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Medications Used to Treat Oral Complications

Abstract

Oral complications, including xerostomia, an odontogenic bacterial infection, or fungal infections, are encountered routinely in clinical practice. In order to adequately treat the patient and his/her condition, the provider must determine an accurate diagnosis, discuss the patient’s risk with and without treatment, and do so in a timely manner. There are numerous prescribing options available to today’s dental practitioners, and the best choice depends on the patient being treated. All medications have side effects, and depending upon the drug selected, these can drastically affect the patient and positively or negatively impact his/her quality of life.

Learning Objectives

  • Understand the importance of a thorough medical history review, including a patient's current medications
  • Review cholinergic agonists that assist xerostomia patients in stimulating saliva production.
  • Highlight prescription of antibiotic therapy tailored to a patient's risk profile
  • Present topical as well as systemic approaches to treat fungal infections.

As a practitioner, the prescription of medication is an act that should never be taken lightly. Even one dosage of a medication has the potential to induce an anaphylactic reaction that could precipitate death. Obtaining a thorough medical history, documenting all known drug allergies, is paramount in avoiding this costly mistake. Numerous resources, such as consulting with the patient’s physician or pharmacist, are at the practitioner’s disposal, and their expertise should never be underestimated in contributing to the highest level of patient care. This review will provide a synopsis of several medications available to treat common oral complications including cholinergic agonists for xerostomia, antibiotics for treatment and prevention of bacterial infections, and antifungals for treatment of oral candidiasis.

Autonomic Drugs

In clinical dentistry, the prescription of autonomic medications is limited but yet still important in treating complications and side effects of other medications that patients may be taking. Many drugs including antiemetics, anti-anxiety agents, decongestants, analgesics, anti-diarrheals, bronchodilators, and skeletal muscle relaxants have the major side effect of xerostomia. Xerostomia puts patients at much higher risk for dental caries, periodontal disease, and other oral complications including fungal infections and halitosis. Without treatment, this can decrease a patient’s quality of life, alter taste sensation, and make mastication extremely difficult.

Acetylcholine (ACh) is the neurotransmitter which induces, amongst other things, the salivary glands to secrete saliva. Cancer treatments such as radiotherapy and chemotherapy can exacerbate xerostomia symptoms, and xerostomia is also a major symptom of Sjögren’s syndrome1 along with others listed in Table 1. In order to combat this, it is recommended to prescribe a cholinergic agonist such as cevimeline (e.g. Evoxac, Daiichi Pharmaceuticals, Montvale, NJ) in cases of Sjögren’s syndrome, or pilocarpine (e.g., Salagen, Pfizer Inc., New York, NY) when the root cause is salivary gland hypofunction secondary to head and neck radiation therapy. Pilocarpine has a high binding affinity to systemic muscarinic cholinergic receptors, promoting generalized fluid secretion, while Cevimeline is more specific and binds with greater affinity to muscarinic receptors in lachrymal and salivary gland epithelium, thus causing fewer side effects in patients where dysfunction can be isolated to a specific type of tissue. Side effects of both drugs include sweating, watering eyes, headache, nausea, upset stomach, diarrhea, and pain around the eyes.2 As a result, the patient’s physician should be involved in the treatment process so as to not interfere with any medical treatments the patient may be concurrently receiving.

Antibiotics

Antibiotics are among the most frequently prescribed classes of medications in clinical dentistry. However, the landscape of available antibiotics has not changed significantly in recent decades. This fact, combined with increased provider prescribing habits, is leading to the proliferation of antibiotic-resistant bacteria. The National Center for Disease Control estimates that up to one third of all outpatient antibiotic prescriptions are unnecessary.3 It is now more important than ever to accurately ascertain if the benefits of placing a patient on antibiotic therapy outweigh the risks, and if so, which antibiotic is best suited to treat or prevent possible infection.

Keep in mind, that an antibiotic such as penicillin can cause an anaphylactic reaction leading to death, and in fact, up to 75% of fatal anaphylaxis cases each year are due to penicillin-related antibiotics.4 It is beneficial to keep in mind that most oral diseases that present in a clinic setting are inflammatory in nature. Even those patients presenting with a chief complaint of pain often have an acute or chronic infection of pulpal tissue which necessitates endodontic treatment or extraction, or a chronic inflammatory periodontal condition, neither of which are indications for prescribing of antibiotic therapy.5

The first choice of antibiotic for many dental providers is amoxicillin. This drug is a relatively broad-spectrum antibiotic with bactericidal effects against both gram-positive and gram-negative microorganisms. It is recommended by the American Heart Association as the first line of defense to prevent infective bacterial endocarditis (IBE) prior to dental procedures in those patients at risk, as well as to treat odontogenic infections (Figure 1). While amoxicillin is the most commonly prescribed antibiotic in dentistry, this review will shed light on the less frequently encountered medications available to treat oral complications.

Clindamycin is typically the second choice for treating odontogenic infections, dental abscesses, and preventing IBE in those patients who either cannot take amoxicillin, or for whom amoxicillin is not indicated. It is used to treat infections caused by aerobic gram-positive cocci and susceptible anaerobes, and has no effect on gram-negative bacteria. In the lincosamide class of antibiotics, clindamycin cannot inhibit translation of the bacterial genome, and thus is widely considered bacteriostatic, though it has been reported to have bactericidal effects on a limited number of species.6 Clindamycin must be used with caution, as a potential side effect includes Clostridium difficile (C. diff) infection. This antibiotic kills some of the stomach’s normal flora, selectively favoring the growth of C. diff, which in turn leads to potentially life-threatening severe watery diarrhea and abdominal cramping.

Tetracyclines are a class of bacteriostatic antibiotic that are most commonly used in dentistry for treating periodontal infections. They are, at best, a third-choice option for odontogenic infections and for prevention of IBE. Each class of antibiotic has a different site of action within the bacterium and thus each will possess different levels of efficacy (Figures 2 and 3). One common side effect of these antibiotics is the incorporation into tissues that are calcifying at the time of administration; they can affect both the primary and permanent dentitions, ranging from a dark-yellow to grey and even brown hue imparted to the enamel.7 Tetracyclines include the drugs tetracycline and its derivatives, doxycycline and minocycline, which are frequently encountered in dentistry. These can be a good alternative to penicillin for patients with ANUG (acute necrotizing ulcerative gingivitis) who require antibiotics, and also are deemed useful in juvenile periodontitis caused by actinobacillus. Minocycline (e.g., Arestin, Orapharma, Bridgewater, NJ) can be dispensed directly into 5 mm to 7 mm periodontal pockets that have not responded to initial periodontal therapy, possibly avoiding the need for surgical intervention. Arestin delivers therapeutic doses of minocycline in a controlled release manner to the periodontal pockets. It is important to note that bacteriostatic antibiotics are not recommended for use in immuno-compromised patients due to the potential for the infection to persist and increased risk of further complications.

First-generation cephalosporins, such as cephalexin and cephradine, also can be used as an alternative to penicillin therapy in treating odontogenic infections. They are more effective in early-stage infections due to their broad spectrum bactericidal effects on gram-positive aerobes, exerting no notable effect on anaerobes present in later-stage infections.8 Due to sharing a common beta-lactam ring with penicillin, there may be cross-reactivity, whereby some studies show up to 10% of the population with an allergy to penicillin will also be allergic to cephalosporins. However, the evidence demonstrates that it is very dependent upon the specific cephalosporin (and perhaps its individual R-chain) prescribed to accurately gauge the risk of allergy (Figure 4).9,10 These antibiotics are also a viable alternative to be used in standard prophylaxis provided that the patient does not have a known allergy to penicillin.

The macrolide class of antibiotics, all of which are bacteriostatic, includes erythromycin, clarithromycin, and azithromycin. Erythromycin, the prototype macrolide, is effective against aerobic gram-positive bacteria as well as many anaerobes. The high rates of resistance of oral streptococci and oral anaerobes to erythromycin and clarithromycin make them poor choices in many clinical scenarios. Erythromycin was the most popular of the three, however, in dentistry, azithromycin is the only one that has recently gained any traction, particularly amongst endodontists when treating oral-facial infections.

Clarithromycin and azithromycin are structural derivatives of erythromycin, and both exhibit a broader spectrum of activity with fewer GI side effects.9 A key advantage of azithromycin is the availability of the Z-pak which offers patients a total of 6 pills with just 5 total doses to complete treatment. This leads to a greater likelihood that a patient will administer all prescribed doses, and decreases the risk for development of resistance. These also may both be used as acceptable alternatives to penicillin in the standard IBE prophylaxis regimen.

Anti-Fungals

Candidiasis infection, commonly referred to as “oral thrush,” is the most frequently encountered fungal infection in dentistry. Caused by yeast such as Candida albicans, this can result is white patches or plaques on the tongue or other oral mucous membranes. While Candida is naturally found on oral soft tissue, those at risk for overgrowth and subsequent infection include patients with HIV/AIDS, cancer, or other immuno-compromised state, diabetics, denture-wearers, and patients who take broad-spectrum antibiotics or inhaled corticosteroids.11

Clotrimazole is an anti-fungal available over the counter as a topical cream, but also prescribed as a lozenge (troche) for the treatment of oral candidiasis. Lozenges are placed in the mouth and dissolved slowly over 15-30 minutes. A standard regimen for treating thrush lasts for 14 days, with dosing 5 times per day.

Fluconazole is an alternative to clotrimazole and is commercially available to be prescribed in tablet form or given by intravenous (IV) administration. This drug is preferred when systemic therapy is required to treat a moderate to severe mucosal candidiasis infection. Like clotrimazole, and other -azole anti-fungals, fluconazole works by inhibiting a key fungal cytochrome P450 enzyme, and is primarily fungistatic, with the exception of a few organisms upon which is exerts fungicidal effects.

Ketoconazole is yet another oral or topical anti-fungal medication. It is not as widely prescribed due to the alternative of fluconazole, discussed above, which is generally less toxic and more effective, especially in systemic form. Ketoconazole is reserved for more severe cases of esophageal candidiasis or systemic fungal infections, often encountered in more developing nations, and is suggested to be used with caution in immuno-compromised patients.

Nystatin (100,000 units: 1 mL) is a polyene anti-fungal drug prescribed as an oral rinse to treat oral or esophageal candidiasis. Useful for patients who prefer a topical treatment, a patient is directed to swish as long as possible before swallowing, with 4-6 mL four times daily with the rinse.

Conclusion

In order to adequately treat oral complications in today’s patient and his/her condition, providers develop an accurate diagnosis, determine the patient’s risk with and without treatment, and engage the patient in the best course of action. Numerous prescribing options are available to dental practitioners, and the optimal choice depends on the patient being treated. All medications have side effects, and depending upon the drug selected, these can drastically affect the patient and positively or negatively impact his/her quality of life.

 

*Regional Operations Supervisor for IMA Group. Dr. Skulsky oversees six practices in Western Pennsylvania and works to improve their clinical and administrative quality and efficiency.


 

References

1. Becker DE. Basic and Clinical Pharmacology of Autonomic Drugs. Anesth Prog 2012;59(4):159– 169.

2. Brimhall J, Jhaveri MA, Yepes JF. Efficacy of Cevimeline vs Pilocarpine in the secretion of saliva: A pilot study. Spec Care Dentist 2013;33:123-127.

3. Swift JQ, Gulden WS. Antibiotic therapy – Managing odontogenic infections. Dent Clin N Am 2002;46:623–633.

4. Sollecito TP, Abt E, Lockhart P.B., et al. The use of prophylactic antibiotics prior to dental procedures in patients with prosthetic joints. Journal Am Dent Assoc 2015;146(1):11-16.

5. Dar-Odeh NS, et al. Antibiotic prescribing practices by dentists: a review. Ther Clin Risk Manag 2010;6:301–306.

6. Shenvi C. The Clindamycin fact sheet. http://www.medpagetoday.com/Blogs/ EPMonthly/53645 Accessed 18 August 2016.

7. Sanchez AR, Rogers RS III, Sheridan PJ. Tetracycline and other tetracycline-derivative staining of the teeth and oral cavity. Int J Dermatol 2004;43(10):709-715.

8. Schwartz S. Commonly Prescribed Medications in Pediatric Dentistry. http://www.dentalcare.com/ en-US/dental-education/continuing-education/ ce336/ce336.aspx?ModuleName=introduction&P artID=-1&SectionID=-1 Accessed 19 August 2016.

9. Pichichero ME. Cephalosporins can be prescribed safely for penicillin-allergic patients. J Fam Pract. 2006;55(2):106-112.

10. Pichichero ME. A review of evidence supporting the American Academy of Pediatrics Recommendation for prescribing cephalosporin antibiotics for penicillin allergic patients. Pediatrics 2005;115(4):1048-1057.

11. Kennedy WA, et al. Occurrence and risk factors of oral candidiasis treated with oral antifungals in seniors using inhaled steroids. J Clin Epidemiol. 2000; 53(7): 696-701.

Tables

Table 1: Presenting Symptoms of Sjögren’s Syndrome

PRIMARY SYMPTOMS

OTHER SYMPTOMS

Dry eye

Gritty, sandy feeling

Stinging feeling

 

Dry mouth

Dry, cracked tongue

Sore throat

Burning throat

Difficulty talking

Difficulty swallowing

Difficulty chewing dry food

Change in sense of taste/smell

Increase in cavities

Mouth sores

Cracked lips

 

Swollen parotid glands

Nausea

Dry skin

Joint pain

Dry nose

Reflux

Muscle pain

Fatigue

Muscle weakness

Low-grade fever

Vaginal dryness

Neuropathy

Dizziness

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