Chloroform Adrenaline

Treatment of chloroform poisoning is symptomatic no specific antidote is known. Adrenalin should not be given to a person suffering from chloroform poisoning. 

Halogenated hydrocarbons depress cardiac contractility, decrease heart rate, and inhibit conductivity in the cardiac conducting system. The cardiac-toxicity of these compounds is related to the number of halogen atoms it increases first as the number of halogen atoms increases, but decreases after achieving the maximum toxicity when four halogen atoms are present. Some of these compounds, e.g., chloroform, carbon tetrachloride, and trichloroethylene, sensitize the heart to catecholamines (adrenaline and noradrenaline) and thus increase the risk of cardiac arrhythmia. 

Acetylgramine. This substance is active (IV. in mice) at doses of 5 mg per kg and less, making it quite potent. It potentiates response to DMPP (l,l-Dimethyl-4-phenylpiperazinium iodide) and blocks response to acetylcholine and adrenalin. Reflux a mixture of 15 g of 5-aeetylindole or analog (in equimolar amount), 7.55 g of 37% aqueous formaldehyde, 17 g of 25% aqueous di-methylamine, 25 ml of acetic acid, and 250 ml of methanol for 3 hours. Concentrate in vacuo to 20% of original volume, treat with 100 ml of water, wash with chloroform, chill in freezer, and make basic with 20% NaOH. Filter off the crystalline precipitate and wash with cold (near freezing) water to get a little over 17 g of the title product. Recrystallize from benzene to purify. It is unknown to me if this is active orally. 

Chloroformates have been widely used to derivatize amines because the derivatives are easily made, even in buffered aqueous solution, and have useful chromatographic properties, especially volatility. The derivatization reactions were studied by Ahnfeldt and Hartvig, who found the trichloroethyl chloroformate an order of magnitude more reactive than alkyl chloroformates. The reactions went faster with the secondary amine studied [148]. Methyl chloroformate was used to derivatize adrenaline and noradrenaline in plasma (1 ml) buffered at pH 7.4. Methyl chloroformate (20 fd) was added and the mixture was stirred for 30 seconds. After 5 minutes the product was extracted into methylene chloride, the extract was evaporated to dryness and the residue was silylated for analysis by gas chromatography [149]. A very similar procedure was developed by Japanese workers around the same time, using ethyl chloroformate to derivatize both amino and hydroxyl groups [150]. 

Ephedrine is an alkaloid, a sympathomimetic amine with molecular formula Cjo Hi5 NOi, a molecular mass of 165.2, and the stmctural name (IR, 25)-2-methylamino-l-phenylpropan-l-ol. This bitter colorless or white solid-crystal is completely soluble in water, alcohol, chloroform, ether, and glycerol. Ephedrine is also produced by chemical synthesis and there is significant documentation of commercial ephedrine production using microbial biotransformation techniques [42]. Ephedrine has a structure close to methamphetamines, and its stimulant actions are comparable to epinephrine (adrenaline), a hormone produces by the adrenal glands that enhances heart rate and constriction of blood vessels in high-stress situations. Medicinal use of ephedrine began around 3000 B.C with the Chinese from md hudng, but its isolation was first reported in 1855 and its pharmaceutical application started in 1930 [22]. Studies on ephedrine s molecular structure show that two asynunetric carbon atoms are involved in ephedrine s molecular skeleton therefore, four optically active stereoisomers forms naturally occur as follows (IR, 2S)-(—)-ephedrine, (IS, 2R)-(+)-ephedrine, (IR, 2R)-( )-pseudoephedrine, (IS, 2S)-(+)-pseudoephedrine (Fig. 27.2). 

Evaporate the combined extracts on a water-bath under a jet of air to about 3 ml, completely transfer the residue with small portions of chloroform to a tared 50-ml beaker, and heat again to evaporate the solvent completely. Heat further at 105° for thirty minutes, cool in a desiccator and weigh the residue of triacetyl adrenaline. Add 5 0 ml of chloroform, cover the beaker, gently swirl until the residue is completely dissolved, and detennine the specific rotation, Ry using a 2-dm, semi-micro polarimeter tube. 

The local risks of vasoconstrictors in local anaesthetic solutions, particularly when the latter are used in the fingers or other extremities, have long been recognized. In addition, it is well known that the use of adrenaline or noradrenaline for this purpose can lead to marked rises in blood pressure, especially in patients who are taking MAO inhibitors the cardiovascular effects can be dangerous in patients with existing cardiovascular disease or where there is simultaneous treatment with either a tricyclic antidepressant (SED VIII) or with those general anaesthetics which sensitize the myocardium to the effects of catecholamines (e.g. chloroform, cyclopropane, halothane). 

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