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INTRODUCTION

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Local anesthetics are used to provide intraoperative regional anesthesia and postoperative analgesia. Synthesized from the coca plant in 1860, cocaine was the first local anesthetic adapted for clinical use. Although quite effective, cocaine has significant limitations. It has addictive potential, can irritate nerves, and is still the only local anesthetic capable of blocking norepinephrine reuptake at postganglionic sympathetic nerve terminals. The introduction of lidocaine in 1948 began the modern era of local anesthetics.

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GENERAL PROPERTIES

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Chemical Structure

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All currently available local anesthetics consist of three components:

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  1. Aromatic benzene ring

  2. Tertiary amine

  3. Intermediate hydrocarbon linkage

    • Ester (–COO–)

    • Amide (–NH–CO–)

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Based on the chemical bond, local anesthetics are classified into two groups: esters and amides (Figure 57-1). Commonly used ester local anesthetics include benzocaine, 2-chloroprocaine, cocaine, procaine, and tetracaine. Since ester links are more easily broken, these drugs are relatively unstable in solution. Commonly used amide local anesthetics include bupivacaine, etidocaine, levobupivacaine, lidocaine, mepivacaine, prilocaine, and ropivacaine. Amide solutions are very stable and can be autoclaved.

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Stereoisomerism

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Stereoisomerism, or chirality, describes molecules with the same structural formula but are different spatial orientations around the specific chiral center. Enantiomers are stereoisomers that exist as nonsuperimposable mirror images when rotating the plane of polarized light. Local anesthetics exist as either single enantiomers or racemic mixtures (solutions containing equal amounts of the two enantiomers). The two isoforms can possess different clinically important pharmacological properties (potency, adverse effects). For example, bupivacaine, a racemic mixture, has greater potential for cardiac toxicity than the single enantiomers, ropivacaine and levobupivacaine. Differences in chirality perhaps lead to differences in affinity for myocardial sodium channels.

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Vasoactivity

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Except for cocaine, all local anesthetics exert a biphasic effect on vascular smooth muscle. At low concentrations (not clinically relevant), they produce vasoconstriction. At high concentrations, such as that used for regional anesthesia, they are local vasodilators. Lidocaine and mepivacaine have greater intrinsic vasodilatory effects than bupivacaine and ropivacaine. This vasodilation leads to greater vascular uptake, increased systemic absorption, and decreased local anesthetic duration.

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PHARMACOKINETICS

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Compared to drugs administered systemically, local anesthetics do not abide closely to classic pharmacokinetics. This is because local anesthetics are deposited directly at the target site, whether in the skin, subcutaneous tissue, muscle, or epidural space. Absorption, distribution, and elimination help to decrease their clinical effects.

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Absorption

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After a local anesthetic is placed around the intended nerve or plexus, some of the drug becomes absorbed into the circulation. Systemic absorption is determined by a variety of factors, including dose, site of injection (vascularity), local tissue blood flow, use of vasoconstrictor adjuvants, and the physiochemical properties of the ...

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