Benzocaine

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Benzocaine
Benzocaine.svg
Benzocaine-from-xtal-3D-balls.png
Clinical data
Trade names Anbesol, Lanacane, Orajel, others
AHFS/Drugs.com Monograph
Routes of
administration 		Topical, Oral
ATC code
Legal status
Legal status
  • UK:GSL, P
  • US: OTC
Identifiers
  • Ethyl 4-aminobenzoate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.002.094 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C9H11NO2
Molar mass 165.192 g·mol−1
3D model (JSmol)
  • O=C(OCC)c1ccc(N)cc1
  • InChI=1S/C9H11NO2/c1-2-12-9(11)7-3-5-8(10)6-4-7/h3-6H,2,10H2,1H3 Yes check.svgY
  • Key:BLFLLBZGZJTVJG-UHFFFAOYSA-N Yes check.svgY
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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.[ medical citation needed ]

Contents

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:

Examples of combination medications of benzocaine include:

Other uses

Jiffy Toothache Drops bottle (7.75% Benzocaine) Jiffy Toothache Drops bottle.jpg
Jiffy Toothache Drops bottle (7.75% Benzocaine)

Benzocaine is used as a key ingredient in numerous pharmaceuticals:

Available forms

Benzocaine can come in a variety of preparations including:

Oral preparations:

Topical preparations:

Otic preparations:

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.[ medical citation needed ] Applying an oral anesthetic and consuming beverages before going to bed can be particularly hazardous.[ medical citation needed ]

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]

Related Research Articles

<span class="mw-page-title-main">Local anesthetic</span> Medications to reversibly block pain

A local anesthetic (LA) is a medication that causes absence of all sensation in a specific body part without loss of consciousness, as opposed to a general anesthetic, which eliminates all sensation in the entire body and causes unconsciousness. Local anesthetics are most commonly used to eliminate pain during or after surgery. When it is used on specific nerve pathways, paralysis also can be induced.

<span class="mw-page-title-main">Methemoglobinemia</span> Condition of elevated methemoglobin in the blood

Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications may include seizures and heart arrhythmias.

<span class="mw-page-title-main">Procaine</span> Local anesthetic drug

Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity of the trade name Novocain or Novocaine, in some regions, procaine is referred to generically as novocaine. It acts mainly as a sodium channel blocker. Today, it is used therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion-enhancing, and mood-enhancing effects.

<span class="mw-page-title-main">Lidocaine</span> Local anesthetic

Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding.

<span class="mw-page-title-main">Menthol</span> Organic compound used as flavouring and analgesic

Menthol is an organic compound, more specifically a monoterpenoid, made synthetically or obtained from the oils of corn mint, peppermint, or other mints. It is a waxy, clear or white crystalline substance, which is solid at room temperature and melts slightly above.

Lidocaine/prilocaine is a eutectic mixture of equal quantities of lidocaine and prilocaine. A 5% emulsion preparation, containing 2.5% each of lidocaine/prilocaine, is marketed by APP Pharmaceuticals under the trade name EMLA. As a spray, it is marketed under the name Tempe (PSD502) that can be used by men to help with premature ejaculation. The spray is manufactured by Plethora Solutions and branded as Fortacin in the UK and Recordati in the EU.

<span class="mw-page-title-main">Teething</span> Infants gaining their first teeth

Teething is the process by which an infant's first teeth appear by emerging through the gums, typically arriving in pairs. The mandibular central incisors are the first primary teeth to erupt, usually between 6 and 10 months of age and usually causes discomfort and pain to the infant. It can take several years for all 20 teeth to complete the tooth eruption. Though the process of teething is sometimes referred to as "cutting teeth", when teeth emerge through the gums they do not cut through the flesh. Instead, hormones are released within the body that cause some cells in the gums to die and separate, allowing the teeth to come through.

Chloraseptic is an American brand of oral analgesic that is produced by Tarrytown, New York–based Prestige Consumer Healthcare, used for the relief of sore throat and mouth pain. Its active ingredient is phenol, a compound whose antiseptic properties were discovered by Friedlieb Ferdinand Runge.

<span class="mw-page-title-main">Cēpacol</span> Brand

Cepacol is an American brand of personal hygiene products, as well as for relief of sore throat. It is distributed in the US by Reckitt. The brand was originally owned by J.B. Williams. Following acquisition by Combe Incorporated, Combe Incorporated sold Cepacol to Reckitt Benckiser in 2011.

<span class="mw-page-title-main">Olopatadine</span> Chemical compound

Olopatadine, sold under the brand name Patanol among others, is an antihistamine medication used to decrease the symptoms of allergic conjunctivitis and allergic rhinitis. It is used as eye drops or as a nasal spray. The eye drops generally result in an improvement within half an hour.

<span class="mw-page-title-main">Phenazone</span> Chemical compound

Phenazone is an analgesic, antipyretic and anti-inflammatory drug. While it predates the term, it is often classified as a nonsteroidal anti-inflammatory drug (NSAID). Phenazone was one of the earliest synthetic medications — when it was patented in 1883, the only synthetic medical chemicals on the market were chloral hydrate, a sedative, trimethylamine, and iodol (tetraiodopyrrol), an early antiseptic. One of the earliest widely used analgesics and antipyretics, phenazone was gradually replaced in common use by other medications including phenacetin, aspirin, paracetamol and modern NSAIDs such as ibuprofen. However, it is still available in several countries either as an over-the-counter or prescribed drug.

<span class="mw-page-title-main">Dyclonine</span> Anesthetic

Dyclonine (Dyclocaine) is an oral anaesthetic that is the active ingredient of Sucrets, an over-the-counter throat lozenge. It is also found in some varieties of the Cepacol sore throat spray. It is a local anesthetic, used topically as the hydrochloride salt.

A topical anesthetic is a local anesthetic that is used to numb the surface of a body part. They can be used to numb any area of the skin as well as the front of the eyeball, the inside of the nose, ear or throat, the anus and the genital area. Topical anesthetics are available in creams, ointments, aerosols, sprays, lotions, and jellies. Examples include benzocaine, butamben, dibucaine, lidocaine, oxybuprocaine, pramoxine, proxymetacaine (proparacaine), and tetracaine.

<span class="mw-page-title-main">Chloroprocaine</span> Local anaesthetic drug

Chloroprocaine is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine vasodilates; this is in contrast to cocaine which vasoconstricts. Chloroprocaine is an ester anesthetic.

<span class="mw-page-title-main">Ear drop</span> Form of medication placed in ears

Ear drops are a form of topical medication for the ears used to treat infection, inflammation, impacted ear wax and local anesthesia. They are commonly used for short-term treatment and can be purchased with or without a prescription. Before using ear drops, refer to the package insert or consult a health professional for the amount of drops to use and the duration of treatment.

Dental anesthesia is the application of anesthesia to dentistry. It includes local anesthetics, sedation, and general anesthesia.

Antipyrine and benzocaine ear drops is a medication for the treatment of ear pain caused by otitis media. It combines antipyrine, an NSAID, and benzocaine, a local anaesthetic in order to treat ear pain, alongside hydroxyquinoline sulfate, an antiseptic and preservative. Its trade names include Auralgan, Aurodex, Auroto, among others, and is abbreviated as A/B otic drops.

In periodontics, there are four reasons to seek medication. Those four reasons include infection, swelling, pain, and sedation. Although some patients may experience pain, swelling, and infection as a result of an acute periodontal problem such as advanced periodontal disease, periodontic patients usually do not need medication until they are faced with surgery. For successful surgery, medication is then introduced prior to the operation, usually the morning before the procedure and is continued for up to two weeks after.

Cetacaine is a topical anesthetic that contains the active ingredients benzocaine (14%), butamben (2%), and tetracaine hydrochloride (2%). Cetacaine also contains small amounts of benzalkonium chloride at 0.5% and 0.005% of cetyl dimethyl ethyl ammonium bromide all in a bland water-soluble base. Although Cetacaine has been widely used in the medical and dental fields, it has yet to be officially approved by the FDA. Cetacaine is produced by the company Cetylite Industries, Inc. and they provide Cetacaine in three forms: liquid, gel, and spray.

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". www.fda.gov. Archived from the original on September 7, 2018. Retrieved May 26, 2018.
  2. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 475. ISBN   9783527607495.
  3. 1 2 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". medlineplus.gov. Retrieved March 28, 2023.
  7. ↑ "Cepacol Sore Throat (Benzocaine-Menthol) Mucous Membrane: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD". www.webmd.com. Retrieved March 28, 2023.
  8. ↑ STING-KILL - benzocaine and menthol solution
  9. ↑ "'Longer-lasting' condom launched". BBC News. June 17, 2002.
  10. ↑ Garner D (December 15, 2002). "Endurance Condoms". The New York Times.
  11. ↑ Eslamian L, Borzabadi-Farahani A, Edini HZ, Badiee MR, Lynch E, Mortazavi A (September 2013). "The analgesic effect of benzocaine mucoadhesive patches on orthodontic pain caused by elastomeric separators, a preliminary study". Acta Odontologica Scandinavica. 71 (5): 1168–1173. doi:10.3109/00016357.2012.757358. PMID   23301559. S2CID   22561192.
  12. ↑ "Produkty | PUDRODERM" (in Polish). Archived from the original on October 18, 2016. Retrieved May 9, 2014.
  13. ↑ "Cepacol". Cepacol.com. Retrieved June 2, 2015.
  14. ↑ "Ultra Chloraseptic Anaesthetic Throat Spray 0.71% - Summary of Product Characteristics (SmPC) - (eMC)". www.medicines.org.uk. Archived from the original on May 5, 2018. Retrieved May 5, 2018.
  15. ↑ "Topex Metered Spray-Sultan Healthcare". Sultanhc.com. Retrieved June 2, 2015.
  16. ↑ "Orajel - Oral Care for the Whole Family". Orajel.com. May 11, 2015. Retrieved June 2, 2015.
  17. ↑ "Kank-A | Canker Sore Treatment & Pain Relief" . Retrieved November 29, 2023.
  18. ↑ "Colgate Orabase Paste with Benzocaine | Indications | Dental Products". Colgateprofessional.com. Retrieved June 2, 2015.
  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. ↑ Shua-Haim JR, Gross JS (May 1995). "Methemoglobinemia toxicity from topical benzocaine spray". Journal of the American Geriatrics Society. 43 (5): 590. doi: 10.1111/j.1532-5415.1995.tb06117.x . PMID   7730550. S2CID   19563675.
  22. ↑ "Benzocaine Topical Products: Sprays, Gels and Liquids – Risk of Methemoglobinemia". Drugs.com. Retrieved March 20, 2014.
  23. 1 2 "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. Retrieved June 2, 2015.
  24. ↑ "Allergy to Benzocaine" (PDF). Archived from the original (PDF) on March 20, 2014. Retrieved March 20, 2014.
  25. ↑ Sidhu SK, Shaw S, Wilkinson JD (June 1999). "A 10-year retrospective study on benzocaine allergy in the United Kingdom". American Journal of Contact Dermatitis. 10 (2): 57–61. doi:10.1016/s1046-199x(99)90000-3. PMID   10357712.
  26. ↑ González-Rodríguez AJ, Gutiérrez-Paredes EM, Revert Fernández Á, Jordá-Cuevas E (March 2013). "Allergic contact dermatitis to benzocaine: the importance of concomitant positive patch test results" (PDF). Actas Dermo-Sifiliograficas. 104 (2): 156–158. doi:10.1016/j.ad.2011.07.023. PMID   22551703. Archived from the original (PDF) on March 3, 2016. Retrieved March 20, 2014.
  27. ↑ Goldman L (February 5, 2008). "Go easy on medicated lotions, creams, gels". CNN. Retrieved March 20, 2014.
  28. 1 2 Cetylite Industries. Cetacaine (benzocaine 14%, tetracaine 2% and butamben 2%) spray, gel and liquid prescribing information. Pennsauken, NJ; 2006 Sept.
  29. ↑ Demare P, Regla I (2012). "Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course". Journal of Chemical Education. 89 (1): 147. Bibcode:2012JChEd..89..147D. doi:10.1021/ed100838a.
  30. ↑ "Benzocaine". PubChem. U.S. National Library of Medicine. Retrieved March 27, 2023.
  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.
  33. ↑ "Drug prices: All cut up : Cocaine is cheaper, but weaker". The Economist . August 11, 2012.
  34. ↑ Salkowski H (1895). "Ueber Esterbildung bei aromatischen Amidosäuren". Berichte der Deutschen Chemischen Gesellschaft. 28 (2): 1917–1923. doi:10.1002/cber.189502802150.
  35. ↑ Erlenmeyer E, Wanklyn JA (1865). "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. doi:10.1002/jlac.18651350202.
  36. ↑ Limpricht H (1898). "Ueber die Verbindungen aus Benzoylchlorid oder Phtalylchlorid und den Estern der drei Oxybenzoësäuren". Justus Liebig's Annalen der Chemie. 303 (3): 274–289. doi:10.1002/jlac.18983030303.
  37. ↑ Adams R, Cohen FL (1928). "Ethyl p-aminobenzoate". Organic Syntheses . 8: 66.; Collective Volume, vol. 1, p. 240
  38. ↑ Ali SL (1983). Benzocaine. Analytical Profiles of Drug Substances. Vol. 12. Academic Press. 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. Archived from the original on September 9, 2017. Retrieved March 14, 2010.
  41. ↑ Auterhoff H (1968). Lehrbuch der pharmazeutischen Chemie. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft.
  42. ↑ Ritsert E (1925). "Über den Werdegang des Anästhesins" [On the development of Anaesthetics]. Pharmazeutische Zeitung (in German). 60: 1006–1008. See also: Friedrich C, Klimonow M (December 2014). "150. Geburtstag: Eduard Ritsert und das Anaesthesin" [150th birthday: Eduard Ritsert and Anästhetsin [Benzocaine]]. Pharmazeutische Zeitung online (in German). Archived from the original on March 20, 2014. First published clinical study demonstrating the efficacy of benzocaine: von Noorden C (1902). "Ueber para-Aminobenzoesäure-Ester als locales Anästhetikum" [On [an] ester of para-aminobenzoic acid as a local anaesthetic]. Klinische Wochenschrift (in German). 39: 373–375.
  43. ↑ Guénette SA, Giroux MC, Vachon P (2013). "Pain perception and anaesthesia in research frogs". Experimental Animals. 62 (2): 87–92. doi: 10.1538/expanim.62.87 . PMID   23615302.
  44. ↑ "Amphibian Anesthesia — Research at Penn State". PennState Animal Resource Program. State College, U.S.: The Pennsylvania State University. November 8, 2010. Retrieved August 24, 2017.
  45. ↑ Barros AL, Lima AP, Fachin-Espinar MT, Nunez CV (2020). "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. Bibcode:2020PLoSO..1543654B. doi: 10.1371/journal.pone.0243654 . PMC   7723253 . PMID   33290419.
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