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Tran Quan Epidemiology Spring 2012 June 12, 2012 Dr. Gordon Avery Orajel for Everyday Toothache One of the most common everyday pains aside from headache is toothache. 1 Toothache usually refers to pain around the teeth or jaws primarily as a result if a dental condition. In most instances, toothaches are caused by tooth problems, such as a dental cavity, a cracked tooth, an exposed tooth root, or gum disease. The severity of a toothache can range from chronic and mild to sharp and excruciating. The pain may be aggravated by chewing or by cold or heat. Topical benzocaine (Orajel) products are widely available over the counter for the treatment of oral or teething pain. 2 Topical benzocaine is a local anesthetic that works by blocking nerve signals in your body. With its short half-life and minimal systemic absorption, Orajel is perceived to be a relatively benign product and is safe to use by everyday users. 3 Orajel topical is used to reduce pain or discomfort caused not only by teething pain , but also minor skin irritations, sore throat, sunburn, vaginal or rectal irritation, ingrown toenails, hemorrhoids, and many other sources of minor pain on a surface of the body. 4 While extremely beneficial and very commonly used, Orajel topical may cause a life-threatening condition in which the amount of oxygen in your blood stream becomes dangerously low. This condition is called methemoglobinemia and it may occur after only one use of benzocaine or after several uses. 5

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There are many evidence put that Orajel is effective in treating toothache and minor surface body pain. Benzocaine was first synthesized in 1890 by the German chemist Eduard Ritsert (1859-1946), is the ethyl ester of p-aminobenzoic acid (PABA) that soluble in dilute acids and ethanol. 6 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. Esters of PABA work as a chemical barrier, stopping the sodium from entering the nerve ending. 7 Prevent the nerve cell to depolarize eliminate the transfer of pain to the cortex, which make Orajel an excellent anesthetic over counter drug. Orajel is commercially available in many dosage forms, which are intented for selfmedication. At Best Buy, I founded the 7.5% gel or swabs used for topical administration to mucous membranes. Whenever toothaches occurred, the patients can buy and topically applies Orajel on top of the aching teeth and feel the relieved almost instantly. Only small amount of Orajel dosage are required to achieve desired response. A pea size amount of gel apply to affected toothache area up to 4 times daily is the recommended amount of Orajel for self medication adult. 8 The American Academy of Pediatrics recently released an article focusing on the effective of Orajel. From their data, they concluded that Orajel was listed as the most popular over the counter medication to reduce discomfort from toothache. 9 When caregivers were

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asked how Orajel works, responses included the statements that it numbs the gum area, the ingredients make it work, it relieves pain, and the gel cools down the gums. But all drugs have side effect, topical application of oral anesthetics such as Orajel can increase the risk of pulmonary aspiration by relaxing the gag-reflex and allowing regurgitated stomach contents or oral secretions to enter the airway. 10 Applying an oral anesthetic and consuming beverages before going to bed can be particularly hazardous. The U.S. Food and Drug Administration (FDA) notified healthcare professionals and patients that FDA continues to receive reports of methemoglobinemia, a serious and potentially fatal adverse effect, associated with benzocaine products. Because it may be used in topical creams with a concentration as much as 20%, it is not difficult to administer a dose sufficient to cause this problem. 11 One of the primary adverse effects reported following topical application of Orajel is sensitivity reaction. Allergic reactions occur with ester local anesthetics such as Orajel because of the PABA core structure. 12 Possible localized allergic reactions or contact dermatitis characterized by erythema and pruritus that may progress to vesiculation and oozing; most common after prolonged or repeated use. 13 If rash, urticaria, edema, irritation, or other manifestations of allergy develop during therapy, discontinue the drug. Methemoglobinemia is an uncommon cause of tissue hypoxia, but it can be life threatening if it is not identified and treated promptly. Methemoglobinemia occurs when iron atoms in hemoglobin molecules are oxidized from their normal ferrous (Fe2+) to a nonfunctional ferric (Fe3+) state, resulting in reduced oxygen delivery at the tissue level. 14

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MetHb is normally present in human blood at levels less than 1% to 2%, and methemoglobinemia occurs when levels exceed this. Cyanosis is observed when MetHb levels reach 5% to 15%. Headaches, dizziness, weakness, dyspnea, and tachycardia occur at levels of 30% to 40%.15 As levels increase to 55% to 60%, lethargy, confusion, stupor, seizures, and coma may result, and levels greater than 70% cause lethal circulatory collapse. The risk factors for the development of MetHb with Orajel have not been clearly defined. Certain risk factors that were suggested include hereditary lack of MetHb reductase, extremes of age (because most cases occurred in infants or elderly people), breaks in the mucosal barrier, concomitant use of other oxidative agents, and in particular, an excessive dose of benzocaine. 16 In addition, underlying cardiac or respiratory conditions may exacerbate the symptoms of MetHb. So while relatively a safe product, it is important for clinicians to be aware that Orajel , even in small quantities, may cause rare but potentially fatal MetHb. Methemoglobinemia caused by benzocaine may require treatment with medications and may require admission to a hospital. Serious cases of methemoglobinemia should be treated promptly. If left untreated or if treatment is delayed, serious cases of methemoglobinemia may cause permanent injury to the brain and body tissues, and even death, due to an inadequate supply of oxygen. 17 Orajel manufacture is aware of the MetHb problem and issue warming on their website. Do not use benzocaine topical if you have ever had methemoglobinemia in the past. An overdose of numbing medications can cause fatal side effects if too much of the medicine is absorbed through your skin and into your blood. This is more likely to occur when using a

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numbing medicine without the advice of a medical doctor (such as during a cosmetic procedure like laser hair removal). Overdose symptoms may include uneven heartbeats, seizure (convulsions), coma, slowed breathing, or respiratory failure (breathing stops). 18 Orajel products can help relieve your tooth pain along with soreness on the surface of your cheeks and lips and tongue. However, the problem with most over-the-counter gels is that they don't last long in the areas where you need them. The other problem is that using these over-the-counter products prevents people from getting the proper diagnosis and treatment they need. 19 When inflammation or an infection is present in the mouth, it's important to determine the precise cause of the problem. Most of the tissue in the mouth is either pink, white, or redish in color, and this can make it difficult, even for a dentist, to provide a diagnosis just by examining the area; sometimes a biopsy, X-ray, or further tests need to be performed. So although Orajel can temporary relieve the pain, it is important to see the dentist for chronic toothache to get proper diagnosis and treatment.

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Works Cited 1) Food and Drug Administration. FDA Public Health Advisory: Benzocaine sprays marketed under different names, including Orajel, Topex, and Cetacaine. 2006 Feb 10. From FDA website. 2) Ludwig SC. Acute toxic methemoglobinemia following dental analgesia. Ann Emerg Med. 1981;10:265-266. 3) Ludwig SC. Acute toxic methemoglobinemia following dental analgesia. Ann Emerg Med. 1981;10:265-266. 4) Cetylite Industries. Orajel (benzocaine 14% , tetracaine 2% and butamben 2%) spray, gel and liquid prescribing information. Pennsauken, NJ; 2006 Sept. 5) Food and Drug Administration. FDA Patient Safety News: Anesthetic sprays and methemoglobinemia. 2003 Jan. From FDA website. 6) Demare, Patricia; Regla, Ignacio (2012). "Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course". Journal of Chemical Education 89: 147. 7) "Monographs: Pharmaceutical substances: Benzocainum - Benzocaine". The International Pharmacopoeia. Retrieved 29 September 2009. 8) Wyeth Pharmaceuticals. Anbesol (benzocaine 20%) gel patient information. Madison, NJ; 9) Cetylite Industries. Orajel (benzocaine 14% , tetracaine 2% and butamben 2%) spray, gel and liquid prescribing information. Pennsauken, NJ; 2006 Sept. 10) Dahshan A, Donovan GK. Severe methemoglobinemia complicating topical benzocaine use during endoscopy in a toddler: a case report and review of the literature. Pediatrics. 2006;117:806-809. 11) Ludwig SC. Acute toxic methemoglobinemia following dental analgesia. Ann Emerg Med. 1981;10:265-266. 12) Demare, Patricia; Regla, Ignacio (2012). "Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course". Journal of Chemical Education 89: 147. 13) Moore TJ, Walsh CS, Cohen MR. Reported adverse event cases of methemoglobinemia associated with benzocaine products. Arch Intern Med. 2004;164:1192-1196. 14) Wurdeman RL, Mohiuddin SM, Holmberg MJ, Shalaby A. Benzocaine-induced methemoglobinemia during an outpatient procedure. Pharmacotherapy. 2000;20:735-738. 15) Food and Drug Administration. FDA Patient Safety News: Anesthetic sprays and methemoglobinemia. 2003 Jan. From FDA website. 16) Cetylite Industries. Orajel (benzocaine 14% , tetracaine 2% and butamben 2%) spray, gel and liquid prescribing information. Pennsauken, NJ; 2006 Sept. 17) Moore TJ, Walsh CS, Cohen MR. Reported adverse event cases of methemoglobinemia associated with benzocaine products. Arch Intern Med. 2004;164:1192-1196. 18) Cetylite Industries. Orajel (benzocaine 14% , tetracaine 2% and butamben 2%) spray, gel and liquid prescribing information. Pennsauken, NJ; 2006 Sept. 19) Moore TJ, Walsh CS, Cohen MR. Reported adverse event cases of methemoglobinemia associated with benzocaine products. Arch Intern Med. 2004;164:1192-1196.