Anaesthesia

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. 

Ethylene when deeply inhaled produces temporary anaesthesia which is almost devoid of unpleasant after-effects hence it has been used for dental surgery, minor operations, etc. 

Acute inhalation exposure of rats to 200,000 ppm VF for 30 minutes or more produced weak anaesthesia and no deaths (90). In rats VF is only slightly metabolized at a rate of one-fifth that of vinyl chloride (91—95). An extensive program of toxicity testing of vinyl fluoride is ia progress (96,97). 

Chemieals whieh give strong aeid reaetions, often on interaetion with water, e.g. mineral aeids. Some organie aeids ean also be eoiTosive. Phenolies ean result in loeal anaesthesia so that the pain will be absent for a time, i.e. eontaet may go unheeded. 

Cocaine. This lias a bitter taste, is mydriatic, produces local anaesthesia and is toxic. After absorption, or when taken internally, it acts chiefly by stimulation of the central nervous system, succeeded by depression. Since the two phases may be present in different areas simultaneously, a mixed result may ensue. With large doses the chief symptoms are those of medullary depression. Death is due to paralysis of the respiratory centre. The main use of cocaine in medicine is as a local anaesthetic. 

Tropacocaine (Benzoyl-i/r-tropine). This resembles cocaine in action, but produces local anaesthesia more rapidly and for a shorter time and causes little or no mydriasis. 

Trachelantamine, according to Syrneva, has a weak atropine-like action and also produces local anaesthesia. Its hydrolytic product, trache-lantamidine, which is structurally identical with tsoretronecanol, yields a p-aminobenzoyl derivative of -which the crystalline hydrochloride, m.p. 230-2°, is said to be as potent a local anaesthetic as cocaine hydrochloride. The chloro- -heliotridane (p. 606) formed by the aetion of thionyl ehloride on trachelantamidine reacts with 6-methoxy-8-aminoquinoline to form 6-methoxy-8-(pseMdoheliotridylamino)-quinoline,... 

FIGURE 9.15 In vivo effec ts o f P-adreno cep tor partial agonis ts o f differing in trinsic efficacy. Changes in heart rate (increases in beats/min) shown in anesthetized cats. Chloralose/pento barbital anesthesia (filled circles) yield low basal heart rates, while urethane/pen to barbital anaesthesia (open circles) yields high basal heart rates. Responses to (in order of descending relative intrinsic efficacy) (a) pirbuterol, (b) prenalterol, and (c) pindolol. Redrawn from [50],... 

Substitution therapy with methadone or buprenorphine has been veiy successfiil in terms of harm reduction. Some opiate addicts might also benefit from naltrexone treatment. One idea is that patients should undergo rapid opiate detoxification with naltrexone under anaesthesia, which then allows fiuther naltrexone treatment to reduce the likelihood of relapse. However, the mode of action of rapid opiate detoxification is obscure. Moreover, it can be a dangerous procedure and some studies now indicate that this procedure can induce even more severe and long-lasting withdrawal symptoms as well as no improvement in relapse rates than a regular detoxification and psychosocial relapse prevention program. 

General anaesthesia can encompass several different end points, the most critical of which can be defined as unconsciousness. A loss of sensation including that of any painful stimulus, and muscle relaxation are also desirable endpoints of general anaesthesia. Modern-day anaesthesia is accomplished using a balanced combination of different drugs to confer these different endpoints. 

General anaesthetics have been in use for the last 100 years, yet their mechanism of action are still not yet clearly defined. For many years it was thought that general anaesthetics exerted their effects by dissolving in cell membranes and perturbing the lipid environment in a non-specific manner. This theory derived from the observation that for a number of drugs which induced anaesthesia, their potency correlated with their oil-water partition coefficients. This Meyer-Oveiton correlation was accepted for a number of years, however in the last 15-20 years evidence has shown that a more likely theory is that of specific interactions of anaesthetics with proteins, particularly those within the CNS that mediate neurotransmission [1]. 

Two methods of anaesthesia are currently in use, the application of inhaled gaseous or volatile anaesthetics such as halothane, sevoflurane and isoflurane to maintain a level of anaesthesia. Older compounds in this category include nitrous oxide and chloroform. 

The other method used is infusion of intravenous anaesthetics such as propofol, etomidate (for induction) and the barbiturates such as thiopental and pentobarbital. Investigations into the mechanism of anaesthesia have made use of all these compounds in order to identify a common mode of action linked to likely mechanisms within the CNS. 

Franks NP, Lieb WR (1994) Molecular and cellular mechanisms of general anaesthesia. Nature 367 607-614... 

Local anaesthetics are drugs that reversibly interrupt impulse propagation in peripheral nerves thus leading to autonomic nervous system blockade, analgesia, anaesthesia and motor blockade in a desired area of the organism. 

Strang], Bearn], Gossop M Opiate detoxification under anaesthesia. BM] 315 1249-1250, 1997... 

Fornazzari L, Wilkinson DA, Kapur BM, et al Cerebellar, cortical and functional impairment in toluene abusers. Acta Neurol Scand 67 319—329, 1983 Franks NP, Lieb WR Molecular and cellular mechanisms of general anaesthesia. Nature 367 607-614, 1994... 

Ortells MO, Lunt GG Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends Neurosci 18 121—127, 1995 Overall JE, Gorham DR The Brief Psychiatric Rating Scale. Psychol Rep 10 799—812,1962 Payne JP The criminal use of chloroform. Anaesthesia 53 685—690, 1998... 

Evans RT, Wroe JM. 1980. Plasma cholinesterase changes during pregnancy. Anaesthesia 35 651-654. 

Dybendal X Guttormsen AB, Elsayed S, Askeland 48 B, Harboe T, Florvaag E Screening for mast cell tryptase and serum IgE antibodies in 18 patients with anaphylactic shock during general anaesthesia. 

Merles PM. Laxenaire MC, Lienhart A, et al Reducing the risk of anaphylaxis during anaesthesia guidelines for clinical practice. J Investig AUergol 49 Chn Immunol 2005 15 91-101. 

Laxenaire MC, Merles PM Anaphylaxis during 8 anaesthesia. Results of a two-year survey in France. BrJAnaesth 2001 87 549. 

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