CHAPTER 1. DRUGS DECREASING SENSITIVITY OF AFFERENT NERVE ENDINGS OR PREVENTING THEIR EXCITATION

1.1. Local anesthetics

Local anesthetic¹ drugs (anesthetics) cause local sensory loss. First, they eliminate painful sensation and this is why they are mainly used for local pain relief (anesthesia). With deepening anesthesia, temperature and other types of sensation are blocked, with touch and pressure reception being the last to go.

Anesthetics hinder the generation and conduction of excitatory impulse by affecting sensory nerve endings and nerve fibers. The mechanism of action of anesthetics is mainly based on voltage-dependent sodium channel blockade. This prevents both the appearance and conductiuon of the action potential (Fig. 1.1). Hydrophobic (non-ionized) compounds are thought to pass through the axonal membrane and block sodium channels from the inside. Hydrophilic compounds have some blocking effect, penetrating through the open sodium channels. This is why the activity of anesthetics that are weak bases depends on the pH of the medium that defines the ratio of ionized and nonionized parts of the drug. In case of inflammation with low pH value (acid medium) anesthetics are less effective since concentration of non-ionized compounds is then decreased.

Structurally, most anesthetics contain three basic fragments: aromatic structure, intermediate chain and amides. Aromatic structure is lipophilic and amides are hydrophilic. The middle part of a molecule is usually an aliphatic chain, structured as esters or amides.

¹ From Greek anesthesia - insensibility (an - without, aesthes - sensation).

Fig. 1.1. Effect of anesthetics on conduction of excitatory impulse along the nervous fiber. A - before anesthetic use. Excitation spreads along the nerve. Local current between points a and b causes weak depolarization in point b area, which increases membrane permeability for sodium ions. Their entrance into the axon increases the degree of depolarization. Above a certain depolarization threshold, action potential appears (the circle shown above indicates the screen of the oscilloscope with action potential) and further spread of the excitatory impulse occurs. B - after anesthetic use. Binding with membrane and blocking Na⁺-channels, the anesthetic hinders sodium ion penetration and membrane depolarization. Action potential does not occur. Conduction of nerve impuls is blocked.