 3: 678-684. DOI:
10.1097/00000542-200309000-00024[4] E. RADA P F Elizabeth C Tharakan. Volatile Anesthetics Reduce Agonist Affinity at Nicotinic Acetylcholine Receptors in the Brain[J]. Anesthesia & Analgesia, 2003, 54 1: 108-111. DOI:
10.1213/00000539-200301000-00023
