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Local and regional anesthesia, defined as the selective numbing of a specific nerve distribution or region of the body to facilitate surgery, appear to be undergoing a renaissance, as judged by attendance at specialty meetings and numbers of published manuscripts. In contrast to general anesthesia, in which the molecular mechanism remains the subject of speculation, the site at which local anesthetic drugs bind to produce nerve blocks has been cloned and mutated. This chapter will focus on mechanisms of anesthesia and toxicity, especially as knowledge of these mechanisms will assist the clinician in conducting safer and more effective regional anesthetics.

The Incas regarded coca as a gift from the son of the sun god and limited its use to the "upper crust" of society.1 The Incas recognized and used the medicinal properties of cocaine long before the compound was brought back to Europe for its properties to be "discovered." The Incas sometimes treated persistent headaches with trepanation (Figure 6–1), and coca was sometimes a part of this procedure. Local anesthesia was accomplished by having the operator chew coca leaves and apply the mascerated pulp to the skin and wound edges while using a tumi knife (Figure 6–2) to bore through the bone.

Fig. 6-1

Skulls showing knife marks from ritual trepanning. This procedure was intended to release spirits causing headaches and other cranial ailments. (Courtesy of Rosamond Purcell ©2000.)

Fig. 6-2

A ceremonial tumi knife of the same shape and size as the less ornate ones that were used by the Incas to bore holes through the skull (trepanning). (Reprinted, with permission, from Sabbatini RME: Brain & Mind Magazine, 1997, June.)

By the sixteenth century, the conquistadors had disrupted Incan society and began paying laborers with cocaine paste. The laborers generally rolled the cocaine leaves into balls (called cocadas), bound together by guano or cornstarch.1,2 These cocadas released the free-base cocaine as a consequence of the alkalinity of the guano and of the practice of chewing the cocadas with ash or lime (such alkaline compounds increase pH, favoring the free-base cocaine form over the positively charged hydrochloride salt). This practice probably marks the birth of “free-basing” cocaine and is the historic antecedent of the “rock” or “crack” cocaine so often abused in Western societies.

Cocaine was brought back to Vienna by an explorer/physician named Scherzer.1 In Vienna, the chemist Albert Niemann isolated and crystallized the pure cocaine hydrochloride in 1860. The Merck Company distributed batches of this agent to physicians for investigational purposes. Sigmund Freud was the most prominent of these cocaine experimenters. Freud reviewed his experimental work in a monograph devoted to cocaine titled Über Coca. Freud and Carl Koller (an ophthalmology trainee) took cocaine orally and noticed that the drug ...

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