Local anesthetics work by blocking sodium (Na+) channels in nerve axons, which are necessary for conducting action potentials. These channels have three states: closed, open, and inactive. Local anesthetics are effective only when these channels are in the open or inactive states, and they must enter the cell's cytoplasm to block these channels, which only the un-ionized form of the drug can do. This effectiveness is reduced in acidic environments, such as inflamed or infected tissues, because there is less un-ionized drug available to enter the cells.
Local anesthetics are particularly effective in nerves that are actively sending pain signals or experiencing frequent action potentials, as these conditions keep the Na+ channels in states that are susceptible to blockage. They are less effective in conditions where signals are infrequent, allowing time for the drug to dissipate and channels to close. High doses can block even infrequent signals, but this can lead to local anesthetic toxicity to the heart and central nervous system. Additionally, local anesthetics are more effective on smaller nerve fibers - the thinly myelinated A delta and the unmyelinated C fibers - which typically carry nociceptive pain signals.
In the app: the Master Anesthesia app's Local Anesthetic calculator (Calculators, then Local) computes maximum safe doses of the common agents from the patient's weight and dosing-weight basis, and flags the thresholds where local anesthetic systemic toxicity becomes a concern.
