Adverse Drug Reactions and Oral Health

Patients who take medications— both prescription and over-the-counter—are common in all dental practices, which is why understanding possible adverse drug reactions that may affect the oral cavity is so important for the dental hygienist. Evaluating these adverse reactions is necessary to accurately assess the patient’s status and to plan for medication-related prevention and treatment interventions throughout the dental hygiene process of care. Oral side effects of medications often significantly impact patients’ quality of life by altering their level of comfort and ability to function.

XEROSTOMIA

More than 500 medications cause xerostomia, the most common oral complaint associated with medication use.^1,2 Xerostomia interferes with the patient’s ability to eat, swallow, and digest food. Patients may also complain of taste alteration, causing a loss of interest in eating, which increases their risk for malnutrition. Loss of lubrication makes wearing dentures and appliances difficult and uncomfortable. Changes in salivary composition increase the patient’s susceptibility to developing bacterial, fungal, and viral infections.³ Dental hygienists must carefully assess the presence of xerostomia and recommend appropriate interventions to improve patient comfort and function. These recommendations include using fluorides, chemotherapeutic mouthrinses, and dentifrices; products for desensitization; methods for pain control; and salivary stimulation and replacement therapies.⁴

ALLERGIC REACTIONS

Drugs are the most common cause of urticarial reactions in adults, affecting approximately 15% to 20% of young adults.⁵ Urticaria is a vascular reaction in the superficial layers of the skin, characterized by localized edema and increased capillary permeability with wheals (hives), often accompanied by severe itching. When this swelling occurs in either the subcutaneous or submucosal tissues, the condition is known as angioedema. Angioedema can also involve other tissues, such as the larynx and tongue. Patients develop allergies to medications following exposure and sensitization to a drug (antigen). Allergic reactions are not dose-related nor are they predictable.

Most drug-induced allergic reactions are termed type I hypersensitivity reactions and are mediated by the humoral immune system. They often occur after the second exposure to the drug or following repeated exposures to the same drug or material. These reactions are mediated by IgE (immunoglobin), causing the release of histamine from mast cells, which causes increased vascular permeability and edema in the surrounding tissues. Antibiotics are associated with this type of allergic response. When mast cells in the bronchi release histamine, the patient will exhibit an anaphylactic response, leading to acute respiratory distress.⁶

Topical anesthetic agents, dental local anesthetics, and drugs are associated with type I hypersensitivity reactions. This type of allergic reaction has a rapid onset, with oral lesions developing in and around the oral cavity, with urticarial swelling or angioedema of the lips, tongue, and oral mucosa. The soft tissue swelling is usually painless but the patient may experience burning or itching. The swelling remains for 1 to 3 days. It should then spontaneously resolve. Oral diphenhydramine (Benadryl) therapy is administered with 50 mg taken every 4 hours for up to three days to assist with resolution of the reaction. If swelling involves the pharynx, larynx, or tongue, an emergency response protocol is implemented to maintain the airway, including epinephrine injected into the tongue or floor of the mouth, and supportive respiratory assistance given to the patient as needed.⁶

Drugs, dental materials, and oral care products can cause a variety of oral ulcerations, often mimicking aphthous stomatitis. This type of allergic response is known as an immune complex reaction or type III hypersensitivity reaction. Erythema multiforme (EM) is an example. Many patients who exhibit EM have either a drug allergy or herpes simplex infection as a predisposing factor for triggering the reaction.^6,7

EM is an inflammatory disease of the skin and mucous membranes, characterized by skin lesions with a bull’s eye appearance. Oral lesions appear as inflamed tissues with vesicles and bullae that rupture quickly. More than 70% of patients with EM have oral lesions.⁸ Oral lesions can occur anywhere in the mouth and patients often exhibit a hemorrhagic crusting of the lips.^7,8 The onset of EM occurs within days to weeks following exposure to the drug.⁹ Sulfa antibiotics and sulfonyl urea oral hypoglycemic agents used to manage type 2 diabetes are the most common drugs associated with EM.6 Other medications associated with EM include nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, allopurinol used to treat gout, and penicillins.⁷ Treatment of EM includes symptomatic therapy with topical anesthetics and analgesics, but severe cases may require treatment with systemic corticosteroids.^6,7

Type IV hypersensitivity reactions are mediated by the cellular immune system and manifest as contact dermatitis. These reactions are usually delayed and appear about 48 to 72 hours after contact with the antigen.⁶ Antigens may include dental materials, toothpaste, mouthrinses, and cosmetics.⁶ Oral tissues may appear red, sloughing, and/or ulcerated. Treatment includes removal of the offending product and symptomatic therapy as needed.⁶ Dental hygienists should note that phenolic compounds found in antiseptic mouthrinses, toothpastes, astringents, and flavoring agents can cause type I, III, and IV hypersensitivity reactions.⁶

Some patients will manifest an oral lichenoid drug reaction, a condition that clinically appears identical to lichen planus. Oral lesions are found on the posterior buccal mucosa with a central erythematous area with radiating white striae. Both lichenoid drug reaction and lichen planus are thought to represent a type IV hypersensitivity reaction, although the exact etiology of this reaction is not known.⁶ Lichenoid reactions resolve in several days to a few weeks when the drug is discontinued.^6,7 Drugs that are commonly associated with this reaction include antihypertensive medications and NSAIDs. Other drugs include antimalarials, gold compounds, hormones, oral hypoglycemics, methyldopa, allopurinol, and photographic dyes.^6,7

TASTE ALTERATION

Many classes of drugs are associated with taste alteration, which manifests as hypogeusia (decreased taste), dysgeusia (distortion of the correct taste), parageusia (bad taste), and ageusia (no taste).⁹ Taste alteration poses significant quality of life problems for patients and negatively impacts food selection, eating behaviors, and nutrition. Often, patients will use excessive quantities of salt or other seasonings in an attempt to heighten the flavor of their foods. Chronic ingestion of spicy foods and cinnamon may lead to burning mouth syndrome. Patients may frequently rinse with mouthwash, suck on breath mints or hard candies, and chew gum to mask adverse taste sensations, which brings only temporary relief. Dental hygienists should examine their patients for tissue irritation, caries, and facial pain resulting from these behaviors, and counsel their patients accordingly.

More than 250 medications cause alterations in taste and smell and several mechanisms of drug-induced taste alteration exist. Drugs may be excreted in the saliva and gingival crevicular fluid, which can modify taste. Drugs that alter salivary flow concentrate the electrolytes in saliva, resulting in a salty or metallic taste. Drugs can also alter the function of taste receptors.10 Dental hygienists are most familiar with taste alteration associated with chlorhexidine use. Drug-induced taste alteration may be dose-related and resolves when the drug is withdrawn.⁷

PIGMENTATION

Tetracycline and minocycline are antimicrobial agents known to stain the teeth. Systemic ingestion of tetracycline causes irreversible staining in developing teeth and bones. Typically, the cervical third is most affected and staining is directly proportional to the age at drug exposure, dosage, and duration of therapy.¹¹

Minocycline is associated with altering pigmentation of the teeth, bones, sclera of the eyes, nails, and oral soft tissues.^12,13 Unlike tetracycline, minocycline staining occurs after the teeth are fully developed and erupted. Minocycline penetrates easily into both soft and calcified tissues. Pigmentation is produced by incorporation of the drug from the pulp into the dentin and enamel. Oxidation from the saliva and gingival crevicular fluid produces a blue-gray staining in the middle and incisal thirds of the teeth. Minocycline staining is irreversible.^12,13

Metals, such as lead or mercury, or drugs that contain metals, such as gold salts, produce pigmentation changes along the gingival margin. These color changes may resolve following discontinuation of the drug, but may be permanent.⁷ Other medications associated with oral pigmentation include drugs to treat malaria and antiretroviral medications.⁷

Black hairy tongue (Figure 1) is a condition where the filiform papilla become elongated and stained from chromogenic bacteria. Staining appears brown or black in color. Black hairy tongue is associated with penicillins and gastrointestinal drugs that contain bismuth (Kaopectate, Pepto- Bismol).⁷ Staining with hairy tongue can also be caused by pigments from food, beverages, and tobacco use.¹⁴

GINGIVAL HYPERPLASIA

Gingival hyperplasia is a known side effect associated with the anticonvulsant phenytoin (Dilantin), the immunosuppressant cyclosporine (Sandimmune), and the calcium channel blockers used for hypertension and angina. Drug-induced gingival enlargement can be localized or generalized and varies with degree of severity. Enlargement typically affects the labial tissues and begins in the interdental papillae. Gingival tissues surrounding the anterior teeth are often affected first. The degree of enlargement observed within the first 6 months of drug treatment is often indicative of the degree of severity of overgrowth that the patient will develop. Severity is directly proportional to the patient’s oral hygiene. The enlarged gingiva appear fibrotic and the patient often develops an overlying inflammation, as hyperplastic tissues can be difficult to keep clean.^15,16

The underlying mechanisms of druginduced gingival overgrowth differ among medications but the clinical manifestation appears similar. Gingival hyperplasia may resolve upon discontinuation of the drug, but it is not always a viable option to withdraw the medication or switch the patient to a drug of a different class. Dental hygienists should teach their patients to perform meticulous oral hygiene to limit the extent and severity of the hyperplasia.^15,16

REFERENCES

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11. Parks ET. Lesions associated with drug reactions. Dermatol Clin. 1996:14:327-337.
12. Hung P, Caldwell JB, James WD. Minocycline-induced hyperpigmentation. J Fam Pract. 1995;40:183-185.
13. Morrow GL, Abbott RL. Minocycline-induced scleral, dental, and dermal pigmentation. Am J Ophthalmol. 1998;125:396-397.
14. Sartii GM. Black hairy tongue. Am Fam Physician. 1990;41:1751-1755.
15. Hassell TM, Hefti AF. Drug-induced gingival overgrowth: old problem, new problem. Crit Rev Oral Biol Med. 1991;2:103-137.
16. Wynn RL. An update on calcium channel blockerinduced gingival hyperplasia. Gen Dent. 1995;43:218-22.

From Dimensions of Dental Hygiene. November 2006;4(11): 22, 24, 26.