Mechanism of Action and Environmental Effects
The action of local anesthetics is based on the blockade of voltage-gated sodium channels in the neuronal membrane. This interaction is reversible and non-covalent. Specificity lies in the fact that these drugs actively bind to the channel only when it is open or inactivated; affinity is minimal in the resting state. The higher the frequency of impulses passing through the nerve, the faster the block develops (a phenomenon known as use-dependence).
An extremely important factor for efficacy is tissue pH. Because anesthetics are weak bases, they become heavily ionized in an acidic environment (e.g., at a site of inflammation). In the ionized form, molecules cannot cross the cell membrane to reach the channel receptor, causing local pain relief to drop sharply.
Blockade quality also depends on anatomy. Sensory fibers are thinner than motor fibers, so the drug diffuses into them more quickly. When a myelin sheath is present, the pattern of diffusion changes, and the block occurs at the nodes of Ranvier.
Types of Local Anesthesia
Depending on the site of administration, several key regional anesthesia techniques are distinguished:
- Surface (topical) anesthesia: application of the agent to mucous membranes (ophthalmology, ENT, endoscopy, burn treatment). The substance must easily penetrate the epithelium to reach receptors.
- Infiltration anesthesia: layered impregnation of tissues in the surgical area using a large volume (200–500 mL) of a low-concentration anesthetic (0.25–0.5%). Isotonic (0.9%) or hypotonic (0.6%) sodium chloride solution is used as a solvent.
- Nerve block (conduction): perineural administration that blocks conduction throughout the entire innervation zone. The more proximal the injection (closer to the spinal cord), the more extensive the anesthesia zone.
- Spinal (subarachnoid) anesthesia: direct injection of a sterile solution into the cerebrospinal fluid at the lumbar level to block nerve roots innervating the pelvis and lower extremities.
- Epidural anesthesia: injection of the anesthetic into the epidural space (above the dura mater).
Classification of Drugs
Based on their chemical structure, all local anesthetics are divided into two major groups, which determines their pharmacokinetics:
- Esters (cocaine, tetracaine, benzocaine, procaine). They are rapidly degraded by plasma esterases, making their effect short-lived.
- Substituted acid amides (lidocaine, trimecaine, bupivacaine, mepivacaine, bumecaine, articaine). They are resistant to tissue esterases and have a significantly longer duration of action.
Based on clinical application, some agents are used exclusively for topical anesthesia (cocaine, tetracaine, benzocaine, bumecaine, pramoxine). They are not used for injections due to high systemic toxicity or water insolubility. Procaine, trimecaine, bupivacaine, and articaine are suitable for infiltration and nerve blocks. Lidocaine is an entirely universal agent suitable for any type of anesthesia.
Prevention of Toxicity
During any regional anesthesia procedure, there is a risk of systemic drug absorption leading to systemic toxicity. To reduce this risk, vasoconstrictors (adrenomimetics, such as epinephrine) are added to anesthetic solutions.
Vasoconstriction at the injection site accomplishes several goals at once: it sharply slows down the penetration of the anesthetic into the bloodstream, reduces systemic toxicity, and keeps the drug near the nerve fiber, thereby prolonging the local effect.