Essentials of Local Anesthetic Pharmacology

Abstract

It is impossible to provide effective dental care without the use of local anesthetics. This drug class has an impressive history of safety and efficacy, but all local anesthetics have the potential to produce significant toxicity if used carelessly. The purpose of this review is to update the practitioner on issues regarding the basic pharmacology and clinical use of local anesthetic formulations. Key Words: Local anesthetic pharmacology GENERAL PROPERTIES OF LOCAL ANESTHETICSLocal anesthetics interrupt neural conduction by inhibiting the influx of sodium ions. In most cases, this follows their diffusion through the neural membrane into the axoplasm, where they enter sodium channels and pre- The aromatic ring improves the lipid solubility of the compound, which can be enhanced further by aliphatic substitutions at locations designated (R). Greater lipid solubility enhances diffusion through nerve sheaths, as well as the neural membranes of individual axons comprising a nerve trunk. This property correlates with potency because a greater portion of an administered dose can enter neurons. Because bupivacaine is more lipid soluble than lidocaine, it is more potent and is prepared as a 0.5% concentration (5 mg/mL) rather than a 2% concentration (20 mg/mL).The terminal amine may exist in a tertiary form (3 bonds) that is lipid soluble or as a quaternary form (4 bonds) that is positively charged and renders the molecule water soluble. As explained above, the aromatic ring determines the actual degree of lipid solubility, but the terminal amine acts as an ''on-off switch'' allowing the local anesthetic to exist in either lipid-soluble or water-soluble conformations. The tertiary and quaternary forms each play a pivotal role in the sequence of events leading to conduction block.For the local anesthetic base to be stable in solution, it is formulated as a hydrochloride salt. As such, the molecules exist in a quaternary, water-soluble state at the time of injection. However, this form will not penetrate the neuron. The time for onset of local anesthesia is therefore predicated on the proportion of molecules that convert to the tertiary, lipid-soluble structure when exposed to physiologic pH (7.4). The ionization constant (pKa) for the anesthetic predicts the proportion of molecules that exists in each of these states. By definition, the pKa of a molecule represents the pH at which 50% of the molecules exist in the lipid-soluble tertiary form and 50% in the quaternary, water-soluble form. The pKa of all local anesthetics is Ͼ7.4 (physiologic pH), and therefore a greater proportion the molecules exists in the quaternary, water-soluble form when injected into tissue having normal pH of 7.4. Furthermore, the acidic environment associated with inflamed tissues favors the quaternary, water-soluble configuration even further. Presumably, this accounts for difficulty when attempting to anesthetize inflamed or infected tissues; fewer molecules exist as tertiary lipid-soluble forms that can penetrate nerves. In these situations, b...

Dentists' knowledge regarding signs and symptoms of the systemic toxicity of local anesthetic solutions

“…The activation of α1 receptor produces the contraction of smooth muscle in blood vessels (vasoconstriction); the binding to β1 receptor, which is found in the heart and small intestine, induces cardiac stimulation and lipolysis; the stimulation of β2, found in bronchial and uterine vascular beds, induces vasodilatation and bronchodilatation [4][5]7 . Excess of VCs may also cause systemic side effects associated with the stimulation of adrenergic receptors, including elevated systolic blood pressure and heart rate, and from simple palpitations to more serious cardiac arrhythmias.…”

“…local anesthetics, vasoconstrictors) with minimal or no systemic toxicity [1][2] . The main mechanism of action proposed for local anesthetics (LAs) is related to the binding of these substances to sodium channels receptors (Na + ), leading to the reduction or elimination of the permeability of these ions and interruption of the nervous conduction [3][4] . The most widely used LAs in dentistry are those containing an amide bond, of which 2-3% lidocaine or mepivacaine, 3% prilocaine, 0.5% bupivacaine, and 4% articaine (injectable form) are available in Brazil.…”

Articaine: a review of the literature

“…The thiophene ring allows greater lipid solubility and potency as a greater portion of an administered dose can enter neurons. 5 It is the only amide anaesthetic containing an ester group, allowing hydrolysation in unspecific blood esterases. 6 Articaine is one of the most recent local anaesthetic drugs made available to dentists worldwide.…”

Efficacy of 4 % Articaine and 2 % Lidocaine: A clinical study

“…Moreover, Articaine is the only amide local anesthetic containing an ester group in its molecular structure-thus allowing metabolization of the drug both by plasma esterases and by liver microsomal enzymes. The clinical advantages of Articaine include the duration of its anesthetic effect-only surpassed by ultralong acting anesthetics such as Bupivacaine, Etidocaine and Ropivacaine-and its superior diffusion through bony tissue [4][5][6][7]. Since its discovery various studies have been carried out which compared Articaine with various anesthetic agents.…”