Mechanism of action of Local anesthetics:
Ref: Miller Textbook of Anaesthesia. 6th editionExplanation:Mechanism of action of Local anestheticsThe primary mechanism of action of local anesthetics is blockade of voltage-gated sodium channels.The excitable membrane of nerve axons, like the membrane ot 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 t+40 mV).As a result of depolarization, 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.Biologic toxins such as batrachotoxin. aconitine, veratridine. and some scorpion venoms bind to receptors within the channel and prevent inactivation. This results in prolonged influx of sodium through the channel and depolarization of the resting potential.The marine toxins tetrodotoxin (TTX) and saxitoxin block sodium channels by binding to channel receptors near the extracellular surface. Their clinical effects superficially resemble those of local anesthetics (ie, block of conduction without a change in the resting potential) even though their receptor site is quite different.The blockade of sodium channels by most local anesthetics is both voltage- and time-dependent: Channels in the rested state, which predominate at more negative membrane potentials, have a much lower affinity for local anesthetics than activated (open state) and inactivated channels, w-hich predominate at more positive membrane potentials.Elevated extracellular calcium partially antagonizes the action of local anesthetics owing to the calcium-induced increase in the surface potential on the membrane (which favors the low-affinity rested state).Increases in extracellular potassium depolarize the membrane potential and favor the inactivated state, enhancing the effect of local anesthetics.
Inhibition of Na+ channels
Inhi bition of Na+ K+ ATPase
Inhibition of K+ channels
Inhibition of Ca2+channels
Miscellaneous (Local and Regional Anesthesia)