Mechanism of action and environmental influence
The action of local anesthetics is based on the blockade of voltage-gated sodium channels in the neuronal membrane. The interaction is reversible and non-covalent. The specificity lies in the fact that the drugs actively bind to the channel only when it is open or inactivated; in the resting state, affinity is minimal. The more frequently an impulse passes along the nerve, the faster the block develops (the "use-dependence" phenomenon).
A critical factor in efficacy is the tissue pH level. Since anesthetics are weak bases, they become heavily ionized in an acidic environment (e.g., in a focus of inflammation). In their ionized form, molecules cannot pass through the cell membrane to the channel receptor, causing the quality of pain relief to drop sharply.
The quality of the blockade also depends on anatomy. Sensory fibers are thinner than motor fibers, so the drug diffuses into them faster. In the presence of a myelin sheath, the pattern of diffusion changes, and the blockade occurs at the nodes of Ranvier.
Types of local anesthesia
Depending on the site of administration, there are several key methods of pain relief:
- Topical (surface) anesthesia: application of the drug to mucous membranes (ophthalmology, ENT, endoscopy, burn treatment). The substance must easily penetrate through the epithelium to the receptors.
- Infiltration anesthesia: tissues in the surgical area are infiltrated layer by layer with 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.
- Conduction (nerve block) anesthesia: perineural administration that blocks conduction throughout the innervation zone. The more proximal (closer to the spinal cord) the injection is made, the more extensive the anesthesia zone.
- Spinal (subarachnoid) anesthesia: administration of a sterile solution directly into the cerebrospinal fluid at the lumbar level to block the roots innervating the pelvis and lower extremities.
- Epidural (peridural) anesthesia: administration of an anesthetic into the epidural space above the dura mater.
Drug classification
According to their chemical structure, all local anesthetics are divided into two large groups, which determines their pharmacokinetics:
- Esters (cocaine, tetracaine, benzocaine, procaine). They are rapidly degraded by plasma esterases, so their effect is short-lived.
- Substituted acid amides (lidocaine, trimecaine, bupivacaine, mepivacaine, bumecaine, articaine). They are not subject to tissue esterases and have a significantly longer duration of action.
Regarding clinical application, some drugs are intended exclusively for topical anesthesia (cocaine, tetracaine, benzocaine, bumecaine, pramocaine). 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. An absolutely universal drug suitable for any type of anesthesia is lidocaine.
Prevention of toxicity
During any type of pain relief, there is a risk of the drug being absorbed into the systemic circulation, causing a resorptive toxic effect. To reduce this risk, adrenomimetics (vasoconstrictors, e.g., epinephrine) are added to anesthetic solutions.
Vasoconstriction at the injection site solves several problems at once: it sharply slows down the penetration of the anesthetic into the blood, reduces systemic toxicity, and keeps the drug near the nerve fiber, thereby prolonging the local effect.
Briefly: answers to topical questions
What are the maximum daily doses of lidocaine and bupivacaine for infiltration anesthesia?
Maximum doses of injectable drugs depend on the presence of a vasoconstrictor and the patient's age.
| Drug | Maximum dose |
|---|---|
| Lidocaine (Lidocaine) | Daily dose — 300 mg (4.4 mg/kg). In children: 3–5 mg/kg without epinephrine, up to 7 mg/kg with epinephrine. |
| Bupivacaine | In children: 1–2 mg/kg without epinephrine, up to 3 mg/kg with epinephrine. |
Precise data on the maximum daily dose of bupivacaine for adults are not presented in the sources.
What symptoms develop during a systemic toxic reaction to an overdose of local anesthetics?
During a local anesthetic overdose, symptoms progress as the drug concentration increases. Dizziness, paresthesia, motor agitation, convulsions (including epileptiform ones), shortness of breath, and collapse are possible. The pathogenesis is associated with impaired neuromuscular transmission and decreased acetylcholine release from motor nerve endings.
Class and exam questions
Why is an anesthetic weakly effective during tooth extraction against the background of purulent inflammation?
In inflamed tissues, the environment becomes acidic. Anesthetics are weak bases, and in an acidic environment, they convert into an ionized form, losing their ability to penetrate through the nerve membrane to sodium channels.
Why is epinephrine added to local anesthesia drugs?
Epinephrine constricts local blood vessels. This slows down the absorption of the anesthetic into the blood, reduces its toxicity to the body, and increases the duration of local pain relief.
Why does pain disappear first after a nerve block, while the ability to move persists longer?
This is due to nerve anatomy: sensory fibers are thinner than motor fibers. The drug diffuses faster into the thin fiber, so the blockade of pain impulses occurs earlier.
How does subarachnoid anesthesia differ from epidural anesthesia?
During subarachnoid anesthesia, the drug is injected directly into the cerebrospinal fluid (CSF), while during epidural anesthesia, it is injected into the space located above the dura mater.
What else to study on this topic
- Dependence of the effect on impulse frequency (use-dependence)
- Pharmacokinetics of amides and their metabolism in the liver
- Symptoms of systemic resorptive toxicity
- Features of the blockade of nodes of Ranvier in myelinated fibers
- Selection of the optimal concentration of solutions for various types of anesthesia
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