Articaine

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Articaine
Articaine.svg
Space-filling model of the articaine molecule
Names
Trade namesSeptocaine, Ultracain, others
Other namesCarticaine, articaine hydrochloride/epinephrine
  • (RS)-Methyl 4-methyl-3-(2-propylaminopropanoylamino)thiophene-2-carboxylate
Clinical data
Drug classLocal anesthetic (amide)[1]
Side effectsHeadache, pain[1]
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
use
Subcutaneous
Onset of actionWithin 6 min[2]
Duration of action1 hr[2]
External links
AHFS/Drugs.comMonograph
US NLMArticaine
Legal
Legal status
Pharmacokinetics
MetabolismLiver, plasma
Elimination half-life30 min
ExcretionLiver and unspecific plasma estearases[3]
Chemical and physical data
FormulaC13H20N2O3S
Molar mass284.37 g/mol
320.836 g/mol (HCl) g·mol−1
3D model (JSmol)
ChiralityRacemic mixture
  • O=C(Nc1c(scc1C)C(=O)OC)C(NCCC)C
  • InChI=1S/C13H20N2O3S/c1-5-6-14-9(3)12(16)15-10-8(2)7-19-11(10)13(17)18-4/h7,9,14H,5-6H2,1-4H3,(H,15,16) checkY
  • Key:QTGIAADRBBLJGA-UHFFFAOYSA-N checkY

Articaine, sold under the brand name Septocaine among others, is a local anesthetic that is injected into an area to decrease feeling in that area.[2] In a nerve block, it is injected around a nerve that supplies an area.[2] It is available mixed with a small amount of epinephrine to increase the duration of its action.[2] Onset is within 6 minutes and effects last about an hour.[2]

Common side effects include headache and pain.[1] Other side effects may include seizures and methemoglobinemia.[1] Safety in pregnancy and breastfeeding is unclear.[4] It of the amide-type.[1]

Articaine came into medical use in Europe in 1976, Canada in 1983, and the United States in 2000.[5] In the United Kingdom 50 doses costs the NHS about £25 as of 2021.[6] It is widely used in a number of European countries.[7]

Medical use

Articaine is used for pain control. Like other local anesthetic drugs, articaine causes a transient and completely reversible state of anesthesia (loss of sensation) during (dental) procedures.[8] Its activity is similar to lidocaine.[2]

In dentistry, articaine is used mainly for infiltration injections. It may be able to penetrate dense cortical bone — as found in the lower jaw (mandible) — more than most other local anaesthetics.

In people with hypokalemic sensory overstimulation, lidocaine is not very effective, but articaine works well.[9]

Studies comparing lidocaine and articaine found that articaine is more effective than lidocaine in anaesthetising the posterior first molar region.[10] Articaine has been found to be 3.81 times more likely than lidocaine to produce successful anaesthesia when used for infiltration injections. However, there is no evidence to support the use of articaine over lidocaine for inferior alveolar nerve blocks.[11] Furthermore, articaine has been demonstrated to be superior to lidocaine for use of supplementary infiltration following persistent pain despite a successful inferior dental nerve block with lidocaine.[12]

Dosage

The maximum recommended dose is 7 mg/kg of articaine with epinephrine.[1]

Contraindications

Articaine is not contraindicated in patients with sulfa allergies, as there is no cross-allergenicity between articaine's sulphur-bearing thiophene ring and sulfonamides.[16]

Methylparaben is no longer present in any dental local anesthetic formula available in North America.[15]

Side effects

Paresthesia, a short-to-long-term numbness or altered sensation affecting a nerve, is a well-known complication of injectable local anesthetics and has been present even before articaine was available.[17][18] Articaine, while not proven, has been associated with a risk of nerve damage when used as a block technique.[19]

An article by Haas and Lennon published in 1993[20] seems to be the original source for the controversy surrounding articaine. This paper analyzed 143 cases reported in to the Royal College of Dental Surgeons of Ontario (RCDSO) over a 21-year period. The results from their analysis seemed to indicate that 4% local anesthetics had a higher incidence of causing paresthesia, an undesirable temporary or permanent complication, after the injection. The authors concluded that “...the overall incidence of paresthesia following local anesthetic administration for non-surgical procedures in dentistry in Ontario is very low, with only 14 cases being reported out of an estimated 11,000,000 injections in 1993. However if paresthesia does occur, the results of this study are consistent with the suggestion that it is significantly more likely to do so if either articaine or prilocaine is used.”

In another paper by the same authors,[21] 19 reported paresthesia cases in Ontario for 1994 were reviewed, concluding that the incidence of paresthesia was 2.05 per million injections of 4% anesthetic drugs. Another follow up study by Miller and Haas published in 2000,[22] concluded that the incidence of paresthesia from either prilocaine or articaine (the only two 4% drugs in the dental market) was close to 1:500,000 injections. (An average dentist gives around 1,800 injections in a year.[23])

Almost all recorded cases of long-term numbness or altered sensation (paresthesia) seem only to be present when this anesthetic is used for dental use (no PubMed references for paresthesia with articaine for other medical specialties). Also, in the vast majority of the reports, only the lingual nerve was affected.

Nonetheless, direct damage to the nerve caused by 4% drugs has never been scientifically proven.[24]

Some research points to needle trauma as the cause of the paresthesia events.[25][26]

Chemistry

The amide structure of articaine is similar to that of other local anesthetics, but its molecular structure differs through the presence of a thiophene ring instead of a benzene ring. Articaine is exceptional because it contains an additional ester group that is metabolized by esterases in blood and tissue.[27][28] The elimination of articaine is exponential with a half-life of 20 minutes.[29][30] Since articaine is hydrolized very quickly in the blood, the risk of systemic intoxication seems to be lower than with other anesthetics, especially if repeated injection is performed.[31]

History

This drug was synthesized by pharmacologist Roman Muschaweck and chemist Robert Rippel.[32] Muschaweck received a "O. Schmiedeberg" medal by the German Society for Experimental and Clinical Pharmacology and Toxicology for his work in 2002.[33] It was brought to the German market in 1976 by Hoechst AG, a life-sciences German company (now Sanofi-Aventis), under the brand name Ultracain.[32][34] This drug was also referred to as "carticaine" until 1984.[35]

In 1983 it was brought into the North American market, to Canada, under the name Ultracaine for dental use, manufactured in Germany and distributed by Hoechst-Marion-Roussel. This brand is currently manufactured in Germany by Sanofi-Aventis and distributed in North America by Hansamed Limited (since 1999). After Ultracaine's patent protection expired, new generic versions arrived to the Canadian market: (in order of appearance) Septanest (Septodont), Astracaine, (originally by AstraZeneca and now a Dentsply product), Zorcaine (Carestream Health/Kodak) and Orabloc (Pierrel).

It was approved by the FDA in April 2000, and became available in the United States of America two months later under the brand name Septocaine, an anesthetic/vasoconstrictor combination with Epinephrine 1:100,000 (trade name Septodont). Zorcaine became available there a few years later, also. Articadent (Dentsply) became available in the United States in October 2010. The three brands currently available in the United States are all manufactured for these companies by Novocol Pharmaceuticals Inc. (Canada). Ubistesin and Ubistesin Forte (3M ESPE) are also widely used in the United States and Europe. Orabloc (Pierrel) is aseptically manufactured and was approved by the FDA in 2010, became available in Canada in 2011, and in Europe from 2013.

Articaine is currently available for the North American dental market:

  • In Canada:
    • As articaine hydrochloride 4% with epinephrine 1:100,000 (0,01 mg/ml)
      • Ubistesin Forte
      • Ultracaine DSF
      • Septanest SP
      • Astracaine Forte
      • Zorcaine
      • Orabloc (articaine hydrochloride 4% and epinephrine 1:100,000)
    • As articaine hydrochloride 4% with epinephrine 1:200,000 (0,005 mg/ml)
      • Ubistesin
      • Ultracaine DS
      • Septanest N
      • Astracaine
      • Orabloc (articaine hydrochloride 4% and epinephrine 1:200,000)
  • In the USA:
    • As articaine hydrochloride 4% with epinephrine 1:100,000
      • Septocaine with epinephrine 1:100,000
      • Zorcaine
      • Articadent with epinephrine 1:100,000
      • Orabloc (articaine hydrochloride 4% and epinephrine 1:100,000)
    • As articaine hydrochloride 4% with epinephrine 1:200,000
      • Septocaine with epinephrine 1:200,000
      • Articadent with epinephrine 1:200,000
      • Orabloc (articaine hydrochloride 4% and epinephrine 1:200,000)

An epinephrine-free (adrenaline-free) version is available in Europe under the brand name Ultracain D. However, version with epinephrine (adrenaline) is available in Europe under the brand name Supracain 4% with epinephrine concentration of 1:200,000.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 "DailyMed - ARTICAINE- articaine hydrochloride and epinephrine injection, solution". dailymed.nlm.nih.gov. Archived from the original on 19 March 2021. Retrieved 16 January 2022.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "Articaine Monograph for Professionals". Drugs.com. Archived from the original on 7 November 2021. Retrieved 16 January 2022.
  3. Oertel R, Ebert U, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet. 1997 Dec;33(6):421
  4. "Articaine / epinephrine Use During Pregnancy". Drugs.com. Archived from the original on 4 December 2020. Retrieved 16 January 2022.
  5. Malamed, Stanley F. (25 April 2014). Handbook of Local Anesthesia - E-Book. Elsevier Health Sciences. p. 66. ISBN 978-0-323-24202-8. Archived from the original on 16 January 2022. Retrieved 16 January 2022.
  6. BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1403. ISBN 978-0857114105.
  7. Oertel, R; Rahn, R; Kirch, W (December 1997). "Clinical pharmacokinetics of articaine". Clinical pharmacokinetics. 33 (6): 417–25. doi:10.2165/00003088-199733060-00002. PMID 9435991.
  8. Malamed SF. Handbook of local anaesthesia, p. 3, 5th ed. St. Louis, Mosby; 2004.
  9. Segal MM, Rogers GF, Needleman HL, Chapman CA (2007). "Hypokalemic sensory overstimulation". J Child Neurol. 22 (12): 1408–10. doi:10.1177/0883073807307095. PMID 18174562. S2CID 35659227.
  10. Katyal, V. (2010). "The efficacy and safety of articaine versus lignocaine in dental treatments: a meta-analysis". J Dent. 38 (4): 307–17. doi:10.1016/j.jdent.2009.12.003. PMID 20006669.
  11. Brandt, Ryan G.; Anderson, Patricia F.; McDonald, Neville J.; Sohn, Woosung; Peters, Mathilde C. (2011-05-01). "The pulpal anesthetic efficacy of articaine versus lidocaine in dentistry: a meta-analysis". Journal of the American Dental Association. 142 (5): 493–504. doi:10.14219/jada.archive.2011.0219. ISSN 1943-4723. PMID 21531931.
  12. Kung, Jason; McDonagh, Marian; Sedgley, Christine M. (2015-11-01). "Does Articaine Provide an Advantage over Lidocaine in Patients with Symptomatic Irreversible Pulpitis? A Systematic Review and Meta-analysis". Journal of Endodontics. 41 (11): 1784–1794. doi:10.1016/j.joen.2015.07.001. ISSN 1878-3554. PMID 26293174.
  13. Malamed SF. Handbook of local anaesthesia, p. 320, 5th ed. St. Louis, Mosby; 2004.
  14. 14.0 14.1 Malamed SF. Handbook of local anaesthesia, p. 65, 6th ed. St. Louis, Mosby; 2013.
  15. 15.0 15.1 Malamed SF. Handbook of local anaesthesia, p. 73, 5th ed. St. Louis, Mosby; 2004.
  16. Becker, DE; Reed, KL: Essentials of Local Anesthetic Pharmacology. Anesth Prog 53:98-109 2006
  17. Pogrel MA, Bryan J, Regezi J. Nerve damage associated with inferior alveolar nerve blocks. J Am Dent Assoc. 1995 Aug;126(8):1150-5.
  18. Pogrel MA, Thamby S. Permanent nerve involvement resulting from inferior alveolar nerve blocks. J Am Dent Assoc. 2000 Jul;131(7):901-7. Erratum in: J Am Dent Assoc 2000 Oct;131(10):1418.
  19. Pogrel MA. Permanent nerve damage from inferior alveolar nerve blocks--an update to include articaine. J Calif Dent Assoc. 2007 Apr;35(4):271-3.
  20. Haas DA, Lennon D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J Can Dent Assoc. 1995 Apr;61(4):319-20, 323-6, 329-30.
  21. Haas DA, Lennon D. A review of local anesthetic-induced paraesthesia in Ontario in 1994. J Dent Res 1996; 75(Special Issue):247.
  22. Miller PA, Haas DA. Incidence of local anesthetic-induced neuropathies in Ontario from 1994–1998. J Dent Res 2000; 79 (Special Issue):627.
  23. Haas DA, Lennon D Local anaesthetic use by dentists in Ontario. J Can Dent Assoc. 1995 Apr;61(4):297-304
  24. Malamed SF. Local anesthetics: dentistry's most important drugs, clinical update 2006. J Calif Dent Assoc. 2006 Dec;34(12):971-6
  25. Pogrel MA, Permanent nerve damage from inferior alveolar nerve blocks—an update to include articaine. J Calif Dent Assoc. 2007 Apr;35(4):271-3
  26. Hoffmeister B, Morphological changes of peripheral nerves following intraneural injection of local anesthetic, Dtsch Zahnarztl Z. 1991 Dec;46(12):828-30
  27. Oertel R, Ebert U, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet. 1997 Dec;33(6):418.
  28. Snoeck, Marc (2012-06-05). "Articaine: a review of its use for local and regional anesthesia". Local and Regional Anesthesia. 5: 23–33. doi:10.2147/LRA.S16682. ISSN 1178-7112. PMC 3417979. PMID 22915899.
  29. HornkeI, Eckert HG, Rupp W. Pharnakokinetik und Metabolismus von Articain nach intramuskularer Injektion am mannlichen Probanden. Dtsch Z Mund Kiefer Gesichts Chir 1984; 8:67-71
  30. Kirch W, Kitteringham N, Lambers G, et al. Die klinische Pharmakokinetik von Articain nach intraoraler und intramuskularer Application. Schweiz Monatsschr Zahnheilkd 1983; 93: 713-9
  31. Oertel R, Ebert U, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet. 1997 Dec;33(6):420.
  32. 32.0 32.1 "Sanofi: 40 Jahre Ultracain in der Lokalanästhesie". zm-online (in Deutsch). Archived from the original on 2021-08-02. Retrieved 2021-08-02.
  33. "dgpt-online.de: O. Schmiedeberg-Plakette". www.dgpt-online.de. Archived from the original on 2021-08-02. Retrieved 2021-08-02.
  34. "Articain". roempp.thieme.de. Archived from the original on 2020-06-03. Retrieved 2021-08-02.
  35. Malamed SF. Handbook of local anaesthesia, p. 71, 5th ed. St. Louis, Mosby; 2004.

External links

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