Chemistry:Benzocaine

From HandWiki
Short description: Local anaesthetic drug
Benzocaine
Benzocaine.svg
Benzocaine-from-xtal-3D-balls.png
Clinical data
Trade namesAnbesol, Lanacane, Orajel, others
AHFS/Drugs.comMonograph
Routes of
administration		Topical, Oral
ATC code
Legal status
Legal status
  • UK: GSL, P
  • US: OTC
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC9H11NO2
Molar mass165.192 g·mol−1
3D model (JSmol)
  (verify)

Benzocaine, sold under the brand name Orajel amongst others, is a local anesthetic, belonging to the amino ester drug class, commonly used as a topical painkiller or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products for oral ulcers. It is combined with antipyrine to form A/B ear drops. In the US, products containing benzocaine for oral application are contraindicated in children younger than two years old.[1] In the European Union, the contraindication applies to children under 12 years of age.

It was first synthesised in 1890 in Germany and approved for medical use in 1902.[2]

Medical uses

Benzocaine is indicated to treat a variety of pain-related conditions. It may be used for:

  • Local anesthesia of oral and pharyngeal mucous membranes (sore throat, cold sores, mouth ulcers, toothache, sore gums, denture irritation)[3]
  • Otic pain (earache)[3]
  • Surgical or procedural local anesthesia[4]
  • Relief of skin pain caused by sunburn, ingrown toenails, hemorrhoids, [5]

Examples of combination medications of benzocaine include:

  • Antipyrine-benzocaine otic consists of antipyrine and benzocaine, and is used to relieve ear pain and remove earwax.[6]
  • Cepacol consists of menthol and benzocaine, and is used to treat sore throat.[7]
  • A solution of benzocaine and menthol is marketed for the treatment of bee stings, mosquito bites, jellyfish stings, and other insect bites[8]

Other uses

Jiffy Toothache Drops bottle (7.75% Benzocaine)

Benzocaine is used as a key ingredient in numerous pharmaceuticals:

  • Some glycerol-based ear medications for use in removing excess wax as well as relieving ear conditions such as otitis media and swimmer's ear.
  • Some previous diet products such as Ayds.
  • Some condoms designed to prevent premature ejaculation. Benzocaine largely inhibits sensitivity on the penis, and can allow for an erection to be maintained longer (in a continuous act) by delaying ejaculation. Conversely, an erection will also fade faster if stimulus is interrupted.[9][10]
  • Benzocaine mucoadhesive patches have been used in reducing orthodontic pain.[11]
  • In Poland it is included, together with menthol and zinc oxide, in the liquid powder (not to be confused with the liquid face powder) used mainly after mosquito bites. Today's ready-made Pudroderm[12] was once used there as pharmaceutical compound.

Available forms

Benzocaine can come in a variety of preparations including:

Oral preparations:

Topical preparations:

Otic preparations:

  • Solution (ex. Allergen)

Side effects

Benzocaine is generally well tolerated and non-toxic when applied topically as recommended.[19]

However, there have been reports of serious, life-threatening adverse effects (e.g., seizures, coma, irregular heart beat, respiratory depression) with over-application of topical products or when applying topical products that contain high concentrations of benzocaine to the skin.[20]

Overapplication of oral anesthetics such as benzocaine can increase the risk of pulmonary aspiration by relaxing the gag-reflex and allowing regurgitated stomach contents or oral secretions to enter the airway. Applying an oral anesthetic and consuming beverages before going to bed can be particularly hazardous.

The topical use of higher concentration (10–20%) benzocaine products applied to the mouth or mucous membranes has been found to be a cause of methemoglobinemia, a disorder in which the amount of oxygen carried by the blood is greatly reduced.[21] This side effect is most common in children under two years of age.[22] As a result, the FDA has stated that benzocaine products should not be used in children under two years of age, unless directed by and supervised by a healthcare professional.[23] In European countries, the contraindication applies to children under 12 years of age. Symptoms of methemoglobinemia usually occur within minutes to hours of applying benzocaine, and can occur upon the first-time use or after additional use.[23]

Benzocaine may cause allergic reactions.[24][25][26][27] These include:

Pharmacology

Pharmacodynamics

Pain is caused by the stimulation of free nerve endings. When the nerve endings are stimulated, sodium enters the neuron, causing depolarization of the nerve and subsequent initiation of an action potential. The action potential is propagated down the nerve toward the central nervous system, which interprets this as pain. Benzocaine acts to inhibit the voltage-gated sodium channels (VGSCs) on the neuron membrane, stopping the propagation of the action potential.[citation needed]

Chemistry

Benzocaine is the ethyl ester of p-aminobenzoic acid (PABA). It can be prepared from PABA and ethanol[29] by Fischer esterification or via the reduction of ethyl p-nitrobenzoate. Benzocaine is sparingly soluble in water; it is more soluble in dilute acids and very soluble in ethanol, chloroform, and ethyl ether. The melting point of benzocaine is 88–92 °C,[30] and the boiling point is about 310 °C.[31] The density of benzocaine is 1.17 g/cm3.

Benzocaine is commonly found, particularly in Britain, as an additive in street cocaine and also as a bulking agent in "legal highs".[32] Benzocaine gives a numbing effect similar to cocaine and as a bulking and binding agent it can not be detected once mixed. It is the most popular cutting agent worldwide.[33]

Treatment of benzocaine with hydrazine leads to aminostimil, a compound related to isoniazid.

Synthesis

Benzocaine can be prepared by esterification using 4-aminobenzoic acid and ethanol.[34][35] It can also be prepared by reduction of ethyl 4-nitrobenzoate to the amine.[36][37] In industrial practice, the reducing agent is usually iron and water in the presence of a little acid.[38]

History

Benzocaine was first synthesized in 1890 by the German chemist Eduard Ritsert (1859–1946),[39] in the town of Eberbach[40] and introduced to the market in 1902 under the name "Anästhesin".[41][42]

Veterinary medicine

Bath solutions of benzocaine and its derivatives are commonly used to anesthetize amphibians for surgery.[43][44] Benzocaine-based anesthetics are potent and highly effective for both anesthesia and euthanasia in amphibians.[45]

References

  1. ↑ "Safety Alerts for Human Medical Products - Oral Over-the-Counter Benzocaine Products: Drug Safety Communication - Risk of Serious and Potentially Fatal Blood Disorder". https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm608612.htm. 
  2. ↑ (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 475. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA475. 
  3. ↑ 3.0 3.1 AHFS Drug Information 2007. McEvoy GK, ed. Benzocaine. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2844-5.
  4. ↑ Sultan Healthcare. Topex metered spray (benzocaine 20%) prescribing information. Englewood, NJ; 2006.
  5. ↑ Benzocaine topical
  6. ↑ "Antipyrine-Benzocaine Otic: MedlinePlus Drug Information" (in en). https://medlineplus.gov/druginfo/meds/a607073.html#:~:text=Antipyrine%20and%20benzocaine%20otic%20is,class%20of%20medications%20called%20analgesics.. 
  7. ↑ "Cepacol Sore Throat (Benzocaine-Menthol) Mucous Membrane: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD" (in en). https://www.webmd.com/drugs/2/drug-164108/cepacol-sore-throat-benzocaine-menthol-mucous-membrane/details. 
  8. ↑ STING-KILL - benzocaine and menthol solution
  9. ↑ "'Longer-lasting' condom launched". BBC News. June 17, 2002. http://news.bbc.co.uk/1/hi/health/2049202.stm. 
  10. ↑ "Endurance Condoms". The New York Times. December 15, 2002. https://www.nytimes.com/2002/12/15/magazine/15ENDU.html. 
  11. ↑ "The analgesic effect of benzocaine mucoadhesive patches on orthodontic pain caused by elastomeric separators, a preliminary study". Acta Odontologica Scandinavica 71 (5): 1168–1173. September 2013. doi:10.3109/00016357.2012.757358. PMID 23301559. 
  12. ↑ "Produkty | PUDRODERM" (in pl). http://www.pampa.com.pl/page.php?cat=produkty&doc=pudroderm. 
  13. ↑ "Cepacol". Cepacol.com. http://www.cepacol.com/. 
  14. ↑ "Ultra Chloraseptic Anaesthetic Throat Spray 0.71% - Summary of Product Characteristics (SmPC) - (eMC)". https://www.medicines.org.uk/emc/product/5708/smpc. 
  15. ↑ "Topex Metered Spray-Sultan Healthcare". Sultanhc.com. http://www.sultanhc.com/sw/swchannel/productcatalogcf_v2/internet/model.asp?ProductMasterID=285313&ParentID=215728&SWID=1. 
  16. ↑ "Orajel - Oral Care for the Whole Family". Orajel.com. May 11, 2015. http://www.orajel.com/. 
  17. ↑ "Kank-A | Canker Sore Treatment & Pain Relief" (in en-US). https://kank-a.com/. 
  18. ↑ "Colgate Orabase Paste with Benzocaine | Indications | Dental Products". Colgateprofessional.com. http://www.colgateprofessional.com/products/colgate-orabase-paste-with-benzocaine/overview. 
  19. ↑ Lexicomp Online, Adult and Pediatric Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2013; April 15, 2013.
  20. ↑ Food and Drug Administration. FDA Public Health Advisory: Life-threatening side effects with use of skin products containing numbing ingredients for cosmetic procedures. 2007 Feb 6, updated 2007 Feb 9. From FDA website
  21. ↑ "Methemoglobinemia toxicity from topical benzocaine spray". Journal of the American Geriatrics Society 43 (5): 590. May 1995. doi:10.1111/j.1532-5415.1995.tb06117.x. PMID 7730550. 
  22. ↑ "Benzocaine Topical Products: Sprays, Gels and Liquids – Risk of Methemoglobinemia". Drugs.com. https://www.drugs.com/fda/benzocaine-topical-products-gels-liquids-risk-methemoglobinemia-12941.html. 
  23. ↑ 23.0 23.1 "FDA Drug Safety Communication: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth". Fda.gov. https://www.fda.gov/drugs/drugsafety/ucm250024.htm#safety. 
  24. ↑ "Allergy to Benzocaine". http://www.bedfordhospital.nhs.uk/upload_folder/patient%20information/allergy%20to%20benzocaine.pdf. 
  25. ↑ "A 10-year retrospective study on benzocaine allergy in the United Kingdom". American Journal of Contact Dermatitis 10 (2): 57–61. June 1999. doi:10.1016/s1046-199x(99)90000-3. PMID 10357712. 
  26. ↑ "Allergic contact dermatitis to benzocaine: the importance of concomitant positive patch test results". Actas Dermo-Sifiliograficas 104 (2): 156–158. March 2013. doi:10.1016/j.ad.2011.07.023. PMID 22551703. http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=90193182&pident_usuario=0&pcontactid=&pident_revista=403&ty=87&accion=L&origen=cardio&web=http://www.revespcardiol.org&lan=en&fichero=403v104n02a90193182pdf001.pdf. Retrieved March 20, 2014. 
  27. ↑ "Go easy on medicated lotions, creams, gels". CNN. February 5, 2008. http://www.cnn.com/2008/HEALTH/02/05/healthmag.creams/index.html?iref=newssearch. 
  28. ↑ 28.0 28.1 Cetylite Industries. Cetacaine (benzocaine 14%, tetracaine 2% and butamben 2%) spray, gel and liquid prescribing information. Pennsauken, NJ; 2006 Sept.
  29. ↑ "Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course". Journal of Chemical Education 89 (1): 147. 2012. doi:10.1021/ed100838a. Bibcode: 2012JChEd..89..147D. 
  30. ↑ "Benzocaine" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/2337#section=Melting-Point. 
  31. ↑ D'Ans-Lax, Taschenbuch für Chemiker und Physiker. Organische Verbindungen (4th ed.). Berlin: Springer Verlag. 1983. ISBN 3-540-12263-X. 
  32. ↑ "Drug war targets cutting agents". BBC News. August 9, 2010. https://www.bbc.com/news/uk-10909884. 
  33. ↑ "Drug prices: All cut up : Cocaine is cheaper, but weaker". The Economist. August 11, 2012. http://www.economist.com/node/21560270?fsrc=scn/tw_ec/all_cut_up. 
  34. ↑ "Ueber Esterbildung bei aromatischen Amidosäuren". Berichte der Deutschen Chemischen Gesellschaft 28 (2): 1917–1923. 1895. doi:10.1002/cber.189502802150. https://zenodo.org/record/1425796. 
  35. ↑ "Ueber das durch Einwirkung von Jodwasserstoff auf Mannit beziehungsweise auf Melampyrin (Dulcit) entstehende β Hexyljodür und einige seiner Derivate". Annalen der Chemie und Pharmacie 135 (2): 129–151. 1865. doi:10.1002/jlac.18651350202. https://zenodo.org/record/1427245. 
  36. ↑ "Ueber die Verbindungen aus Benzoylchlorid oder Phtalylchlorid und den Estern der drei Oxybenzoësäuren". Justus Liebig's Annalen der Chemie 303 (3): 274–289. 1898. doi:10.1002/jlac.18983030303. https://zenodo.org/record/1427505. 
  37. ↑ "Ethyl p-aminobenzoate". Organic Syntheses 8: 66. 1928. http://www.orgsyn.org/demo.aspx?prep=CV1P0240. ; Collective Volume, 1, pp. 240 
  38. ↑ Benzocaine. Analytical Profiles of Drug Substances. 12. Academic Press. 1983. pp. 73–104. doi:10.1016/S0099-5428(08)60164-1. ISBN 978-0-12-260812-4. 
  39. ↑ Biography of Eduard Ritsert (in German): Deutsche Biographie: Ritsert, Eduard.
  40. ↑ "100 years of Dr. Ritsert". Dr. Ritsert Pharma. http://www.ritsert.de/index.php?option=com_content&task=view&lang=en&id=13&Itemid=27. 
  41. ↑ Lehrbuch der pharmazeutischen Chemie. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft. 1968. 
  42. ↑ "Über den Werdegang des Anästhesins" (in German). Pharmazeutische Zeitung 60: 1006–1008. 1925.  See also: "150. Geburtstag: Eduard Ritsert und das Anaesthesin" (in German). Pharmazeutische Zeitung online. December 2014. http://www.pharmazeutische-zeitung.de/index.php?id=31537.  First published clinical study demonstrating the efficacy of benzocaine: "Ueber para-Aminobenzoesäure-Ester als locales Anästhetikum" (in German). Klinische Wochenschrift 39: 373–375. 1902. 
  43. ↑ "Pain perception and anaesthesia in research frogs". Experimental Animals 62 (2): 87–92. 2013. doi:10.1538/expanim.62.87. PMID 23615302. 
  44. ↑ "Amphibian Anesthesia — Research at Penn State" (in en). State College, U.S.: The Pennsylvania State University. November 8, 2010. http://www.research.psu.edu/arp/anesthesia/amphibian-anesthesia.html. 
  45. ↑ "Evaluation of benzocaine-based anesthetic gel in anuran skins extracts: A case study using the frog Lithodytes lineatus (Anura: Leptodactylidae)". PLOS ONE 15 (12): e0243654. 2020. doi:10.1371/journal.pone.0243654. PMID 33290419. Bibcode: 2020PLoSO..1543654B. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Benzocaine&oldid=3322908"