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in Practice

Jeannette y. wick

understanding frailty in the Geriatric Population Clinicians who work with the frail elderly know what frailty looks like, but until recently, they have had no science-based definition of this condition. Frailty is classified as a medical syndrome, and Fried et al. were among the first to standardize the definition of frailty as a distinct syndrome with biologic underpinnings. Their definition describes a clinical phenotype of decreased reserve and resistance to stressors, with clinical manifestations of a mutually exacerbating cycle of negative energy balance, sarcopenia, diminished strength, and exertion intolerance. Age is no longer considered a defining characteristic, although frailty is still considered primarily a geriatric problem. Approximately two-thirds of affected individuals enter frailty in a slow, progressive way, while one-third become frail cataclysmically. Weakness is a common early sign, and exhaustion and weight loss are often late manifestations. Observing early behavioral changes before frailty develops could provide insight into its development and suggest early interventions. Since frailty is clearly associated with adverse outcomes, a healthy, active lifestyle is the cornerstone of prevention, and many researchers suggest that resistance training can reverse some muscle loss and improve functioning. When the health care team proposes any change in care, including a new medication, it should be prepared to describe how the intervention may affect cognition, memory, energy, or function.

Key words: Frail elderly, Frailty, Grip strength, Unintentional weight loss, Weakness.

abbreviaTions: ADL = Activity of daily living, BMI = Body mass index, CHS = Cardiovascular Health Study, WHAS = Women’s Health and Aging Studies.

T he beginning of my association with The Consultant Pharmacist 15 years ago, was, like the start of any worker’s first days at a new

job, instructive. In peer review process, the reviewers frequently would ask, in one way or another, for me to “Speak more to the frail long-term care resident,” or “How does this disease (or side effect or morbidity) manifest in frailty?” Normally I would head for a dictionary when I think—but am not sure—how to define a word. Looking for a definition of frailty in the mid-1990s was almost futile; it hadn’t yet been developed. Regardless, clinicians who worked with the frail elderly knew what frailty looked

like when they saw it and how it could undermine a diagnosis, a treatment plan, and, sadly, a life.

About 10 years ago, several researchers began a quest to define frailty and look for its signs, symptoms, and, possibly, its causes. By 2004, a common criterion indi-cated a patient might be considered frail if he or she was older than 85 years of age, dependent in more than one activity of daily living (ADL), had three or more comor-bid conditions, and had one or more geriatric syndrome (incontinence, dementia, delirium, falls, neglect/abuse, osteoporosis).1 This was a good start.

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Fried et al. were among the first to standardize the definition of frailty as a distinct syndrome with biologic underpinnings. They described a clinical phenotype of frailty so precise and suggestive of the typical long-term care resident’s decreased reserve and resistance to stressors, it resonated with clinicians. The clinical manifestations they described—a mutually exacerbating cycle of negative energy balance, sarcopenia, diminished strength, and exertion intolerance—elucidated a problem long-term care providers had struggled with daily.2 By finding that name for this chronic state of vulnerability and identifying its characteristics, we have started to understand how we may someday defeat this foe.

Pharmacists, recognizing that certain comorbidities are likely to occur, can address frailty using careful drug regimen review.

defining frailtyCentral to what is now called Fried’s definition of frailty is the requirement that patients have three of five pheno-typic criteria—low grip strength, low energy, and slowed walking. Other researchers also use a 30- to 70-item frailty index (FI) that predicts adverse health outcomes more sensitively—it counts the patient’s deficits accumu-lated over time, including disability, diseases, physical and cognitive impairments, psychosocial risk factors, and geriatric syndromes such as falls, delirium, and uri-nary incontinence. The comprehensive nature of the FI, including its length and complexity, preclude the use of this instrument routinely in clinical settings.3,4 In addi-tion, these researchers designate a “prefrail condition,” in which the patient meets one or two criteria. Patients con-sidered prefrail are at high risk of progression to frailty.2 Age is no longer considered a defining characteristic, although frailty is still considered primarily a geriatric problem. Although people who are considered frail tend to be elderly, younger people can be frail as well.5,6

Currently, frailty is classified as a medical syndrome. Medical syndromes: • Aregroupsofsignsandsymptomsthataggregatein

a hierarchical order • Maytriggeracascadeofalterationsacrossothersystems• Characterizeaparticularabnormality

Current definitions of frailty are based in large part on findings from the U.S. Cardiovascular Health Study (CHS) and the Women’s Health and Aging Study (WHAS) II (Table 1).2,7 Fried used the CHS data, but excellent information came from WHAS II, a 7.5-year longitudinal study with 420 participants that describes the typical onset of frailty over time. Although women who became frail over the course of observation noted a variety of manifestations when their decline began, weakness was the most common first manifestation. Further, weakness, slowness, and low physical activity preceded exhaustion and weight loss in 76% of the women who were not frail at baseline, but became frail.7 This may be related to the now recognized decline in muscle strength beginning in midlife or with sarcopenia.8,9 It is unclear why sarcopenia occurs over time, but age-related declines in alpha-motor neurons, growth-hormone

Most, but not all, frail individuals are elderly.

source: istockphoto.com.

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undersTandinG frailTy in The GeriaTric PoPulaTion

production, sex steroid levels, and physical activity seem to contribute. Fat gain, increased catabolic cytokine production, and reduced dietary energy and protein may also be causes.9

Elders accumulate frailty criteria in different ways, and probably do so as the result of different causative pathways. They progress at different rates, with around two-thirds of affected individuals entering frailty in a slow, progressive way, and one-third becoming frail cataclysmically. Individuals may reach the terminal point of their frailty with organ-specific symptoms or systemic physiologic dysregulation.7,10 The points at which patients progress from nonfrail to prefrail to frail are called transitions. Approximately 80% of transitions to frailty involve adding exhaustion or weight loss to other criteria; weakness is a common early sign, and exhaustion and weight loss are often late manifestations. If exhaustion or weight loss are early manifestations, however, frailty is more likely to occur, and progression may be faster than in others.5,7

Age is no longer considered a defining characteristic, although frailty is still considered primarily a geriatric problem.

The frail few Using frailty criteria developed in CHS, researchers looked at community-dwelling adults 65 years of age or older who were not disabled at baseline in four essential ADLs (bathing, dressing, walking inside the home, and transferring from a chair). They found the overall preva-lence of frailty ranged from 7% to 12%. Its prevalence was lowest in the group 65 to 74 years of age (3.9%) and increased to 25% in participants older than 85 years of age, with a slightly higher prevalence in women.2

As individuals become overtly frail, they tend to adapt behaviorally as they realize their physiologic reserve and capacity to meet environmental challenges is declining. Observing early behavioral changes in the period before frailty develops could provide insight

into its development and suggest early interventions.11 Decreasing life space—the size of the area people pur-posely move through in their daily life and the frequency of travel in a specific time frame—is an example of a parameter that could be observed as a behavioral precur-sor to frailty. Life space measures spatial mobility as well; put more simply, life space is range, independence, and frequency of movement.12,13 In a study that looked at life space among women (N = 599) 65 years of age and older enrolled in the WHAS, women who left their neighbor-hood fewer than four times per week were 1.7 times more likely to become frail than those who left more often. Those who never left their homes experienced a three-fold increase in death before the onset of frailty. This study also found that for many patients, declining mobility, instrumental ADLs, and ADLs alone did not necessarily reduce life space; a subset of participants adapted. This suggests strongly that a slightly constricted life space may increase risk for frailty and may be a use-ful screening tool or intervention target.14

Frailty isn’t a unidirectional syndrome, however, as a study in New Haven, Connecticut, demonstrated. Following 754 subjects age 70 and older, the Precipitating Events Project used the five frailty criteria discussed above. After 54 months, 57.6% of study subjects made at least one transition. From baseline to 36 months, 19% worsened from prefrail to frail. Remarkably, 16.5% also moved from prefrail to nonfrail during the observation period. This study was observational, so no interven-tions were identified to promote improvement. It does highlight the possibility for prevention and reversal of frailty.15

associating frailty with adverse outcomesFrailty is clearly associated with adverse outcomes. The most obvious—increasing dependence and the need for increased and increasing personal care—leads to greater use of health care services and higher mortality.6,16 Elders who have a greater number of frailty criteria generally have longer hospital stays, more postoperative complication, and greater likelihood of discharge institutionalization if they require surgery.5 Frailty is also associated with other comorbidities and conditions

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Table 1. comparison of Two frailty-defining criteria

weight loss Unintentional weight loss of Weight loss of > 10% of weight after age 60

10 pounds (4.5 kg) or more in Follow-up:

one year BMI < 18.5 kg/m2 or an unintentional weight loss > 5% of

baseline in a year

exhaustion Self-report of either: Self-report of:

• “EverythingIdidinthelastweek •Energylevellowerthanusualor

wasaneffort,”or • Feelingunusuallytiredinthelastmonthor

• “Icouldnotgetgoinginthe • Feelingunusuallyweakinthelastmonth

last week”

low energy expenditure Based on an 18-item activity scale: Based on an 18-item activity scale:

•Womenused<90kcal •Women used < 270 kcal

•Menused<128kcal •Men used < 383 kcal

slowness When asked to walk 15 feet (4.57 m) When asked to walk 13 feet (4 m) at usual pace:

atusualpace: •Women:

•Women: Speed ≤ 4.57 m in 7 seconds for height ≤ 159 cm

Time ≥ 7 s for height ≤ 159 cm Speed ≤ 4.57 m in 6 seconds for height > 159 cm

Time ≥6sforheight>159cm •Men:

•Men: Speed ≤ 4.57 m in 7 seconds for height ≤ 173 cm

Time ≥ 7 s for height ≤ 173 cm Speed ≤ 4.57 m in 6 seconds for height >173 cm

Time ≥ 6 s for height > 173 cm

weakness

note: Criteria for men in the Women’s Health and Aging Studies column extrapolated.

abbreviations: BMI = Body mass index, m = meters.

source: References 2, 7.

characteristics cardiovascular health study women’s health and aging studies

Grip strength

•Women:

≤ 17 kg for BMI ≤ 23

≤ 17.3 kg for BMI 23.1-26

≤18 kg for BMI 26.1-29

≤ 21 kg for BMI > 29

•Men:

≤ 29 kg for BMI ≤ 24

≤ 30 kg for BMI 24.1-26

≤ 30 kg for BMI 26.1-28

≤ 32 kg for BMI > 28

undersTandinG frailTy in The GeriaTric PoPulaTion

DALIRESP™ (roflumilast) tablets Rx OnlyBrief Summary of Full Prescribing InformationInitial U.S. Approval: 2011

INDICATIONS AND USAGEDALIRESP™ is indicated as a treatment to reduce the risk of COPDexacerbations in patients with severe COPD associated with chronicbronchitis and a history of exacerbations.Limitations of UseDALIRESP is not a bronchodilator and is not indicated for the reliefof acute bronchospasm.

CONTRAINDICATIONSThe use of DALIRESP is contraindicated in the following conditions:Moderate to severe liver impairment (Child-Pugh B or C) [seeClinical Pharmacology (12.3)and Use in Special Populations (8.6)].

WARNINGS AND PRECAUTIONSTreatment of Acute BronchospasmDALIRESP is not a bronchodilator and should not be used for therelief of acute bronchospasm.Psychiatric Events including SuicidalityTreatment with DALIRESP is associated with an increase in psychi-atric adverse reactions. In 8 controlled clinical trials 5.9% (263) ofpatients treated with DALIRESP 500 mcg daily reported psychiatricadverse reactions compared to 3.3% (137) treated with placebo.The most commonly reported psychiatric adverse reactions wereinsomnia, anxiety, and depression which were reported at higherrates in those treated with DALIRESP 500 mcg daily (2.4%, 1.4%,and 1.2% for DALIRESP versus 1.0%, 0.9%, and 0.9% for placebo,respectively) [see Adverse Reactions (6.1)]. Instances of suicidalideation and behavior, including completed suicide, have beenobserved in clinical trials. Three patients experienced suicide-relatedadverse reactions (one completed suicide and two suicide attempts)while receiving DALIRESP compared to one patient (suicidalideation) who received placebo.Before using DALIRESP in patients with a history of depressionand/or suicidal thoughts or behavior, prescribers should carefullyweigh the risks and benefits of treatment with DALIRESP in suchpatients. Patients, their caregivers, and families should be advisedof the need to be alert for the emergence or worsening of insomnia,anxiety, depression, suicidal thoughts or other mood changes,and if such changes occur to contact their healthcare provider.Prescribers should carefully evaluate the risks and benefits of con-tinuing treatment with DALIRESP if such events occur.Weight DecreaseWeight loss was a common adverse reaction in DALIRESP clinicaltrials and was reported in 7.5% (331) of patients treated withDALIRESP 500 mcg once daily compared to 2.1% (89) treated withplacebo [see Adverse Reactions (6.1)]. In addition to being reportedas adverse reactions, weight was prospectively assessed in twoplacebo-controlled clinical trials of one year duration. In these stud-ies, 20% of patients receiving roflumilast experienced moderateweight loss (defined as between 5-10% of body weight) comparedto 7% of patients who received placebo. In addition, 7% of patientswho received roflumilast compared to 2% of patients receivingplacebo experienced severe (>10% body weight) weight loss.During follow-up after treatment discontinuation, the majority ofpatients with weight loss regained some of the weight they had lostwhile receiving DALIRESP. Patients treated with DALIRESP shouldhave their weight monitored regularly. If unexplained or clinicallysignificant weight loss occurs, weight loss should be evaluated, anddiscontinuation of DALIRESP should be considered.Drug InteractionsA major step in roflumilast metabolism is the N-oxidation ofroflumilast to roflumilast N-oxide by CYP3A4 and CYP1A2. Theadministration of the cytochrome P450 enzyme inducer rifampicinresulted in a reduction in exposure, which may result in a decreasein the therapeutic effectiveness of DALIRESP. Therefore, the useof strong cytochrome P450 enzyme inducers (e.g. rifampicin,phenobarbital, carbamazepine, phenytoin) with DALIRESP is notrecommended. [see Drugs That Induce Cytochrome P450 (CYP)Enzymes (7.1) and Clinical Pharmacology (12.3)].

ADVERSE REACTIONSThe following adverse reactions are described in greater detail inother sections:

• Psychiatric Events Including Suicidality [see Warnings andPrecautions (5.2)]

• Weight Decrease [see Warnings and Precautions (5.3)]Adverse Reactions in Clinical StudiesBecause clinical trials are conducted under widely varying condi-tions, adverse reaction rates observed in the clinical trials of a drugcannot be directly compared to rates in the clinical trials of anotherdrug and may not reflect the rates observed in practice.The safety data described below reflect exposure of 4438 patients toDALIRESP 500 mcg once daily in four 1-year placebo-controlled tri-als, two 6-month placebo-controlled trials, and two 6-month drugadd-on trials [see Clinical Studies (14.1)]. In these trials, 3136 and1232 COPD patients were exposed to DALIRESP 500 mcg once dailyfor 6 months and 1-year, respectively.

The population had a median age of 64 years (range 40-91), 73%were male, 92.9% were Caucasian, and had COPD with a mean pre-bronchodilator forced expiratory volume in one second (FEV1) of8.9 to 89.1% predicted. In these trials, 68.5% of the patients treatedwith DALIRESP reported an adverse reaction compared with 65.3%treated with placebo.The proportion of patients who discontinued treatment due toadverse reaction was 14.8% for DALIRESP-treated patients and9.9% for placebo-treated patients. The most common adversereactions that led to discontinuation of DALIRESP were diarrhea(2.4%) and nausea (1.6%).Serious adverse reactions, whether considered drug-related or notby the investigators, which occurred more frequently in DALIRESP-treated patients include diarrhea, atrial fibrillation, lung cancer,prostate cancer, acute pancreatitis, and acute renal failure.Table 1 summarizes the adverse reactions reported by ≥ 2% ofpatients in the DALIRESP group in 8 controlled COPD clinical trials.

Table 1: Adverse Reactions Reported by ≥ 2% of PatientsTreated with DALIRESP 500 mcg daily and Greater Than Placebo

TreatmentAdverse Reactions DALIRESP Placebo(Preferred Term) (N=4438) (N=4192)

n (%) n (%)Diarrhea 420 (9.5) 113 (2.7)Weight decreased 331 (7.5) 89 (2.1)Nausea 209 (4.7) 60 (1.4)Headache 195 (4.4) 87 (2.1)Back pain 142 (3.2) 92 (2.2)Influenza 124 (2.8) 112 (2.7)Insomnia 105 (2.4) 41 (1.0)Dizziness 92 (2.1) 45 (1.1)Decreased appetite 91 (2.1) 15 (0.4)Adverse reactions that occurred in the DALIRESP group at afrequency of 1 to 2% where rates exceeded that in the placebo groupinclude:Gastrointestinal disorders - abdominal pain, dyspepsia, gastritis,vomitingInfections and infestations - rhinitis, sinusitis, urinary tract infection,Musculoskeletal and connective tissue disorders - muscle spasmsNervous system disorders - tremorPsychiatric disorders - anxiety, depression

DRUG INTERACTIONSA major step in roflumilast metabolism is the N-oxidation ofroflumilast to roflumilast N-oxide by CYP3A4 and CYP1A2 [seeClinical Pharmacology (12.3)].Drugs That Induce Cytochrome P450 (CYP) EnzymesStrong cytochrome P450 enzyme inducers decrease systemicexposure to roflumilast and may reduce the therapeutic effective-ness of DALIRESP. Therefore the use of strong cytochrome P450inducers (e.g., rifampicin, phenobarbital, carbamazepine, and pheny-toin) with DALIRESP is not recommended [see Drug Interactions(5.4) and Clinical Pharmacology (12.3)].Drugs That Inhibit Cytochrome P450 (CYP) EnzymesThe co-administration of DALIRESP (500 mcg) with CYP3A4inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2simultaneously (e.g., erythromycin, ketoconazole, fluvoxamine,enoxacin, cimetidine) may increase roflumilast systemic exposureand may result in increased adverse reactions. The risk of suchconcurrent use should be weighed carefully against benefit. [seeClinical Pharmacology (12.3)].Oral Contraceptives Containing Gestodene and Ethinyl EstradiolThe co-administration of DALIRESP (500 mcg) with oral contracep-tives containing gestodene and ethinyl estradiol may increaseroflumilast systemic exposure and may result in increased sideeffects. The risk of such concurrent use should be weighedcarefully against benefit [see Clinical Pharmacology (12.3)].

USE IN SPECIFIC POPULATIONSPregnancyTeratogenic effects: Pregnancy Category C: There are no adequateand well controlled studies of DALIRESP in pregnant women.DALIRESP was not teratogenic in mice, rats, or rabbits. DALIRESPshould be used during pregnancy only if the potential benefitjustifies the potential risk to the fetus.DALIRESP induced stillbirth and decreased pup viability in miceat doses corresponding to approximately 16 and 49 times, respec-tively, the maximum recommended human dose (MRHD) (ona mg/m2 basis at maternal doses > 2 mg/kg/day and 6 mg/kg/day,respectively). DALIRESP induced post-implantation loss in rats atdoses greater than or equal to approximately 10 times the MRHD(on a mg/m2 basis at maternal doses ≥ 0.6 mg/kg/day). No treat-ment-related effects on embryo-fetal development were observedin mice, rats, and rabbits at approximately 12, 3, and 26 times theMRHD, respectively (on a mg/m2 basis at maternal doses of 1.5,0.2, and 0.8 mg/kg/day, respectively).

Nonteratogenic effects: DALIRESP has been shown to adverselyaffect pup post-natal development when dams were treated with thedrug during pregnancy and lactation periods in mice. These studiesfound that DALIRESP decreased pup rearing frequencies at approx-imately 49 times the MRHD (on a mg/mg2 basis at a maternal doseof 6 mg/kg/day) during pregnancy and lactation. DALIRESP alsodecreased survival and forelimb grip reflex and delayed pinnadetachment in mouse pups at approximately 97 times the MRHD(on a mg/m2 basis at a maternal dose of 12 mg/kg/day) duringpregnancy and lactation.Labor and DeliveryDALIRESP should not be used during labor and delivery. There areno human studies that have investigated effects of DALIRESP onpreterm labor or labor at term; however, animal studies showed thatDALIRESP disrupted the labor and delivery process in mice.DALIRESP induced delivery retardation in pregnant mice at dosesgreater than or equal to approximately 16 times the MRHD (on amg/m2 basis at a maternal dose of > 2 mg/kg/day).Nursing MothersRoflumilast and/or its metabolites are excreted into the milk oflactating rats. Excretion of roflumilast and/or its metabolites intohuman milk is probable. There are no human studies that haveinvestigated effects of DALIRESP on breast-fed infants. DALIRESPshould not be used by women who are nursing.Pediatric UseCOPD does not normally occur in children. The safety and effective-ness of DALIRESP in pediatric patients have not been established.Geriatric UseOf the 4438 COPD subjects exposed to DALIRESP for up to 12months in 8 controlled clinical trials, 2022 were > 65 years of ageand 471 were > 75 years of age. No overall differences in safety oreffectiveness were observed between these subjects and youngersubjects and other reported clinical experience has not identifieddifferences in responses between the elderly and younger patients,but greater sensitivity of some older individuals cannot be ruled out.Based on available data for roflumilast, no adjustment of dosage ingeriatric patients is warranted [see Clinical Pharmacology (12.3)].Hepatic ImpairmentRoflumilast 250 mcg once daily for 14 days was studied in subjectswith mild-to-moderate hepatic impairment classified as Child-PughA and B (8 subjects in each group). The AUCs of roflumilast androflumilast N-oxide were increased by 51% and 24%, respectivelyin Child-Pugh A subjects and by 92% and 41%, respectively in Child-Pugh B subjects, as compared to age-, weight- and gender-matchedhealthy subjects. The Cmax of roflumilast and roflumilast N-oxidewere increased by 3% and 26%, respectively in Child-Pugh Asubjects and by 26% and 40%, respectively in Child-Pugh Bsubjects, as compared to healthy subjects. DALIRESP 500 mcg hasnot been studied in hepatically impaired patients. Clinicians shouldconsider the risk-benefit of administering DALIRESP to patients whohave mild liver impairment (Child-Pugh A). DALIRESP is notrecommended for use in patients with moderate or severe liverimpairment (Child-Pugh B or C) [see Contraindications (4) andClinical Pharmacology (12.3)].Renal ImpairmentIn twelve subjects with severe renal impairment administered asingle dose of 500 mcg roflumilast, the AUCs of roflumilast androflumilast N-oxide were decreased by 21% and 7%, respectivelyand Cmax were reduced by 16% and 12%, respectively. No dosageadjustment is necessary for patients with renal impairment [seeClinical Pharmacology (12.3)].

OVERDOSAGEHuman ExperienceNo case of overdose has been reported in clinical studies withDALIRESP. During the Phase I studies of DALIRESP, the followingsymptoms were observed at an increased rate after a single oraldose of 2500 mcg and a single dose of 5000 mcg: headache,gastrointestinal disorders, dizziness, palpitations, lightheadedness,clamminess and arterial hypotension.Management of OverdoseIn case of overdose, patients should seek immediate medical help.Appropriate supportive medical care should be provided. Sinceroflumilast is highly protein bound, hemodialysis is not likely to bean efficient method of drug removal. It is not known whetherroflumilast is dialyzable by peritoneal dialysis.Manufactured by:Nycomed GmbHProduction Site OranienburgLehnitzstrasse 70 – 9816515 OranienburgGermanyManufactured for:Forest Pharmaceuticals, Inc.Subsidiary of Forest Laboratories, Inc.St. Louis, MO 63045, USA© 2010 Forest Laboratories, Inc.84-1020598-BS-RMC17137-FEB11Please also see full Prescribing Information at www.daliresp.com

72341fo_a-b 3 7/6/11 5:36 PM

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undersTandinG frailTy in The GeriaTric PoPulaTion

(Table 2).

interventionsSome researchers think that frailty can be prevented or even reversed. To do this, we need to know more about frailty’s individual components—low grip strength, low energy, slowed walking speed, low physical activity, and unintentional weight loss—and what causes them. Since frailty occurs on a continuum, addressing it means assessing the individual patient and matching interven-tions to the patient’s physical, psychological, social, and environmental needs.20 Intuitively, we can see that a healthy, active lifestyle is the cornerstone of preventing frailty. Many researchers propose resistance exercise that can reverse some muscle loss and improve functioning. The results of clinical trials are difficult to interpret and inconsistent, since the “dose” of exercise is difficult to define, and many patients have trouble adhering to regu-lar exercise routines. Additionally, a “dose” of exercise that is too high could be harmful.21-24

Intuitively, we can see that a healthy, active lifestyle is the cornerstone of preventing frailty.

Recognizing frailty as a complicating factor can help clinicians work with elders and their families. If surgery is necessary, for example, clinicians should be realistic about the elevated risk and potential discharge to a long-term care facility (if the patient is community-dwelling).16 In fact, when the health care team proposes any change in care, including a new medication, they should be prepared to discuss whether the frail patient may react differently than others to the proposed inter-vention. They should also describe how the intervention may affect cognition, memory, energy, or function directly and honestly.25

In the case of medication, many clinicians believe the frail elderly are more vulnerable to adverse drug reactions. A recent study of 377 patients 65 years of age or older found no association between degree of frailty and a patient’s risk of adverse drug reactions. It also

found that the greatest risk factor for an adverse drug reaction was the number of new medications recently added to a patient’s medication regimen.26

Pharmacists, recognizing that certain comorbidities are likely to occur, can address frailty using careful drug regimen reviewing, with an eye toward reducing unnec-essary polypharmacy.17 In the frail elderly, it is prudent to studiously avoid unnecessary drugs. The Beers criteria, which list drugs inappropriate for use in elders 65 years of age or older, can provide a beginning framework for eliminating unnecessary drugs. But these criteria do not include additional drugs that are not appropriate for significantly older or more frail persons.27,28 In particular, pharmacists should be wary of drugs that cause fatigue as a side effect. Additionally, they should recognize that many frail elders will have osteoarthritis and need analgesics, but pain is also independently associated with frailty.18 Using the basic precepts of pain management is critical.

Early findings in community-dwelling older women suggest that mildly low and low-normal hemoglobin levels increase frailty risk, and comorbid cardiovascular disease also increases this risk. This identifies another potentially modifiable risk factor for frailty that pharma-cists can address with the health care team.29

l Polypharmacy l Osteoarthritis l Analgesic use l Heart failure and cardiovascular disease l Risk of falling l Depressive symptoms l Cognitive dysfunction

Sorted by strength of association, i.e., polypharmacy strongest, cognitive function weakest

source: Adapted from References 2, 17-19.

Table 2. commorbidities and conditions

associated with frailty

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end noteFrailty can take on a poetic persona; “human frailty” is used to explain mistakes and excuse indiscretions. For residents of long-term care facilities, however, frailty is an energy-robbing presence that signifies life is coming to an end. Finding ways to prevent and reverse frailty could empty many long-term care beds. n

Jeannette Y. Wick, RPh, MBA, FASCP, is a senior clinical research pharmacist, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. She is a contributor to The Consultant Pharmacist. Views expressed in this article are those of the authors and not those of any government agency. Consult Pharm 2011;26:634-45. © 2011 American Society of Consultant Pharmacists, Inc. All rights reserved. Doi:10.4140/TCP.n.2011.634.

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