Agerelated Changes

In basic terms, pharmacokinetics is what the body does to the drug, whereas pharmacodynamics is what the drug does to the body. All four components of pharmacokinetics—absorption, distribution, metabolism, and excretion—are affected by aging, the most clinically important and consistent being the reduction of renal elimination of drugs12 As people age, they become frailer and are more likely to experience altered and variable drug pharmacokinetics and pharmacodynamics than younger patients. Even though this alteration is influenced more by a patient's clinical state than their chronological age, the older patient is more likely to be malnourished and suffer-

ing from diseases that affect pharmacokinetics and pharmacodynamics. An example is the greater impact chronic, uncontrolled diabetes has on reducing renal function than the age-related decline. Clinicians have the responsibility to use pharmacokinet-ic and pharmacodynamic principles to improve the care of elderly patients and avoid harmful side effects of the drugs used.

FIGURE 2-1 Percentage of people aged 65 years and over who reported having selected chronic conditions, by sex, 2005 to 2006. Note: Data are based on 2-year average from 2005 to 2006. Reference population: These data refer to the civilian noninstitutionalized population. (From Centers for Disease Control and Prevention, National Center for Health Statistics, National Health Interview Survey.)

FIGURE 2-1 Percentage of people aged 65 years and over who reported having selected chronic conditions, by sex, 2005 to 2006. Note: Data are based on 2-year average from 2005 to 2006. Reference population: These data refer to the civilian noninstitutionalized population. (From Centers for Disease Control and Prevention, National Center for Health Statistics, National Health Interview Survey.)

Pharmacokinetic Changes Absorption

Multiple changes occur throughout the GI tract with aging, but there is little evidence that drug absorption is significantly altered. The changes include decreases in overall surface of the intestinal epithelium, gastric acid secretion, and splanchnic blood 12

flow. Peristalsis is weaker and also gastric emptying is delayed. These changes slow absorption in the stomach, especially for enteric-coated and delayed-release preparations. Despite the decreased rate, the extent of absorption is not significantly altered. Similarly, reduced gastric acid with aging has not been shown to affect drug absorption. Relative achlorhydria and reduction in intrinsic factor production are caused by atrophy of gastric cells in the stomach. These changes can decrease the absorption of

nutrients such as vitamin B12, calcium, and iron.

The majority of medications are absorbed by passive diffusion in the GI tract. Drugs that require passive diffusion have a slower absorption in the elderly due to decreased jejunal surface area and reduced splanchnic blood flow. Delayed absorption may lead to a longer time required to achieve peak drug effects, but it does not

12 13

significantly alter the amount of drug absorbed. ' Thus, despite the well-reported changes in gastric motility and blood flow with aging, the efficiency of drug movement from the GI tract into circulation is not meaningfully altered.

Aging facilitates atrophy of the epidermis and dermis along with a reduction in barrier function of the skin. Tissue blood perfusion is reduced leading to decreased or variable rates of transdermal, subcutaneous, and intramuscular drug absorption. Therefore, intramuscular injections should generally be avoided in the elderly due to unpredictable drug absorption.12 Additionally, because saliva production decreases with age, medications that need to be absorbed rapidly by the buccal mucosa are absorbed at a slower rate.13 However, for the majority of drugs, absorption is not significantly changed in elderly patients and the changes described above are clinically inconsequential.14


Elderly patients can undergo significant structural changes in the body that alter drug distribution, half-life, and duration of action. Main factors that affect distribution of drugs in the body are changes in body fat and water and changes in protein binding. Lean body mass can decrease by as much as 12% to 19% through loss of skeletal muscle in the elderly. Thus, blood levels of drugs primarily distributed in muscle increase, an example being digoxin. Low body weight, in addition to advanced age, represents a risk factor for overmedication.13 A concern with frail elderly, having low muscle mass, is the risk of adverse effects when they receive higher doses per unit of body weight. While lean muscle mass decreases, adipose tissue can increase by 14% to 35% in the elderly (18% to 36% in men and 33% to 45% in women). Fat-soluble drugs have an increased volume of distribution (Fd), leading to higher tissue concentrations and prolonged duration of action. Higher Fd leads to an increased half-life and an increase in time required to reach a steady-state serum concentration with regular use. Examples of lipophilic drugs with increased Fd are diazepam (lipophilic benzodiazepine), amiodarone, and verapamil.12,13

Total body water decreases by about 10% to 15% by the age of 80 years. This lowers the volume of distribution of hydrophilic drugs leading to higher plasma drug


concentrations than in younger adults when equal doses are used. Toxic drug ef fects may be enhanced when dehydration occurs and when the extracellular space is reduced by diuretic use. Examples of commonly used hydrophilic drugs are aspirin, lithium, and ethanol. Elderly also experience a decline in gastric alcohol dehydrogenase, further increasing the peak effect of ethanol. Likewise, plasma albumin concentration decreases by 10% to 20%, though disease and malnutrition con-

tribute more to this decrease than age alone. In patients with an acute illness or malnutrition, rapid decreases in serum albumin can increase drug effects. Examples of highly protein-bound drugs include warfarin, phenytoin, nonsteroidal anti-inflam-

matory drugs (NSAIDs), furosemide, diazepam, and sulfonylureas. While plasma albumin, which primarily binds acidic drugs, decreases, ai-acid glycoprotein, which primarily binds alkaline drugs, increases, although this increase is attributed more to inflammatory disease, cancer, or trauma than to aging. Serum concentration of basic drugs such as propranolol and imipramine can be reduced when a1-acid glycoprotein level increases. Nevertheless, during chronic dosing, free drug concentrations tend to "renormalize" and age-related changes in drug binding may not be as clinically important. Thus for most drugs, above changes can alter peak levels of single doses, but mean serum concentrations at steady state are not altered unless clearance is affected. This means that the maintenance dose usually does not need to be adjusted for changes in distribution.13

The clinical importance of the decrease in binding proteins and increase in free fraction of drugs lies in the interpretation of serum drug levels of highly protein-bound drugs with narrow therapeutic indices. Most labs measure and report the total amount of drug in the serum, both bound and unbound. As it is the unbound (free) drug that is pharmacologically active, this concentration is more clinically relevant. In a malnourished patient with hypoalbuminemia, a higher percentage of the total drug level consists of free drug than in a patient with normal serum albumin. A common example is phenytoin. If a hypoalbuminemic patient has a low or low-normal total phenytoin level, a clinician could increase the phenytoin dose for greater effect. This may actually cause the free phenytoin concentration to increase to a toxic level.14


Drug metabolism is affected by age, acute and chronic diseases, and drug-drug interactions. The liver is the primary site of drug metabolism, which undergoes changes with age. The effect of age on hepatic drug metabolism is somewhat controversial, and there is not a consistent decline in the capacity of the liver to metabolize all drugs, but older patients have decreased metabolism of many drugs.12,14 There is also a decline with age in the liver's ability to recover from injury. Liver mass is reduced by 20%

to 30% with advancing age, and hepatic blood flow is decreased by as much as 40%.

These changes can drastically reduce the amount of drug delivered to the liver per

unit of time, reduce its metabolism, and increase the elimination half-life. Metabolic clearance of some drugs is decreased by 20% to 40% (e.g., amiodarone, amitriptyline, warfarin, and verapamil), but for others it is unchanged. This is partially due to whether the drug has a high or low extraction by the liver. Drugs that have high extraction ratios also have significant first-pass metabolism resulting in a higher bioavailability in older adults. For example, the effect of morphine is increased due to a decrease in clearance by around 33%. Similar increases in bioavailability associated with reduced clearance can be seen with propranolol, levodopa, and hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors (statins). Elderly patients may experi-

ence a similar clinical response to that of younger patients, but at lower doses. Drugs

with a low hepatic extraction are usually not affected by hepatic hemoperfusion.

The effect of aging on liver enzymes (cytochrome P450 system, known as the CYP450 system) may lead to a decreased elimination rate of drugs that undergo oxidative phase-I metabolism, but this is controversial.13 Originally, it was thought that the CYP450 system was impaired in the elderly, leading to a decrease in drug clearance and increase in serum half-life. Studies have not consistently confirmed this and although there is an age-related increase in half-life of some drugs, it may be attributed to other factors like changes in volume of distribution. Thus, variations in the CYP450 activity may not be due to aging, but due to lifestyle (e.g., smoking), illness, and drug interactions.13,14 A patient's nutritional status plays a role in drug metabolism as well. Frail elderly have a more diminished drug metabolism than those with healthy body weight.12 Age does not have an effect on phase-II hepatic metabolism, known as conjugation or glucuronidation, but conjugation is reduced with frailty. Temazepam and lorazepam are examples of drugs that undergo phase-II metabolism.13


The most clinically important pharmacokinetic change in the elderly is the decrease in renal drug elimination.12 As people age, renal blood flow, renal mass, glomerular filtration rate, filtration fraction, and tubular secretion decrease. After age 40, there is a decrease in the number of functional glomeruli, and renal blood flow declines by approximately 1% yearly. From age 25 to 85 years, average renal clearance declines by as much as 50% and is independent of the effects of disease.12-14 The effect of age on renal function can be variable and is not always a linear decline.14 Longitudinal studies have suggested that a percentage (up to 33%) of elderly patients do not experience this age-related decline in renal function. Clinically significant effects of decreased renal clearance include prolonged drug half-life, increased serum drug level, and increased potential for adverse drug reaction (ADR). Special attention should be given to renally eliminated drugs with a narrow therapeutic index (e.g., digoxin, aminoglycosides). Monitoring serum concentration and making appropriate dose adjustment for these agents can prevent serious ADR that may result from drug accu-

mulation. It is important to note that despite a dramatic decrease in renal function (creatinine clearance) with aging, serum creatinine may remain fairly unchanged and within normal limits. This is because elderly patients, especially the frail elderly, have decreased muscle mass resulting in less creatinine production for input into circulation.12,13 Because chronic kidney disease can be overlooked if a clinician focuses only on the serum creatinine value, drugs can be dosed inappropriately.

For reasons stated above, creatinine clearance should always be calculated when starting or adjusting drugs in the elderly. Clearance measure using 24-hour urine collection is impractical, costly, and often done inaccurately. The Cockcroft-Gault equation is the most widely used formula for estimating renal function and adjusting drug doses. It incorporates serum creatinine, age, gender, and weight. See Chapter 25 (Table 25-1) in this book for more details.

This equation is also used by drug manufacturers to determine dosing guidelines. The Cockcroft-Gault equation provided the best balance between predictive ability and bias in a study that compared it to the Modification of Diet in Renal Disease (MDRD) and Jeliffe "bedside" clearance equations.13 A limitation of the MDRD equation is that it was not validated for patients older than 70 years.14 Understand that the predictive formulas can significantly overestimate actual renal function, especially in the chronically ill, debilitated elderly.

Pharmacodynamic Changes

Pharmacodynamics refers to the actions of a drug at its target site and the body's response to that drug. Pharmacodynamic changes associated with aging are not as well known as that of pharmacokinetics, but a better understanding of these effects can enhance the quality of medication prescribing. In general, the pharmacodynamic changes that occur in the elderly tend to increase their sensitivity to drug effects. Most pharmacodynamic changes in the elderly are associated with a progressive reduction in homeostatic mechanisms and changes in receptor properties. Although the end result of these changes is an increased sensitivity to the effects of many drugs, a decrease in response can also occur.15 The changes in the receptor site include alterations in binding affinity of the drug, number or density of active receptors at the target organ, structural features, and postreceptor effects (biochemical processes/signal transmission). These include receptors in the adrenergic, cholinergic, and dopaminer-

12 13

gic systems, as well as gamma aminobutyric acid (GABA) and opioid receptors. '

Patient Encounter 2

KS is a 79-year-old white female who has a long history of seizure disorder. She has been taking phenytoin 100 mg three times a day, but states that her doctor thought she may need to double her dose. She was recently hospitalized for dehydration and is recovering from "low kidney function."

VS: BP 122/70, P 72, RR 14, T 38.6°C (101.5°F), ht: 5'2" (1.57 m), wt: 55 kg

Labs: Na 140 mEq/L (140 mmol/L), K 4.7 mEq/L (4.7 mmol/L), Cl 99 mEq/L (99 mmol/L), CO2 25 mEq/L (25 mmol/L), BUN 60 mg/dL (21.4 mmol/L), creatinine 1.8 mg/dL (1.59 micromoles/L), albumin 2.5 g/dL (25 g/L)

What is KS's estimated creatinine clearance?

How does phenytoin serum concentration react to KS S albumin level?

What other factors need to be considered before making phenytoin dosage adjustment in this patient?

Cardiovascular System

Decreased homeostatic mechanisms in elderly patients increase their susceptibility to orthostatic hypotension when taking drugs that affect the cardiovascular system and lower the arterial blood pressure. This is explained by a decrease in arterial compliance and a decreased baroreceptor reflex response, which limits their ability to quickly compensate for postural changes in blood pressure. It has been estimated that as many as 5% to 33% of the elderly experience drug-induced orthostasis. Examples of drugs, other than typical antihypertensives, that have a higher likelihood of causing orthostatic hypotension in geriatric patients are tricyclic antidepressants, antipsychotics, loop

12 13 15

diuretics, direct vasodilators, and opioids. ' ' Although older patients have a decreased ^-adrenergic receptor function and are less sensitive to ^-agonists and ^-ad-

renergic antagonists effects in the cardiovascular system and possibly in the lungs,


their response to a-agonists and antagonists is unchanged. ' Increased hypotensive and heart rate response (to lesser degree) to calcium channel blockers (e.g., verapamil) are reported. Increased risk of developing drug-induced QT prolongation and torsades de pointes is also present.15 Therefore, clinicians must start medications at low doses and titrate slowly, closely monitoring the patient for any adverse response.

Central Nervous System

Overall, geriatric patients exhibit a greater sensitivity to the effects of drugs that gain access to the CNS. In most cases, lower doses are required for adequate response and patients have a higher incidence of adverse effects. The blood-brain barrier becomes more permeable as people age; thus, more medications can cross the barrier. Examples of problematic medications include benzodiazepines, antidepressants, neuroleptics, and antihistamines. There is a decrease in the number of cholinergic neurons as well as nicotinic and muscarinic receptors, decreased choline uptake from the peri-


phery, and increased acetylcholinesterase. ' The elderly have a decreased ability to compensate for these imbalances in the neurotransmitters, which can lead to movement and memory disorders. Older patients have increased number of dopamine type 2 receptors, which makes them more susceptible to delirium from anticholinergic and dopaminergic drugs. On the other hand, they have reduced number of dopamine and dopaminergic neurons in the substantia nigra of the brain resulting in higher incidence of extrapyramidal symptoms from antidopaminergic medications (e.g., antipsychotics).12,1 Lower doses of opioids provide sufficient pain relief for older patients, whereas conventional doses can cause oversedation and respiratory depression


due to increased response to the drug. ' ' Fluids and Electrolytes

Fluid and electrolyte homeostatic mechanism is decreased in the geriatric population. The elderly experience more severe dehydration with equal amounts of fluid loss compared to younger patients. The multitude of factors involved include decreased thirst and cardiovascular reflexes, decreased fluid intake, decreased ability of the kidneys to concentrate urine, increased atrial natriuretic peptide, decreased aldosterone response to hyperkalemia, and decreased response to antidiuretic hormone. The result is an increased incidence of hyponatremia, hyperkalemia, and prerenal azotemia, especially when the patient is taking a thiazide or loop diuretic (e.g., hydrochlorothiazide, fur-osemide). Angiotensin-converting enzyme inhibitors also have an increased potential to cause hyperkalemia and acute renal failure, thus the need to start low, titrate slowly,

12 15

and monitor frequently. ' Glucose Metabolism

An inverse relationship between glucose tolerance and age has been reported. This is likely due to a reduction in insulin secretion and sensitivity (greater insulin resistance).

Consequently, there is an increased incidence of hypoglycemia when using sulfonylur-

eas (e.g., glyburide, glipizide). Due to an impaired autonomic nervous system, elderly patients may have a decreased response to, or awareness of, hypoglycemia (may not experience the sweating, palpitations, or tremors, but instead will experience the neurologic symptoms of syncope, ataxia, confusion, or seizures).


The geriatric population is more sensitive to anticoagulant effects of warfarin compared to younger people. When similar plasma concentrations of warfarin are attained, there is greater inhibition of vitamin K-dependent clotting factors in older patients than in young. Overall the risk of bleeding is increased in the elderly, and when overanticoagulated, the likelihood of morbidity and mortality is higher. This is further complicated by presence of concomitant herbals/supplements, multiple drug-drug interactions, nonadherence, confusion, and acute illness. Close monitoring of international normalized ratio (INR) and screening for appropriate use is paramount. In

contrast, there is no association between age and response to heparin. DRUG-RELATED PROBLEMS

O Comorbidities and polypharmacy complicate elderly health status, particularly when polypharmacy includes inappropriate medications that lead to drug-related problems. It is reported that 28% of hospitalizations in older adults are due to medication-related problems including nonadherence and ADRs. Studies using the Beers' criteria indicate that 14% to 40% of the frail elderly are prescribed at least one inappropriate drug, and unnecessary medication use was detected in 44% of older veterans at the time of hospital discharge.16 Drug-related problems, including ADRs and therapeutic failure, lead to morbidity and mortality in nursing facilities and accrue

health care cost of nearly $4 billion yearly. Collaboration among multidisciplinary providers and older patients can minimize adverse drug events, maximize medication adherence, and ensure appropriate therapy.


Polypharmacy is defined as taking multiple medications concurrently (some report at least four and others at least five). Polypharmacy is prevalent in older adults who comprise 14% of the U.S. population, but receive 36.5% of all prescription drugs.16 According to the Centers for Disease Control and Prevention, polypharmacy is the primary cause of drug-related adverse events in older adults. Medication use rises with age, resulting in over 90% of elders in the United States taking at least one medication a week. An estimated 50% of the community-dwelling elderly take five or more medications and 12% of them take 10 or more.18 Also, common use of dietary supplements and herbal products in this population adds to the polypharmacy. In nursing home settings, patients receiving nine or more chronic medications increased from 17% in 1997 to 27% in 2000.16 Among various reasons for polypharmacy, an apparent one is a patient receiving multiple medications from different providers who treat the patient's comorbidities. Thus, medication reconciliation will become increasingly important as aging population continues to grow.

A recent review that analyzed studies aimed at reducing polypharmacy in elderly emphasized complete evaluation of all medications by health care providers at each patient visit to prevent polypharmacy.19 Efforts should be made to reduce polypharmacy by discontinuation of any medication without an indication. However, clinicians should also understand that appropriate polypharmacy is indicated for patients who have multiple diseases, and support should be provided for optimal adherence. Drug-related problems associated with polypharmacy can be identified by performing a comprehensive medication review during each patient encounter (see Patient Care and Monitoring box).

Inappropriate Prescribing

Inappropriate prescribing is defined as prescribing medications that cause a significant risk of an adverse event when there is an effective and safer alternative. It also includes prescribing a medication outside the bounds of accepted medical standards. The incidence of prescribing potentially inappropriate drugs to elderly patients has been reported to be as high as 12% in those living in the community and 40% in nurs-

20 21

ing home residents. ' At times, medications are continued long after the initial indication has resolved. The clinician prescribing for older adults must understand the rate of adverse reactions and drug-drug interactions, the evidence available for using a specific medication, and patient use of over-the-counter (OTC) medications and herb-

20 22

al supplements.

Screening tools have been developed to help the clinician identify potentially inappropriate drugs. The most utilized and well known is the Beers' criteria, which was first developed in 1991. It was revised in 2003 to include community-dwelling individuals, lists of specific medications to avoid, and warnings regarding disease/medication combinations. It identifies 48 medications and 20 disease/medication combinations that are deemed inappropriate in elderly patients.

Some of the more common medications referred to in the Beers' criteria include the following:

• Amitriptyline (strong anticholinergic and sedative properties)

• Propoxyphene and combination products (side effects of narcotics with similar analgesic benefits to acetaminophen)

• Indomethacin (most CNS side effects of all the NSAIDs)

• Long-acting benzodiazepines like diazepam (increased sedation; risk of falls and fractures)

• Antihistamines like diphenhydramine (confusion and sedation with a prolonged effect)

• Long-term use of full-dose NSAIDs (increased potential to cause GI bleeding, renal failure, hypertension, and heart failure)

• Fluoxetine (long-acting selective serotonin-reuptake inhibitor [SSRI] that causes sleep disturbance, increased agitation and excessive CNS stimulation)

Examples of drug/disease combinations reported as potentially inappropriate are as follows:

• NSAIDs and aspirin 325 mg or higher daily in patients with gastric/duodenal ulcers

• Anticholinergic antihistamines and patients with bladder outlet obstruction or benign prostatic hyperplasia

• Metoclopramide and typical antipsychotics and patients with Parkinson's disease

• Barbiturates, anticholinergics, antispasmodics, and muscle relaxants with cognitive impairment

• Bupropion and seizure disorders (lowers seizure threshold)

As noted above, the consequences of inappropriate prescribing are widespread and vary in severity. It is important to note that these medications are "potentially" inappropriate and alternatives should be used or focused monitoring for adverse effects should be provided. Practical strategies for appropriate medication prescribing include establishing a partnership with patients and caregivers to enable them to understand and self-monitor their medication regimen. Providers should perform drug-drug and drug-disease interaction screening, and use time-limited trials to evaluate the benefits

and risks of new regimens. Undertreatment

Much has been written about the consequences of overmedication and polypharmacy in the elderly. However, underutilization of medications is harmful in the elderly as well, resulting in reduced functioning and quality of life, and increased morbidity and mortality. There are instances when an indicated drug is truly contraindicated appropriately preventing its use, when a lower dose is indicated, or when prognoses dictate withholding of aggressive therapy. Outside of these scenarios, many elders do not receive the therapeutic interventions that would clearly provide benefit. This occurs for many reasons including the belief that treatment of the patient's primary problem is enough intervention, cost, concerns of nonadherence, fear of adverse effects and associated liability, starting low and slow and failing to increase to an appropriate dose, skepticism regarding secondary prevention for elders, or frank ageism. A study found evidence of underprescribing in 64% of older patients, and those on more than eight medications at the highest risk. Interestingly, the lack of proven beneficial therapy was not dependent on age, race, sex, comorbidity, cognitive status, and dependence in

activities of daily living. Common categories of geriatric undertreatment are listed in Table 2-2.

A reasoned clinical assessment strategy to weigh the potential benefit versus harm of the older patient's complete medication regimen is required. Once frank contraindications have been dismissed, the patient's (a) goals and preferences, (b) remaining life expectancy, and (c) time until therapeutic benefit will be achieved should be taken into consideration to determine whether the therapy can meet treatment goals. Under-prescribing can best be avoided by using careful clinical assessment strategies, improving adherence support, and increasing financial coverage of expensive drugs.

Table 2-2 Common Categories of Geriatric Undertreatment



Anticoagulation in patients with atrial fibrillation Malignant and nori malignant pain complaints or uncontrolled pain

Antihypertensive therapy

^Blocker treatment in heart failure

Statin treatment for hyperlipidemia

Treatment of osteopenia/ osteoporosis in men and women at risk of fractures

Providers may be overly concerned with general risk of bleeding, or the risk ot falls if anticoagulated Providers are often hesitant to prescribe opioids due to possible cognitive and bowel side effects, or concerns about addiction, and patients may often be hesitant to take opioids Providers may underestimate the benefit on stroke and cardiovascular events, and/or fail to add the second or third medication needed to attain control Providers are concerned ¿about complications in high-risk patients despite the substantial evidence of mortality reduction Providers may underestimate benefit, or have high concerr for adverse events

Providers often fail to screen for bone mineral density and are therefore unprepared to offer treatment

Adverse Drug Reaction

ADR is defined by the World Health Organization as a reaction that is noxious and unintended, which occurs at dosages normally used in humans for prophylaxis, diagnosis, or therapy, increases with polypharmacy. (See the glossary for the American

Society of Health-System Pharmacists' definition of an ADR. ) Older adults com monly experience ADRs. In fact, ADR is the most frequently occurring drug-related problem among elderly nursing home residents, and the yearly occurrence in outpatient elderly is noted to be 5% to 33%26

Seven predictors of ADRs in older patients have been identified : (a) taking more than four medications; (b) longer than 14-day hospital stay; (c) having more than four active medical problems; (d) general medical unit admission versus geriatric ward; (e) alcohol use history; (f) lower Mini-Mental State Exam score (confusion, dementia); and (g) two to four new medications added during a hospitalization. Similarly,

there are four predictors for severe ADRs experienced by the elderly : (a) use of certain medications including diuretics, NSAIDs, antiplatelets, and digoxin; (b) number of drugs taken; (c) age; and (d) comorbidities. Suggested strategies to preventing

ADRs in older adults are described in Table 2-3. Particular care must be taken when prescribing drugs that can alter cognition of the elderly, including antiarrhythmics, antidepressants, antiemetics, antihistamines, anti-Parkinson's, antipsychotics, benzodiazepines, digoxin, histamine-2 receptor antagonists, NSAIDs, opioids, and skeletal muscle relaxants.21

Table 2-3 Strategies to Preventing ADRs in Older Adults

• Evaluating comorbidities, frailty, and cognitive function

• Identifying caregivers to take responsibility for medication management

• Evaluating renal function and adjusting doses appropriately

• Monitoring drug effects

• Recognizing that clinical signs or symptoms can be an ADR

• Minimizing number of medications prescribed

• Adapting treatment to patient's life expectancy

• Realizing that self-medication and nonadherence are common and can induce ADRs

One of the most damaging ADRs occurring in older adults is medication-related falls. Falls are associated with poor prognosis ranging from premature institutional-ization to early mortality. Extrinsic factors for falling include taking certain medications or polypharmacy. A recent systematic review concluded that psychotropic med-

ications including benzodiazepines, antidepressants, and antipsychotics have strong association to increased risk for falls, where antiepileptics and antihypertensives have weak association. Multifactorial interventions to preventing falls should always involve medication simplification and modification in order to prevent and resolve ADRs.


"America's other drug problem" is the term given to medication nonadherence by the

National Council on Patient Information and Education. Nonadherence to chronic pharmacotherapies is prevalent and escalates health care costs associated with worsen-

ing disease and increased hospitalization. Medication adherence is a term describing a patient's medication-taking behavior, generally defined as the extent to which a patient adheres to an agreed regimen derived from collaboration between the patient and their health care provider. The word "adherence" is often preferred over "compliance" because medication compliance implies the patient passively complying to provider's medication orders with no attempts made at collaboration.3

® Elderly patients are at greater risk for medication nonadherence due to high prevalence of multiple comorbidities and polypharmacy use leading to complex regimens. Numerous barriers to optimal medication adherence exist and include patient's lack of understanding, provider's failure to educate, polypharmacy leading to complex regimen and inconvenience, treatment of asymptomatic conditions (such as hy-

pertension and hyperlipidemia), and cost of medications. Factors influencing medication nonadherence are listed in Table 2-4.

Table 2-4 Factors Influencing Medication Nonadherence

Three or more chronic medical conditions Tlve or more chronic rmed¡cations Three times or more per day dosing or ]2 or n>ore medication doses per day

Four or more medication changes in past months Three or more prescribed Significant cognitive or physical impairments

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