**4. Mechanism of action of local anesthetics**

Local anesthetics inhibit depolarization of the nerve membrane by interfering with both Na+ and K+ currents. The action potential is not propagated because the threshold level is never attained.

Although the exact mechanism by which local anesthetics retard the influx of sodium ions into the cell is unknown, two theories have been proposed.

The membrane expansion theory postulates that the local anesthetic is absorbed into the cell membrane, expanding the membrane and leading to narrowing of the sodium channels. This hypothesis has largely given way to the specific receptor theory.

This theory proposes that the local anesthetic diffuses across the cell membrane and binds to a specific receptor at the opening of the voltage-gated sodium channel. The local anesthetic affinity to the voltage-gated Na+ channel increases markedly with the excitation rate of the neuron. This binding leads to alterations in the structure or function of the channel and inhibits sodium ion movement.

Blockade of leak K+ currents by local anesthetics is now also believed to contribute to conduction block by reducing the ability of the channels to set the membrane potential.

On the basis of their diameter, nerve fibers are categorized into 3 types. Type A fibers are the largest and are responsible for conducting pressure and motor sensations. Type B fibers are myelinated and moderate in size. Type C fibers, which transmit pain and temperature sensations, are small and unmyelinated. As a result, anesthetics block type C fibers more easily than they do type A fibers.

All local anesthetics have a similar chemical structure, which consists of three components: an aromatic portion, an intermediate chain, and an amine group. The aromatic portion, usually composed of a benzene ring, is lipophilic, whereas the amine portion of the anesthetic is responsible for its hydrophilic properties.

The degree of lipid solubility of each anesthetic is an important property because its lipid solubility enables its diffusion through the highly lipophilic nerve membrane. The extent of an anesthetic's lipophilicity is directly related to its potency.

Local anesthetics are weak bases that require the addition of hydrochloride salt to be water soluble and therefore injectable. Salt equilibrates between an ionized form and a nonionized form in aqueous solution.

Once membrane depolarization is complete, the membrane becomes impermeable to sodium ions again, and the conductance of potassium ions into the cell increases. The process restores the excess of intracellular potassium and extracellular sodium and

Alterations in the nerve cell membrane potential are termed the action potential. Leak currents are present through all the phases of the action potential, including setting of the

Local anesthetics inhibit depolarization of the nerve membrane by interfering with both Na+ and K+ currents. The action potential is not propagated because the threshold level is never

Although the exact mechanism by which local anesthetics retard the influx of sodium ions

The membrane expansion theory postulates that the local anesthetic is absorbed into the cell membrane, expanding the membrane and leading to narrowing of the sodium channels.

This theory proposes that the local anesthetic diffuses across the cell membrane and binds to a specific receptor at the opening of the voltage-gated sodium channel. The local anesthetic affinity to the voltage-gated Na+ channel increases markedly with the excitation rate of the neuron. This binding leads to alterations in the structure or function of the channel and

Blockade of leak K+ currents by local anesthetics is now also believed to contribute to conduction block by reducing the ability of the channels to set the membrane potential.

On the basis of their diameter, nerve fibers are categorized into 3 types. Type A fibers are the largest and are responsible for conducting pressure and motor sensations. Type B fibers are myelinated and moderate in size. Type C fibers, which transmit pain and temperature sensations, are small and unmyelinated. As a result, anesthetics block type C fibers more

All local anesthetics have a similar chemical structure, which consists of three components: an aromatic portion, an intermediate chain, and an amine group. The aromatic portion, usually composed of a benzene ring, is lipophilic, whereas the amine portion of the

The degree of lipid solubility of each anesthetic is an important property because its lipid solubility enables its diffusion through the highly lipophilic nerve membrane. The extent of

Local anesthetics are weak bases that require the addition of hydrochloride salt to be water soluble and therefore injectable. Salt equilibrates between an ionized form and a nonionized

reinstates the negative resting membrane potential.

resting membrane potential and repolarization.

attained.

inhibits sodium ion movement.

easily than they do type A fibers.

form in aqueous solution.

anesthetic is responsible for its hydrophilic properties.

an anesthetic's lipophilicity is directly related to its potency.

**4. Mechanism of action of local anesthetics** 

into the cell is unknown, two theories have been proposed.

This hypothesis has largely given way to the specific receptor theory.

Equilibration is crucial because, although the ionized form is injectable, the nonionized base has the lipophilic properties responsible for its diffusion into the nerve cell membrane. The duration of action of an anesthetic or the period during which it remains effective is determined by its protein-binding activity, because the anesthetic receptors along the nerve cell membrane are proteins.

The intermediate chain, which connects the aromatic and amine portions, is composed of either an ester or an amide linkage. This intermediate chain can be used in classifying local anesthetics.
