Specifics and mechanism of action
Local anesthetics are specific chemical tools whose main task is to act strictly locally. The drug must exert its effect exclusively at the site of its direct administration or application to tissues.
The primary target of such drugs is sensory nerve endings. The anesthetic interrupts the transmission of the pain signal right at the start. A crucial property of quality anesthesia is its absolute reversibility: as soon as the active substance wears off, the function of nerve conductors and endings is fully restored.
Clinically correct work of these pharmacological tools looks like this: pain is completely eliminated, but the patient does not lose consciousness, allowing the physician to maintain constant verbal contact throughout the procedure. Any systemic effects that develop after the absorption of drug molecules into the general circulation are regarded in clinical practice strictly as adverse and undesirable.
Factors influencing blood absorption
To minimize side effects and keep the drug in the working area, it is necessary to control the process of its transition into the systemic circulation. The absorption of local anesthetics depends on several key variables:
- Drug dose (total amount of administered substance).
- Solution concentration (the higher it is, the more actively diffusion into blood vessels can proceed).
- Presence of a vasoconstrictor (a substance that narrows blood vessels and prevents rapid washout of the anesthetic).
- Site of administration (features of blood supply to a specific anatomical region).
- Rate of administration of the solution into tissues.
Law of simple diffusion and the role of pKa
The penetration of the anesthetic through the nerve fiber membrane obeys the law of simple diffusion. However, not every form of the drug crosses the membrane. The effectiveness of anesthesia is directly proportional to the concentration of the anesthetic base that accumulates on the outer surface of the nerve membrane.
The rate of formation of this active base depends on the process of hydrolysis, which, in turn, is regulated by the dissociation constant (pKa). The main rule is: the closer the pKa value of a particular anesthetic is to the pH level of the surrounding tissues, the faster and more actively hydrolysis proceeds.
If we compare drugs in healthy (intact) tissues, we will see a clear dependency:
- Procaine has a high pKa value (8.9–9.1). Because of this, hydrolysis is slow, and it takes from 10 to 18 minutes for the clinical effect to set in.
- Articaine, lidocaine, and mepivacaine have a pKa at the level of 7.6–7.9. Their hydrolysis occurs significantly more efficiently, which is why profound anesthesia develops in just 1–5 minutes.
Reduced efficacy in inflammation
In the focus of inflammation, pharmacological tools often fail. The local anesthetic activity of administered solutions drops sharply, and there are three fundamental reasons for this.
First, tissue acidosis occurs. The acidic environment of inflamed tissues catastrophically impairs drug hydrolysis. As a result, critically little active anesthetic base is formed capable of penetrating the nerve membrane. There is a strict pattern: the higher the pKa of the drug, the more its activity will drop in an acidic environment (this is precisely why procaine is least active in the focus of inflammation).
Second, the drug concentration in the focus itself drops. Inflammation is always accompanied by hyperemia (increased blood flow), pronounced tissue edema, and increased vascular wall permeability. Under such conditions, the administered solution is instantly diluted by edema fluid and washed out into the systemic circulation very quickly.
Third, the sensitivity of the nerve tissue itself changes. The inflammatory infiltrate on its own is capable of increasing nerve conduction. In addition, aggressive inflammatory mediators accumulate in the focus (such as serotonin, bradykinin, prostaglandins). They directly affect receptors, significantly lowering the patient's baseline pain sensitivity threshold.
Briefly: answers to topical questions
What groups are local anesthetics divided into according to their chemical structure?
According to their chemical structure, local anesthetics are divided into two main groups: esters and amides (substituted acid amides).
- Esters — procaine (novocaine), benzocaine (anesthesin), tetracaine (amethocaine), cocaine. They are rapidly hydrolyzed by plasma and tissue esterases, which is why they are characterized by a short duration of action.
- Amides — articaine, bumecaine (pyromecaine), bupivacaine (marcaine), lidocaine, mesocaine (trimecaine), mepivacaine, ropivacaine. They are metabolized by liver enzymes, are not destroyed by esterases, act longer, and diffuse better into tissues.
Which specific vasoconstrictors are added to local anesthetic solutions?
The sympathomimetics adrenaline (epinephrine) and noradrenaline are added as vasoconstrictors to local anesthetic solutions.
- Adrenaline (epinephrine) — used in concentrations of 1:100,000 to improve hemostasis and 1:200,000 as the optimal dose for routine outpatient procedures.
- Noradrenaline — also used as a vasoconstrictor substance subject to rapid oxidation in solutions.
Vasoconstrictors are added to enhance and prolong the effect of local anesthetics.
Which ion channels does the local anesthetic bind to in order to block the impulse?
Local anesthetics bind to voltage-gated sodium channels of the neuronal membrane. Drugs in the non-ionized form penetrate the membrane, become ionized inside the axon, and block the channels from the inner side. This prevents the entry of sodium ions and the depolarization of the cell membrane. Binding is reversible (non-covalent) in nature. The anesthetic interacts with the receptor predominantly when the channel is in the activated (open) or inactivated state, whereas in the resting state, affinity is minimal.
What are the maximum permissible doses of articaine and mepivacaine for adults?
Sources indicate the maximum dose only for mepivacaine; the exact dosage of articaine is not provided. The maximum total dose of mepivacaine for injection in adults is 4.4 mg/kg, but not more than 300 mg. For articaine, it is only noted that in dentistry it is used as a 4% solution due to its low toxicity, although specific values for the maximum permissible dose are absent.
What clinical symptoms occur during the toxic effect of an anesthetic on the central nervous system?
During the toxic effect of local anesthetics on the central nervous system, excitation occurs followed by depression. Clinical symptoms escalate as the drug concentration increases and include:
- euphoria and depression;
- dizziness and paresthesia;
- motor excitation;
- speech, swallowing, and visual disturbances;
- seizures (including epileptiform ones);
- dyspnea and respiratory depression;
- collapse and coma.
The higher the pKa, the weaker the anesthetic during inflammation. Novocaine (pKa ~9) yields first due to tissue acidosis.
Class and exam questions
In what form does a local anesthetic penetrate the nerve membrane?
The drug penetrates the nerve fiber membrane strictly according to the law of simple diffusion in its active form as the uncharged anesthetic base.
Why is systemic absorption of an anesthetic into the bloodstream considered undesirable?
Because local anesthetics must act strictly locally at the injection site. Any effects arising after their absorption into the systemic circulation are adverse.
Why is the drug less effective in the presence of pronounced edema?
Due to hyperemia and high vascular permeability, the drug is rapidly washed out from the focus, and due to an abundance of fluid, it is diluted, which sharply reduces its working concentration.
What else to study on this topic
- Mechanism of action of inflammatory mediators (prostaglandins, bradykinin, serotonin) on the pain sensitivity threshold
- Comparative characteristics of the rate of hydrolysis of articaine, lidocaine, and mepivacaine
- Effect of vasoconstrictors on the locality of the drug's action
- Features of the diffusion of the anesthetic base through the nerve fiber membrane
Master the entire topic in the course "Surgical Dentistry"
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Local Anesthesia Tools" and 866 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 28 video lessons on the subject
Other topics in "Chapter 4. Anesthesia in Oral Surgery (S.A. Rabinovich, S.T. Sokhov)"
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.