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Cocaine is a naturally occurring alkaloid with unique local anesthetic and sympathomimetic activity, which served as the prototype for the synthesis of local anesthetics. Unlike other local anesthethics, cocaine has both anesthetic and vasoconstrictive properties, however many otolaryngologists no longer use cocaine because of its toxicity profile.142 Cocaine is also a prevalent drug of abuse producing the characteristic sympathomimetic toxic syndrome that includes hypertension, tachycardia, tachypnea, hyperthermia, diaphoresis, mydriasis, and severe psychomotor agitation. The study of cocaine metabolism led early insights into pharmacogenetics, and the understanding of cocaine toxicity sheds light into the interactions of the control of the sympathetic nervous system.

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Cocaine is contained in the leaves of Erythroxylum coca, a shrub that grows abundantly in Colombia, Peru, Bolivia, the West Indies, and Indonesia. As early as the 6th century, the inhabitants of Peru chewed or sucked on the leaves for social and religious reasons. In the 1100s, the Incas used cocaine-filled saliva as local anesthesia for ritual trephinations of the skull.73

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In 1859, Albert Niemann isolated cocaine as the active ingredient of the plant. By 1879 Vassili von Anrep demonstrated that cocaine could numb the tongue.120 However, Europeans knew little about cocaine until 1884, when the Austrian ophthalmologist Karl Koller introduced cocaine as an effective local anesthetic for eye surgery and Koller's colleague, Sigmund Freud, wrote extensively on the psychoactive properties of cocaine.60 Following these revelations, Merck, Europe's main cocaine producer, increased production from less than 0.75 pounds in 1883 to more than 150,000 pounds in 1886.114

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Simultaneously, reports of complications from the therapeutic use of cocaine began to appear. In 1886, a 25-year-old man had a "pulseless" syncopal event after cocaine was applied to his eye to remove a foreign body.229 By 1887 more than 30 cases of severe toxicity were reported,195 and by 1895 at least 8 fatalities resulting from a variety of doses and routes of administration were summarized in one article.62 Recreational cocaine use was legal in the United States until 1914, when cocaine was restricted to medical use. It was not until 1982, however, that the first cocaine-associated myocardial infarction was reported in the United States.29

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Currently, cocaine is an approved pharmaceutical. It is used primarily for topical anesthesia of cutaneous lacerations or during otolaryngology procedures as a vasoconstrictor and topical anesthetic. Although multiple factors have fostered a decline in the medicinal use of cocaine,19,68,142 the recreational use of cocaine remains a significant problem. Recent estimates suggest that almost 34 million Americans have used cocaine at least once, with 1.7 million of those dependent or addicted.43 European Union statistics estimate that cocaine has been used at least once by more than 12 million Europeans, representing almost 4% of all adults.50

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The alkaloid form of cocaine (benzoylmethylecgonine) is extracted from the leaf by mechanical degradation in the presence ...

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