Adverse Oral and Dental Effects of Medications
Case Western Reserve University School of Medicine
Associate Clinical Professor of Pharmacy Practice
* The author wishes to thank and acknowledge Wendy Gesaman and Sandy
Discuss the various categories of adverse dental and oral effects of
Provide specific examples of drugs that are associated with corresponding
Describe the mechanisms by which drug -induced adverse dental and oral
Discuss the role o f the pharmacist in limiting the incidence and/or severity
of adverse dental and oral effects of medication.
INTRODUCTION
Numerous drugs can adversely affect the oral cavity and dentition.
Patients who develop oral problems will seek help and treatment from their
dentist, pharmacist, or prescribing physician. These clinicians must work in
collaboration in order to reverse or resolve the patient’s condition. It may be
necessary to discontinue an agent if the oral effects are severe enough. While
adverse effects to medications can affect anyone, it is important to recognize that
elderly patients, or those with nutritional deficiencies, may be at increased risk for
developing iatrogenic oral problems. Patients older than sixty-five years of age,
are often on multiple chronic medications in order to manage a number of
medical conditions, such as diabetes mellitus, arthritis, congestive heart failure,
In order for the physician, pharmacist or dentist to properly assess and
manage a patient, a complete medication history must be conducted. It is
imperative inquires be made not only about prescription medications, but also
over-the-counter (OTC) and herbal medication use. Drugs have the potential to
affect the oral cavity in a number of ways and this continuing education lesson
will specifically reflect on eight conditions. The conditions addressed herein
include: xerostomia, intraoral hemorrhage, candidia albicans (oral thrush),
gingival hyperplasia, taste changes, tooth discoloration, stomatitis, and ulceration
or necrosis. Table 1 provides an overview of common medications and the
associated dental or oral side effect. It is important that healthcare professionals
understand the impact and severity that medications can have on the oral health
Xerostomia (dry mouth)
Dryness of the mouth, or xerostomia, results from diminished secretions of
saliva. More than two 250 medications claim xerostomia as a side effect. Drugs
that produce xerostomia as a side effect include anticholinergics,
antidepressants, anti-Parkinson’s drugs, antihistamines/decongestants, urinary
antispastics, antipsychotics, diuretics, hypnotics, systemic bronchodilators,
muscle relaxants, reserpine, methyldopa, laxatives, beta-blockers, narcotics,
guanabenz, a nd clonidine. A more comprehensive listing of drugs associated
with dry mouth is shown in Table 2. Medications that produce xerostomia, also
may increase the incidence of root surface caries (cavities). Medications with
significant anticholinergic activity, such as oxybutynin, hyoscyamine, and
scopolamine (Table 2), have the potential to cause xerostomia.
Xerostomia is a common complaint of numerous dental patients,
especially the elderly patients who take some of these medications on a regular
basis for a prolonged period of time. In the absence of medication use in a
patient with xerostomia, the dentist is also positioned to screen for medical
disorders associated with dry mouth, such as diabetes mellitus. An in-depth
review of the patient’s medication history should be conducted. Furthermore, a
complete history and physical exam, and lab testing may be necessary to
properly diagnosis and treat xerostomia. Upon examination patients with
xerostomia may complain of generalized mouth soreness, dry mouth, painful or
burning tongue, reduced denture retention, taste changes, difficulty in chewing,
and problems with talking and swallowing. Clinical presentation of xerostomia
includes oral fissuring, ulceration, and epithelial atrophy. Xerostomia is managed
symptomatically by increasing the patient’s water intake, using saliva substitutes,
and oral lubricants. Saliva stimulation is a way to manage xerostomia. The
patient can be instructed to suck on grape or lemon sugarless gum or candies in
order to increase saliva. It is known that the flow of saliva occurs during eating,
so another way to increase saliva stimulation is by increasing the frequency of
eating more small meals. Finally, agents such as citric acid, neostigmine, and
cholinergic agents such as pilocarpine and bethanecol can also be used to
Intraoral Hemorrhage
Intraoral hemorrhage is another condition which can be drug-induced.
Intraoral hemorrhage can be associated with numerous factors such as
thrombocytopenia, defective vascular integrity, or alterations in coagulation. A
majority of bleeding episodes occur as a result of a decrease in the number of
platelets or thrombocytopenia. Numerous agents have been implicated to cause
thrombocytopenia including sulfonamides, quinine, quinidine, thiazide diuretics,
allopurinol, methyldopa, antineoplastic agents, digitalis, heparin, phenytoin,
coumadin, and gold salts. Numerous antibiotics such as cephalosporins,
penicillin, and tetracyclines have also been associated with intraoral hemorrhage.
Certain patients are at increased risk for developing intraoral hemorrhage.
Patients who have cardiovascular disease and are on long term aspirin therapy
should be anticipated to have a reduction in platelet aggregation. Also patients
who are o n long term antibiotic therapy may have a reduction in synthesized
vitamin K. Vitamin K is necessary for the production of clotting factors II, VII, IX,
and X. Antibiotics reduce the intestinal flora’s ability to synthesize vitamin K,
which could cause potential oral hemorrhage problems with prolonged use.
Alcohol also has the propensity to reduce platelet lifespan, which can lead to
bleeding problems. Many patients may be stabilized on warfarin prophylaxis or
for treatment of venous thrombosis, pulmonary embolism, and thromboembolic
disorders. Since warfarin interferes with hepatic synthesis of vitamin K dependent
clotting factors, the international normalized ratio (INR) and prothrombin time
time (PT) must be closely monitored, especially in patients with perioral
Thrombocytopenia clinically may present as petechiae, which are small
round flat dark-red spots caused by bleeding beneath the mucous membranes.
The petichiae in the mouth are most commonly found as very tiny bleeding points
in the palatel mucosa. In order to diagnosis drug induced thrombocytopenia, a
platelet count, and medication history need to be conducted. To resolve the
thrombocytopenia the dentist or pharmacist may need to contact the prescribing
physician in order to discontinue the offending medication.
Dysguesia (taste changes)
Individuals taking any variety of medications may present with subjective
complaints of taste changes. Patients may have complaints of a bitter, metallic,
unpleasant or altered taste, “medication” taste, complete loss of taste, and
decreased taste sensation. There are more than 200 drugs in the that have the
potential to cause changes in taste sensations. Numerous drugs can cause taste
changes including clarithromycin, captopril, enalapril, griseofulvin, penicillamine,
metronidazole, carbenicillin, chlorhexidine, diltiazem, chloral hydrate, gold salts,
flecanide, lithium, vitamin D, and sulfasalazine. The most common complaint by
patients taking medications is a sense of altered taste.
The mechanisms by which drugs affect the taste sensations vary.
Researchers propose three mechanisms involved in medication taste disorders.
First, there is the influence of saliva on taste, i.e. the drug itself may be secreted
into the saliva, producing dyguesia. Another potential mechanism is the effect of
drug metabolite which could possibly interact with taste buds or saliva. Finally,
drugs may directly damage the taste buds. There may be age-related effects on
taste that can enhance medication taste disorders. The dentist will likely do a
complete medication history in patients that present with complaints of taste
changes. Once the offending agent has been identified, patients are usually
relieved just to know that the medication is the cause of the alteration in taste
perception. Fortunately, many medications that cause taste disturbances, such
as antibiotics, are only prescribed for a limited time period. However, some
individuals may present with severe symptoms and may require a change in their
Oral Candidiasis (thrush)
Candidiasis is the most common oral opportunistic infection seen in dental
practices. Patients usually present with creamy, white plaques on the tongue and
buccal mucosa. When scraped the lesions leave a red, painful ulcerated surface
exposed. Immunocompromised patients such as AIDS and cancer patients may
be more susceptible to oral infections since they have defects in cell-mediated
immunity. Immunosuppressed patients are more likely to develop complications
from candidiasis, such as infection in the esophagus, ulcerations, mucosa
perforation and invasive disease. Therefore, candidiasis has the capability to
become life threatening in some immunocompromised patients.
Drugs either act locally or systemically to predispose patients to
superinfection with Candida albicans. Broad spectrum antibiotics, antineoplastic
agents (cancer chemotherapy), corticosteroids (including metered-dose inhalers),
and immunosuppressive agents used to prevent rejection of transplant organs
are all drugs which have the potential to produce oral candidiasis.
Patients who present with an early Candida infection usually have mild
symptoms. The diagnosis of candidiasis is based upon history and clinical exam
findings, but is confirmed by the presence of yeast forms or pseudohyphae. Oral
candidiasis related to drug therapy can present in various forms. The forms
include acute atropic candidiasis (antibiotic sore mouth), chronic atropic
candidiasis (denture sore mouth), or acute pseudomembranous candidiasis
(thrush). Nystatin suspensions or clotrimazole troches are extremely effective in
It is known that in chronic asthma patients, inhaled corticosteroids are
efficacious in controlling symptoms and reducing oral corticosteroid dependency.
In order to achieve these outcomes inhaled corticosteroids may need to be used
at very high doses. With high doses of inhaled corticosteroids also comes the
increased risk of developing oral thrush via local deposition of glucocorticoid.
This complication can lead to poor compliance with asthma medications. The use
of a metered-dose inhaler (MDI) plus a spacer device, such as an Aerochamber
will decrease the incidence of oral-pharnygeal Candida superinfections and
reduces fungal colonization. It is imperative for the pharmacist, prescribing
physician, or dentist to prevent the development of thrush secondary to inhaled
steroid use. The use of a MDI plus a spacer device is an easy way to decrease
the incidence of oral candidiasis infections in asthma patients. It is also
recommended that patients adequately rinse their mouth or brush their teeth
following the administration of corticosteroid inhalers.
Gingival Hyperplasia (enlarged gums)
Patients may present to the dentist with gingival enlargement if they have
been taking agents such as phenytoin, nifedipine, or cyclosporin A (CsA).
Gingival hyperplasia occurs when there is an increased production and growth of
normal gingival cells. The affected area becomes larger but maintains its normal
form. Gingival hyperplasia occurs in roughly 50% of patients taking phenytoin for
the chronic management of epileptic seizures. Within two or three months of
taking phenytoin, gingival enlargement presents as a painless enlargement of
interdental papillae. Phenytoin can produce gingival enlargement which is severe
enough to completely cover the teeth. The severity of gingival hyperplasia is
related to the degree of local irritation and inadequacy of oral hygiene and not
generally related to the duration of therapy or dosage. The exact mechanism by
which phenytoin induces hyperplasia is not completely understood. However,
phenytoin may increase the expression of the gene for platelet derived growth
factor B (PDGF-B). When gingival macrophages are exposed to phenytoin they
secrete increased amounts of PDGF which may increase the proliferation of
gingival cells and alveolar bone cells. Patients who are started on a strict
program of oral hygiene within ten days of initiation of therapy may be able to
minimize the occurrence of gingival enlargement. Phenytoin-induced gingival
hyperplasia can also be treated surgically. Patients using phenyton are at risk for
gingival hyperplasia, and should be supplemented with 1mg folic acid 1-3 times
Approximately 5% of patients taking the calcium channel blocker
nifedipine will present with gingival enlargement. Nifedipine induces gingival
overgrowth when numerous inflammatory cells replace the collagen of
connective tissues. Nifedipine produces alterations of the intracellular calcium
levels in gingival cells and can produce local inflammatory factors to elicit gingival
Cyclosporin A (CsA) has also been associated gingival enlargement. CsA
is given to transplant recipients in order to prevent transplant rejection.
Approximately 25% percent of patients who are treated with CsA will have some
degree of gingival enlargement. Enlargement is correlated to gingival irritants,
such as dental calculus, imperfections in dental restorations, dental plaques, and
the effects of mouth breathing. Meticulous plaque control before initiation of
therapy and during therapy is a preventive measure against gingival
enlargement. Plaque control can be enforced and followed by the dental clinician.
Tooth Discoloration
Numerous drugs are noted to have the capability to produce tooth
discoloration. One of the most highly profiled drugs to cause tooth discoloration
in young adults is tetracycline. However, other agents such as minocycline,
isoproterenol, iron salts, ciprofloxacin, chlorhexidine, and methacycline all have
reportedly caused tooth discoloration. It is important for health professionals to
be aware of the consequences of using these drugs and how they can affect the
oral hygiene of patients. Some of these medications will cause only cosmetic
problems with discoloration and others will cause permanent tooth staining.
Tetracyclines are most noted for their ability to penetrate bony tissues, especially
the growing dentition o f young children. Tetracyclines are able to widely distribute
throughout the body; therefore, they are able to deposit in the growing dentition
and other bony tissues. It is disputable whether tetracycline is specifically
incorporated into the dentin or the enamel to produce its characteristic yellow-
brownish discoloration. Females who are exposed to tetracycline during the
second or third trimester of pregnancy, may give birth to a child who will develop
tooth staining. The teeth will become bright yellow upon development and the
stains will eventually turn to gray or brown over time. These effects can also
occur in the permanent teeth of children between the ages of two and eight years
old who have received tetracycline. In pediatric patients who have received
tetracyclines, one-third of them have reports of tooth staining. The staining that
occurs in pediatric patients is a permanent tooth discoloration. Discoloration
occurs with the greatest frequency when total dosage administration is over three
Tooth discoloration occurs when tetracyclines are deposited in calcifying
areas of teeth and bone. The mechanism by which tetracycline is incorporated
into the mineralizing tissues in not completely understood. However, it is
theorized that a chelate of calcium and tetracycline is incorporated into the
mineralized tissues. Depending on the specific tetracycline used, the type and
severity of discoloration may vary. Tetracycline and oxytetracycline cause a
yellow discoloration, whereas chlortetracycline produces a gray-brown
discoloration. Evidence suggests that of all the tetracyclines, oxytetracycline
Other agents such as minocycline, iron, ciprofloxacin, and cholrhexidine
have been documented to cause tooth discoloration. Minocycline is often given to
adult patients and adolescents to control acne. Minocycline produces
pigmentation changes of permanent teeth when it chelates with iron to form
insoluble complexes. Oral iron solutions can cause superficial discoloration of
teeth. In this case the discoloration can be removed with proper oral hygiene.
Ciprofloxacin given intravenously to infants at doses of ten to forty
milligrams/kilogram/day for Klebsiella pneumonia has been associated with tooth
discoloration. A greenish discoloration which could not be removed was noted
when infants teeth developed. Finally, chlorhexidine tooth staining occurs in fifty
percent of patients after a few days of use. The most common side effect of oral
chlorhexidine mouth rinse is the formation of yellow-brown stains. Fortunately,
the staining that occurs with chlorhexidine can be removed by professional
Stomatitis
Stomatitis is an inflammation of the mucous lining of the mouth and is
characterized as painful, generalized erythema. Severe cases of stomatitis can
develop into ulcerations The most common cause of nonspecific stomatitis is the
use of antineoplastic agents. Agents which have the potential to cause stomatitis
include melphalan, thiopeta, doxarubicin, epirubicin, idarubicin, busulfan,
procarbazine, dactinomycin, mitoxantrone, methotrexate, fluorouracil, cytarabine,
Chemotherapeutic agents are frequently used to treat a wide array of
malignant neoplasms, and o ral complications due to chemotherapy are often
overlooked. Oral complications due to antineoplastic agents can jeopardize the
effectiveness of treatment by allowing development of a focus for infection.
Additionally, patients may not eat, or may discontinue further chemotherapy
treatments due to the development of stomatitis. Oral/dental care is often
overlooked in cancer patients until a problem such as stomatitis occurs.
Clinicians can have a great impact on cancer patients treated with antineoplastic
agents by recommending meticulous dental care prior to, during, and after
Antineoplastic agents do not have the ability to differentiate between
rapidly growing malignant cells and normal cells. Normal cells most affected by
anticancer drugs are the ones with the highest turnover rate including hair
follicles, gastrointestinal mucosa, and bone marrow. Over time the antineoplastic
agents cause the oral mucosa to become thin. The atropic mucosa is more
susceptible to stomatitis and ulceration due to the rubbing of the mucosal
surfaces on one another, or on adjacent teeth. Mild forms of stomatitis can be
managed by cleansing the oral cavity with a soft tooth brush and rinsing with a
saline solution. Mouth rinses such as Kaopectate® have been successful in
Oral Ulceration and Necrosis
Ulceration and necrosis of the oral mucosa occurs when patients use
medications that are not intended for topical therapeutic use or they are taking
medications incorrectly. The classic “aspirin burn” is a good example of what can
happen when patients try to self medicate. Aspirin is one of the best-known
locally toxic substances to oral mucus membranes. When a patient has a
toothache they may try to relieve the pain by placing an aspirin in the muco-
buccal fold opposite the toothache. However, the tissue exposed to the aspirin
will become white and depending on the severity of tissue destruction, the
lesions may be scraped off. Once the lesion is scraped off, the result is a painful
bleeding area. Drugs capable of producing stomatitis can potentially produce
reactions that are severe and lead to ulcerations. Drugs capable of causing
ulceration or mucosal necrosis include aspirin, phenylbutazone, indomethecin,
silver nitrate, hydrogen peroxide, isoproterenol, phenols, acids or alkalis, and
Conclusion
Hundreds of medications have the capability to cause adverse effects
within the oral cavity. Drugs have the potential to cause conditions such as
xerostomia, intraoral hemorrhage, oral candidiasis, gingival overgrowth, taste
changes, tooth discoloration, stomatitis, ulceration and necrosis. It is imperative
that health professionals understand the severe complications that medications
can have on the oral health of their patients. Pharmacists can educate physicians
and dentists on the adverse effects drugs have on oral health. By making health
professionals aware of the drug consequences, preventative measures can often
be implemented before a problem begins. In order to properly manage patients, a
complete medication history including prescription medications, OTC, and dietary
supplements must be conducted. A thorough medication history may enable the
healthcare team to identify the offending agent.
DRUGS THAT AFFECT THE ORAL CAVITY
Choose the correct response for each question below 1.
Which of the following drugs cause xerostomia via anticholinergic
Which of the following antidepressants is most likely to cause xerostomia:
Which of the following statements is true regarding chronic, drug-induced
it can increase susceptibility to dental carries
phenothiazine antipsychotics (e.g. thioridazine) can cause xerostomia
it may be treated with either pilocarpine
Which of the following antihypertensive drugs is associated with causing
Medications associated with causing gingival hyperplasia include:
Which of the following drugs is associated with taste disturbances?
Use of a tube spacer, such as an Aerochamber, can reduce the incidence
of oral candidiasis associated with corticosteroid MDI use. a.
Which of the following can cause mucosal ulceration when applied
The staining of teeth associated with chlorhexidine is permanent and
cannot be removed by brushing the teeth : a.
The staining of teeth associated with tetracycline is permanent and cannot
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JULIE EVANS (TVN) Abertawe Bro Morgannwg University Health Board, Rehab Engineering Unit, Morriston Hospital, Swansea, UK. [email protected] Introduction: Patients may succumb to infections from a variety of ÂopportunisticÊ bacteria as a result Table 1 -Sequence of intervention and associated wound response of concurrent co-morbidities. The Centers for Disease Cont
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