Articaine: Pharmacology, Efficacy and Safety

General Description

Articaine, a unique amide local anesthetic with a thiophene ring, exhibits enhanced lipid solubility and potency. Its rapid metabolism by blood esterases into inactive articainic acid contributes to lower systemic toxicity and wider therapeutic range. Age affects its clearance and distribution. Despite controversy over potential neurotoxicity in dental procedures like IANB, articaine is generally considered safe and effective, with minimal adverse events compared to lignocaine. It offers reliable anesthesia for various procedures, with no significant clinical advantage between 2% and 4% solutions. Further research is needed to clarify safety concerns and optimize its usage.

Figure 1. Articaine

Pharmacology

Articaine is a unique amide local anesthetic with distinct pharmacological properties. Unlike other amide local anesthetics, Articaine contains a thiophene ring instead of a benzene ring, which enhances its lipid solubility and potency. This structural difference allows a larger portion of the administered dose to enter neurons, leading to increased efficacy. One of the key features of Articaine is its metabolism. The presence of an ester group in Articaine allows hydrolysis by unspecific blood esterases. Approximately 90% of Articaine undergoes rapid hydrolysis in the blood to form its inactive metabolite, articainic acid, which is then excreted by the kidneys. This rapid metabolism contributes to Articaine's lower systemic toxicity and wider therapeutic range compared to other amide local anesthetics. The metabolism of Articaine is age-dependent, with clearance and volume of distribution decreasing with increasing age. Despite a relatively slow biotransformation process in the liver, Articaine is rapidly inactivated by serum esterases immediately after injection. The elimination half-life of Articaine is 20 minutes, while that of articainic acid is 64 minutes. The high degree of protein binding of Articaine may contribute to its longer duration of clinical activity by enhancing its attachment to protein receptor sites. In clinical practice, Articaine's high concentration can be used safely due to its equal analgesic efficacy and low systemic toxicity. The local saturation of serum esterases may lead to a slower and prolonged metabolism, contributing to the sustained local anesthetic effect and minimal systemic impact. Overall, Articaine offers effective and safe anesthesia for various procedures, with a unique pharmacological profile that sets it apart from other amide local anesthetics. ¹

Efficacy

Articaine is a local anesthetic that has demonstrated clinically effective pain relief for various dental procedures, comparable to other commonly used local anesthetics. Studies have shown that Articaine can provide sufficient anesthesia even for complex procedures such as the reduction of orbitozygomatic fractures under local anesthesia. The concentration of the anesthetic, whether 2% or 4% Articaine with 1:200,000 adrenaline, does not significantly impact its clinical efficacy. In vitro studies have revealed that both 2% and 4% Articaine are more effective in depressing the compound action potential of sensory nerves compared to other local anesthetics like lignocaine and mepivacaine. Additionally, 4% Articaine was found to be more effective than 2% Articaine in this regard. Despite these findings, the reason why Articaine is predominantly manufactured in a 4% solution remains unclear, especially since there seems to be no clear clinical advantage over a 2% preparation. Furthermore, the addition of vasoconstrictors like adrenaline at different concentrations has shown minimal impact on certain clinical properties of Articaine. Studies comparing different concentrations of adrenaline with Articaine have found no significant differences in terms of anesthesia duration, postoperative analgesia, or overall clinical efficacy. Overall, Articaine has proven to be a reliable and effective choice for dental anesthesia, with its unique pharmacological profile contributing to its widespread use in various dental procedures. ²

Safety

Articaine is considered one of the safer local anesthetics due to its rapid metabolism into an inactive metabolite, which reduces the risk of systemic toxicity and overdose, even with repeated injections. Early studies on articaine showed no toxic reactions from a significant number of injections in pediatric patients. While adverse reactions to articaine have been reported, including hypersensitivity and ophthalmologic complications, it has generally shown a low number of adverse events comparable to lignocaine. However, there is some controversy surrounding articaine's safety, particularly in non-surgical dental procedures involving the inferior alveolar nerve block (IANB). Some data suggest that articaine may have a higher incidence of paraesthesia, with the lingual nerve being the most commonly affected. This has raised concerns about potential neurotoxicity associated with articaine use. It is important to note that the methodology of data collection in studies on articaine safety needs careful examination. Some reports indicating articaine's neurotoxic potential were based on voluntary reporting, which may lead to underreporting and bias in the collected data. Further research is needed to better understand the reasons for reporting adverse outcomes and to ensure more accurate assessments of articaine's safety profile. In conclusion, while articaine is generally considered safe and effective for local anesthesia, particularly in dental procedures, the potential for adverse reactions such as paraesthesia should be carefully monitored and further investigated to ensure patient safety. ²

Reference

1. Oertel R, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet. 1997; 33: 417-425.

2. Yapp KE, Hopcraft MS, Parashos P. Articaine: a review of the literature. Br Dent J. 2011; 210(7): 323-329.

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