Chloroform Epinephrine

Morris LE, Noltensmeyer MH, White JM Jr. 1953. Epinephrine induced cardiac irregularities in the dog during anesthesia with trichloroethylene, cyclopropane, ethyl chloride and chloroform. Anesthesiology 14 153-158. 

In rats, 90 day exposures to 1000 and 5000 ppm caused bilateral hair loss, extensive liver damage, and excessive mortality. The chronic toxicity of dichlorofluoromethane appears to be quite different from difluorinated methanes and more similar to the hepatotoxin chloroform. In mice 100,000 ppm induced arrhythmias and sensitized the heart to epinephrine. 

TLC separation of DNS-amines is usually made on layers of silica gel with solvents covering a range of polarity, e.g., chloroform, ethyl acetate, diisopropyl ether and methanol. Seiler and Wiechmann [97] developed 30 solvent systems for the separation of DNS derivatives of over 100 biogenic amines on TLC plates of silica gel. The selective reaction of DNS-C1 with the amino group of catecholamines has been examined [98]. The drugs dopamine, norepinephrine and epinephrine are adsorbed on alumina which protects their hydroxyl groups from dansylation. The N-dansylated compounds are separated with benzene-dioxane-acetic acid (90 25 4) on layers of silica gel. 

Ephedrine occurs in white, rosette, or needle crystals, or as an unctuous mass. It is soluble in water, alcohol, chloroform, ether, and in liquid petrolatum, the latter solution being turbid if the ephedrine is not dry. Ephedrine melts between 34 and 40°C, depending upon the amount of water it contains it contains not more than 0.1% of ash its solutions are alkaline to litmus it readily forms salts with acids and it responds to the usual tests for alkaloids. Ephedrine excites the sympathetic nervous system, depressing smooth and cardiac muscle action, and produces effects similar to those of epinephrine. It produces a rather long-lasting rise of blood pressure and mydriasis and diminishes hyperemia. The alkaloid may be used in 0.5 to 2% oil spray. 

R-8I8 (17) prevented chloroform-induced ventricular fibrillation in mice as well as arrhythmias caused by hydrocarbon-epinephrine, ouabain, aconitine and coronary occlusion in dogs.5° The activity of numerous analogs in the mouse chloroform test has been described.57... 

Crystals from aq ethanol, mp 206°. Slightly sol in water, chloroform. Sol in acetone, methanol. DMF, aq solns above pH 8.0. Less sol in ethanol. Pharmaceut. Incompat Calcium gluconate, ascorbic acid, tetracyclines, urea, epinephrine. LDga orally in female, male rats 2600, 2820 mg/kg (Goldenthal). 

The EPA defines hazardous wastes in the RCRA. This waste also includes pharmaceutical wastes that contain toxic chemicals or exhibit properties that make them hazardous to the environment and/or humans. RCRA wastes include broken or spilled vials, partial vials, expired products, and patient s personal medications. EPA limits hazardous waste maximum storage time to 90 or 180 days based on generator status. All wastes must be stored in a separate and locked area clearly marked so that it cannot become a food source or breeding place for insects or animals. Like infectious wastes, there is no time limit to fill the container. Not all states mandate the same storage requirements. Contact local and state authorities for additional information. EPA s P-listed chemicals (40 CFR 261.33) include such pharmaceuticals as epinephrine, nicotine, chloroform, and warfarin over 0.3%. The U-listed chemicals (40 CFR 261.33) include many used in chemotherapy, such as paraldehyde, mercury, phenol, and warfarin under 0.3%. 

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). 

The answer is 3 [IIC Tible 15-1]. The halocarbon compounds (e.g., chloroform, halothane, freon) and the fumes from overheated synthetic fluorine-containing resin-coated (Teflon) cookware are indirectly car-diotoxic because they sensitize the heart to sympathomimetic amines such as epinephrine. Following exposure to these substances, even the release of endogenous epinephrine associated with stress can pose a hazard. Yew plants contain a cardioactive alkaloid that inhibits depolarization and produces bradycardia and diastolic heart block. Furazolidone interferes with intermediary metabolism, resulting in a lack of energy arid a dilated, weak heart "round heart." Digitalis aflecTs potassium content in the cell. Monensin is an ionophore that alters the sodium-to-calcium ratio arid leads Id cardiac necrosis. 

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