Jeannie K. Lee, Damian M. Mendoza,
M. Jane Mohler, and Susan J. Morris
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Explain the growth pattern of the elderly population.
2. Discuss age-related pharmacokinetic and pharmacodynamic changes.
3. Identify drug-related problems and associated morbidities commonly experienced by elderly.
4. Describe major components of geriatric assessment.
5. Recognize multidisciplinary patient care functions in various geriatric practice settings.
KEY CONCEPTS
Population aging is an incontrovertible trend.
Older Americans use considerably more health care services than younger Americans, and their health care needs are often complex.
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 drugs.
In general, the pharmacodynamic changes that occur in the elderly tend to increase their sensitivity to drug effects.
Comorbidities and polypharmacy complicate elderly health status, particularly when polypharmacy includes inappropriate medications that lead to drug-related problems.
Elderly patients are at greater risk for medication nonadherence due to high prevalence of multiple comorbidities and polypharmacy use leading to complex regimens.
The clinical approach to assessing older adults frequently goes beyond a traditional “history and physical” used in general internal medicine practice.
Considering geriatric patients’ vision, hearing, swallowing, cognitive impairment, motor impairment, and education and literacy levels during the education sessions can lead to successful drug regimen adherence.
Long-term care geriatric practices emphasize the interdisciplinary team approach.
The continual growth of the aging population requires that health care professionals gain knowledge specific to meeting the needs of this patient group. Despite the availability and benefit of the numerous pharmacotherapies to treat their diseases, elderly patients often experience various drug-related problems resulting in additional morbidities. Therefore, it is essential for clinicians serving older adults in diverse health care settings to understand epidemiology of aging, age-related physiologic changes, drug-related problems prevalent in elderly, comprehensive geriatric assessment, and multidisciplinary approaches to geriatric care.
EPIDEMIOLOGY AND ETIOLOGY
As humans age, they are at increasingly elevated risk of disease, disability, and death primarily for three reasons: (a) genetic predisposition, (b) reduced immunological surveillance, and (c) the accumulated effects of physical, social, environmental, and behavioral exposures over the life course. Human relationships, social conditions, and networks interact with these accumulating exposures, and differences in time and place influence health outcomes by age cohort. Combined, these factors result in considerable variation in health states and health care requirements, by age. All elders experience increasing vulnerability and homeostenosis. Although resilient elders are able to successfully maintain high levels of physical and cognitive functioning, avoid chronic conditions, and remain socially engaged, others suffer functional decline, frailty, disability, or death. There is an urgent need for all clinicians to better understand the epidemiology of aging in order that health care needs of the elderly can be comprehensively addressed, and so that safe, quality services can be provided efficiently to optimize functioning and health-related quality of life for the aged.1
Sociodemographics
Population
Population aging is an incontrovertible trend. In 2006, 37 million U.S. residents were aged 65 and above years (more than 12.4% of the total population), nearly 5.3 million people were aged more than or equal to 85 years (the “oldest-old”), and over 73,000 were centenarians.2 When the Baby Boomers (those born between 1946 and 1964) begin turning 65 years in 2011, the number of elders will double to 71.5 million in 2030, representing nearly 20% of the total U.S. population.2 In 2006, there were a total of 21.6 million women and 15.7 million men (a ratio of 138:100, respectively) aged more than or equal to 65 years; this ratio widens as elders age. The oldest-old are projected to increase from 5.3 million in 2006 to nearly 21 million in 2050.2 In addition, minority elder populations are projected to increase to 8.1 million in 2010 (20.1%), and up to 12.9 million in 2020 (23.6%), including disproportionate increases in Hispanics (254%); Asians and Pacific Islanders (208%); African Americans (147%); and Native Americans, Eskimos, and Aleuts (143%).2 Surviving Baby Boomers will be proportionally more women, more racially diverse, better educated, and have more financial resources than were elders in previous generations.
Economics
More elders are enjoying higher economic prosperity than ever before, with net worth increasing by nearly 80% for older Americans over the past 20 years. Still, major inequalities persist, with older blacks and those without high school diplomas reporting smaller economic gains, and fewer financial resources.3 Considerable disparities exist; the 2005 median net worth of households headed by Caucasians greater than or equal to 65 years was $226,900 compared to black elder household net worth of $37,800 (a sixfold difference).3
Education and Health Literacy
By 2007, more than 75% of U.S. elders had graduated from high school, and nearly 20% had a bachelor’s degree or higher. Still, substantial educational differences exist among racial and ethnic minorities. While over 80% of non-Hispanic white elders had high school degrees in 2007, only 72% of Asians, 58% of blacks, and 42% of Hispanic elders were graduates. Nearly 40% of people aged more than or equal to 75 years have low health literacy, more than any other age group.3 Despite these limitations, the Pew Trust reports that over 8 million Americans (22%) aged more than or equal to 65 years increasingly use the Internet,4 and large health care plans such as the Veterans Administration are increasingly offering online health information to support this need. These advances in literacy are important because communication between health care providers and elders is vitally important in providing quality care, supporting self-care, and in negotiating the health care system.
Health Status
Life Expectancy
Though Americans are living longer than ever before, an estimated average of 78.14 years overall in 2008, U.S. life expectancy lags behind that of many other industrialized nations.5 There is nearly a 6-year gap between 2008 estimated life expectancy in males (75.29 years) and females (81.13 years).6 Disparities in mortality persist, with estimated 2008 life expectancy in the white population nearly 5 years higher than that of the black population.6 More than one-third of U.S. deaths in 2000 were attributed to three risk behaviors: smoking, poor diet, and physical inactivity, accounting for nearly 35% of deaths in 2000 (Table 2–1). Currently, only 9% of Americans over 65 years smoke; however, nearly 54% of men and 21% of women are former smokers.7 Overweight elders aged 65 to 74 years increased from 57% to 73% in 2004 largely due to inactivity and a diet high in refined foods, saturated fats, and sugared beverages, and deficient in whole grains, fruits, vegetables, nuts, and seeds.3 Despite the proven health benefits of regular physical activity, more than half of the older population is sedentary; 47% of those aged 65 to 74 years, and 61% over 75 years report no physical activity.8
The 2007 National Health Interview Survey indicated that 39% of non-Hispanic, white elders reported “very good” or “excellent” health, compared with 29% of Hispanics, and 24% of blacks.9 Chronic diseases disproportionately affect older adults and are associated with disability, diminished quality of life, and increased costs for health care and long-term care. About 80% of older adults have at least one chronic condition, and 50% have at least two. The prevalence of certain chronic conditions differs by sex, with women reporting higher levels of arthritis (54% versus 43%), and men reporting higher levels of heart disease (37% versus 26%) and cancer (24% versus 19%).4 Though many older Americans report multiple chronic health conditions, the rate of functional limitations among elderly has actually declined between 1992 and 2005 from 49% to 42%.4 Among the 15 leading causes of death, age-adjusted death rates decreased significantly from 2004 to 2005 for the top three leading causes—heart disease (33%), cancer (22%), and stroke (8%), though chronic lower respiratory diseases, unintentional injuries, Alzheimer’s disease, influenza and pneumonia, hypertension, and Parkinson’s disease increased.5 Figure 2–1specifies the most common chronic conditions of elders, by sex. Frailty is a common biological syndrome in the elderly. Once frail, elders may rapidly progress toward failure to thrive and death. Only 3% to 7% of elders between the ages of 65 and 75 years are frail, increasing to more than 32% in those aged more than 90 years.10
Table 2–1 Top Five Actual Causes of Death Among Persons of All Ages in the United States, 2000
Health Care Utilization and Cost
Older Americans use considerably more health care services than younger Americans, and their health care needs are often complex. Although in 2005, hospital stays for those 65 years or older were one-half of what they had been in 1970 (5.5 versus 12.6 days), they accounted for over 65% of hospitalizations overall, with longer lengths of stay corresponding to increasing age.11 Nine persons per 1,000 aged 65 to 74 years lived in nursing homes in 2004, compared with 36 of 1,000 aged 75 to 84 years, and 139 of 1,000 aged 85 years or older;11 as the aged live longer, more will require institutional care. After adjusting for inflation, health care costs increased significantly among older Americans from $8,644 in 1992 to $13,052 in 2004, three to five times greater than the cost for someone younger than 65 years. Medicare spending has grown nearly ninefold in the past 25 years, to over $507 billion in 2008, and Medicare roles are expected to increase to $78 million by 2030.4
By knowing and applying the epidemiology of aging, clinicians can better understand the multiple points of potential pharmaceutical intervention to postpone disease, disability, and mortality, to avoid error, and to promote health, functioning, and health-related quality of life.
Patient Encounter 1
JM is a 69-year-old Hispanic male who understands English, speaks English fairly well, but does not read. He came into the Geriatric Primary Care Clinic for a cholesterol screening because he “has been eating bad food” for over 10 years and not exercising. He smokes one pack of cigarettes and drinks two to three beers a day. He takes a “baby aspirin” daily ever since he suffered a “mini-stroke” 2 years ago. His other medical conditions include hypertension, arthritis, chronic obstructive pulmonary disease, allergies, and Parkinson’s disease. He was hospitalized for pneumonia 2 months ago. He takes nine chronic medications including his inhalers.
What information is consistent with epidemiology of aging?
Which of JM’s medical conditions are commonly found in older adults?
What additional information do you need before recommending drug therapy for JM?
AGE-RELATED 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 drugs.12 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 suffering from diseases that affect pharmacokinetics and pharmacodynamics.13 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 pharmacokinetic 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.)
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 flow.12 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.13
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 significantly alter the amount of drug absorbed.12,13 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
Distribution
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 (Vd), leading to higher tissue concentrations and prolonged duration of action. Higher Vd 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 Vdare 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.12,13 Toxic drug effects 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 contribute more to this decrease than age alone.12 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-inflammatory drugs (NSAIDs), furosemide, diazepam, and sulfonylureas.13 While plasma albumin, which primarily binds acidic drugs, decreases, α1-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 α1-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
Metabolism
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.13 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 ratiosalso 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 experience a similar clinical response to that of younger patients, but at lower doses.13 Drugs with a low hepatic extraction are usually not affected by hepatic hemoperfusion.13
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
Elimination
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).12 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 accumulation.13 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 dopaminergic systems, as well as gamma aminobutyric acid (GABA) and opioid receptors.12,13
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.”
PE:
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 diuretics, direct vasodilators, and opioids.12,13,15 Although older patients have a decreased β-adrenergic receptor function and are less sensitive to β-agonists and β-adrenergic antagonists effects in the cardiovascular system and possibly in the lungs, their response to α-agonists and antagonists is unchanged.13,15 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 periphery, and increased acetylcholinesterase.13,15 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).12,15 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.12,13,15
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, furosemide). Angiotensin-converting enzyme inhibitors also have an increased potential to cause hyperkalemia and acute renal failure, thus the need to start low, titrate slowly, and monitor frequently.12,15
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 sulfonylureas (e.g., glyburide, glipizide).12 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).
Anticoagulants
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.12
DRUG-RELATED PROBLEMS
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.17 Collaboration among multidisciplinary providers and older patients can minimize adverse drug events, maximize medication adherence, and ensure appropriate therapy.
Polypharmacy
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.19Efforts 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 nursing home residents.20,21 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 herbal supplements.20,22
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’ criteria23 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.22
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.24 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. Underprescribing 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
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.25) Older adults commonly 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 identified26: (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 elderly27: (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 2–3.27 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
From Ref. 27.
One of the most damaging ADRs occurring in older adults is medication-related falls. Falls are associated with poor prognosis ranging from premature institutionalization to early mortality. Extrinsic factors for falling include taking certain medications or polypharmacy. A recent systematic review concluded that psychotropic medications including benzodiazepines, antidepressants, and antipsychotics have strong association to increased risk for falls, where antiepileptics and antihypertensives have weak association.28 Multifactorial interventions to preventing falls should always involve medication simplification and modification in order to prevent and resolve ADRs.
Nonadherence
“America’s other drug problem” is the term given to medication nonadherence by the National Council on Patient Information and Education.29 Nonadherence to chronic pharmacotherapies is prevalent and escalates health care costs associated with worsening disease and increased hospitalization.29 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.30
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 hypertension and hyperlipidemia), and cost of medications.30 Factors influencing medication nonadherence are listed in Table 2–4.
Table 2–4 Factors Influencing Medication Nonadherence
Following is a list of six questions that can be asked when assessing medication adherence32:
1. How do you take your medications?
2. How do you organize your medications to help you remember to take them?
3. How do you schedule your meal and medication times?
4. How do you pay for your medications?
5. How do you think the medications are working for your condition?
6. How many times in the last week/month have you missed a dose?
Although no one intervention has found to consistently improve adherence, patient-centered, multicomponent interventions such as combining education, convenience aid, and serial follow-up have resulted in positive impact on medication adherence and associated health outcomes.33 Additionally, there is a need for adherence studies evaluating belief-related variables, including personal and cultural beliefs, in larger and more ethnically diverse samples of older populations.
GERIATRIC ASSESSMENT
The term geriatric assessment is used to describe the interdisciplinary team evaluation of the frail, complex elderly patient. Such a team may include but is not limited to a geriatrician, nurse, pharmacist, case manager/social worker, physical therapist, occupational therapist, speech therapist, psychologist, nutritionist, dentist, optometrist, and audiologist. Assessment may be performed in a centralized geriatric clinic, or by a series of evaluations performed in separate settings. The team may conduct an interdisciplinary case conference to discuss the patient’s assessment and plan. For a healthy, active elderly patient, the assessment might require only two to three members of this team, with coordination of care provided by the patient’s geriatrician.
Patient Interview
The clinical approach to assessing older adults frequently goes beyond a traditional “history and physical” used in general internal medicine practice.31 Functional status must be determined, which includes the patient’s activities of daily living (ADLs) and instrumental activities of daily living (IADLs). Refer to Table 2–5 for descriptions of ADLs and IADLs. Evidence of declining function in specific organ systems is sought. Of particular importance is cognitive assessment, which may require history gathering from family, friends, or other caregivers, and is important in determination of the patient’s competence to consent to medical treatment.34 The mini-cog mental status exam,35 shown in Figure 2–2, is a quick tool to assess patient’s cognitive impairment. Commonly there is decreased visual acuity, hearing loss, dysphagia, and manual dexterity. Decreased skin integrity, if present, greatly increases risk for pressure ulcers. Sexual function is a sensitive but important area, which should be specifically inquired about. Cardiac, renal, hepatic, and digestive insufficiencies can have significant implications for pharmacotherapy. Inadequate nutritional status may lead to weight loss, and impaired functioning at the cellular or organ level as discussed previously. See Table 2–6 for common problems experienced by older adults.
Patient Encounter 3
PW is an 83-year-old African American male who has been living in a long-term care facility for 4 years after his wife passed away. He has been eating one to two meals a day with complaints of trouble swallowing, constipation, depressed mood, and fatigue. He has lost 2 kg in last 6 months and has developed a new coccyx ulcer.
PMH: Hypertension, diabetes, hyperlipidemia, hypothyroidism, Parkinson’s disease, osteoarthritis, constipation, allergic rhinitis
FH: Father died of stroke at age 82; mother died of breast cancer at age 67
SH: 40-year smoking history but quit 9 years ago; no alcohol drinking
Allergies: NKDA
Meds: (1) Aspirin 81 mg daily, (2) hydrochlorothiazide 25 mg daily, (3) lisinopril 10 mg twice daily, (4) glipizide 5 mg twice daily, (5) metformin 500 mg twice daily, (6) levothyroxine 25 mcg daily, (7) carbidopa/levodopa 25 mg/100 mg three times daily, (8) ibuprofen 600 mg three times daily, (9) docusate sodium 100 mg twice daily, (10) lorazepam 2 mg twice daily, (11) diphenhydramine 25 mg at bedtime, (12) amitriptyline 10 mg at bedtime
PE: Ht: 5′8″, wt: 65 kg, BMI: 21.8 kg/m2
VS: BP 122/62, P 60, RR 14, T 36.8°C (98.3°F), pain 3/10 (on scale of 0–10)
Labs: Complete metabolic panel is within normal limits; CBC pending
What potential drug-related problems does PW have?
What quality indicators can you identify in this nursing home resident?
What recommendations can be made about his medication regimen?
Table 2–5 ADL and IADL
Three item recall
1. Ask the patient if you may test his or her memory.
2. Give the patient 3 words (e.g., apple, table, penny) to repeat and remember.
3. Have the patient repeat the 3 words from memory later (e.g., after the clock drawing test).
Clock drawing test
1. Have the patient draw the face of a clock, including numbers.
2. Instruct the patient to place the hands at a specific time, such as 11:10.
FIGURE 2–2 The mini-cog mental status exam. (Adapted from Ref. 35.)
Table 2–6 The Is of Geriatrics: Common Problems in Older Adults
It is important to identify “geriatric syndromes” which may be present in the patient. Frailty, instability and falls, osteoporosis, insomnia, and incontinence impact quality of life and must be recognized. Common diseases such as thyroid dysfunction and depression often present in an atypical manner in the geriatric population as many common conditions may present as delirium. It is also important to assess for caregiver stress and be aware of the support systems the older patient relies on. These may include family, friends, religious and social networks, as well as home health aides, homemakers, or sitters. Without such networks, the older adult may not be able to continue to live independently. Assessment of safety in the home is often necessary for the frail elderly. In addition, look for signs and symptoms of elder abuse, neglect, or exploitation. Health professionals are required to report suspicion of elder mistreatment to Adult Protective Services.36
Drug Therapy Monitoring
Geriatric patients often are frail, and have multiple drugs, medical comorbidities, and prescribers. It is essential that there be a single individual, a pharmacist, nurse, or primary care physician, who oversees the patient’s drug therapy. The providers need to be aware of the patient’s Medicare Part C or D plan, and what type of coverage these plans afford. What is the copayment for generic, preferred, and nonpreferred drugs? Is the patient responsible for all drug costs during the Medicare “donut hole” period? (The first $2,250 of medication is partially subsidized, but the patient pays 100% of the next $2,850.37) Many Medicare patients, especially the socioeconomically challenged, have limited understanding of the complex Medicare drug benefit. This problem is compounded when the prescriber also does not understand the patient’s insurance program.38 Providers can assist patients by prescribing generic medication that are offered through retail pharmacy discount plans ($4 retail pharmacy programs do not bill insurance, so the cost of those medications are not counted toward the $2,250 benefit), and help patients apply for the medication assistance programs offered by drug manufacturers. Particularly challenging in the geriatric population is identifying the cause(s) of nonadherence to medical regimens. Providers assessing elderly patients’ medication regimens should keep the following questions in mind:
• Are medications skipped or reduced due to cost?
• Can the patient benefit from sample drugs? Starting a patient on a free drug sample may increase patient costs in the long term, since samples typically are newer, expensive drugs.38
• Is there an educational barrier such as low health literacy?
• Does the patient speak English, but only read in another language?
• Can the patient see labels and written instructions?
• Does the patient have hearing problems? Patients with deficits might not admit they cannot hear or understand questions or instructions.
• Can the patient manipulate pill bottles, syringes, inhalers, eye/ear drops?
• Has the patient’s cognitive functioning worsened over time such that they can no longer follow the medication regimen?
Homeostenosis and comorbidities require more frequent monitoring for adverse effects: symptoms, abnormal laboratory results, drug interactions, and drug levels—see Table 2–7.
Documentation
Clear, current, and correct medication lists must be available to patients and all individuals involved with their care. It is especially important for geriatric patients to bring their list, or preferably their medication containers, to each visit with medical providers. Medications taken may require verification with the pharmacist, caregivers, or family. Transitions in patient care, such as hospital to subacute nursing facility or home, are points of vulnerability to medication errors because medications may have been deleted or added.39 It is now standard of care to conduct medication reconciliation upon hospital admission and discharge to facilitate appropriate medication use and documentation.
Patient Education
Poor adherence in the geriatric age group could be related to inadequate patient education. “Ask me 3” cues the patient to ask three important questions of their providers to improve health literacy:
1. What is my main problem?
2. What do I need to do?
3. Why is it important for me to do this?
Table 2–7 Centers for Medicare and Medicaid Services Guidelines for Monitoring Medication Use
The provider can assess patient grasp of medication instructions by asking the patient to repeat instructions initially and again in 3 minutes.40
Considering geriatric patients’ vision, hearing, swallowing, cognitive impairment, motor impairment, and education and literacy levels during the education sessions can lead to successful drug regimen adherence. Specific routes of drug administration, such as metered dose inhalers, ophthalmic/otic drops, and subcutaneous injections, may be difficult for older patients. More time needs to be spent in advising the patient and/or caregivers of potential ADRs and when to notify the provider about ADRs. (See Patient Care and Monitoring box for detailed information regarding patient education.)
GERIATRIC PRACTICE SITES
Ambulatory Geriatric Clinic
Ambulatory geriatric clinics are established to provide a multitude of primary care needs specifically tailored to the elderly population. Patients are usually referred by their primary care physicians due to the desire for increased access to services (patients-to-physician ratio), the complexity of the patient’s chronic conditions and medications, and the need for specialized knowledge in geriatric treatment. It is common for the appearance of cognitive impairment to be the catalyst for a referral to such clinic. These clinics take advantage of the enhanced knowledge base gained from utilizing multiple members of the health care team. Interdisciplinary geriatrics primary care teams can consist of one or more of the following: geriatrician, clinical pharmacist, nurses (registered nurse [RN], licensed practical nurse [LPN]), social worker, physical/occupational therapist, and nutritionist. Regular interdisciplinary meetings to discuss patients and combine input on their care plans from each specialty area are conducted. The geriatrician assumes the overall care of the patient. They have specialized training in treating the older population encompassing patient’s physical, medical, emotional, and social needs. The clinical pharmacist assists in optimizing medication regimen by conducting comprehensive medication review, screening and resolving potential drug-related problems, and educating patients and caregivers about medications and monitoring parameters. Clinical pharmacists’ effectiveness can be enhanced with the specialty certification in geriatrics. Nurses provide medical triage and day-to-day patient care activities such as obtaining vitals and providing wound care. Social workers are involved in various aspects from assessing mood and cognitive status of patients to obtaining placement in higher levels of care. Physical/occupational therapists are often involved in assessing the patient’s functional status and the need for further therapy, and help maintain a safe home environment. They provide adaptive equipments such as grab bars, raised toilet seat and shower bench for the bathroom, and cane or walker for ambulation. Nutritionists evaluate the patient’s nutritional status and educate on proper diet and weight management. From these successful clinical strategies, specialty geriatric clinics have developed including multidisciplinary geriatric oncology clinic41 and community-based memory clinic.42
Long-Term Care
Long-term care provides support for people who are dependent to varying degrees in ADLs and IADLs, numbering about 9 million people over age 65 years as of 2008.43 Care is provided in the patient’s home, in community settings such as adult care homes or assisted living facilities, as well as in nursing homes. Long-term care is expensive, typically several thousand dollars per month. Most care is provided at home by unpaid family members or friends. Medicare covers all or part of the cost of skilled nursing care for a limited period posthospitalization.43,44 Medicare does not cover long-term care. Financing of long-term care comes from patients’ and family savings and/or private long-term care insurance. When a patient’s assets have been depleted, Medicaid provides basic nursing home care.44 However, this care is heavily discounted, often resulting in economizing such as lower caregiver-to-patient ratios and higher number of patients per room. Nursing homes are highly regulated by state and federal government through the Center for Medicare and Medicaid Services.43,45 Initial and continuing certification of the facility depends upon periodic state and federal review of the facility. Auditors’ ratings are available to consumers in an online Nursing Home Report Card.46,47 Quality indicators are used by facility administrators and government overseers to identify problem areas, including48:
• Use of nine or more medications in single patient
• Prevalence of indwelling catheters
• Prevalence of antipsychotic, anxiolytic, and hypnotic use
• Use of physical restraints
• Prevalence of depression in patients without antidepressant therapy
• Clinical quality measures such as decubitus ulcers
• Moderate daily pain or any excruciating pain in residents
Long-term care geriatric practices emphasize the interdisciplinary team approach. The medical director leads regular meetings with all disciplines delivering care. These may include director of nursing, rehabilitation services (physical, occupation, and speech therapy), pharmacist, social worker, nutritionist, case manager, and psychologist. The pharmacist conducts a monthly drug regimen review of each patient’s medication list.39 The physician is alerted to medication concerns and must approve the patient’s orders every 60 days. Such a team approach is vital to coordinate care for the typical frail, complex long-term care patient.
Patient Care and Monitoring
1. Drug-related problems in the elderly patient can be identified by performing a comprehensive medication review.
2. Have the patient bring all of their medication bottles to the medication review including:
• Prescription medications
• OTC drugs
• Vitamin supplements
• Herbal products
3. Review the indication for all medications taken by the patient.
4. Review the doses taken to identify any underdose or overdose of medications.
5. Screen for any drug–drug, drug–disease, drug–vitamin/herbal, drug–food interactions.
6. Ensure that patient is not taking any medications to which he/she has allergies or intolerances.
7. Assess medication adherence by single or combination methods (use combination methods whenever possible):
• Self-report
• Refill history
• Tablet count
8. Inquire about any adverse drug reactions experienced by the patient.
9. Identify any untreated indication or suboptimal treatment, including preventative therapy such as aspirin, calcium + vitamin D, etc.
10. Assess vitals signs including pain.
11. Evaluate laboratory findings to assess the following:
• Renal function
• Hepatic function
• Therapeutic drug monitoring (e.g., digoxin, warfarin, phenytoin)
• Therapeutic goals for chronic disease (e.g., HgbA1c, LDL-C)
12. Perform medication regimen tailoring when indicated:
• Discontinue unnecessary drugs
• Simplify dosing times to minimize complex regimen
• Tailor regimen to patient’s daily routine to improve adherence
13. Recognize any physical or functional barriers that can be overcome, such as providing nonchild-resistant caps and tablet cutters.
14. Provide medication education and adherence aid:
• Verbal and written information about medications and/or disease states
• Special product counseling for inhalers, insulins, ophthalmic/otic drops, etc.
• List of medications to include generic and brand names, indications, doses, directions for use, timing of doses, etc.
• Information on medication storage
• Pill box or patient-specific blister packs
• List of future appointments
15. Promote self-monitoring and lifestyle modification:
• Use of blood pressure device and glucometer
• Diet and exercise
• Smoking cessation
• Immunizations
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
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