Anaesthetic

Oxygen Derivatives of Commerciai Interest. — Inhalation Anaesthetics. CF8-CH2 0CHF2 + Brs at 450-475 °G GFaGHBrOGHFs.  

Paige and J. Passmore, Inorg. Nuclear Chem. Letters, 1973, 9, 277. 

Polymers. Film-forming fluoroaliphatic-linked polysulphonates from HO CHa (CFa) X-OH [a = 2,X = 0 (CFa)a-CHaorO (CFa)4 0 (CFa)a-CHa  

Sulphor Derivatives of Commercial Interest.—Medicinals. m-HaN C6H4 S CF8+ 2-chloronicotinic acid or its esters - 2-(m-CF3 S C6H4 NH)CsH3N COaR-3 (R = H, Me, or Et). i m-H2N C8H4-S CF3 + o-BrCeH4 COaK -(m-CFs-S-C6H4 NH)C6H4-COaH. is CFa-SOa-Substituted aromatics. i CFs-S-Substi-tuted cephalosporins, Use of CFs-SOa CHa-CFs in the synthesis of anaesthetic CFs CHa O-subsdtuted aromatics.  

20) The words anaesthesia and anaesthetic were first used by Oliver Wendell Holmes in a letter to the surgeon William Morton dated 21st November 1846. The Association of Anaesthetists of Great Britain and Ireland have a museum in central Lon- 

Better Looking (II) and Better Living (I) Medical Advances 

The best anaesthetic vapour was found to be a 1 2 3 mixture of alcohol, chloroform, and ether, known as ACE. Despite being widely used, it was always known that ACE presented a risk, and yet it was the anaesthetic of choice for more than 100 years. Ether caused serious fires and explosions in operating theatres and while the risk of this was small - about one serious incident every 100,000 operations - it was alarming when it happened. Chloroform was not a fire risk but it could be deadly to some patients, killing them within minutes in certain tragic cases, and seriously damaging the liver of others. (Nitrous oxide was less risky, and continues to be used even today, but it does not produce deep anaesthesia.) 

In the 1980s two more anaesthetics came into use enflurane and isoflurane. These were not metabolised by the liver to the same extent, 2% in the case of enflurane, and only 0.2% of isoflurane. Enflurane was introduced into clinical use in 1981, but isoflurane was delayed because some research appeared to show that it caused liver cancer in mice. This research was repeated by others and shown to be wrong and isoflurane came into general use in 1984. What operating theatre personnel did not like was its off-putting smell. Were there health risks associated with the new anaesthetics A statistical analysis of the side-effects experienced by 17,201 patients on whom they were used was compared with the effects experienced by a similar group on whom halothane had been used. Patients on the newer anaesthetics were more likely to suffer a heart attack and, with isoflurane, palpitations were more common. However, there was no increased risk of the patient dying. 

These drugs are used in surgical operations to induce unconsciousness and, therefore, abolish the sensation of pain. 

Later on, William Morton — a Boston dentist demonstrated the anaesthetic actions of diethyl ether in 1846 at the historical Ether Dome located at the Massachusetts General Hospital. In actual practice, the usage of diethyl ether followed by cyclopropane were withdrawn completely for being highly toxic amalgamated with equally dangerous physical properties, such as flammable and explosive. 

The anaesthetic agents that have gained cognizanee today are invariably hydrocarbons and ethers with halogen (F, Br, Cl) substitution. 

The general anaesthetics may be divided into three groups based solely on the method of administration. These are inhalation anaesthetics intravenous anaesthetics and basal anaesthetics. 

The above three categories of general anaesthetics shall be discussed here with appropriate examples. 

A number of HPLC-ED methods have been described for the general anaesthetic propofol (2,6-di-isopropylphenol) in plasma. Mazzi and Schinella used a phenyl-propyl-modified silica column and a GCE (+0.8 V vs Ag/AgCl). The eluent was 

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C. It is secreted along with noradrenaline by the adrenal medulla, from which it may be obtained. It may be synthesized from catechol. It is used as the acid tartrate in the treatment of allergic reactions and circulatory collapse. It is included in some local anaesthetic injections in order to constrict blood vessels locally and slow the disappearance of anaesthetic from the site of injection. Ultimately it induces cellular activation of phosphorylase which promotes catabolism of glycogen to glucose. 

Me2NCH2) C2H5)(Me)C-OOC Ph-HCI. Colourless crystalline powder with a bitter taste, m.p. 177-179"C. Prepared by the action of ethyl magnesium bromide on dimethyl-aminoaceione. It is a local anaesthetic, mainly used to produce spinal anaesthesia. 

White crystals, m.p. 90-9 rC. Prepared fromp-nitrotoluene by way of p-aminobenzoic acid. It is used as a local anaesthetic on mucous surfaces internally and by injection, and is taken internally to relieve gastric pain. 

Chloroform is a potent volatile anaesthetic, but is little used due to its potential hepato-toxicity. It is used principally for the manufacture of chlorofluorohydrocarbon refrigerants ( Arctons and Freons ) and certain polymers. 

Cocaine is the oldest of the local anaesthetics. It is a central nervous system stimulant and is habit-forming. See ecgonine. 

Prepared by treating 1,3-dibromopropane with zinc. It is a powerful gaseous anaesthetic, non-irritant and non-toxic to the liver and kidneys, but it is a respiratory depressant. 

CifiHijClNj. White plates m.p. 125 C. Diazepam is one of several benzodiazepines which are very widely used as minor tranquillizers for allaying anxiety, as hypnotics or, in sufficiently high dosage given intravenously, as pre-anaesthetic sedatives. 

Dinitrogen oxide, nitrous oxide, N2O. Colourless gas, m.p. —9T C, b.p. —88-5°C (heat on NH4NO3). Decomposes to N2 and O2 above SOO C can be detonated. Linear molecule NNO. Used as a mild anaesthetic. 

Most of the trichloroethylene produced is used for metal degreasing. Other important uses are in the scouring of wool and as an extractive solvent, e.g. for olive and soya bean oils. Minor uses are as a heat transfer medium, anaesthetic, insecticide and fumigant, paint remover and fire extinguisher. 

Trilene A trade name for trichloroethylene when used as an anaesthetic. It is given by inhalation for short operative procedures. 

Colourless prisms m.p. 49-50 C, b.p. 184 C. Prepared by the action of ammonia on ethyl chloroformate. Used as a long-acting anaesthetic for laboratory animals. 

By far the largest use of hydrogen fluoride is in the manufacture of fluorocarbons which find a wide variety of uses including refrigerants, aerosol propellants and anaesthetics. Hydrogen fluoride is also used in the manufacture of synthetic cryolite, Na3AIFg, and the production of enriched uranium. 

Diethyl ether is a mobile, colourless liquid having b.p. 35° and dy 0720. It has a characteristic odour, and a burning taste. It is used chiefly as a solvent, and was formerly widely used as an anaesthetic owing to its chemical non-reactivity, it is very seldom used actually as a reagent, except in the preparation of Grignard reagents (p. 280) where probably its chemical properties reinforce its solvent action. 

Chloroform was formerly used in medicine as an anaesthetic. One disadvantage for this purpose is the ready oxidation which chloroform undergoes on exposure to light and air, generating the poisonous phosgene, or carbonyl chloride, COCU- This is counteracted by storing the liquid in dark amber-... 

In addition to chloroform, many other compounds containing the trichloro-methyl group, CI3C-, show marked physiological action. Thus trichloro-acetaldehyde or chloral hydrate, Cl3C CH(OH) (p. 342), and trichloro-tertiary-butanol or chloretone, CUC CfCHaliOH, are both hypnotics. Similarly, tribromo-ethanol or avertin, BraC-CHjOH, has strong anaesthetic properties. 

Physical Properties. All th e ethers are insoluble in water. The aliphatic ethers have strong characteristic odours, have anaesthetic properties and are extremely inflammable. 

The p-substituted amino ketones can be reduced readily to the more stable P-dialkylamino alcohols, many of which are useful local anaesthetics. Thus the local anaesthetic Tutocaine is made from the Mannich base derived from formaldehyde, methyl ethyl ketone and dimethylamine, followed by reduction and conversion into the p-aminobenzoate ... 

Chloroform - a very common solvent which has a rather unpleasant smell. Try not to get too close to this stuff as it has anaesthetic properties which you don t really want to find out about. 

The metabolite of 2-amino-4-phenylthiazole (used as an anaesthetic for fish) was identified (223) as 2-amino-4-phenylthiazole 2-N, -d-glucopyranosiduronic acid (71) (Scheme 50). The formation of this compound probably involves the reaction of the exocyclic nitrogen on the Open-chain form of the acid. The isolation of this metabolite is part of a very Systematic study by Japanese researchers related to the anaesthetic... 

A. B. Vaughan, in Anaesthetics, Oxford University Press, London, 1969. 

Note that the relative spatial arrangement of the phenyl, amine, and hydroxyl functionahties are identical for (R)-alprenolol and (5)-sotalol. In addition to P-blocking activities, some of these compounds also possess potent local anaesthetic activity (see Anesthetics). The membrane stabilizing activity, however, is not stereoselective and correlates directly with the partition coefficient (hydrophobicity) of the compound. 

Mice are utilized for testing antiseptics for appHcation to cuts, wounds, and incisions (339). The test bacteria, type 1 pneumococcus and hemolytic streptococcus, ate appHed to the taHs of anaesthetized mice. The tip of the taH is then dipped into the antiseptic for 2 min, after which one-half inch of the taH is removed and inserted into the peritoneal cavity and the incision is closed. If after 10 days the animals survive, the product is considered satisfactory for use as a skin antiseptic. The blood of dead animals is sampled and streaked on blood agar for confirmation of infection from the test bacteria as the cause of death. Since lack of toxicity is another requirement of a product to be appHed to wounds, this test has been combined with a toxicity test (340). 

The pseudo-barbiturate , 2-methyl-3-o-tolylquinazolin-4(3H)-one (methaqualone, Revonal 1017) has an even wider spectrum of activities than do the barbiturates proper it appears to be quite widely used as- a sedative, hypnotic, anticonvulsant, antispasmodic and local anaesthetic agent (63MI21301, b-75MI21301>. 

Aceto-2,6-xylidide, diethylamino-as local anaesthetic, 1, 179 N-Acetylation... 

LL-Z1220, 7, 192 Local anaesthetics, 1, 178 Loffler-Freitag reaction... 

Piperidine, l-(2-hydroxythiobenzoyI)-neutron diffraction, 2, 116 Piperidine, 4-hydroxy-2,2,6-trimethyI-as local anaesthetic, 1, 179 Piperidine, JV-methoxycarbonyl-electrolytic oxidation, 2, 374 Piperidine, 2-methyl-synthesis, 2, 524 Piperidine, 3-methyI-mass spectrometry, 2, 130 Piperidine, C-methyl-NMR, 2, 160 Piperidine, JV-methyl- C chemical shifts, 2, 15 catalyst... 

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