Inhalation anaesthetics ethers

A nonconventional synthesis of the known inhalation anaesthetic, 2-bromo-2 chloro-l,l,l-trifluoroethane (Halothane), based on the reaction of ethyl 1,2 di bromo-1,2-dicliloroethyl ether with anhydrous hydrogen fluoride and sulfur tetrafluoride, has been patented The reaction presumably involves cleavage of the ether linkage, followed by fluorination of the intermediate bromochloroacetyl halide with sulfur tetrafluoride, ethyl halides are the by-products [2] (equation 2)... 

Baden JM, Kelley M, Mazze Rl, et al. 1979. Mutagenicity of inhalation anaesthetics Trichloroethylene, divinyl ether, nitrous oxide, and cyclopropane. Br J Anaesth 51 417-421. 

Diethyl ether has been used widely as an inhalation anaesthetic. But due to its slow effect and an unpleasant recovery period, it has been replaced, as an anaesthetic, by other compounds. 

The ethers are also an homologous series. We will only use the common compound simply called ether as a further example. It is really diethyl ether or ethoxy ethane, C2H5 O C2H5. Ether was one of the earliest inhaled anaesthetics and it has a sweet sickly smell. Diethyl ether has a low boiling point (no hydrogen bonding unlike ethanol) and is easily evaporated at room temperatures. If you leave the bottle open it will soon evaporate into a heavy vapour which is extremely flammable. Never use ether near flames or sparks because fire and explosions are possible. 

It was William Morton, in 1846, who first noted that ether could be used as an anaesthetic for dentistry and surgery. Before that all surgery was conducted on conscious patients. Chloroform, CHCI3, was developed later and Queen Victoria gave the process of anaesthesia credence when she gave birth to a child in 1853 and suffered little or no pain. More recent inhaled anaesthetics include isofluorane , CF3 CH(C1) O CHF2. Draw its structure (hint it is also an ether). 

Inhalation anaesthetics are either gases or volatile liquids. Apart from nitrous oxide, which is still widely used, earlier inhalation anaesthetics are no longer used. Ether is not suitable because it is explosive and irritant to the respiratory tract. Chloroform cannot be used because it is toxic to the liver. Inhalation anaesthetics currently in use are the volatile liquids halothane (since 1956) and more recently isoflurane, desflurane and sevoflurane and nitrous oxide gas. 

What are the advantages of the inhalation anaesthetics isoflurane, desflurane and sevoflurane over the older ones ether, chloroform and halothane ... 

Anaesthesia in the presence of beta blockers normally appears to be safer than withdrawal of the beta blocker before anaesthesia, provided certain inhalational anaesthetics are avoided (methosy-flurane, cyclopropane, ether, trichloroethylene) and atropine is used to prevent bradycardia. Bradycardia and marked hypotension occurred in a man using timolol eye drops when he was anaesthetised. 

It used to be thought that beta bloekers should be withdrawn from patients before surgery beeause of the risk that their cardiac depressant effects would be additive with those of inhalational anaesthetics, resulting in a reduction in cardiac output and blood pressure, but it seems that any effect depends on the anaesthetic used. It has been suggested that the ranking order of compatibility (from the least to the most compatible with beta blockers) is as follows methoxyflurane, ether, cyclopropane, trichloroethylene, enflurane, halothane, isoflurane. ... 

A risk of cardiac depression certainly seems to exist with cyclopropane and ether because their depressant effects on the heart are normally counteracted by the release of catecholamines, which would be blocked by the presence of a beta blocker. There is also some evidence (clinical and/or animat) that unacceptable cardiac depression may occur with methoxytlu-rane and trichloroethylene when a beta blocker is present. This has been the subject of two re views.For these four inhalational anaesthetics it has been stated that an absolute indication for their use should exist before giving them in combination with a beta blocker. ... 

Patients anaesthetised with inhalational anaesthetics (particularly cyclopropane and halothane, and to a lesser extent desflurane, enflurane, ether, isoflurane, methoxyflurane, and sevoflurane) can develop cardiac arrhythmias if they are given adrenaline (epinephrine) or noradrenaline (norepinephrine), unless the dosages are very low. Children appear to be less susceptible to this interaction. file addition of adrenaline to intrathecal tetracaine enhances the sedative effects of propofol. 

The effects of neuromuscular blockers are increased by inhalational anaesthetics, the greater the dosage of the anaesthetic the greater the increase in blockade. In broad terms desflurane, ether, enflurane, isoflurane, methoxyllurane and sevoflurane have a greater effect than halothane, which is more potent than cyclopropane, whereas nitrous oxide appears not to interact significantly with competitive blockers. " ... 

Chemical synthesis did not seem, at first, a likely source of useful remedies. However, after Wohler s synthesis of urea, in 1828, a whole range of synthetic organic chemicals was introduced into medical practice. After several false starts, some relatively simple substances were adopted as inhalation anaesthetics, namely nitrous oxide, ether, and chloroform (1844-7) which, by giving the surgeon adequate time for his task, initiated a tremendous refinement and extension of the possibilities of surgery. 

Most major and widely-used inhalant anaesthetics are regarded as safe or safer than general opiods and relaxant anaesthetic [176], but ever since Pringle, Maunsell and Pringle [177] and Thompson [178] in 1905 reported that diethyl ether and chloroform anaesthesia reduced urine output closer attention has been paid to the effect of all anaesthetics. Hence, an important application of the fluoride ion-selective electrode combines fluoride levels in blood and other fluids in connection with the administration of fluorine-containing inhalant anaesthetics. The wide range of such studies merits the detailed discussion in the section following the non-blood fluids. 

The early members of the homologous series of ethers are low boiling, flammable liquids. Diethylether was an early anaesthetic but it is little used now, having been replaced with non-flammable inhalation anaesthetics such as enflurane, which is a halogenated ether (Fig. 5.21). Such anaesthetics act via a non-spedlic mechanism where they dissolve in lipid membranes and, in the case of anaesthesia, they dissolve in neurological membranes, thus preventing them from functioning properly. 

The presence of ethers in the atmosphere is almost entirely the result of direct emissions from anthropogenic sources (e.g., Arif et al., 1997 Intergovernmental Panel on Climate Change, 2001 Johnson and Andino, 2001 http //en.wikipedia.org/wiki/Ethers and references therein). These sources can be quite varied and species dependent for example, many ethers are commonly used as industrial solvents many are formed as combustion intermediates and in the burning of biomass various branched ethers (e.g., methyl tert-butyl ether) are (or have been) used as fuel additives to increase octane number and reduce CO emissions dimethyl ether has being proposed as an alternative diesel fuel many fluorinated species have been manufactured, evaluated and used as possible chlorofluorocarbon (CFC) and hydrochlorofluorocarbon (HCFC) replacement compounds some halogenated species are used as inhalation anaesthetics or as chlorofluorocarbon replacements and polybrominated diphenyl ethers (PBDEs) are used as flame retardants. There are no major routes to ether formation in the atmosphere itself. 

An increase in alveolar ventilation will cause an increase in the alveolar concentration of inhaled agent when semi-closed or open breathing circuits are employed. The effect is most noticeable with a highly soluble anaesthetic, such as diethyl ether. With modern, relatively insoluble agents, such as isoflurane and desflurane, the effects of changes in alveolar ventilation are less pronounced. 

Sevoflurane is a chemical analogue of isoflurane. It is less chemically stable than the other volatile anaesthetics in current use. About 3% is metabolised in the body and it is degraded by contact with carbon dioxide absorbents, such as soda lime. The reaction with soda lime causes the formation of a vinyl ether (Compound A), which may be nephrotoxic. Sevoflurane is less soluble than isoflurane and is very pleasant to breathe, which makes it an excellent choice for inhalational induction of anaesthesia, particularly in children. The respiratory and cardiovascular effects of sevoflurane are very similar to isoflurane. 

Diethyl ether is a colorless, volatile, flammable liquid with a characteristic pleasant odor. It causes fainting when inhaled, which explains its use as an anaesthetic in medicine. 

A volatile anaesthetic administered by inhalation, it is 4 times as potent as ether. Its prolonged inhalation for long operations is rather harmful because of the risk of liver necrosis. 

It is a relatively safe potent volatile anaesthetic administered by inhalation. It is twice as potent as chloroform and 4 times that of ether. It may produce any depth of anaesthesia without causing hypoxia. Being a non-irritant, its inherent hypotensive effect retards capillary bleeding and renders a comparatively bloodless field. 

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