Describe the pharmacokinetics of local anesthetics.
The blood concentration of local anesthetics is determined by the following: the amount injected, the rate of absorption from the site of injection, the rate of tissue distribution, and the rate of biotransformation and excre-tion of the drug. Local absorption is a function of the site selected, dose injected, and blood flowing through the area. Of all the traditional locations, absorption of local anesthetics is most rapid following application to airway epithelium (especially alveoli). Other types of blockade have been assessed with regard to associated blood levels of local anesthetic. In decreasing order of associated local anesthetic blood concentrations, they are intrapleural, intercostal, lumbar epidural, brachial plexus, and subcuta-neous. Consequently, local anesthetic administered into the airway is more likely to result in dangerously high blood levels than the same dose injected subcutaneously. Absorption is, also, dependent on perfusion of the injection site. As blood flow past the area is diminished, absorption of local anesthetic is decreased. For this reason, vasoconstrictors are often added to local anesthetic solutions. Epinephrine, 5 μg/ml (1:200,000), is frequently mixed with lidocaine or mepivacaine regardless of the site of injection. Although epinephrine will reduce absorption of bupivacaine and etidocaine during major nerve blocks, it does not significantly alter plasma concentrations following lumbar epidural blockade.
Absorbed local anesthetics are distributed first to highly perfused tissues, such as lung, brain, and heart. This is the α-elimination phase. A short α-elimination phase indi-cates rapid distribution from blood to tissues. Residual local anesthetics in plasma are next distributed to poorly perfused areas (β-elimination phase) as well as being metabolized and excreted (γ-elimination phase).
Ester local anesthetics are hydrolyzed by plasma pseudocholinesterases. Qualitative or quantitative pseudo-cholinesterase deficiencies may impair ester local anesthetic metabolism. Para-aminobenzoic acid is an important ester degradation product because it is a highly allergenic molecule. Amides are metabolized in the liver to a variety of by-products. Sources of impaired hepatic function such as extremes of age, congestive heart failure, and hepatitis will decrease amide biotransformation.