The purpose of this activity is to enable the learner to understand the definition of polypharmacy and how it affects patient populations, specifically the elderly population. When, why and how polypharmacy can be avoided and finally the role that nursing plays in mitigating the effects of polypharmacy.
At the completion of this activity, the participant will be able to:
The most frequent medical intervention performed by clinicians is writing a prescription. Pharmacotherapy is a vital part in the maintenance of health. There are innumerable conditions that rely on medication to alleviate, maintain and slow progression of the disease. However, there are significant side effects associated with the use of medications. Every time clinicians prescribe medication, the risk to benefit ratio must be carefully evaluated. By the same token, every time a medication is administered nurses must be cognizant of the side effect profile and remain alert in identifying potential side effects. The World Health Organization (WHO) defines adverse drug effects as “noxious and unintended responses to drugs occurring at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function” (Alhawassi et al., 2014). The WHO goes on to further describe the various subsets of adverse reactions appropriately termed WHO’s Adverse Reaction Terminology (WHO-ART). Adverse drug reactions are classified into six different subtypes which are: dose related reactions (Augmented), non-dose related (Bizarre), dose-related and time-related (Chronic), time-related (Delayed), withdrawal related (End of use), and finally, failure of therapy (Failure).
Adverse drug events and adverse drug reactions are often used erroneously as interchangeable terms. However, Adverse Drug events comprise of adverse drug reactions and as well as reactions secondary to medical error. Adverse Drug Reactions (ADR) have significant ramifications on health with an estimated 5% to 7% of all hospitalizations being secondary to an ADR. In addition, 10% to 20% of all hospitalized patients will experience an adverse drug reaction during their hospital stay. In the United States, it has been estimated that up to 6% of ADRs have fatal or serious consequences thereby increasing morbidity and mortality from adverse reactions. Approximately 140,000 fatalities caused by ADRs are reported to occur in the United States each year. The financial impact on hospitals has been reported to exceed $30 billion and approximately 5% of the annual hospital running costs (Alhawassi et al., 2014). Using an increased number of drugs has also been independently linked to increased risk for hospital admissions.
Alhawassi et al. conducted a systematic review and reported that the mean prevalence of ADRs leading to hospitalization was 11% while the prevalence of ADRs occurring during hospitalization was also 11%. Their review concluded that one in ten older patients would experience an adverse drug reaction either leading to a hospital stay or during a hospital stay. Also, older patients with increased disease burden and using multiple drugs were at increased risk of an adverse drug reaction. They also identified the need for a more accurate definition of what should be considered an adverse drug reaction in future research endeavors.
There is a symbiotic relationship between adverse drug reactions and polypharmacy with each causing or occurring as a result of the other.
Polypharmacy is defined simply as the concurrent use of multiple medications by a single patient. The actual number of medications used to define polypharmacy varies depending on the age group and the situation. Although there is no consensus, most experts agree that the number ranges from 5 to 10. When addressing polypharmacy, we usually think about prescription medication. However, we must consider the number of over-the-counter drugs and herbal supplements that patients use.
In recent decades, there has been a shift in healthcare to provide evidenced based practices to patients in our care. This shift has created a culture of guideline-driven medicine leading to many disease processes being treated by multidrug regimens. The goal being to obtain maximum results for that patient by encouraging standardized care. Also, the fact that a financial incentive has been tied to performance has only increased the use of guideline-driven medical practices.
No one doubts the use of certain drug regimens such as the use of beta-blockers in preventing recurrent myocardial infarctions or the use of statins in to reduce the risk of cardiovascular events and mortality in patients with and without known cardiovascular disease. However, the full ramifications of these multidrug regimens in patients with multiple comorbid conditions, in the long run, have not been fully understood.
According to the Centers for Medicaid and Medicare Services, during the years 2007 to 2014 about 13% of their members registered for Medicare fee-for-service program had more than five chronic conditions. 22% of patients had 4 to 5 chronic conditions. It was established that more than a third of all registered participants had greater than three chronic conditions. The Slone survey showed that over 50 percent of Medicare beneficiaries reported receiving five or more medications.
In a recent study among ambulatory older adults with cancer, 84 percent were reported to receive five or more, and 43 percent were receiving 10 or more medications (Nightingale et al., 2015). With the increasing life expectancy in the United States, clinicians have to take care of more and more patients with chronic conditions, and this becomes even more challenging when a single patient has several chronic conditions.
Field et al., 2001 noted that several factors are linked to adverse drug effects including; taking five or more medications and having multiple chronic conditions. Their recommendations to clinicians prescribing are that they pay special attention to drug classes in residents with multiple medical conditions and multiple drug regimens.
It is well established that the issue of polypharmacy affects older people more often when compared to younger age groups, which is expected given that they have more disease conditions. Also, the fact that life expectancy continues to increase implies that this is a condition that we will have to deal with on a more frequent basis.
Older patients are most susceptible to side effects of polypharmacy for multiple reasons such as a greater risk for adverse drug events due to decreased drug clearance by the hepatic and renal systems associated with aging. Also, the risk is compounded by the increased number of drugs.
Polypharmacy increases the risk of potential drug-drug interactions as well as the risk of sustaining a hip fracture, especially specific drugs associated with falls such as central nervous system active drugs. Overall, older adults have trouble with medication adherence which is exacerbated by cognitive and visual limitations.
It is not clear what the benefits and harm associated with the combination of all these multidrug regimens. While most people tout the adherence to disease-specific guidelines, there is very little information about the risk associated with merging multiple disease-specific drug regimens. In a study examining the potential pitfalls of disease-specific guidelines for patients with multiple conditions, an example of a 70-year-old woman was discussed. She had the common combination of hypertension, myocardial infarction, depression, diabetes mellitus, and osteoporosis. Based on the adherence to disease guidelines, the patient may be required to take aspirin, an ACE inhibitor, a beta-blocker, a bisphosphonate, calcium, a diuretic, a selective serotonin-reuptake inhibitor, a statin, a sulfonylurea drug, perhaps a thiazolidinedione, and vitamin D. This list of medications do not include the treatment of common conditions such as pain and heartburn which are commonly treated with over-the-counter medications. When viewed in this perspective, the question is raised whether what is good for the disease is always best for the patient (Tinetti et al., 2004). Increased pill burden has been described to increase the risk of drug-drug, drug-food, and drug-herbal interactions.
Recent studies have shown that elderly patients vary regarding the importance they place on health outcomes such as longer survival, the prevention of specific disease events, as well as the risk they are willing to take regarding the adverse events they are will have to tolerate.
Clinicians understand that when prescribing medications to a patient the plan must be individualized with the patient’s overall health taken into account. However, one of the challenges clinicians face is adhering to disease-specific guidelines that have been put in place by quality assurance programs. These guidelines were developed to reduce the variations in practice patterns among providers. Because it is difficult to distinguish between appropriate and inappropriate variation in practice, there is constant discord between the standardized treatment of diseases the individualized care of patients.
To further expand on this disconnect, it is critical to realize that while clinicians focus on disease-specific outcomes, such as maintenance of disease-free intervals as well as the prevention of specific outcomes like pulmonary emboli, a patient is more concerned about specific factors. Examples of patient’s concerns include; side effects of medications, time of the medication to take effect, the convenience of medication regimen and the cost associated with the prescribed regimen (Tinetti et al., 2004). In a nutshell, clinicians may be focused on the disease process while a patient is focused on their current quality of life and how it is affected by the medication regimen.
As a matter of fact, a recently published study by Kalogianis et al., 2015 showed that up to 40.5% of residents in residential aged care facilities reported a desire to stop taking one or more of their medications. Almost 80% of residents (78.8%) were willing to have one or more of their medications discontinued. The study focused on examining if residents were willing to have medications deprescribed because, after all, the point is moot if residents are not willing to participate in deprescribing interventions. Specifically, residents taking 9 or more medications were more likely to believe that their medications were causing side effects.
We must understand that patients with multiple conditions present unique challenges regarding disease diagnosis and management. Another factor that potentiates the issue of polypharmacy is the fact that patients with chronic conditions are usually treated by multiple specialists who do not always communicate with each other.
Some general principles that can be used to mitigate the effects of polypharmacy in the elderly include:
According to the American Cancer Society, it is estimated that by the year 2030, 70% of all cancers in the United States will be diagnosed in the elderly population. The challenge faced in the management of this group is the multiple layers of professionals that are involved in caring for this group such as geriatricians, oncologist, radiologists, pharmacists, allied health professionals such as nurses, speech therapists, occupational therapists and social workers. Most medication errors are attributed to medication changes, complex regimens and inadequate communications between providers caring for a specific patient. Polypharmacy increases the vulnerability of the older population because it increases the risk of falls, fractures, cognitive impairment and delirium, all of which affect morbidity in this population.
Multiple national organizations such as the National Comprehensive Cancer Network Older Adult Oncology guidelines recommend a comprehensive medication assessment which consists of the following: A thorough review of the patient’s medication, Discontinuation of any nonessential medications, Evaluation for drug interactions and adverse effects and Assessment of patient adherence.
The conundrum with all these recommendations is that they do not specify which health care professional should be responsible for performing the medication assessment. Often this duty has been relegated to primary care providers. The challenge is patient may see other specialized providers more frequently than they see their primary care providers.
The following case study published by Rosenberg et al., 2014 in the Journal of the American Geriatrics Society exemplifies the challenge faced with addressing the implications and consequences of polypharmacy. The patient is a 70-year-old male with a subdural and bilateral frontal lobe contusions after sustaining an unwitnessed fall in his home. Upon admission, he was noted to have an elevated salicylate level. An abdominal x-ray done on admission showed a radiopaque in his colon in spite of the fact that he had not received any contrast material. Because no collateral history was available, the assumption was made that the salicylic acid toxicity was secondary to medication misadministration. His pharmacy was able to confirm that he had not purchased any acetylsalicylic acid either prescribed or over the counter. His medications included: donepezil, calcium carbonate, alendronate, pravastatin, ezetimibe, omeprazole, and perindopril, with no history of a medication overdose. All of these medications were long-standing, except donepezil which is a cholinesterase inhibitor. Upon further review, it was noted that the patient was diagnosed with mild Alzheimer's disease two months earlier. Shortly after initiating donepezil, he visited his family physician complaining of persistent abdominal discomfort and diarrhea, for which he was referred to a gastroenterologist.
A close friend eventually revealed that he had self-medicated with large amounts of bismuth subsalicylate (Pepto-Bismol) because it provided some temporary relief of his abdominal discomfort. Pepto-Bismol contains 8.7 mg of salicylic acid per mL and can cause both acute and chronic salicylate toxicity when excessively consumed.
The friend specifically recalled that the patient's cognitive status had acutely and progressively worsened shortly after Pepto-Bismol was initiated. His gait and functional impairment concurrently deteriorated and culminated in the traumatic fall. Bismuth is also slightly radiopaque, explaining the contrast material visualized throughout the colon on pelvic X-ray. This case involves three relevant medication issues: a prescribing cascade, salicylate toxicity, and bismuth neurotoxicity.
The salicylate toxicity and subsequent traumatic fall were probably secondary to self-medication with OTC bismuth subsalicylate for gastrointestinal symptoms temporally related to the initiation of a cholinesterase inhibitor. This pattern represents a prescribing cascade, in which an adverse drug reaction to a medication is misinterpreted as a new medical condition, leading to another drug being prescribed to treat the adverse effect. Both the patient and his physician misinterpreted the adverse gastrointestinal effects of the cholinesterase inhibitor as a new medical condition, leading to self-medicating with an additional over-the-counter drug at toxic doses.
Gastrointestinal symptoms are a known side effect of Donepezil and side effects usually experienced include abdominal pain, nausea, anorexia, diarrhea, and weight loss. Given that many older adults with dementia are malnourished, providers prescribing cholinesterase inhibitors must inform them about these potential adverse events.
The neurotoxicity caused by bismuth subsalicylate is usually not diagnosed despite its long history of use for multiple gastrointestinal disorders. Two distinct toxicities must be considered: salicylate toxicity and bismuth toxicity. Salicylate toxicity is described in the above case study. Bismuth neurotoxicity can provoke delirium, psychosis, ataxia, myoclonus, and seizures and is reversible over several weeks once bismuth intake is discontinued.
In conclusion, this case highlights the potential for prescribing cascades involving OTC preparations that are sometimes missed when taking a medication history.
In short, there is always a possibility that an adverse drug event could be masquerading as a prescribing cascade. Thus, the possibility of a prescribing cascade should always be carefully considered when evaluating an older adult, and any new symptom should be considered to be drug related until proven otherwise.
Prescribing cascades are described as scenarios occurring when a new drug is prescribed to treat symptoms arising from an unrecognized side effect of a drug the patient is already taking. Older adults are particularly susceptible to prescribing cascades which develop when an adverse drug event is misinterpreted as a new medical condition, and additional drug therapy is subsequently prescribed to treat this medical condition. Prescribing cascades are particularly common when drug-induced symptoms are indistinguishable from illnesses that are common in older persons.
A commonly identified prescribing cascade is the initiation of anti-Parkinson therapy for symptoms arising from the use of drugs such as antipsychotics or metoclopramide. These new anti-Parkinson drugs, in turn, cause new symptoms including orthostatic hypotension and delirium which may or may not be treated by the prescription of new drugs.
As an alterantive to prescribing medications leading to prescribing cascades, the following alternatives have been proposed:
Silva et al., 2016 provided a summary of cases which showed that 41 cases of acute pancreatitis were associated with antipsychotics with over 53% of the cases associated with polypharmacy.
Hopper et al., 2015 conducted a randomized control trial which showed that certain drug classes, namely Statins and Aspirin, have been shown to neither reduce mortality or cardiovascular events in heart failure. Whereas cessation of ACE inhibitors, beta-blockers, and diuretics, was associated with worsening of heart failure clinical status. The need for this study was engendered by the fact that Polypharmacy was increasing in heart failure patients due, in part, to the widespread adoption of medications guidelines for heart failure.
Let us consider the following case study: A 75-year-old man comes into a primary care clinic where you are working as a nurse manager in charge of managing the onboarding process for new patients. He is coming to establish care and has the following diagnoses: hypertension, heart failure, diabetes mellitus type 2, chronic kidney disease - stage 2 and metastatic prostate cancer. He is currently taking the following medications; Aspirin, Metoprolol, Thiazide diuretic, Lasix, Metformin, Oxycodone, Ibuprofen and other herbal supplements which he is unable to recall at this time. He recently relocated from out of state and is now establishing care with a new physician. He lives with his daughter and her family who moved him in to stay with her because she was worried about his safety. Of note, the patient was recently diagnosed with chronic kidney disease (2 months ago) after he reported that he was titrating his dose of Lasix based on his daily weights. This information is provided to you by the intake nurse at your clinic who is tasked with obtaining clinical histories on patients prior to being seen in the clinic.
As a clinic nurse, you must ensure that you call the patient prior to his first visit and ask that he bring all medications he is taking in a brown paper bag. Secondly, request that he be accompanied by his daughter, if possible, given she may be a source of additional clinical information as well as a caregiver who will potentially need medication regimens clarified. Thirdly, the nurse must attempt to obtain all medical records from previous clinicians in other states. Fourthly, ensure that all medications include the name of the providing clinician as well as the date when they were started. Time of onset of medications is especially critical in this patient given that he was recently diagnosed with chronic kidney disease but is currently taking multiple nephrotoxic drugs and is specifically taking one of them in excess. All of this information will prove critical for the clinician seeing the patient and could be useful in exposing potential prescription cascades in this patient taking over eight medications potentially prescribed by more than one prescriber.
Let us consider a second case study with nursing implications. You are a Registered Nurse working as a charge nurse in a skilled nursing facility, and you are taking care of 70-year-old female who is admitted for rehabilitation after surgical repair of a broken hip. She reports that she was very fit prior to the fall leading to a broken hip and does not believe in taking “western medication” unless absolutely beneficial. She believes in a more naturopathic approach to health and has been practicing that for the past year. She reports that while in the hospital setting she was in too much pain to actively participate in her care but in the current setting, she would like to supplement her medication regimen with some herbal supplements.
Her diagnoses include; Hypertension, hip fracture status post left hip arthroplasty, osteoporosis, depression and hyperlipidemia. Her discharge medications from the hospital include; Oxycodone, Enoxaparin, Aspirin, Simvastatin, Labetalol and Lorazepam. She currently wants to start taking black cohosh, St. John’s Wort, garlic supplements and Kava Kava.
As the nurse taking care of the patient, your duty is to contact the physician to report the patient’s interest in resuming her previous herbal supplements. You recognizing that there are potentially dangerous drug combinations such as the hypotensive effects of black cohosh, the toxic effects of the Kava Kava on the liver when combined with Simvastatin, as well as the combination of garlic supplements and Enoxaparin which increases the risk for bleeding given the anticoagulant effects of garlic. The nurse must be careful not to be dismissive of the patient’s concerns because the patient may take the medications unbeknownst to the nurse. Another concern with this patient is she is not taking any medications to address the osteoporosis which was likely a contributory factor to her fall. Upon discussing the case with the patient, she reports starting Fosamax 2 weeks prior to her fall, but she forgot to inform the hospital upon admission.
It is important that nurses remain valiant patient advocates while maintaining safe health practices. Often a physician makes changes to the medication regimen, and the nurses are left to explain these changes to the patient. Polypharmacy is a major problem in this era of guideline-driven medicine and nurses play an important role as a checkpoint for the necessity of pharmacotherapy, especially in the elderly population.
Alhawassi, T. M., Krass, I., Bajorek, B.V., Pont, L.G. (2014) A systematic review of the prevalence and risk factors for adverse drug reactions in the elderly in the acute care setting. Clinical Interventions in Aging, Vol.9, p.2079-2086
Davies, E.C., Green, C.F., Mottram, D.R., Pirmohamed, M. (2007) Adverse drug reactions in hospitals: a narrative review. Current Drug Safety DS,2(1), 79–87.
Field, T. S., Gurwitz, J. H., Avorn, J., Mccormick, D., Jain, S., Eckler, M.,Besner, M. Bates, D. W. (2001). Risk Factors for Adverse Drug Events Among Nursing Home Residents. Arch Intern Med Archives of Internal Medicine, 161(13), 1629.
Hopper, I., Skiba, M., Windebank, E., Brack, J., Tonkin, A., & Krum, H. (2016). Polypharmacy in heart failure — Is reducing medication safe?International Journal of Cardiology. doi:10.1016/j.ijcard.2015.09.093
Kalogianis, M.J., Wimmer, B.C., Turner, J.P., Tan, E.C., Emery, T., Robson, L., Reeve, E., Hilmer, S.N., Bel,l J.S.(2015). Res Social Adm Pharm. Are residents of aged care facilities willing to have their medications deprescribed? Dec 19. pii: S1551-7411(15)00278-8. doi: 10.1016/j.sapharm.2015.12.004.
Kaufman, D. W., Kelly, J. P., Rosenberg, L., Anderson, T. E., & Mitchell, A. A. (2002). Recent Patterns of Medication Use in the Ambulatory Adult Population of the United States. Jama, 287(3), 337.
Nightingale, G., Hajjar, E., Swartz, K., Andrel-Sendecki, J., & Chapman, A. (2015). Evaluation of a Pharmacist-Led Medication Assessment Used to Identify Prevalence of and Associations With Polypharmacy and Potentially Inappropriate Medication Use Among Ambulatory Senior Adults With Cancer. Journal of Clinical Oncology, 33(13), 1453-1459.
Rosenberg, J., Rochon, P. A., & Gill, S. S. (2014). Unveiling a Prescribing Cascade in an Older Man. Journal of the American Geriatrics Society J Am Geriatr Soc, 62(3), 580-581. doi:10.1111/jgs.12714
Silva, M. A., Key, S., Han, E., & Malloy, M. J. (2016). Acute Pancreatitis Associated With Antipsychotic Medication. Journal of Clinical Psychopharmacology, 36(2), 169-172. doi:10.1097/jcp.0000000000000459
Tinetti, M. E., Bogardus, S. T., & Agostini, J. V. (2004). Potential Pitfalls of Disease-Specific Guidelines for Patients with Multiple Conditions. New England Journal of Medicine N Engl J Med, 351(27), 2870-2874. doi:10.1056/nejmsb042458
