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This sacred plant of the Incas, Erythroxylum coca, caught the attention of Europeans who took it to the old continent at the end of the 16th century. In addition, as a powerful stimulant, the coca leaf was chewed to mitigate the effects derived from altitude, hunger or fatigue and as a medicine for gastrointestinal discomfort, colds, or bruises. In the Andean Mountains, centuries ago, the Incas began using cocaine leaves which they chewed or ingested in the form of potions that provided them with plenty of energy to carry out their religious rituals. Brief history of the discovery and evolution of LAs In this introductory chapter, the most important properties of LAs are detailed, emphasizing their pharmacological classification, pharmacokinetic profile, action mechanisms, side effects, and some relevant clinical aspects, as well as their nonanesthetic uses.ΔΆ.
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Centbucridine is a nonester, nonamide drug still under clinical investigation. Sameridine, on the other hand, has mixed effects as an opioid agonist and LA properties under investigation for intrathecal use. Articaine is classified into the amide group, it is fat soluble and short acting and has intermediate potency, with rapid metabolism due to an ester group in its structure. There are three LAs that due to their chemical structure differ from the classic LAs: articaine, sameridine, and centbucridine. They are the only drugs used in regional anesthesia, although it has been described that other drugs with different molecular structure such as amitriptyline, meperidine, eugenols, beta-adrenergic antagonists, alpha 2 agonists, spasmolytics, anticonvulsants, and antihistamines have local anesthetic effects. LAs are grouped into two categories: those of the ester type and those of the amino-amide group. The main clinical use of LAs is to achieve pain insensitivity, although they have other pharmacological uses such as antiarrhythmic, anti-asthmatic, anti-inflammatory, antithrombotic, bacteriostatic, and bactericidal effects that have been demonstrated, as well as antitumoral agent enhancer activity. Myotoxic effects have also been described. Local neuro toxicity has also been described when injected in the vicinity of the peripheral nervous system or at subarachnoid or epidural space. LAs are safe and effective drugs, although when wrongly managed, they can reach high plasma concentrations and produce systemic toxicity (LAST) that manifests primarily in the central nervous system (CNS) and cardiovascular system (CVS), causing side effects that can occasionally lead to death. This inhibitory phenomenon is reversible and transitory and is known as regional anesthesia and is classified into local, peripheral nerves, nervous plexuses, peridural, subarachnoid, and intravenous anesthesia. Local anesthetics (LAs) are drugs commonly used in medicine and especially in anesthesiology, which when administered in the vicinity of peripheral neural tissue produce changes in the conformation of voltage-dependent sodium channels that depolarize the neural tissue and produce analgesia, anesthesia, and sympathetic and motor block in the dermatomes of the affected nerves without altering consciousness. Nonanesthetic properties of LAs such as their antimicrobial, antineoplastic, antiarrhythmics, antitussive, and antiasthmatics effects have been described and are briefly reviewed. The quality of anesthesia and analgesia depends on the type of LA, dose, and application technique, while the deleterious effects are secondary to its plasma concentration. The pharmacological and toxic mode of action is primarily in the voltage-dependent sodium channels located in the cell membrane, which clinically produces analgesia, anesthesia, seizures, arrhythmias, and cardiac arrest. According to their chemical structure, these drugs are classified into two main groups: esters and amino amides however, there are three LAs with different characteristics: articaine, sameridine, and centbucridine. Since then, the evolution of LAs has been closely related to research motivated by its efficacy and safety versus toxicity. The use for anesthetic purposes dates back to 1884. The fascinating history of local anesthetics (LAs) began in South America with the herbal and traditional use of cocaine leaves by the indigenous peoples of Peru and Bolivia, the sacred plant of the Incas Erythroxylum coca.