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Articaine 20 Years Later

Categories: Anesthesia and Sedation

Author(s): Stanley F. Malamed, DDS

Date: 06-24-2020 07:17:11 am

Local anesthetics (LAs) form the backbone of pain control techniques in dentistry. Prior to the year 2000, dentists in the United States had a choice offour excellent LAs: bupivacaine, lidocaine, mepivacaine, and prilocaine, available in various formulations with and without a vasoconstrictor (Table 1). On April 3, 2000, the United States Food and Drug Administration approved the safety and efficacy of articaine. It entered the dental market in June of that year with the proprietary name Septocaine. Over the next 20 years, articaine has become the second most used dental LA in the United States.1
In recognition of articaine’s 20 years of use in the United States, this article briefly reviews its history and clinical characteristics, and provides recommendations for its most effective use. A more in-depth paper on the history, development and clinical indications for articaine, was published in 2016 to celebrate articaine’s 30 years in Canada.2

History and Development of Articaine

Carticaine was synthesized in Germany by Rusching and colleagues in 1969.3 When it was introduced into dentistry in Germany in 1976 its generic name was changed to articaine. Articaine represents the first, and still only, local anesthetic designed specifically for the dental profession. Its use gradually spread, entering North America in Canada in 1983.4 The United Kingdom launched the drug in 1998, and Australia followed in 2005. The most common formulations of articaine are 4% with epinephrine in a 1:100,000 and 1:200,000 concentration. Outside of North America, articaine is available in other formulations as well (Table 2).
Articaine has become an extremely popular local anesthetic wherever it has been made available. The market share of articaine in several European countries is presented in Table 3. Of the 1.96 billion dental LA cartridges manufactured worldwide each year, only lidocaine (1 billion cartridges) is more popular than articaine (600 million cartridges). Proprietary names of articaine in the United States are: Articadent, Orabloc, Septocaine, and Zorcaine. Generic articaine is also available in dental cartridges.

Articaine HCl – The Molecule

LAs are classified as either amino-esters (esters) or amino- amides (amides). The ester LAs, including procaine and tetracaine, are seldom, if ever, administered by injection in the dental profession today. The amide LAs (Table 1) have replaced the esters almost entirely.
Articaine – The Hybrid Molecule. Articaine, though classified as an “amide” is, actually, both an ester and amide (Figure 1). This confers a number of advantages to articaine when compared to other amide LAs. Amide LAs undergo biotransformation (metabolism, detoxification) primarily in the liver (lidocaine - 70% hepatic), a relatively slow process.
The elimination half-life of lidocaine (and  mepivacaine and prilocaine) is approximately 90 minutes. Ester LAs are metabolized in blood by nonspecific plasma esterases. The elimination half-life of procaine is 6 minutes. Ninety to ninety- five percent of articaine is metabolized by plasma esterases.5 The elimination half-life of articaine in adults, children, and elderly patients has been shown to be between 18.5 minutes (children) and 27 minutes (adults and elderly).6-8
In six half-lives, the blood level of a LA decreases by 98.25%. For amide LAs, the drug is eliminated in 9 hours (6 x 90 minutes). Articaine is eliminated from the blood in 2 hours 42 minutes (6 x 27 minutes).
TABLE 1. Local anesthetics available in the United States (February 2020)
Drug Vasoconstrictor Category
Articaine 4% 1:100,000 epi Intermediate
1:200,000 epi Intermediate
Bupivacaine 0.5% 1:200,000 epi Long
Lidocaine 2%
1:50,000 epi Intermediate
1:100,000 epi Intermediate
Mepivacaine 3%   Short
Mepivacaine 2% 1:20,000 levo Intermediate
Prilocaine 4%   Short
  1:200,000 epi Intermediate
epi – epinephrine
levo - levonordefrin   

Articaine – More Lipid Soluble. A local anesthetic must be lipid soluble to diffuse across the nerve membrane to block nerve conduction. An aromatic ring confers lipid solubility. Most amide and ester LAs possess a benzene ring. However, articaine has a thiophene ring – considerably more lipid soluble than benzene (Figure 1).
The shorter elimination half-life and greater lipid solubility provide articaine with several advantages compared to other amide LAs. The shorter half-life becomes clinically significant when treating patients who are: 1) pregnant;
2) nursing; and 3) children (weighing up to 30 kg). The advantage of increased lipid solubility is noted in articaine’s ability to provide pulpal anesthesia when administered by buccal infiltration in the mandible of adult patients.
TABLE 2. Articaine formulations – Worldwide
4% articaine HCl with epinephrine 1:100,000
4% articaine HCl with epinephrine 1:200,000
4% articaine HCl with epinephrine 1:400,000 (not available in North America)
4% articaine HCl plain (not available in North America)
2% articaine HCl with epinephrine 1:200,000 (not available in North America)

Clinical Properties of Articaine

The two North American formulations of articaine are classified as “intermediate” duration. They provide approximately 60 minutes of pulpal anesthesia and between 3 to 5 hours of soft tissue anesthesia, similar to other intermediate duration LAs.
Articaine by Buccal Infiltration in the Adult Mandible. Results of large, Phase 3 clinical trials in the United States, comparing articaine to lidocaine, failed to demonstrate any clinical advantages (onset of anesthesia and efficacy) of articaine over lidocaine.9-11 In these clinical trials, “traditional” injection techniques were employed: inferior
alveolar nerve block (IANB), maxillary infiltration, posterior superior alveolar (PSA), anterior superior alveolar (ASA) nerve blocks. However, when articaine was used by buccal infiltration in the mandibular molar region of adults
(similar to maxillary infiltration), significant differences in both successful pulpal anesthesia and faster onset were observed.12 Articaine provided an 87% success rate vs 57% for lidocaine following infiltration of 1.8 mL by the mandibular first molar.12 Onset of anesthesia for articaine was 4.2 minutes vs 7.7 minutes for lidocaine.12
Kanaa et al. administered articaine by mandibular buccal infiltration (mandibular first molar) following IANB with lidocaine with epinephrine.13 The 55.6% success rate for IANB with only lidocaine with epinephrine 1:80,000 became 91.7% following administration of an articaine buccal infiltration. At the conclusion of the study (45 minutes) there was still no indication of the articaine anesthesia disappearing.
Articaine in Pediatrics. LA systemic toxicity (LAST) (also known as overdose), though rare, most often occurs in younger, lighter weight (<30 kg) patients who receive an overly large dose of LA. The considerably shorter elimination half-life of articaine (18.5 to 23.6 minutes) in children minimizes the risk of LAST in these patients.6
In the United States, the articaine drug package insert states that the drug is recommended for administration to patients from 4 years of age up though 79 years.14 Why 4 years of age? In the Phase 3 clinical trial with children, patients were enrolled from the age of 4 years and older.11 Articaine can be, and has been, administered safely to patients younger than 4 years of age.15
Articaine in Pregnancy. Though all local anesthetics can be administered safely to the pregnant patient, only lidocaine is classified by the FDA as a category ‘B’ drug. All other LAs, including articaine, are category ‘C’. Given that the half-life of articaine is significantly shorter than other dental LAs, it seems logical that fetal exposure is limited when articaine is used.
Articaine in Nursing. Nursing mothers frequently request that any drug that will be found in their milk not be administered, this in spite of clinical evidence16 and recommendations that breastfeeding not be interrupted following local anesthetic administration.17 However, when pain control with a local anesthetic is required, a drug that is eliminated more quickly is preferred. Its 27 minute elimination half-life makes articaine the preferred LA when the patient is nursing.

Is Articaine a More Effective Local Anesthetic?

YES. Meta-analyses have concluded that articaine has a statistically higher probability of anesthetic success, superior to lidocaine for both infiltration and IANB, both in nonpulpally involved teeth18-20 and in the presence of symptomatic irreversible pulpitis.21-26

What about Articaine and Paresthesia?

All local anesthetics are neurotoxic. Paresthesia has existed since local anesthetics were first injected. On its introduction in 2000, there was controversy regarding reports that the 4% LAs, prilocaine and articaine, possessed a greater likelihood of producing paresthesia following IANB than 2% and 3% LAs.27 Today, in 2020, it has been demonstrated that the risk of neural damage resulting from articaine administration is either equal to, or less than, that of lidocaine and other amide LAs10,28-29 and that most injection-related paresthesia results from mechanical trauma (metal needle contacting nerve) rather than neurotoxicity of the drug.

TABLE 3. Articaine Market Share
Country Articaine market share Source
Germany 98% GFK data*
Poland 90% Keystone^
France 70% Estimated sales
Spain 68% Keystone^
Italy 53% Keystone^
United States 39% 2018 (2nd quarter)
*GFK – Gesellschaft fur Konsumforschung.
^ Keystone – Keystone Consultancy
Data courtesy of Dr. Wolfgang Jakobs and Septodont NA (United States)

Conclusion and Recommendations.

It is this authors opinion that articaine represents the preferred dental LA when treating younger children (up to 30 kg weight); and patients who are pregnant or nursing. The use of articaine by buccal infiltration in the mandible, either as a sole injection or as a supplement to IANB with any LA, has been shown to provide high degrees of successful anesthesia.
I highly recommend the infiltration – on a routine basis – of one-third to one-half a cartridge of articaine in the buccal fold adjacent to whatever mandibular molar teeth are being treated, following an IANB or Gow-Gates mandibular nerve block. With regard to neural injury, all LAs can, and do, produce paresthesia. Recent research has demonstrated that articaine is no more neurotoxic than other dental local anesthetics.


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