Over the next several decades, rates of aged populations will increase rapidly. These populations are susceptible to multimorbidities and polypharmacy (concurrently, prescribed 5 or more medications). Many medications have side effects that manifest orally. Therefore, it essential to possess current pharmacologic knowledge to diagnose and treat oral implications of commonly prescribed medications. This article details common medication-induced oral lesions and patient assessment of risk factors for polypharmacy and provides a template to integrate medication reconciliation into dental clinical practice.
Key points
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Aged populations are at risk for polypharmacy.
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Medications have adverse side effects with oral manifestations.
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Diagnosis, treatment, and management of oral lesions are essential.
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Medication reconciliation should be integrated.
Introduction
Global demographics are being transformed by rapid acceleration of populations aged 65 and older and increasing life expectancy. For instance, over one decade (2010–2019) in the United States the size of the 65-and-older population increased by one-third, the fastest growth of any age group. The magnitude of this growth varies by state and ranges from 11% to 21% of the national population. The US Census Bureau estimates by 2034 for the first time in the nation’s history those 65 and older will outnumber children. Simultaneously, life expectancy is increasing worldwide, but this trend is not associated with healthier populations. The World Health Organization reports a contributor to a negative association between extended life expectancy and lack of health is multimorbidity, the presence of more than 1 chronic condition, which is elevated in aged populations. The cumulative effect of chronic conditions on multiple body systems places aged populations at increased risk for common clinical geriatric syndromes, such as falls, frailty, cognitive decline, delirium, incontinence, and polypharmacy.
Most efforts to define the phenomenon of polypharmacy have primarily focused on a numerical threshold of coprescribed medications as a required criterion. Results of a recent review confirmed 46.6% of studies selected defined polypharmacy primarily in terms of a numerical threshold of coprescribing 5 or more medications. A small minority, 6% of studies, described an evolving concept focused on distinctions between inappropriate and appropriate polypharmacy. Other researchers have sought to gauge appropriateness of polypharmacy. A challenge of evaluating the appropriateness of polypharmacy is that multiple drugs are often prescribed with inadequate clinical indications or a lack of evidence base as an effective, safe, treatment strategy. Subsequently, patients potentially receive inappropriate polypharmacy and take prescriptions for extended periods and/or at excessive doses.
Prevalence
Some experts believe that prevalence of multimorbidities is a driver of polypharmacy rates for older adults. In 2012, for Americans aged 65 or older, 61% had 2 or more chronic conditions. Surveys in 2016 confirmed 41% of Americans, aged 65 or older was prescribed 5 or more drugs in the past 30 days. Forty percent of community-dwelling and 75% of institutionalized older adults are concurrently prescribed 5 or more medications, whereas approximately 10% of older adults are prescribed 10 or more.
Nature of the problem
Risks and challenges of polypharmacy are listed in Box 1 .
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Adverse drug reactions a
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Potentially inappropriate prescriptions a
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Medication nonadherence a
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Drug duplication a
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Drug-drug interactions a
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Higher health care costs a
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Morbidity and mortality a
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Complexities associated with multimorbidities and polypharmacy increase the risk of fatal adverse drug events in aged populations (currently one of the 10 most common causes of death). b
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Older patients are predisposed to adverse drug reactions because of consumption of large quantities of drugs and because of age-related changes in metabolism and patterns of drug usage. c
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For all health care providers, presence of multimorbidities increases the challenges of assessing the safety and appropriateness of polypharmacy.
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Other challenges in delivery and assessment of appropriate polypharmacy include lack of provider-provider care coordination, segregation of medical and dental care, limited clinician time to review and assess adverse reaction profiles of multiple drugs, and limitations in drug information resources to evaluate multiple drug-drug interactions. d
Clinical Relevance
Increases in aged populations ensure that oral health providers will more frequently encounter patients with age-related physiologic changes in the oral cavity caused by comorbidities of chronic illnesses and changes resulting from medications used to manage diseases. Therefore, it is essential to be trained to recognize risk factors of polypharmacy, diagnose, and treat oral lesions related to oral manifestations of clinical pharmacology and potential adversities to ensure delivery of safe and effective dental care.
Discussion
The 2000 Surgeon General’s Report on Oral Health involved understanding of oral health and described its essential role in systemic health and well-being. This report also highlighted the concept of the oral cavity as the “window” to the body and the importance of the oral-systematic connection. This connection is evident with estimates that more than one hundred systematic conditions and nearly five hundred medications exhibit oral manifestations.
With increases in systemic diseases, comorbidities, and life expectancy, oral health care providers will have to be knowledgeable and ready to apply principles of geriatric medicine for the provision of care. Polypharmacy is one of the most common geriatric disorders ( Table 1 ).
| Several chronic medical conditions | Attempts to direct how/what is prescribed |
| Aged 75 or older | Frailty |
| Deficient care coordination | Use of over-the-counter medications and/or herbal supplements |
| Frequent hospitalizations and/emergency room visits | Lack of caregivers |
| Nursing home placement | Multiple physicians from different specialties |
| Cognitive impairment | Socioeconomic factors (access to consistent care, inability to afford medications) |
| Use of additional substances (nonprescribed) to manage drug-induced condition |
Oral Manifestations of Polypharmacy (Multiple Medications)
The indication for prescribed medications must be balanced against the potential for adverse effects. Drug-induced cutaneous reactions are common and varied in presentation, but only a limited number of reaction patterns occur in the oral cavity. The most common medication-induced oral manifestations are detailed in this review and summarized in Box 2 .
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Aphthous-like and non-aphthous-like ulcers
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Angioedema
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Dysesthesias (alteration in taste and burning mouth syndrome)
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Fungal and viral infections
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Fibrovascular hyperplasia
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Lichenoid reaction/lichen planus
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Xerostomia/salivary hyposalivation (caries risk, dysphagia)
Aphthous-Like and Non-Aphthous-like Ulcers
“Aphthous-like” ulcers are oral ulcers whereby there is a known cause, resolving when the underlying cause is effectively managed. This type of ulcer has a multifactorial cause and is frequently observed when dry mouth is associated with loss of lubrication and resultant trauma. Many case reports document that exposure to certain medications produces aphthous lesions as well. Medications, including nonsteroidal anti-inflammatory drugs, antibiotics, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and antianginal medications, have all been implicated with oral ulceration lesions.
A multivariate paired analysis revealed a significant association between nonsteroidal anti-inflammatory agents combined with β-blocker use and aphthous stomatitis. Drug-induced ulcers are located on the side of the tongue, are solitary, and are resistant to usual treatments until the suspect medication is discontinued. Nicorandil, prescribed to manage coronary artery disease, is linked to recurrent oral ulceration. It is also associated with a deferred appearance of oral and gastrointestinal ulcers, and delayed appearance can take as long as 74 weeks to develop, with patients on high-dose regimens presenting sooner ( Fig. 1 ).
Observational data and case studies report that many other drugs are associated with aphthous ulceration and stomatitis, including gold salts used for rheumatoid arthritis, and some selective serotonin reuptake inhibitors used for depression, ACE inhibitors, and drugs that affect the immune system, including interferons ( Table 2 ).
| Clinical presentation |
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| Risk factors considerations |
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| Topical treatment recommendations | |
| Therapeutic options for pain management |
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| Systemic options |
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| Measures of effective treatment |
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Angioedema (Swelling)
(ACE inhibitors are the most prescribed class of hypertension and heart failure medications, accounting for approximately 35% of antihypertensive prescriptions in the United States. Although rare (0.7%), severe adverse drug effects, such as angioedema, can occur.
The accumulation of bradykinins results in ACE-inhibitor angioedema and is usually slower in onset than histamine-mediated angioedema. Swelling may involve different body organs, and in the orofacial area, the lips and tongue are the most common compromised locations. With the potential risk of limiting the airway, angioedema can be life threatening ( Fig. 2 ). Most cases occur within the first 3 months of initiating the medication ( Table 3 ).
| Clinical presentation |
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| Risk factors considerations |
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| Pharmaceutical recommendations |
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Dysesthesias (Altered Taste)
Alteration in taste
Medications have the potential to alter taste perception, although these mechanisms are not well understood. One belief is that drugs may alter the concentration of trace metals or alter receptors involved with taste and smell. Research has identified in some cases that loss of taste in geriatric populations may result from physiologic changes in the cells initiating taste perception, declining olfactory function, poor nutrition, certain diseases, medications, and inadequate dentition. Adverse drug reactions that affect taste include distortion of taste (dysgeusia), loss of ability to perceive certain taste sensations (hypogeusia), and loss of taste sensation (ageusia).
Dysgeusia (altered sense of taste) is often seen in older patients because of chronic disease and polypharmacy, as well as physiologic, psychosocial, and emotional stress that can contribute to poor nutrition. Dysgeusia is further worsened by habits, such as tobacco and alcohol use, both of which cause an alteration in salivary flow, resulting in xerostomia. Patients may seek relief by sucking hard candy as a way to mitigate the metallic taste and the lack of saliva, which lowers the pH in the saliva, increasing caries risk. Alterations in taste significantly affect quality of life and can negatively affect diet choices and nutritional standing ( Table 4 ).
| Therapeutic recommendations |
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| Risk factors considerations |
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| Nutritional recommendations |
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Glossodynia (burning mouth syndrome)
Common systemic diseases and polypharmacy combinations used to manage conditions in aged populations have overlapping risk factors for burning mouth syndrome (BMS). Worldwide, prevalence ranges from 1% to 4.8%, and it occurs in both men and women, with the latter being predisposed at a ratio of 6:1.
BMS presents as burning sensations within the oral cavity (ie, tongue, lips, and oral mucosa) that are continuous and increase in intensity throughout the day. The greatest frequency occurs on the anterior one-third of the tongue, followed by the gingiva and palate. Up to 50% of cases report concomitant xerostomia and dysgeusia, and the latter may be a result of a dysfunction of the sensory input to the tongue (ie, chorda tympani nerve). , This condition is likely of multifactorial origin, often idiopathic, and its etiopathogenesis remains largely enigmatic. In the scientific community, there is no consensus on the diagnosis or classification for BMS. More often, it is a diagnosis of exclusion and may be associated with other oral manifestations, such as fungal infections and lichen planus, and may be exacerbated by nutritional deficiencies ( Table 5 ).
| Therapeutic options |
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| Risk factors considerations |
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| Pharmaceutical recommendations |
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| Measures of effective treatment |
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