Chapters authored
Pharmacokinetics and Pharmacodynamics of Local Anesthetics
Local anesthetics are basically weak bases whose structure consists of an aromatic half connected to a substituted amine through an ester amide linkage. The pKa values of local anesthetics are close to physiological pH, both protonated and unprotonated forms are present. The individual structures confer different physiochemical and clinical characteristics. Potency is correlated to lipid solubility in vitro, but less so in vivo. The duration of action is associated with the extent of protein binding. The onset of action is related to pKa. The intrinsic vasodilator activity varies between drugs and influences potency and duration of action. Local anesthetics block nerve conduction and interact directly with specific receptor on the Na+ channel, inhibiting Na+ ion influx and impairing Propagation of the action potential in axons. There are some characteristics in the blocking of nerve conduction and are related to size and function of the peripheral nerves, and to the fact that a specific concentration of local anesthetics may produce a different intensity of block. Some pathological states like decreased cardiac output, severe hepatic disease, renal disease, cholinesterase activity, fetal acidosis, sepsis, etc. altered the pharmacokinetics and pharmacodynamics of local anesthetics.
Part of the book: Topics in Local Anesthetics