PHARMACOLOGY AND THERAPEUTICS-LOCAL ANAESTHETICS-PHARMACODYNAMICS-MEMBRANE POTENTIALS
The primary mechanism of action of local anesthetics is blockade of voltage-gated sodium channels. The excitable membrane of nerve axons, like the membrane of cardiac muscle and neuronal cell bodies, maintains a resting transmembrane potential of –90 to –60 mV. During excitation, the sodium channels open, and a fast, inward sodium current quickly depolarizes the membrane toward the sodium equilibrium potential (+40 mV). As a result of this depolarization process, the sodium channels close (inactivate) and potassium channels open. The outward flow of potassium repolarizes the membrane toward the potassium equilibrium potential (about –95 mV); repolarization returns the sodium channels to the rested state with a characteristic recovery time that determines the refractory period. The transmembrane ionic gradients are maintained by the sodium pump. These ionic fluxes are similar to, but simpler than, those in heart muscle, and local anesthetics have similar effects in both tissues.
