What is the mechanism of action of local anesthetics?

• A. Block voltage-gated calcium channels on nerve membranes
• B. Block voltage-gated sodium channels on nerve membranes
• C. Inhibit COX enzymes
• D. Inhibit serotonin reuptake

Answer: (B)

Local anesthetics block voltage-gated sodium channels on nerve membranes, preventing depolarization and the propagation of action potentials. They diffuse into the nerve as nonionized molecules, then become ionized inside the cell and bind to the intracellular portion of the sodium channel, stabilizing it in the inactivated state and stopping Na+ influx when the neuron would normally fire. This halts impulse transmission, especially in small, myelinated fibers that carry pain signals, producing regional numbness. The acidity of the tissue can affect onset, since more acidic environments reduce the amount of nonionized drug available to cross membranes; and the block is use-dependent, becoming more pronounced with active nerve fibers. These drugs do not work by blocking calcium channels, COX enzymes, or serotonin reuptake.