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." 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 . The World Health Organization suggest that while the definition is numerical, emphasis should be on evidence-based practice and that the goal must be to reduce inappropriate polypharmacy.
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 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.
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.
The 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.
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.
Polypharmacy increases the 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, clinical veridic examples are reported in the literature   . 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, diarrhoea, incontinence, loss of appetite, confusion, falls, depression, or lack of interest in usual activities, may be confused with symptoms of normal ageing or sometimes lead to the prescription of more drugs to treat the new symptoms.
The 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. 
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 complementary medicine with their medical providers.  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.
Changes in Pharmacokinetics Associated with Aging
Pharmacokinetics refers to drug absorption, distribution, metabolism, and elimination.
Distribution refers to where in the body a drug penetrates and how it is spread through the body . It is expressed as the volume of distribution (Vd), with units of volume (litres) or volume per weight(L/kg).
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, drug clearance of some drugs by the liver may be decreased by up to 30% in older adults. Drug metabolism occurs through either phase 1 pathways/reactions or phase 2 pathways.
The phase I reactions, catalyzed by cytochrome P450, are more likely to be impaired in the elderly than phase II reactions thus, medications metabolized through phase 2 pathways are preferred for older adults. 
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.
Age-Associated Changes in Pharmacodynamics
The molecular, biochemical, and physiologic effects of a drug are studied by pharmacodynamics ; pharmacodynamics can change with aging, but the changes are specific to the drug studied and to the effect measured, generalizations cannot be made. Controlled studies of drug effects require plasma or site of action drug concentrations to can establish age differences in drug responses, as for example, elderly patients present a reduced beta-adrenergic receptor response to some ligands, salbutamol, a beta2-agonist and the beta-antagonist, propranolol, show reduced responses due to reduced post-receptor events, specifically, a reduction on cyclic AMP synthesis. 
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.
Strategies to Prevent Polypharmacy
Every healthcare worker, including the pharmacist and nurse practitioner, must regularly determine what medications each patient is taking; monitoring the patient's medications is an interprofessional team effort. Duplicate medications require removal from the patient's regimen 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 suspects duplicate therapy, they should consult with a pharmacist and bring it to the prescriber's attention. The key reason for checking medications is to prevent polypharmacy. Each year, thousands of elderly patients suffer injury 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 interprofessional 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 5]
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