KDA Today

KDA Today

For Immediate Release

Date: Sep 12th, 2016
Contact: Dr. Demetra Antimisiaris
Phone: 800-292-1855
Email: info@kyda.org

Polypharmacy: A Geriatric Syndrome with Serious Implications for Oral Health


Modern medicine has made living with multiple chronic diseases possible, but now faces the difficult balance of improving quality of life, and managing the means by which this is achieved. Today, we are able to extend life expectancy due to improvements in sanitation, living conditions and medical technology, including the use of various pharmaceutical products. Polypharmacy, the use of multiple medications at the same time is considered a geriatric syndrome, and is a side effect of modern medicine. Geriatric syndromes are conditions that are multifactorial health conditions occurring due to accumulated effects of impairments in multiple systems, but are not necessarily specific organic disease processes, such as incontinence, dizziness, cognitive impairment, falls, delirium and frailty.

In 1900, those aged 65 years and older constituted four percent of the population, which had a life expectancy of 46 years. Today, those over 65 represent 13-16 percent of the population, which enjoys a life expectancy of 75 years for men and 80 years for women (1). By 2030 elders will constitute 22 percent of the population with the percent over 80 years of age set to quadruple (2). Elders are most vulnerable to medication problems, and suffer increased exposure to medication. They are frailer and lack the physiological reserve to survive interventions and medical events.

The PDR in 1969 contained 1,415 pages, inclusive of Over the Counter (OTC) products. In 2008, the PDR held 3,482 pages of prescription products with a separate OTC and dietary supplements book. In addition to the supervised use of medications, there is an unprecedented level of self-medication due to direct to consumer marketing and more prescription items going over the counter, annually. Surveys of mean daily OTC drug use in people over 65-years-old range from 31-96 percent of the population, with a 70 percent average (3). A 2004 Boston College survey reports that 42 percent of all adults take vitamins, daily, and 19 percent take herbals and supplements, daily. In any given week, 82 percent of U.S. adults take at least one medication (prescription or nonprescription drug, vitamin/mineral, herbal/natural supplement), while 30 percent take at least five (4).

The use of multiple medications is accompanied by significant risk due to anything from drug-drug and drug-disease interactions to a patient's own cognitive ability to manage his or her medications. A linear relationship exists between the number of medications taken and the risk of adverse reactions. The same linear relationship has been seen with the number of medications used and mortality, even after adjusting for disease severity (5, 6). At particular risk are the elderly. Eighty-eight percent of people over 65 live with chronic health problems. Adults over 65 years of age currently account for just 13 percent of the general population, but constitute 40 percent of all hospitalizations and 50 percent of hospital days. Approximately one third of hospital admissions in the elderly result from medication related problems (7, 8). With increasing pressure on primary care physicians to manage complex medical problems in less time, it is not surprising that adverse events occur. Similarly, sub-specialists adhering to practice guidelines may excessively treat an older, frail adult, with negative consequences.

If medication-related problems were a disease, it would rank fifth of the top ten with regard to the economic impact of diseases affecting Americans 65 years of age and older (9). That places medication-related problems behind diabetes and in front of osteoarthritis. The state of Kentucky leads the country for expenditure on antidiabetics, antihypertensives, GI medications and analgesics/anti- inflammatory meds, and antidepressants. Kentucky also leads the overall scripts per capita statistics for the United States; ahead of West Virginia, Alabama, Mississippi, Louisiana, and Arkansas (10). With such unusually high medication, OTC, herbal and supplement use in Kentucky, all stake holders are obligated to consider the implications and risks.

Considerations in caring for older adults with high medication use burdens:

Frailty and Physiological Reserve
The majority of the medications that are used in the elderly were brought to market based on safety and efficacy studies performed in either younger or healthier subjects than those actually taking the medications. To participate in a safety and efficacy drug trial, the exclusion criteria eliminate frailest patients with multiple co morbidities. Additionally, the frailest of the frail cannot even make their way to clinic to participate in studies. Be cautious using medications new to the market. Rofecoxib (Vioxx®) was introduced with claims of improved safety, but was found in post marketing data to cause adverse cardiac effects and increased mortality.

Impaired physiology is important to take into account when prescribing for elders. Current science pertaining to our understanding of the physiology of aging is changing daily, thus our understanding of how drugs behave in elders is also changing rapidly. Hepatic metabolism slows with age resulting in impaired first pass effect. Renal function is impaired with age in all persons. With every decade of age over 40-years-old, a person loses 1 ml/min of creatinine clearance of renal function per year (and at 40 years of age, typical CrCl-100ml/min). This renal slowing occurs regardless of renal insults such as environmental toxicity, diabetes and the like. Renal dose adjustment is often overlooked leading to adverse medication events. Many drugs such as memantine, and levofloxacin require renal dosage adjustment, or are contraindicated in elders with moderate to severe renal impairment such as bisphosphonates. As a class of drugs, antibiotics have many which require renal dose adjustment, and NSAIDs (non-steroidal anti-inflammatory drugs) are acceptable for most patients in treating transient pain and inflammation, but might not be in those with severe renal impairment, high blood pressure and concomitant use of anticoagulants.

A deceiving feature of elderly patients is that their serum creatinine level may seem normal despite marked renal impairment. Most labs do report Glomerular Filtration Rate, however they calculate using the MDRD, which has not been validated in elderly subjects. The Cockcroft-Gault Equation is recommended because it has better validation in elders and is the FDA renal dose adjustment standard.

The use of medications in older adults requires consideration of their diminished physiological reserve and altered pharmacokinetics; resulting in a decreased ability to adjust to neurotransmitter alterations, changes in blood pressure, glucose and other parameters influenced by medications and disease states. These cardiovascular, renal, neural hormonal, endocrine and other changes, result in the elderly patients being less able to recover from challenges such as hypoglycemia, hypotension, confusion and delirium.

It is useful to recognize that the goals of care may be quite different in elders. Tight glucose control may not be the goal of treatment in elders due to their increased risk of falls, decreased ability to survive hypoglycemic events and decreased need to prevent end organ damage with respect to their expected survivability. (11) A relaxed approach is useful also with respect to blood pressure control in elders. The JNC 8 blood pressure guidelines markedly relaxed blood pressure goals for the elderly in acknowledgement of the fact that elders have different long term goals than younger persons and less reserve to tolerate aggressive medication management of blood pressure.

As healthcare providers for older adults, it is advisable to be as conservative as possible with medication use and other interventions because of their lack of physiological reserve. Individualization is important regarding the care of older adults because age is just a surrogate marker of frailty. We all know older adults who seem far more robust than their age and vice versa. So a 70-year-old who is very active may tolerate medical interventions (including medications) just as a middle-aged adult could. Conversely, a 60-year-old, living with high disease burden and frailty may require more conservative management.

Adverse drug outcomes in dental practice
Xerostomia: The most common adverse drug reaction effecting oral health are those causing xerostomia. In particular, anticholinergic drug effects. But, other medication causes of xerostomia are often present, including dehydration due to diuretic use, decongestants, pain medications, muscle relaxants, antidepressants, anti-seizure medications and more. Estimates range from 300-500 prescription and over the counter medications are linked to xerostomia. The risk of xerostomia compounded by polypharmacy is highest in patients who live with multi-morbidity and take multiple medications. Additionally, with the aging of the population, cancer is increasingly being considered a chronic disease (thanks to treatment successes and the ability for people to live with cancer longer), thus chemotherapy and radiation therapy are significant irreversible causes of xerostomia. Nerve damage, and chronic disease, including diabetes, HIV, Sjogren’s Syndrome, and others layer on top of polypharmacy leading to significant xerostomia prevalence in older adults.

Sometimes less anticholinergic and xerostomia chronic disease medication choices can be made such as managing hypertension without a “water pill”, or choosing a sertraline over amitriptyline for depression therapy. But, chances are, the xerostomia an older patient experiences is to some degree a chronic condition. In that case, encouraging the use of products to treat xerostomia would be appropriate.

Lichenoid Reaction: A common inflammatory condition is lichen planus (LP). LP is an immune mediated process where T-cells mediate the destruction of basal cells of the epithelium. Many medications are linked to cutaneous lichenoid hypersensitivity reactions (LHR), and they are often difficult to distinguish from idiopathic reactions. The postulation is that active thiol groups in the chemical structure of multiple medications can trigger LP reactions. Two classes often linked to LP are nonsteroidal anti-inflammatory agents, and antihypertensive agents such as beta blockers, ACE inhibitors, and diuretics (hydrochlorothiazide). Antidiabetic medications, including sulfonylureas (glipizide), anticonvulsants, sulfasalazine, allopurinol and lithium have all been reported to cause LR. (13)

Aphthous-like Ulcers: another oral problem that has been linked to a multitude of drug classes. The mechanism of ulceration is beyond this discussion, however, the drugs linked to aphthous ulcers and aphthous-like ulcers are diverse and reflect the collections of medications not uncommon to the older adult.

Osteonecrosis of the Jaws (ONJ): dental professionals are well versed in the risks associated with bisphosphonate use and ONJ. We often associate ONJ with bisphosphonate use, but with the introduction of denosumab to the market (Prolia®, Xgeva®), we have to also know that although these are not bisphosphonates (they are monoclonal antibodies or “mabs”), they do work through the mechanism of bone density. They have only been on the market approximately seven years, and initially didn’t claim any ONJ results in their FDA safety and efficacy trials (of course, because there were not enough subjects for a long enough time to have that adverse effect surface), but there have been a few case reports, and eight cases in the FREEDOM trial, as would be expected with any antiresorptive drug. (15, 16)

Given that this type of antiresorptive drug is reported in studies to be very effective in avoiding skeletal complications of metastatic bone disease, future use is expected to rise. As for bisphosphonates, patients who are elderly and have received bisphosphonate therapy for osteoporosis (not bone metastasis) might consider discontinuation of therapy if they have received many years of therapy and begin a drug holiday, as bisphosphonates have a very long t½, and the FIT/FLEX trial demonstrated protection from fracture up to five years post discontinuation of use when used for five years, minimum. (17) In other words, bisphosphonates incorporate into the bone matrix and take a long time to come out. These bisphosphonate patients have to be monitored closely and urged to continue high level oral health care beyond the stop date of bisphosphonate use. As for the denosumab patients after discontinuation of therapy, the need to monitor is not as clear. It appears that the drug clears the body swiftly, but consider that there are atypical fractures associated with denosumab use (meaning that there is some rearrangement of bone architecture as with bisphosphonates), and many of patients receiving denosumab have received bisphosphonates, previously. The risk of ONJ post discontinuation of denosumab is yet to be seen.

Medications have been linked to many oral problems ranging from LP to pigmentation, fibrovascular hyperplasia, keratosis/epithelial hyperplasia, dysesthesias and osteonecrosis of the jaws. (14) Again, the review of polypharmacy involvement in these conditions is beyond the scope of this discussion.

Anticoagulation: mindfulness regarding bleeding risk is always at the forefront of dental practice due to the invasive nature of procedures and routine office dental care. There are the well-known anticoagulants such as warfarin, aspirin, ibuprofen, naproxen, and the new novel oral anticoagulants such as dabigatran, rivaroxaban, apixaban and edoxaban. There are the low molecular weight injectables, such as dalteparin, tinzaparin and enoxaparin that you might run across if treating nursing home patients or patients who are bed or chair bound and high clot risk patients.

The hidden anticoagulation threats are the herbals, supplements and some antidepressants. (Did you know platelets have serotonin receptors?) When assessing your patient for anticoagulation risk, it would be prudent to use a database such as Lexicomp®, Epocrates®, Micromedex®, Drugs.com®, Drugs Facts and Comparisons® or others, and run an interaction checker, not just for drug anticoagulant synergy, but in general.

In addition to medication-induced problems, it is important for the health care provider to appreciate the barriers to and difficulty in implementation of care in older adults who are taking complex medication regimens. There are cognitive and physical problems which can impair successful treatment and follow up. These impairments may, themselves, be medication induced.

Healthcare providers of all disciplines should keep medication-induced problems high on the differential diagnosis list. Remember, at minimum, to do an interaction checker listing all prescriptions, OTC products, supplements and herbs. Also keep in mind that what may look like a physiological or organic problem might actually be a medication-induced problem, particularly in older medically complex adults. A well-respected scholar from U Mass, Jerry Gurwitz MD, once said, “Whenever an elderly patient experiences a status change, medication-related problems have to be ruled out”.

1. US Census Data accessed July 2015
2. AGS: Underrepresentation of Older Adults in Clinical Trials. http://www.americangeriatrics.org/policy/clinical_trials.shtml
3. Hanlon JT, et al. Epidemiology of over-the-counter drug use in community dwelling elderly: United States perspective. Drugs Aging. 2001;18:123-131
4. Slone Survey, Boston College. Patterns of Medication Use in the United States. http://www.bu.edu/slone/files/2012/11/SloneSurveyReport2005.pdf
5. Denham MJ, Adverse Drug Reactions. Brit Med Bull 1990 (46): 53-62
6. Bath, PA et al. Identification of Risk Factors for 15-year Mortality Among Community-Dwelling Older People Using Cox Regression and a Genetic Algorithm. Journal of Gerontology, 2005. (60A) 8, 1052-1058.
7. Woodford H, Walker R. Emergency hospital admissions in idiopathic Parkinson's disease. Mov Disord. 2005; 20:1104-1108.
8. Hanlon JT, Schmader KE, Ruby CM, Weinberger M. Suboptimal prescribing in older inpatients and outpatients. J Am Geriatr Soc. 2001; 49:200-209.
9. Alzheimer’s Disease Foundation and Referral Center, National Cancer Institute, Am Diabetes Assoc, Arthritis Foundation, National Center for Health Statistics, National Parkinsons Foundation, National Stroke Foundation.
10. Kaiser Foundation Scripts per Capita http://kff.org/other/state-indicator/retail-rx-drugs-per-capita/
11. The Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD) Effects of Intensive Glucose Lowering in Type 2 Diabetes NEJM 358;24 www.nejm.org June 12, 2008
12. James, P, Oparil S, Carter B, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults. A report from the panel members appointed to the Eight Joint National Committee (JNC8). JAMA Feb 5, 2014. Vol 311, No. 5: 507-520.
13. Schlosser B. Lichen planus and lichenoid reactions of the oral mucosa: case report. Dermatol. Ther. 2010; 23:251-267.
14. Yuan A, Woo S. Adverse drug events in the oral cavity. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2015; 119: 35-47.
15. Uyanne J, Calhoun C, Le A. Antiresorptive drug-related osteonecrosis of the jaw. Dent. Clin. North. Am. 2014 Apr, 58(2): 369-84.
16. Papadopoulos S, Lippuner K, Roux C, et al. The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporosis Int. 2015 Dec; 26 (12): 2773-83.
17. Black D, Schwartz A, Ensrud K. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension: a randomized trial. JAMA. 2006 Dec 27; 296 (24): 2927-38.

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Oct 21st, 2014Postscript for an Editors Passing
Oct 21st, 2014and he did what?!: Giving a Professional Second Opinion
Aug 21st, 2014Your KDA is Working Hard for You!
Aug 21st, 2014Nobody Goes Into Dentistry Because They Love Molars!
Aug 21st, 2014Synergy
Jun 16th, 2014Think Big. Think Positively. Think Proactively.
Jun 16th, 2014Denigration
Jun 16th, 2014YOU HAD TO BE THERE!
Jun 16th, 2014New Friendships and Lasting Connections Creating a Stronger Interest in Organized Dentistry
Jun 16th, 2014New Friendships and Lasting Connections Creating a Stronger Interest in Organized Dentistry
Apr 24th, 2014I Only Have A Loose Screw!
Apr 24th, 2014Dare to Dream!
Apr 24th, 2014I am the KDA! You are the KDA! WE are the KDA!
Apr 24th, 2014The Dentists Guide to Social Media Marketing
Feb 20th, 2014Where Do We Go From Here?
Feb 20th, 2014Medicaid: An Example of Missing the Goals for Oral Health in Kentucky
Feb 20th, 2014UKCDs First Regional Dental Program: The First Ten Years
Feb 20th, 2014UofL Brightening the Smiles of Children
Feb 20th, 2014Go Tell It on the Mountains
Dec 23rd, 2013Letting the Secret Out
Dec 23rd, 2013It Is What They Left Behind
Dec 23rd, 2013Dr. John Thompson Awarded Distinguished Editor Award
Dec 23rd, 2013Teamwork Creates Champions: the Kentucky Meeting: March 13-16, 2014
Dec 23rd, 2013Listen to Interviews with our Speakers!
Dec 23rd, 2013Welcome Dental Students and New Dentists!
Dec 23rd, 20132014 Kentucky Meeting Details
Oct 17th, 2013I Still Like Maps!
Oct 17th, 2013Ground Game
Oct 17th, 2013Kentucky Department of Insurance, HB 497 and Non-covered Services
Oct 17th, 2013Dr. Janet Faraci Lees Legacy
Oct 17th, 2013Dr. Janet Faraci Lee Leadership Development Award
Aug 12th, 2013The Affordable Care Act: What does it mean for Our Members?
Aug 12th, 2013All Membership Is Local
Aug 12th, 2013White Crosses
Aug 12th, 2013KDA MembershipWhere Do We Go from Here?
Aug 12th, 2013Thoughts from a New Dentist: the Top Three Reasons that I am Involved with Organized Dentistry
Aug 12th, 2013How can KDAIS Benefit You, as a KDA member?
Aug 12th, 2013Beyond the Website: Marketing on the Modern Web
Aug 12th, 2013Delinquent Accounts.Collections..YUCK!
Aug 12th, 2013Every Patient Matters. So Does Every Transaction.
Jun 13th, 2013Preaching to the Choir
Jun 13th, 2013Something I Wish I Didn't Know!
Jun 13th, 2013The Foundation of the Kentucky Dental Association: Positioned to Make a Powerful Statement
Apr 15th, 2013Participate in Your KDPAC! Contribute and Deliver
Apr 15th, 2013The Pediatric Dental Benefit: Must Offer, May Purchase
Apr 15th, 2013Exchange What?
Apr 15th, 2013So Long, Farewell, Auf Wiedersehen, Adieu
Apr 15th, 2013United We Stand, Divided We Fall
Feb 12th, 2013Its a Dentist Thing
Feb 12th, 2013A Profession in Flux
Feb 12th, 2013Living Is What You Do When Life Gets In the Way
Feb 12th, 2013The Tip of the Iceberg: Actions by the Kentucky Department for Medicaid Services Which May Sink KMAP
Oct 19th, 2012Membership Matters
Oct 19th, 2012House Bill 1 and What It Means to You
Oct 19th, 2012Self-Regulation
Aug 21st, 2012The Perception of Dentistry
Aug 21st, 2012Sarrell Dental: Beyond the Operatory
Jun 18th, 2012Leadership or Politics?
Jun 18th, 2012What Part of the “Affordable Care Act” Has Been Affordable?
Jun 18th, 2012I Had an Uncle…
Apr 6th, 2012Many Thanks for a Great and Memorable Year
Apr 6th, 2012What a Year, so far!
Apr 6th, 2012The "New Old" Still have Teeth
Feb 21st, 2012Happy New Normal
Feb 21st, 2012All for One and One for All!
Dec 19th, 2011Access to Care?
Dec 19th, 2011The Wide World of Sports
Oct 28th, 2011Report of the Sixth District Trustee
Oct 28th, 2011To the KDA Executive Board and the entire KDA
Oct 18th, 2011Word-of-Mouth on Steroids!
Oct 18th, 2011Managed Care and Dentistry in Kentucky: a Dentist’s Dilemma
Oct 18th, 2011Why We Shouldn't Lose Sight of Our Purpose...
Aug 4th, 2011Mentor a Young Dentist and Change a Life
Aug 4th, 2011OMG, what is EBD?
Aug 4th, 2011CAPWIZ: Legislative Advocacy Made Easy
Jun 13th, 2011I Might Soon Be Coming to a Town Near You...
Jun 13th, 2011Outside Our Line
Apr 18th, 2011Let Me Ask For a Minute of Your Time
Apr 18th, 2011I Pledge to Be your Humble Servant…
Apr 18th, 2011Blindsided
Apr 18th, 2011On Your Side, Not Your List
Feb 17th, 2011Dr. Andy Elliott for President-elect of the American Dental Association
Feb 4th, 2011A Little Planning Really Helps
Feb 4th, 2011Adjusting Attitudes
Jan 4th, 2011Dental Management of Patients Taking Antiplatelet Medications
Nov 30th, 2010Holiday Greetings to All
Nov 30th, 2010Delegates Report from the 2010 American Dental Association House of Delegates, Orlando, Florida
Nov 30th, 2010Dental Education Found Worthy
Oct 25th, 2010Delegates Report from the 2010 American Dental Association House of Delegates, Orlando, Florida
Oct 7th, 2010What Happens in Alaska, doesn’t Stay in Alaska
Oct 7th, 2010We Need To Do a Better Job of Communicating
Oct 7th, 2010What If …?
Oct 7th, 2010I’m in a Hurry!
Oct 7th, 2010Who Will Speak for Me?
Aug 6th, 2010The Times They Are Changing
Aug 6th, 2010Kentucky's Dental Practice Act: The Passing of an Old Friend
Jun 10th, 2010How a Star was Born
Jun 10th, 2010I Need Your Help…
Apr 20th, 2010KDA and Louisville Water Company Share 150th Birthday and Public Health Vision
Apr 20th, 2010President's Message MA 2010
Apr 20th, 2010Getting It Right!
Feb 25th, 2010What is a Legacy?
Feb 25th, 2010Please Join Us for an Exciting, Event-Filled Year Ahead!
Dec 14th, 2009Holiday Reflections…
Dec 14th, 2009Challenging the Myth of the Suicide-Prone Dentist
Dec 14th, 2009There is Hope: Suicide Awareness and Prevention in Kentucky
Nov 6th, 2009Don’t Balance Health Care Books by Shortchanging Physicians
Nov 6th, 2009Break your Right Arm and Suddenly You have Time to Study Economics.
Jun 26th, 2009Making the World a Better Place, One Village at a Time!
Apr 13th, 2009Breaking Glass
Feb 20th, 2009At the Heart of any Worthy Project is a Committed Volunteer