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  • Image not available. Sodium (Na) channels are membrane-bound proteins that are composed of one large α subunit, through which Na ions pass, and one or two smaller β subunits. Voltage-gated Na channels exist in (at least) three states—resting (nonconducting), open (conducting), and inactivated (nonconducting). Local anesthetics bind a specific region of the α subunit and inhibit voltage-gated Na channels, preventing channel activation and the Na influx associated with membrane depolarization.
  • Image not available. Sensitivity of nerve fibers to inhibition by local anesthetics is determined by axonal diameter, myelination, and other anatomic and physiological factors.
  • Image not available. Potency correlates with octanol solubility, which in turn reflects the ability of the local anesthetic molecule to permeate lipid membranes. Potency is increased by adding large alkyl groups to a parent molecule. There is no measurement of local anesthetic potency that is analogous to the minimum alveolar concentration of inhalation anesthetics.
  • Image not available. Onset of action depends on many factors, including lipid solubility and the relative concentration of the nonionized lipid-soluble form (B) and the ionized water-soluble form (BH+), expressed by the pKa. The pKa is the pH at which the fraction of ionized and nonionized drug is equal. Less potent, less lipid-soluble agents generally have a faster onset than more potent, more lipid-soluble agents.
  • Image not available. Duration of action correlates with potency and lipid solubility. Highly lipid-soluble local anesthetics have a longer duration of action, presumably because they more slowly diffuse from a lipid-rich environment to the aqueous bloodstream.
  • Image not available. In regional anesthesia local anesthetics are typically injected or applied very close to their intended site of action; thus their pharmacokinetic profiles are much more important determinants of elimination and toxicity than of their desired clinical effect.
  • Image not available. The rate of systemic absorption is related to the vascularity of the site of injection: intravenous (or intraarterial) > tracheal > intercostal > paracervical > epidural > brachial plexus > sciatic > subcutaneous.
  • Image not available. Ester local anesthetics are predominantly metabolized by pseudocholinesterase. Amide local anesthetics are metabolized (N-dealkylation and hydroxylation) by microsomal P-450 enzymes in the liver.
  • Image not available. The central nervous system is vulnerable to local anesthetic toxicity and is the site of premonitory signs of rising blood concentrations in awake patients.
  • Image not available. Major cardiovascular toxicity usually requires about three times the local anesthetic concentration in blood as that required to produce seizures.
  • Image not available. Unintentional intravascular injection of bupivacaine during regional anesthesia may produce severe cardiovascular toxicity, including left ventricular depression, atrioventricular heart block, and life-threatening arrhythmias such as ventricular tachycardia and fibrillation.
  • Image not available. True hypersensitivity reactions to local anesthetic agents—as distinct from systemic toxicity caused by excessive plasma concentration—are uncommon. Esters appear more likely to induce a true allergic reaction (due to IgG or IgE antibodies) especially if they are derivatives (eg, procaine or benzocaine) of p-aminobenzoic acid, a known allergen.

Local and regional anesthesia and analgesia techniques depend on a group of drugs—local anesthetics—that transiently inhibit sensory, motor, or autonomic nerve function, or a combination of these functions, when the drugs are injected or applied near neural tissue. This chapter presents the mechanism of action, ...

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