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9/27/2019 7:09:26 PM


The term polypharmacy was used over one and a half centuries ago to refer to issues related to multiple-drug consumption and excessive use of drugs. Since then, it has evolved with different meanings and different situations including but not limited to "unnecessary drug use" and "medication use without indication."[1] Based on the review of current data, the use of 5 or more medications is an acceptable definition of polypharmacy. This cut off point of 5 medications has been shown to be associated with the risk of adverse outcome such as falls, frailty, disability, and mortality in older adults.

Issues of Concern

Polypharmacy in the Elderly

Even though persons aged 65 years and older comprise about 14% of the total population, they account for over one-third of total outpatient spending on prescription medications in the United States. Based on a recent population bulletin, the number of people over age 65 is projected to at least double from 46 million today to more than 98 million by 2060. Polypharmacy is a particular concern in older people[2] due to the following reasons.


Aging places individuals at risk of multi-morbidity (coexistence of 2 or more chronic health conditions) due to associated physiological and pathological changes and increases the chances of being prescribed multiple medications.[3]

Adverse Drug Effects

An adverse drug effect (ADE) refers to an injury resulting from the use of a drug. An adverse drug reaction (ADR) is an ADE that refers to harm caused by a drug at usual dosages. ADEs are estimated to be indicated in 5% to 28% of acute geriatric medical admissions. Preventable ADEs are among one of the serious consequences of inappropriate medication use in older adults. The drug classes commonly associated with preventable ADEs are cardiovascular drugs, anticoagulants, hypoglycemics, diuretics, and NSAIDs. Adverse drug effects are higher in older adults due to metabolic changes and decreased drug clearance that come with age. This risk compounds by increasing numbers of drugs used. The Beer’s criteria  and STOPP (Screening Tool Of Older Persons' Potentially inappropriate medications) criteria are frequently used tools to detect potentially inappropriate medications in the elderly and hence to guide proper medication prescribing in the elderly.[4][5]

Drug Interactions

Use of multiple medications increases the potential for drug-drug interactions and for prescription of potentially inappropriate medications. A drug-drug interaction refers to the pharmacologic or clinical response to the administration of a drug combination that differs from the response expected from the known effects of each of these two agents when given alone. Cardiovascular drugs are most commonly involved in drug-drug interactions. The most common adverse events related to drug-drug interactions are neuropsychological (delirium), acute renal failure, and hypotension.

Medication Non-Adherence

Polypharmacy can lead to problems with medication adherence in older adults, especially if associated with visual or cognitive decline, associated with aging and resulting in bad outcomes like treatment failure or hospitalizations.[3]

Prescribing Cascades

Polypharmacy increases possibility of prescribing cascades when additional drugs are prescribed to treat the adverse effects (ADE) of other drugs by misinterpreting the ADE as a new medical condition. Polypharmacy can be overlooked because the symptoms it causes as a result of drug interactions or side effects of drugs, for example, tiredness, sleepiness, decreased at alertness, constipation, diarrhea, incontinence, loss of appetite, confusion, falls, depression, or lack of interest in usual activities, may be confused with symptoms of normal aging or sometimes lead to prescription of more drugs to treat the new symptoms.

Risk for Hip Fracture

Polypharmacy has been shown as an independent risk factor for hip fractures in older adults in some case-control studies; although the number of drugs may have been an indicator of a higher likelihood of exposure to specific types of drugs like central nervous system (CNS)-active drugs associated with falls. [6]

Use of Over-the-Counter and Complementary Medications

The use of over-the-counter (OTC) medications has increased over the past decade with studies showing that these agents are highly prevalent in the elderly population. The challenging part is only less than half of the patients discuss the use of herbal supplements or other products or complimentary medicine with their medical providers. [7] Analgesics, laxatives, vitamins, and minerals are among some of the most commonly used classes of OTCs. The FDA is not authorized to evaluate or regulate the use of dietary supplements, and proper knowledge of exact ingredients or consequences of their use is not available. There are safety issues regarding their use including risks for herb-drug interactions.

Transitions of Care

Transitions in care, between hospital and home or institutional setting like a nursing home, are a common source of medication errors and puts patients at risk for polypharmacy. This is because many times, patients start new medications or stop previous medications, which can cause a lot of medication errors and negative outcomes.[8]

Changes in Pharmacokinetics Associated with Aging

Pharmacokinetics refers to drug absorption, distribution, metabolism, and elimination.[9]


  • Aging does not affect the extent of drug absorption significantly. But the rate of absorption may be slower. Because of this, the peak serum concentration of a drug may be lower and the time to reach it delayed in older patients. But the overall amount absorbed (bioavailability) does not differ in patients based on age. There are exceptions to this scenario and includes those drugs with an extensive first-pass effect may have higher serum concentrations or increased bioavailability as liver size and hepatic blood flow decreases with aging and hence less drug is extracted by the liver.
  • Other factors impacting drug absorption include the way medications are taken, what it is taken with, comorbidities, or inhibition or induction of enzymes in the gastrointestinal (GI) tract.


Distribution refers to where in the body a drug penetrates and the time required for the drug to reach these locations. It is expressed as the volume of distribution (Vd), with units of volume (liters) or volume per weight(L/kg).

  • Older adults have less body water and lean body mass. Hence, hydrophilic (water-soluble) drugs have a lower volume of distribution. Examples are ethanol or lithium.
  • Another typical change with aging is increased fat stores; therefore. lipophilic (fat-soluble) drugs have an increased volume of distribution. Examples are diazepam, trazodone, and flurazepam.
  • Albumin is usually lower in older adults. This is the primary plasma protein to which drugs bind. Because of that, there is a higher proportion of unbound (free) and pharmacologically-active drug, which is not a problem in younger patients as normally, additional unbound drugs are eliminated. However, with aging there is a decrease in elimination resulting in accumulation of the unbound drug in the body. Examples are ceftriaxone, phenytoin, valproate, warfarin, diazepam, and lorazepam.


Metabolic conversion of drugs can occur in the liver, intestinal wall, lungs, skin, kidneys, and other organs. With aging, there is a decrease in hepatic blood flow and liver size, so metabolic clearance by the liver may be decreased in older adults. Drug metabolism occurs through either phase 1 pathways/reactions or phase 2 pathways.

  • Phase 1 pathways include hydroxylation, oxidation, dealkylation, and reduction. Most drugs metabolized through this pathway can be converted to metabolites of lesser, equal, or greater pharmacological effect than the parent compound. An example is diazepam.
  • Phase 2 pathways include glucuronidation, conjugation, and acetylation. Drugs metabolized through phase 2 pathways are converted to inactive compounds. An example is lorazepam.

Medications metabolized through phase 2 pathways are preferred for older adults (inactive metabolites and no accumulation).


Elimination refers to a drug’s final routes of exit from the body. The terms used to express elimination are a drug's half-life and clearance. For most drugs, elimination is through kidneys as either the parent compound or as a metabolite or metabolites.

  • With aging, renal size and renal blood flow decreased and hence glomerular filtration declines.
  • Also, due to a decrease in lean muscle mass with aging, the production of creatinine is reduced. The reduction of glomerular filtration rate counters the decreased creatinine production, and serum creatinine stays in the normal range. Serum creatinine is not an accurate reflection of creatinine clearance in the elderly. When prescribing a new medication or changing doses, the Cockcroft- Gault equation can be used to estimate a patient’s creatinine clearance.

Age-Associated Changes in Pharmacodynamics

The time, course, and intensity of the pharmacologic effect is referred to as the pharmacodynamic action of a drug. This can change with aging, and usually, these differences are due to pharmacokinetic changes as mentioned above like decreased elimination. 

Clinical Significance

The care of older adults can be challenging because they may require multiple medications to manage their complex medical problems. Optimizing their medication regimen is one of the critical elements in comprehensive geriatric care. Preventable adverse drug events are one of the serious consequences of polypharmacy, and this possibility should always be considered when evaluating an older patient with a new symptom until proven otherwise. This strategy can prevent prescribing cascades and even risk of hospitalizations. Also, being cognizant of specific issues related to polypharmacy like increased risk for hip fractures, falls and decrease in cognitive functions can help avoid a lot of negative outcomes like falls and decrease health care costs. While prescribing multiple medications cannot be avoided in a specific patient scenario, healthcare professionals should aim for a balance between over-prescribing and under-prescribing and consider medication appropriateness based on life-expectancy and goals of care.

Other Issues

Strategies to Prevent Polypharmacy

  • Maintain an accurate medication list and medical history and update whenever possible
  • Encourage patients to bring all medications including prescription, OTC drugs, supplements, and herbal preparations
  • Review any changes with patient and caregiver and if possible, provide all the changes in writing
  • Use the fewest possible number of medications and the simplest possible dosing regimen
  • Try to link each prescribed medication with its diagnosis
  • Discontinue all unnecessary medications
  • Screen for drug-drug and drug-disease interactions
  • Use a team approach if possible involving the caregiver or family and pharmacist (community pharmacist)
  • Avoid starting potentially harmful medications; use Beer’s criteria
  • Try to start a new medication at the lowest dose and then titrate slowly
  • Avoid starting medications to combat the potential side effects of other medications
  • Careful medication reconciliation during transitions of care including proper communication handoffs to accepting providers. Ensuring a close post discharge follow up for updating medical history and medications can help in preventing medication errors, treatment failures, and rehospitalizations[10].
  • Consider goals of care and life-expectancy of patients when assessing medication appropriateness

Enhancing Healthcare Team Outcomes

Every healthcare worker, including the pharmacist and nurse practitioner, must regularly determine what medications each patient is taking. Duplicate medications must be removed after consulting with the clinician who initially prescribed it. The date of prescribing and duration must be stated during each clinic visit. If nursing staff suspect duplicate therapy, they should consult with a pharmacist and bring it to the prescriber's attention. The key reason for checking medications is to ensure that there is no polypharmacy. Each year, thousands of elderly patients are injured because of adverse effects from multiple medications. The pharmacist must have a list of all patient medications and continually update the physician and nurse practitioner for duplicates and unnecessary medications. All members of the healthcare team (physicians, nurses, pharmacists) need to educate the patient on why they are taking a given drug and help them, or their caregiver to understand the regimen as much as possible. This type of information must be made available to the entire interprofessional healthcare team, so duplicate and extraneous agents can be deleted from the patient's regimen, and medication therapy optimized. [Level V]

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Polypharmacy - Questions

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A 76-year-old female presents with numerous medical complaints. She is tired, has a very poor appetite, and does not sleep well at night. She denies any fevers, chills, chest pain, or shortness of breath. Her ECG and chest x-ray are normal. Her physical examination is entirely normal. She cannot remember which medications she takes. What is the most important factor in adverse drug reactions in the elderly population?

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Which of the following is true about polypharmacy?

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Which of the following age groups is the largest consumer of prescription and nonprescription medications in the United States?

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A 64-year-old lady is seen in the emergency department for evaluation of generalized weakness and gait unsteadiness of about 1-week duration which seems to be worse now. She has a past medical history of hypertension, hyperlipidemia, type2 diabetes mellitus, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and coronary artery disease. She was diagnosed with otitis media of her left ear and was started on trimethoprim-sulfamethoxazole 800/160 BID 1 week ago. Her other medications include metoprolol succinate 100 mg daily, aspirin 81 mg daily, clopidogrel 75 mg daily, metoprolol succinate 100 mg daily, atorvastatin 80 mg at bedtime, lisinopril 10 mg daily, tiotropium18 mcg inhalation daily, albuterol 1- 2 puffs q4-6 hr prn. Her vitals are temperature - 98.4 F, heart rate 79 bpm, blood pressure 106/65 mmHg, respiratory rate 16, and pulse oximetry 94% on room air. Her physical examination was otherwise unremarkable except for the fact that she appeared clinically hypovolemic. Her routine labs showed hemoglobin of 13.1 g/dl, hematocrit 42%, WBC 8.9 K/microL, platelets 193 k/microL, glucose 97 mg/dl, BUN 52 mg/dl, creatinine 3.4 mg/dl, sodium 135 mmol/L, potassium 5.7 mmol/L, chloride 104 mmol/L, bicarbonate 24 mmol/L. Her creatinine 1 month ago was 0.8 mg/dl, and potassium was 3.8 mmol/L. Urinalysis showed 0-2 RBCs, 0-2 WBCs, 5-10 hyaline casts. Which of the following medications most likely contributed to her current presentation of acute kidney injury and hyperkalemia?

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An elderly woman with uncontrolled hypertension is newly started on amlodipine for blood pressure control. She has no history of heart disease or prior history of congestive heart failure. She starts developing lower extremity edema and is in follow-up by her doctor and get started on furosemide 40 mg daily for treatment of this lower extremity edema. This is a classic example of which of the following?

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Polypharmacy - References


von Buedingen F,Hammer MS,Meid AD,Müller WE,Gerlach FM,Muth C, Changes in prescribed medicines in older patients with multimorbidity and polypharmacy in general practice. BMC family practice. 2018 Jul 28     [PubMed]
Masnoon N,Shakib S,Kalisch-Ellett L,Caughey GE, What is polypharmacy? A systematic review of definitions. BMC geriatrics. 2017 Oct 10     [PubMed]
Hosseini SR,Zabihi A,Jafarian Amiri SR,Bijani A, Polypharmacy among the Elderly. Journal of mid-life health. 2018 Apr-Jun     [PubMed]
Machado-Duque ME,Castaño-Montoya JP,Medina-Morales DA,Castro-Rodríguez A,González-Montoya A,Machado-Alba JE, Drugs With Anticholinergic Potential and Risk of Falls With Hip Fracture in the Elderly Patients: A Case-Control Study. Journal of geriatric psychiatry and neurology. 2018 Mar     [PubMed]
Rolita L,Freedman M, Over-the-counter medication use in older adults. Journal of gerontological nursing. 2008 Apr     [PubMed]
Villanyi D,Fok M,Wong RY, Medication reconciliation: identifying medication discrepancies in acutely ill hospitalized older adults. The American journal of geriatric pharmacotherapy. 2011 Oct     [PubMed]
Reeve E,Trenaman SC,Rockwood K,Hilmer SN, Pharmacokinetic and pharmacodynamic alterations in older people with dementia. Expert opinion on drug metabolism     [PubMed]
Sakr S,Hallit S,Haddad M,Khabbaz LR, Assessment of potentially inappropriate medications in elderly according to Beers 2015 and STOPP criteria and their association with treatment satisfaction. Archives of gerontology and geriatrics. 2018 Sep - Oct     [PubMed]
Grace AR,Briggs R,Kieran RE,Corcoran RM,Romero-Ortuno R,Coughlan TL,O'Neill D,Collins R,Kennelly SP, A comparison of beers and STOPP criteria in assessing potentially inappropriate medications in nursing home residents attending the emergency department. Journal of the American Medical Directors Association. 2014     [PubMed]
Calkins DR,Davis RB,Reiley P,Phillips RS,Pineo KL,Delbanco TL,Iezzoni LI, Patient-physician communication at hospital discharge and patients' understanding of the postdischarge treatment plan. Archives of internal medicine. 1997 May 12     [PubMed]


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