All<unk> s are membrane-stabilizing drugs; they reversibly decrease the rate of depolarization and repolarization of excitable membranes (like nociceptors). Though many other drugs also have membrane-stabilizing properties, not all are used as<unk> s (propranolol, for example, though it has<unk>  properties).<unk>  drugs act mainly by inhibiting sodium influx through sodium-specific ion channels in the neuronal cell membrane, in particular the so-called voltage-gated sodium channels. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel.<unk>  drugs bind more readily to sodium channels in an activated state, thus onset of neuronal blockade is faster in rapidly firing neurons. This is referred to as state-dependent blockade.<unk> s are weak bases and are usually formulated as the hydrochloride salt to render them water-soluble. At a pH equal to the protonated base's pKa, the protonated (ionized) and unprotonated (unionized) forms of the molecule exist in equimolar amounts, but only the unprotonated base diffuses readily across cell membranes. Once inside the cell, the<unk>  will be in equilibrium, with the formation of the protonated (ionized) form, which does not readily pass back out of the cell. This is referred to as "ion-trapping". In the protonated form, the molecule binds to the<unk>  binding site on the inside of the ion channel near the cytoplasmic end. Most<unk> s work on the internal surface of the membrane - the drug has to penetrate the cell membrane, which is achieved best in the nonionised form. This is exemplified by the permanently ionised<unk>  RAC 421-II which cannot diffuse across the cell membrane but, if injected into the cytosol of a nerve fibre, can induce NaKATPase blockage and anaesthetic effects. Acidosis such as caused by inflammation at a wound partly reduces the action of<unk> s. This is partly because most of the anesthetic is ionized and therefore unable to cross the cell membrane to reach its cytoplasmic-facing site of action on the sodium channel. All nerve fibers are sensitive to<unk> s, but due to a combination of diameter and myelination, fibers have different sensitivities to<unk>  blockade, termed differential blockade. Type B fibers (sympathetic tone) are the most sensitive followed by type C (pain), type A delta (temperature), type A gamma (proprioception), type A beta (sensory touch and pressure), and type A alpha (motor). Although type B fibers are thicker than type C fibers, they are myelinated, thus are blocked before the unmyelinated, thin C fiber.
Local anesthetic
Muscle relaxant
Equianalgesic
Inhalational anesthetic
General anaesthetic
Querulant
Analgesic
Local anesthesia