Physicochemical Properties and Dosing Regimens
Chemically, the drug is the $\beta$-diethylaminoethyl ester of $p$-aminobenzoic acid. It is available as a hydrochloride salt, which is highly soluble in water (1:1 ratio) and readily soluble in alcohol (1:8). When injected into tissues, it provides pronounced but short-acting anesthesia.
The choice of solution concentration depends on the type of anesthesia performed:
- Infiltration anesthesia: 0.25%–0.5% solutions are standard.
- Vishnevsky method (tight creeping infiltration): requires the lowest concentrations — 0.125%–0.25%.
- Nerve block anesthesia: 1%–2% solutions are used.
- Spinal anesthesia: rarely used in modern practice; a highly concentrated 5% solution is utilized.
The drug is practically never used for topical (surface) anesthesia. This is because it penetrates mucous membranes extremely poorly, and achieving an effect would require a concentration of about 10%.
Metabolism and Drug Interactions
In the body, the drug undergoes relatively rapid hydrolysis involving plasma cholinesterase and various tissue esterases. The rationale for many clinical effects and drug interactions stems precisely from the properties of the resulting breakdown products.
Molecule degradation yields two key metabolites:
- Para-aminobenzoic acid (PABA). It shares a chemical similarity with sulfonamides and acts as their competitive antagonist. If administered simultaneously, the local anesthetic will attenuate the antimicrobial action of sulfonamides.
- Diethylaminoethanol. This metabolite exhibits a pronounced vasodilating effect. Due to local vasodilation, the absorption of the anesthetic itself into the bloodstream is accelerated. This is an undesirable phenomenon because it increases the risk of systemic toxicity while simultaneously shortening the duration of local anesthesia.
To counteract the vasodilating effect of diethylaminoethanol, a vasoconstrictor (e.g., 0.1% epinephrine solution) is added to the solution. This slows resorption, reduces the likelihood of toxic effects, and significantly prolongs local anesthesia.
Resorptive (Systemic) Effects
When the drug is absorbed into the bloodstream, systemic effects develop, predominantly directed toward the depression of various bodily functions.
Effects on the Nervous System and Synaptic Transmission The drug depresses visceral reflexes and suppresses polysynaptic spinal reflexes. It also exerts an anticholinergic effect, reducing the release of the neurotransmitter acetylcholine from preganglionic fibers (autonomic ganglion blockade develops). In high doses, the drug is capable of reducing acetylcholine release from motor nerve terminals, leading to impaired neuromuscular transmission.
Effects on Smooth Muscle and the Cardiovascular System Upon entering the systemic circulation, the drug exerts a spasmolytic effect, reducing smooth muscle spasms in internal organs. The cardiovascular system exhibits a hypotensive effect (decreased blood pressure) and a transient antiarrhythmic effect. The latter is due to the drug's ability to decrease myocardial automaticity and excitability, as well as increase its effective refractory period.