LIDOCAINELidocaine (XYLOCAINE, others), an aminoethylamide (Figure 201), is the prototypical amide local anesthetic.Pharmacological Actions. Lidocaine produces faster, more intense, longer-lasting, and more extensive anesthesia than does an equal concentration of procaine.Lidocaine is an alternative choice for individuals sensitive to ester-type local anesthetics.Absorption, Fate, and Excretion. Lidocaine is absorbed rapidly after parenteral administration and from the GI and respiratory tracts. Although it is effectivewhen used without any vasoconstrictor, epinephrine decreases the rate of absorption, such that the toxicity is decreased and the duration of action usually isprolonged. In addition to preparations for injection, lidocaine is formulated for topical, opthalmic, mucosal, and transdermal use.A lidocaine transdermal patch (LIDODERM) is used for relief of pain associated with postherpetic neuralgia. An oral patch (DENTIP ATCH) is available forapplication to accessible mucous membranes of the mouth prior to superficial dental procedures. The combination of lidocaine (2.5%) and prilocaine (2.5%) in anocclusive dressing (EMLA, others) is used as an anesthetic prior to venipuncture, skin graft harvesting, and infiltration of anesthetics into genitalia. Lidocaine incombination with tetracaine (P LIAGLIS) in a formulation that generates a peel is approved for topical local analgesia prior to superficial dermatologicalprocedures such as filler injections and laser-based treatments. Lidocaine in combination with tetracaine is marketed in a formulation that generates heat uponexposure to air (SYNERA), which is used prior to venous access and superficial dermatological procedures such as excision, electrodessication, and shave biopsy ofskin lesions. The mild warming is intended to increase skin temperature by up to 5C for the purpose of enhancing delivery of local anesthetic into the skin.Lidocaine is dealkylated in the liver by CYPs to monoethylglycine xylidide and glycine xylidide, which can be metabolized further to monoethylglycine andxylidide. Both monoethylglycine xylidide and glycine xylidide retain local anesthetic activity. In humans, 75% of the xylidide is excreted in the urine as thefurther metabolite 4-hydroxy-2, 6-dimethylaniline (Arthur, 1987).Toxicity. The side effects of lidocaine seen with increasing dose include drowsiness, tinnitus, dysgeusia, dizziness, and twitching. As the dose increases, seizures,coma, and respiratory depression and arrest will occur. Clinically significant cardiovascular depression usually occurs at serum lidocaine levels that producemarked CNS effects. The metabolites monoethylglycine xylidide and glycine xylidide may contribute to some of these side effects.Clinical Uses. Lidocaine has a wide range of clinical uses as a local anesthetic; it has utility in almost any application where a local anesthetic of intermediateduration is needed. Lidocaine also is used as an antiarrhythmic agent (Chapter 29).

Procaine. Procaine (NOVOCAIN, others), introduced in 1905, was the first synthetic local anesthetic and is an amino ester. It has been supplanted by newer agents,and its use now is confined to infiltration anesthesia and occasionally for diagnostic nerve blocks. This is because of its low potency, slow onset, and shortduration of action. While its toxicity is fairly low, it is hydrolyzed in vivo to produce para-aminobenzoic acid, which inhibits the action of sulfonamides. Thus,large doses should not be administered to patients taking sulfonamide drugs.

Goodman Gillman