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Keywords:

  • Local anesthetics;
  • Local anesthetics chemistry;
  • Pharmacokinetic variables;
  • Analytical methods

Abstract

Local anesthetics (LA) are used for the prevention and relief of both acute and chronic pain. The local anesthetic molecule consists of three components; each of these contributes distinct properties to the molecule. The onset of action is determined by tissue pH, the pKa of the particular agent used, and the amount of nonionized drug available in the tissue. The duration of action depends on the length of time that the drug binds to the membrane. Most local anesthetics were produced as enantiomeric mixtures known as racemates, although it is recognized that each enantiomer possesses quite different pharmacological properties. All amide-type local anesthetics, except for lidocaine, contain a chiral center, meaning that two enantiomers exist. Enantiomers have the same physicochemical properties and differ only in the way that they rotate plane-polarized light. However, their biological behavior, in terms of pharmacokinetic and pharmacodynamic characteristics, can be very different. The clinical response to a particular local anesthetic or its toxicity may vary substantially from patient to patient; dosing often requires careful titration. Interindividual variability is caused by several factors including the pharmacokinetics features of the drug, pharmacodynamic properties or patient's characteristics.