Geriatrics

Geriatrics
Jennifer P. Dugan, Pharm.D., BCPS
Clinical Assistant Professor
University of Colorado
Colorado, Denver

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Geriatrics

Learning Objectives:

The following case pertains to questions 2 and 3.
J.T. is an 82-year-old community-dwelling woman with a history of stage III Parkinson disease, hypertension, and urinary incontinence (UI). She is receiving carbidopa/levodopa, pramipexole, selegiline, tolterodine, diazepam, metoprolol, and hydrochlorothiazide. When she comes to your pharmacy to get her prescriptions, she walks slowly with a cane, and she is stooped over.

1. Identify age-related pharmacokinetic and pharmacodynamic changes in older people.
2. Evaluate the pharmacotherapy regimens of older people to support the maintenance of optimal physical and mental function.
3. Identify inappropriate medication prescribing in older people.
4. Recommend appropriate pharmacotherapy for patients with dementia.
5. Evaluate the risks and benefits of the use of antipsychotics (APs) (including atypical APs) in older patients with dementia.
6. Recommend appropriate interventions for patients suffering from behavioral symptoms related to dementia. 7. Identify the types of urinary incontinence and recommend appropriate treatments.
8. Given a patient’s American Urology Association
Symptom Index for benign prostatic hyperplasia, recommend appropriate therapy.
9. Recommend appropriate analgesic therapy for older patients with osteoarthritis.
10. Discuss risks and benefits of medication classes used to treat rheumatoid arthritis.

2. Which of the following is the single most important intervention you can make to reduce her risk of falls? A. Suggest to J.T. that her neurologist reassess her Parkinson disease medications.
B. Advise J.T. that she should speak to her internist about discontinuing diazepam.
C. Suggest to J.T. that she see a physical therapist to institute a therapeutic exercise program. D. Take J.T.’s BP to rule out postural effects from treatment of her disease conditions.
3. While picking up her prescriptions at your pharmacy, J.T. buys incontinence supplies. She confides in you that her incontinence is severer because she cannot get to the bathroom in time.
On further questioning, you learn that J.T. believes her slowed movement is a worsening problem.
Which one of the following types of incontinence does J.T. describe?

Self-Assessment Questions:
Answers to these questions may be found at the end of this chapter.

A.
B.
C.
D.

1. R.J. is a 79-year-old woman you see in the clinic who has a history of mild dementia (Mini-Mental
State Examination [MMSE] 23/30), hypertension, hypothyroid, depression, and neuropathic pain.
She has been taking atenolol 25 mg twice daily, levothyroxine 125 mcg/day, amitriptyline 25 mg at bedtime, and citalopram 20 mg/day. Her husband reports that she has been more confused in the past
2 weeks. R.J.’s laboratory values are within normal limits, including a normal thyroid-stimulating hormone (TSH) and negative urinalysis. Her blood pressure (BP) is 145/85 mm Hg and heart rate (HR) is 65 beats/minute. Which one of the following is the most likely contributor to her confusion?

Stress incontinence.
Urge incontinence.
Functional incontinence.
Overactive bladder.

4. An 85-year-old woman is taking ferrous sulfate to treat an iron deficiency anemia. Changes in which one of the following pharmacokinetic properties associated with aging can alter the expected outcome to treatment?
A. Absorption.
B. Distribution.
C. Metabolism.
D. Renal elimination.

A. Her depression is not adequately treated.
B. Amitriptyline has anticholinergic effects.
C. Her dementia is worsening.
D. Her urinalysis is falsely negative and should be repeated. The following case pertains to questions 5–8.
W.G. is a 75-year-old African American man with coronary artery disease, hypertension, type 2 diabetes mellitus, chronic low back pain caused by osteoarthritis
(OA) of the spine, peripheral neuropathy, and benign

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prostatic hypertrophy (BPH). W.G. weighs 72 kg, and his serum creatinine (SCr) is 1.4 mg/dL. W.G.’s medications include metoprolol extended release 50 mg 2 times/ day, lisinopril 20 mg/day, metformin 1000 mg 2 times/ day, gabapentin 900 mg 3 times/day, glipizide extended release 10 mg/day, citalopram 20 mg/day, acetaminophen 1000 mg 3 times/day, Tylenol PM as needed at night, and hydrocodone-acetaminophen 5/500 1 tablet as needed for pain every 4–6 hours.

D. NPI score of 20/120.
10. Initiating a cholinesterase inhibitor in a patient with Alzheimer’s disease may improve cognition but worsen which one of the following?
A. Hypertension.
B. Depression.
C. Hallucinations.
D. Urge incontinence.

5. Based on pharmacokinetic changes in W.G., for which one of the following medications should the dosage be reduced?

The following case on L.M. pertains to questions 11–14.
L.M. is a 92-year-old woman who is admitted to a nursing facility after treatment of urosepsis at the local hospital. Her diagnoses include hypertension, generalized anxiety disorder, dementia, transient ischemic attacks, frequent urinary tract infections, OA, and incontinence. L.M.’s medications include aspirin 81 mg/day, a multivitamin daily, amlodipine 5 mg/day, omeprazole
20 mg at night, sertraline 100 mg/day, cranberry capsules 4 times/day, donepezil 10 mg at night, lorazepam
0.5 mg every 8 hours as needed for anxiety, quetiapine
25 mg 3 times/day, and the house bowel regimen. L.M. weighs 62 kg; her laboratory parameters are within normal limits except for an SCr of 1.5 mg/dL and blood urea nitrogen of 22 mg/dL. Her Tinetti fall risk assessment is 9/28 (high risk), MMSE is 21/30, and Geriatric
Depression Scale (GDS) is 1/15 (low risk).

A. Metoprolol.
B. Metformin.
C. Glipizide.
D. Gabapentin.
6. For W.G., which one of the following is most strongly linked to his likelihood of experiencing a medication adverse event?
A.
B.
C.
D.

Advanced age.
Use of many medications.
Diagnosis of lower back pain.
Renal insufficiency.

7. For W.G., which one of the following interventions should be implemented to avoid liver toxicity?

11. L.M. is somnolent for most of the day and unable to participate in activities on the unit. Which one of the following interventions is recommended?

A. Decrease the dose of gabapentin.
B. Decrease the dose of glipizide.
C. Decrease the dose of acetaminophen from all sources. D. Discontinue metformin.

A. Reduce the dose of quetiapine over 1 month and discontinue.
B. Discontinue donepezil.
C. Add a 7-day course of levofloxacin.
D. Discontinue the cranberry supplement.

8. For W.G., which one of the following drugs should be discontinued to avoid urinary symptoms from
BPH?

12. Based on this patient’s medication regimen, which one of the following is L.M. at increased risk of?

A. Tylenol PM.
B. Glipizide.
C. Citalopram.
D. Hydrocodone with acetaminophen.

A. Agitation.
B. Weight loss.
C. Death.
D. Pain.

9. A patient with a recent diagnosis of Alzheimer’s disease is considering treatment with a cholinesterase inhibitor. Which one of the following parameters best justifies therapy initiation?

13. L.M. is combative during her personal hygiene care in the morning, which is a change in behavior for this patient. Which one of the following is the best approach to this behavioral problem?

A. MMSE score of 20/30.
B. Neuropsychiatric Inventory (NPI) score of
75/120.
C. MMSE score of 10/30.

A. Treat L.M. with acetaminophen 500 mg 3 times/day for pain.

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B. Avoid confrontation with L.M. and discontinue the personal care.
C. Allow L.M. to sleep longer in the morning to avoid fatigue.
D. Evaluate L.M. for reversible causes of combative behavior.
14. The nursing staff wants to initiate analgesic treatment of L.M.’s OA. Which one of the following is the best therapy to recommend?
A.
B.
C.
D.

Ibuprofen 200 mg 4 times/day.
Acetaminophen 650 mg 3 times/day.
Tramadol 25 mg 3 times/day.
Oxycodone 5 mg 4 times/day.

15. S.C. is a 69-year-old woman with a history of rheumatoid arthritis admitted to a nursing facility after a 2-week hospitalization for sepsis. She reports pain in her hands and wants treatment. Her laboratory tests are within normal limits, except for SCr
1.2 and glucose 180. Which one of the following is preferred? A.
B.
C.
D.

Start etanercept.
Start naproxen.
Start prednisone.
Start golimumab.

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I. Principles to Promote Optimal Medication Use in Older People
A. General Information About Aging in the United States
1. Aging is a process that converts healthy adults into frail adults with diminished reserves in physiologic processes and increased vulnerability to many diseases and death.
a. The United States is projected to have 50 million people older than 65 years by 2020, 70 million by 2030, and 80 million by 2050.
b. Even more dramatic increases are projected for people older than 85 years: 6 million by
2020, 8 million by 2030, and more than 18 million by 2050.
c. If a person survives to age 65, it is likely he or she will live an additional 13–20 years.
d. If a person survives to age 85, it is likely he or she will live an additional 6–7 years.
2. There is a large amount of heterogeneity in older people; some people live independently into their 90s and beyond, whereas others become frail and dependent at a younger age.
3. Measurement of aging with years of life is insensitive to the differences between older people.
4. The elderly consist of about 13% of the population, but they are also responsible for:
a. 34% of pharmaceutical spending
b. 36% of hospital stays
c. 40% of medication-related hospitalizations
d. 50% of medication-related deaths
5. At least $30 billion/year is spent on medication-related morbidity.
B. Optimal Pharmacotherapy in Older People
1. An optimal pharmacotherapy regimen is one in which patients receive effective medications to treat conditions in the correct doses and dosage forms for the appropriate duration.
Whenever possible, the agent should be chosen to avoid drug-induced loss of patient function and drug-related problems.
2. The doses of many medications must be adjusted in older people because of age-associated changes in drug pharmacokinetics and pharmacodynamics.
3. Drug pharmacokinetic changes
Table 1. Physiologic Changes with Age That May Change Drug Pharmacokinetics
Organ System

Physiologic Change with Aging

Resulting Effect on Pharmacokinetics

Gastrointestinal

á Stomach pH â Gastrointestinal bloodflow
Slowed gastric emptying
Slowed gastrointestinal transit
Thinning of dermis
Loss of subcutaneous fat

â Absorption of some drugs and nutrients â In first-pass extraction/metabolism
Rate of absorption may be prolonged

â Total body water â Lean body mass á Body fat â Or unchanged serum albumin á a1-Acid glycoprotein

á Volume of distribution and accumulation of lipid-soluble drugs Liver

â Liver mass â Bloodflow to the liver â Or no change in cytochrome P450 enzymes No change in phase II drug metabolism â Or no change in phase I metabolism á Half-life and â clearance of drugs with a high first-pass extraction/metabolism Renal

â Glomerular filtration rate âRenal bloodflow â Tubular secretion â Renal mass

â Renal elimination of many medications á Half-life of renally eliminated drugs and metabolites

Skin
Body
composition

â Or no change to drug reservoir formation with transdermal formulation â Volume of distribution of water-soluble drugs

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a. Absorption
i. Iron, vitamin B12, and calcium are decreased with hypo- or achlorhydria. ii. Slower gastric emptying can increase risk of ulceration from aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs). iii Most drugs are absorbed by passive diffusion without significant changes with aging. iv. Transdermal formulations usually require a subcutaneous fat layer to form a drug reservoir for absorption. Use with caution in individuals who are small or cachetic.
b. Distribution
i. Lipid-soluble benzodiazepines have an increased half-life in older people. ii. Highly albumin-bound drugs such as phenytoin may have a larger fraction of free
(active) drug. iii. P-glycoprotein, an efflux transporter for several organs including the brain, is decreased with aging, which may lead to higher brain concentrations of medications.
c. Metabolism
i. Morphine and propranolol clearance are substantially reduced because of a reduction in first-pass metabolism. ii. Changes in metabolism through phase I (oxidative) and cytochrome P450 (CYP) enzymes are variable and confounded by age, sex, concomitant drugs, and genetics. iii. Lorazepam, oxazepam, and temazepam are dependent on phase II metabolism and are less affected by age-related changes in metabolism.
d. Elimination
i. Drugs eliminated through glomerular filtration must be dosed on the basis of the patient’s estimated renal function. ii. The Cockcroft-Gault equation is the most widely accepted method to estimate creatinine clearance in the elderly. iii. The four-variable Modification of Diet in Renal Disease equation is the most accepted method to estimate glomerular filtration rate for diagnosing chronic kidney disease. Table 2. Differences in CrCl Estimation with Accepted Formulas
Patient
85-year-old person with a serum creatinine of 1 mg/dL
5′4′′ white woman weighing 60 kg

Cockcroft-Gault
(mL/minute)

BSA-Adjusted
Cockcroft-Gault
(mL/minute/1.73m2)
41

Four-Variable MDRD
(chronic kidney disease stage)

56 mL/minute/1.73m 2
(stage 3)
5′4′′ black woman weighing 60 kg 39
41
68 mL/minute/1.73m 2
(stage 2)
5′10′′ white man weighing 75 kg
57
51
75 mL/minute/1.73m 2
(stage 2)
5′10′′ black man weighing 75 kg
57
51
91 mL/minute/1.73m 2
Cockcroft-Gault: CrCl = [(140 − age) × weight in kg]/[(72 × serum creatinine)] × 0.85 if female
[use actual weight if it is less than ideal body weight]
BSA-adjusted Cockcroft-Gault: (Cockcroft-Gault/Patient’s BSA) × 1.73 m 2/BSA
Four-variable MDRD: eGFR= 186 × [serum creatinine]-1.154 × [age]-0.203 × [0.742 if female] × [1.210 if African
American]
39

BSA = body surface area; CrCl = creatinine clearance; eGFR = estimated glomerular filtration rate; MDRD = Modification of
Diet in Renal Disease (study).

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4. Drug pharmacodynamic changes
a. Change in receptor number and/or affinity
i. More sensitive to benzodiazepines ii. More sensitive to opioids iii. Increased response to warfarin iv. Decreased response to β-blockers
v. More sensitive to extrapyramidal effects and tardive dyskinesia
b. Age-related changes in homeostatic response
i. Decreased baroreceptor response leading to orthostatic hypotension ii. Sodium and water conservation iii. Mobility and balance
5. Drug-related problems in the older person
a. Overuse of medications
i. May be the result of prescribing cascade ii. Puts patient at higher risk of adverse drug effects and drug interactions
b. Underuse of medications
i. May include aspirin, angiotensin-converting enzyme inhibitors, β-blockers, pain medications, thrombolytics, antidepressants, and osteoporosis treatment ii. Fear of falls may lead to underuse of warfarin, even in high-risk patients.
c. Nonadherence
i. Intentional nonadherence is related to a patient’s beliefs about treatment, including the need for it and concerns about adverse effects. ii. Unintentional nonadherence results from practical barriers such as misunderstanding instructions, forgetfulness, or lack of resources to pay for treatment.
d. Use of inappropriate medications
e. Adverse drug events
f. Drug interactions
6. Function in the elderly
a. Good function may be more important than duration of life.
b. Physical function is evaluated through one’s ability to complete basic and instrumental activities of daily living (ADLs and IADLs).
c. Many elderly people are also screened for their risk of falls with instruments that evaluate gait and balance.
d. Activities of daily living (ADLs)
i. Feeding ii. Dressing iii. Bathing iv. Toileting
v. Ambulation vi. Transferring
e. Instrumental activities of daily living (IADLs)
i. Cleaning ii. Writing/reading iii. Managing medications iv. Shopping
v. Cooking vi. Managing money

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f. Mental function is evaluated with mental status examinations and additional screening for depression. g. It is important to consider the role of drugs on function in the elderly.
h. Examples of medications that can improve function in the elderly
i. Diuretics can improve dyspnea in heart failure. ii. Analgesics can decrease pain. iii. Bronchodilators can improve dyspnea in chronic obstructive pulmonary disease. iv. Antidepressants can decrease anhedonia.
Table 3. Function and Medications
Example Drugs That May Impair
Function

Interventions That May Promote
Function

Glucocorticosteroids
Long-term use of proton pump inhibitors Phenytoin

Vitamin D
Calcium
Bisphosphonates
Resistance exercises

Balance/dizziness/falls

Sedative hypnotics
Antihypertensives
Long half-life benzodiazepines
Large doses of benzodiazepines
Tricyclic antidepressants (TCAs)
Antipsychotics
Anticonvulsants

Tai chi exercises
Correction of vision problems
Environmental evaluation to remove hazards Reduction in polypharmacy

Extrapyramidal symptoms

Typical antipsychotics
Metoclopramide

Functional Domain
Mobility
Bone and muscle integrity

Mental state
Anticholinergic agents
Benzodiazepines
Pentazocine
Skeletal muscle relaxants
Amitriptyline, TCAs
Gastrointestinal antispasmodics
Diphenhydramine, antihistamines

Reading, playing games, and working puzzles Exercise
Cholinesterase inhibitors (CIs)

Methyldopa
Reserpine
Anastrozole
Interferon a-2b
Tamoxifen

Socialization
Cognitive behavioral therapy
Health promotion interventions
Appropriate use of antidepressants

Anticholinergics α-Blockers α-Agonists
Alcohol
Acetylcholinesterase inhibitors
Diuretics

Toileting schedules
Pelvic floor exercises
Proper diagnosis of incontinence with individualized treatment

Emotional state

Continence

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Patient Case
1. N.H. is an 85-year-old woman who resides in a nursing home. She weighs 65 kg. Her medical history is significant for type 2 diabetes mellitus, hypertension, and moderate dementia, likely attributable to vascular changes.
Two years ago, she had a cerebrovascular accident, and 1 year ago, she had a right hip fracture. Her regularly scheduled medications include glyburide 10 mg/day, lisinopril 10 mg/day, metformin 500 mg 2 times/day, donepezil 10 mg/day, aspirin 81 mg/day, and a multivitamin daily. Her as-needed medications include zolpidem 5 mg/day as needed for sleep, meclizine 25 mg ½ tablet 3 times/day as needed for dizziness, and the house bowel regimen. When recommending medication changes for this patient, which one of the following functional assessments is most important to evaluate?
A.
B.
C.
D.

IADLs.
Assessment for depression.
Assessment for gait and balance.
Assessment for pressure sores.

2. Your further evaluation of N.H. reveals that she has not used any of her as-needed medications in 2 months.
In addition, her laboratory results reveal the following: fasting plasma glucose 90 mg/dL, sodium 138 mEq/L, potassium 4.5 mEq/L, chloride 102 mEq/L, CO2 25 mEq/L, blood urea nitrogen 30 mg/dL, SCr 1.8 mg/dL, and TSH 4.0 mU/L. Which one of the following pharmacokinetic parameters is most likely to be changed in N.H.?
A. Oral absorption.
B. Distribution.
C. Metabolism.
D. Renal excretion.
3. Based on your assessment of age- and disease-related changes in N.H., which one of the following areas of pharmacotherapy should be addressed first?
A.
B.
C.
D.

Diabetes treatment.
Alzheimer’s disease treatment.
Hypertension treatment.
Stroke prevention.

7. Potentially inappropriate medications
a. Presence of inappropriate medication use in the elderly is often used as a quality assurance measure.
b. Measures often include both medications/classes to avoid in general and medications to be avoided in certain diseases or conditions.
c. Beers List
i. Initially identified drugs with a high likelihood of causing problems in long-term care residents ii. Developed through a consensus criteria process iii. Refined during the past 10 years to improve applicability, including communitydwelling elderly iv. Examples include long half-life benzodiazepines, certain antihistamines, skeletal muscle relaxants, drugs with anticholinergic effects, some narcotics, and some
NSAIDs.
v. Limitations of using Beers List
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(a) Does not consider appropriate medications used inappropriately
(b) Does not consider other drug-related problems
(c) Addresses only medications about which a consensus could be reached
(d) Conflicting evidence exists on how the use of medications on Beers List affects function and mortality.

Patient Case (N.H. continued from above)
4. To maintain and improve function in N.H., which one of the following interventions should be implemented? A.
B.
C.
D.

Add a calcium and vitamin D supplement.
Add simvastatin 10 mg/day.
Add warfarin.
Assess for incontinence and treat with anticholinergic agents.

8. Creation of an optimal pharmacotherapy regimen
a. Use as few medications as possible.
b. Every drug used should have evidence-based literature to support treatment of the particular indication.
c. All drugs should be screened to avoid drug-drug and drug-disease interactions.
d. Evaluate the drug dose for possible adjustments caused by pharmacokinetic changes.
e. Evaluate the drug for proper therapy duration.
f. Avoid duplicate therapy.
g. Ensure it is affordable for patient.
h. Evaluate unexplained patient symptoms to rule out drug adverse effects.
II. DEMENTIA
A. Epidemiology
1. Dementia affects 4–5 million people in the United States.
2. Disease is strongly associated with advancing age.
a. 2% prevalence in 65 year olds
b. Up to 30% prevalence in 85 year olds
B. Definitions
1. Mild cognitive impairment
a. Transitional stage between normal aging and early dementia
b. 5%–25% will progress to develop dementia.
2. Delirium
a. Mental status change with recent onset and fluctuation
b. Includes two of the following:
i. Misinterpretation, illusions, hallucinations ii. Incoherent speech at times iii. Disturbance in sleep-wake cycle iv. Change in psychomotor activity
c. Usually related to medical illness or medications and is reversible
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3. Dementia
a. Progressive, irreversible decline in mental function, marked by memory impairment
b. Not a normal part of aging
c. Symptoms include functional disability, cognitive impairments, and behavioral and psychological symptoms.
C. Reversible Causes of Mental Status Change
1. Alcohol abuse
2. Normal pressure hydrocephalus
3. Thyroid dysfunction
4. Dehydration and electrolyte disturbance
5. Vitamin B12 deficiency
6. Medications
a. Anticholinergics and drugs with anticholinergic properties
b. Opioids
c. Glucocorticosteroids
d. Benzodiazepines and other sedative/hypnotics
e. Antiparkinsonian medications
D. Most Common Types of Dementia
1. Alzheimer’s disease
2. Lewy body dementia
3. Vascular causes of dementia
4. Frontotemporal lobe dementia (Pick disease)
5. Mixed dementia

Patient Case
5. An 85-year-old woman is assessed at a memory loss clinic to determine the cause of her dementia. Her most recent score on the MMSE is 24/30. Present diagnoses include Parkinson disease, hypothyroidism, and OA of both knees. She has had these conditions for more than 10 years, is stable, and is independent in her ADLs.
Her present medications include carbidopa/levodopa continuous release, trihexyphenidyl, celecoxib, levothyroxine, docusate, and bisacodyl. Which one of the following medication changes is best to consider first?
A.
B.
C.
D.

Add donepezil 5 mg/day.
Slow dosage reduction of carbidopa/levodopa.
Slow dosage reduction and discontinue trihexyphenidyl.
Replace celecoxib with acetaminophen.

E. Pathophysiology of Alzheimer’s Disease
1. Precise cause is not known.
2. Several interrelated causative factors
a. Genetics and the apolipoprotein E4 allele
b. Environment
c. Accumulation of β-amyloid
d. Tau
e. Inflammation
f. Neurotransmitter deficiency (acetylcholine, norepinephrine, serotonin)
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3. Common assessment instruments used for Alzheimer’s disease
a. Mental state
i. Folstein MMSE
(a) 30-point scale, with higher scores indicating better mental functioning
(b) If patient is untreated, score usually decreases 3 or 4 points a year. ii. Alzheimer Disease Assessment Scale – Cognitive (ADAS-cog)
(a) 70-point scale, with lower scores indicating better mental functioning
(b) Used in most research iii. St. Louis University Mental Status Examination (SLUMS)
(a) 30-point scale, with higher score indicating better mental functioning
(b) Similar to MMSE; adjust for education status iv. Mini-Cog Assessment
(a) Combines a clock-drawing test with a three-item recall test
(b) Used in clinical practice because of ease of administration (less than 5 minutes)
b. Function
i. Alzheimer Disease Cooperative Study Activities of Daily Living Inventory (ADCSADL): 54-point scale, with higher scores indicating better function ii. Functional Assessment Staging (FAST)
(a) 7-point scale
(b) 1 indicates normal adult, 7 indicates patient requires total care iii. Various scales to measure IADLs
c. Global assessment: Clinician Interview–Based Impression of Change (CIBIC-Plus) Plus
Caregiver Input
i. 7-point scale ii. 1 shows marked improvement, 7 shows marked deterioration, 4 is no change
F. Clinical Presentation and Classification
Table 4. Stages of Alzheimer’s Disease

Mild

Folstein MiniMental State
Examination (of 30)
20–24

Moderate

10–19

Severe

< 10

Examples of Cognitive Loss
Some short-term memory loss; word-finding problems

Examples of Functional Loss
Loss of IADLs such as laundry, housekeeping, and managing medications; may get lost in familiar places
Needs assistance with ADLs such as bathing, dressing, and toileting

Disorientation to time and place, inability to engage in activities and conversation
Loss of speech and ambulation, Dependency in basic ADLs such as incontinence of bowel and feeding oneself; often requires around-thebladder clock care

ADLs = activities of daily living; IADLs = instrumental activities of daily living.

G. Treatment
1. Goals
a. Treat cognitive symptoms.
b. Maintain function.
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2. Nonpharmacologic therapy
a. Education, particularly directed toward the caregiver
b. Reduction in environmental triggers
c. Optimal management of comorbid diseases
d. Environmental changes to create a serene environment
3. Pharmacologic therapy
Table 5. Comparison of Drugs for the Treatment of Alzheimer’s Disease
Starting
Dose
Cholinesterase inhibitors
Donepezil
5 mg/day
(Aricept);
donepezil oral disintegrating tablets (Aricept
ODT)
1.5 mg 2
Rivastigmine
times/day
(Exelon);
Rivastigmine patch (Exelon
Patch)

Maintenance Dosage
Dose
Forms

Pharmacologic
Properties

10 mg/day

Acetylcholinesterase inhibitor; metabolized in part by CYP2D6 and CYP3A4

5-, 10-, and 23-mg tablets, 5- and
May also
10-mg oral increase to 23 disintegrating mg/day tablets
3–6 mg 2
1.5-, 3-, 4.5-, times/day and 6-mg capsules; 2 mg/mL of oral solution

9-mg patch 18 mg patch
(delivers 4.6 (delivers 9.5 mg/day) mg/day)
4 mg 2
Galantamine
times/day
(Razadyne);
galantamine extended release
(Razadyne ER)

Glutamatergic therapy
Memantine
5 mg once
(Namenda)
daily

8–12 mg 2 times/day or
8–24 mg ER once daily

10 mg 2 times/day Acetyl and butylcholinesterase inhibitor. Cholinergic adverse effects of nausea, vomiting, and diarrhea seem more
Transdermal intense than with other patch delivers CIs drug over 24 hours 4-, 8-, 12-mg A selective tablets; 8-, competitive, 16-, 24-mg reversible inhibitor of extendedacetylcholinesterase release and a nicotine receptor modulator Metabolized capsules; 4 in part by CYP2D6 mg/mL of oral solution and CYP3A4
5- and 10-mg tablets; 2 mg/ mL of oral solution N-methyl-d-aspartate receptor antagonist that blocks glutamate transmission Comments
Labeled for mildmoderate and severe
Alzheimer’s disease.
Risk of bradycardia and syncope is increased with all CIs
Labeled for mildmoderate Alzheimer’s disease as well as mildmoderate dementia with
Parkinson disease

Preferable to administer with food. Syncope is seen more often at higher dosages

Labeled for use in patients with moderate to severe Alzheimer’s disease; may be used in combination with donepezil. In general, well tolerated but confusion sometimes seen CI = cholinesterase inhibitor; CYP = cytochrome P450; ER = extended release.

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Patient Case
6. An 87-year-old man with Alzheimer’s disease began therapy with rivastigmine. He has been titrated up to rivastigmine 6 mg 2 times/day. His family notes improvement in his functional ability but reports that he is experiencing nausea and vomiting that seem related to rivastigmine. Which one of the following is the best course to take?
A.
B.
C.
D.

Advise the patient to take his drug with an antacid.
Add prochlorperazine 25 mg by rectal suppository with each rivastigmine dose.
Discontinue rivastigmine and initiate memantine 5 mg twice daily.
Change rivastigmine to the daily patch that delivers 9.5 mg/day.

4. Review of consensus treatment guidelines from the American College of Physicians and
American Academy of Family Physicians
a. Therapy initiation
i. For patients with mild-moderate Alzheimer’s disease, begin therapy with a cholinesterase inhibitor when the benefits of treatment outweigh the risks and are consistent with individual patient goals. ii. Evidence from high-quality studies often shows statistically significant differences in measures of cognition, global assessment, and, occasionally, ADL function. iii. Often, the statistically significant differences found in the high-quality research are not deemed clinically meaningful. iv. A subset of patients may experience clinically meaningful improvement, but there is no way to determine who these individuals are before initiating therapy.
v. There is no evidence that any one cholinesterase inhibitor is better than another. vi. Results for memantine are similar to those for cholinesterase inhibitors: Statistically significant but not clinically meaningful changes. Memantine is labeled for use in patients with moderate-severe Alzheimer’s disease.
b. Therapy duration
i. Evaluation at 3–6 months for stabilization (prevention of decline) or improvement ii. Conflicting evidence exists regarding therapy discontinuation, should a patient decline or become unresponsive to treatment. iii. When prevention of decline is no longer a therapeutic goal for a patient, consider discontinuing drug treatment. iv. A taper is recommended if a patient is at a higher dose.
v. Rebound agitation may occur for the first 1–2 weeks.

Patient Case
7. R.A. is a 75-year-old woman with Alzheimer’s disease who has been treated with donepezil 10 mg/day for about 3 years. When she initiated therapy, her MMSE was 21/30, and her present MMSE is 17/30. R.A. is living at home with her husband. She cannot perform most IADLs but can perform most ADLs with cueing.
R.A.’s husband asks about changing her drug treatment to help maintain her function. Which one of the following is the best course of action?
A.
B.
C.
D.

Change her treatment from donepezil to rivastigmine.
Stop donepezil.
Add memantine 5 mg/day.
Add vitamin E 400 units 2 times/day.

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III. Behavioral symptoms of dementia
A. Epidemiology
1. More than 50% of people with dementia have significant behavioral and psychological symptoms.
2. These symptoms are associated with high rates of disability and functional decline, poor health outcomes, physical injury, increased rates of nursing home placement, greater use of emergency services, and difficulty with nurse retention.
B. Types of Behavioral Symptoms
1. Psychosis
a. Delusions
b. Paranoia
c. Hallucinations
2. Agitation
a. Aggression and combativeness
b. Hyperactivity (wandering and pacing)
c. Hyper-vocalization
d. Disinhibition
C. Measurement of Behavioral Symptoms
1. Neuropsychiatric Inventory (NPI)
a. 144-point scale
b. Higher scores indicate severer behavioral problems.
2. Behavioral Pathology in Alzheimer’s Disease (BEHAVE-AD)
a. 75-point scale
b. Higher scores indicate more behavioral problems.
3. Cohen-Mansfield Agitation Inventory (CMAI)
a. 203-point scale
b. Higher scores indicate more behavioral problems.
4. Scales are not always used; generally, clinicians identify “target behavior.”
D. Management of Behavioral Symptoms
1. Determine the cause.
a. Pain
b. Constipation
c. Hunger and dehydration
d. Depression
e. Fear
f. Anxiety
g. Loss of sleep
h. Infection
i. Drug adverse effects
2. The 5 Rs
a. Reassess
b. Reconsider
c. Rechannel
d. Redirect or remove
e. Reassure
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3. Nonpharmacologic interventions
a. Educate caregivers.
b. Patient interventions
i. Correct underlying factors that may contribute to agitation. ii. Establish a routine. iii. Orientation aids iv. Segment task.
v. Music, pet, and other forms of behavioral therapy
c. Environmental interventions
i. Improve safety. ii. Appropriate lighting iii. Appropriate amount of sensory stimulation iv. Increase in personal space
Table 6. Examples of Nonpharmacologic Interventions
Behavior
Agitation

Paranoia

Insomnia

Causes
Pain, discomfort
Physical illness
Overstimulation
Forgot where object placed
Misinterpreting actions or words
Change in environment
Depression
Less need for sleep

Management
Assess and manage pain, constipation, possible infection
Evaluate medically and treat
Reduce noise and stress, limit TV, avoid crowding
Offer to help find; have more than one of same object
Do not argue or try to reason, do not take personally; distract
Familiarize, reassure, set routine
Treat with antidepressant
Later bedtime, more exercise, monitor daytime napping

4. Pharmacologic interventions
a. Cholinesterase inhibitors
i. Cochrane comprehensive review showed a small improvement in the NPI with donepezil and galantamine. ii. A more recent randomized, controlled trial did not show improvement in the NPI with donepezil treatment. iii. An increase in agitation can occur with cholinesterase inhibitor treatment. iv. Cholinesterase inhibitors are first line for psychosis in Lewy body dementia.
b. Atypical antipsychotics (APs)
i. No AP approved by the U.S. Food and Drug Administration (FDA) for the treatment of dementia-related psychosis ii. No clear standard on when to use, but generally should be reserved for patients who are aggressive, pose a danger to self or others, have symptoms that are interfering with function, or experience delusions or hallucinations that are distressing to patient iii. Cochrane comprehensive review suggests olanzapine and risperidone have the most evidence for use in psychosis and aggression. iv. APs have a high rate of adverse effects such as sedation, orthostasis, dose-dependent movement disorders, and increased risk of stroke and mortality.
v. Conventional APs do not appear to be any safer. vi. Discuss risks and benefits with patient’s family. vii. Use quetiapine if patient has comorbid Parkinson disease or Lewy body dementia. viii. Use for shortest time possible.
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c. Other medications
i. Antidepressants
(a) Especially useful for patients with underlying anxiety or depression
(b) Selective serotonin reuptake inhibitors usually first line
(c) Start at low dose to avoid increasing agitation.
(d) Watch for GI symptoms and hyponatremia. ii. Valproic acid/carbamazepine
(a) May be useful for target symptoms of labile or irritable mood, impulsivity, or combativeness (b) Conflicting evidence to support
(c) Use lower doses; drug levels do not correlate with efficacy in dementia. iii. Memantine
(a) Minimal evidence that patients taking memantine may experience less agitation
(b) Clinical trials under way for treatment of agitation

Patient Cases
8. You are evaluating the medication profile of an 87-year-old female nursing home resident. She resides in a secure advanced dementia unit. Her medical history includes dementia probably caused by Alzheimer’s disease, Parkinson disease, and OA. She requires assistance with all ADLs including total assistance with bathing and dressing and help with feeding. She ambulates with the assistance of a four-wheeled walker.
Her medication regimen includes donepezil 10 mg/day, memantine 10 mg 2 times/day, carbidopa/levodopa
25/100 mg 4 times/day, oxybutynin extended release 5 mg/day, quetiapine 25 mg 2 times/day, and a multivitamin supplement daily. The patient’s MMSE score is 5/30, and her GDS is 4/15. When reviewing the nursing notes, there are several references to the patient continuously crying out, “Help me, help me.” Which one of the following additional information is necessary in assessing this patient?
A.
B.
C.
D.

The Brief Psychiatric Rating Scale.
Functional Assessment Staging.
An evaluation of incontinence.
Framingham Risk Assessment.

9. Which one of the following recommendations would reduce inappropriate medications?
A.
B.
C.
D.

Change carbidopa/levodopa to a continuous-release formulation.
Discontinue oxybutynin.
Discontinue memantine.
Reduce quetiapine to 12.5 mg 2 times/day.

10. This patient is medically assessed, and reversible causes of her hyper-vocalization are ruled out. Which one of the following represents the best approach to treating her behavioral symptoms?
A.
B.
C.
D.

Implement a behavioral approach.
Add valproic acid.
Increase the dose of quetiapine.
Add citalopram.

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Table 7. Analysis of Significant Research on AP Use in the Elderly
Study
Study Parameters
Outcome
Comments
Research evaluating drug efficacy in patients with behavioral disorders related to dementia
Ballard, Cochrane
Database 2008

Meta-analysis to assess whether evidence supports the use of atypical APs for the treatment of aggression, agitation, and psychosis in people with Alzheimer’s disease Evidence suggests that risperidone and olanzapine are useful in reducing aggression and that risperidone reduces psychosis, but both are associated with serious adverse cerebrovascular events and extrapyramidal symptoms Schneider, N Engl J
Med 2006

Double-blind placebocontrolled trial of 421 patients with Alzheimer’s disease and behavioral symptoms randomized to olanzapine, quetiapine, or risperidone.
Main outcome was time to discontinuation of AP for any reason Double-blind, randomized trials (or meta-analyses of the above) were evaluated for
APs, antidepressants, CIs, and mood stabilizers used among patients with behavioral symptoms caused by dementia

No difference in the time to discontinuation for any of the three APs. A high rate of discontinuation of APs occurred because of patient intolerance (parkinsonism, sedation, confusion, and weight gain)

(CATIE-AD)

Sink, JAMA 2005

Evidence to support the efficacy of typical and atypical APs is weak with significant adverse events; treatment with antidepressants improves depression but not other neuropsychiatric symptoms; no clear evidence to support valproate or carbamazepine; small but consistent results with CIs

Authors’ conclusion: “Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is severe distress or risk of physical harm to those living and working with the patient.”
The dose of quetiapine was about one-half to one-fourth of what is generally used in this patient population. Overall, the median time to discontinuation was 5–8 weeks, and about half of the patients had discontinued by 8 weeks In general, minimal evidence to support drug treatment of neuropsychiatric symptoms caused by dementia. The studies evaluated often had inconsistent results among differing measures of behavior

Research involving risk of mortality in patients with dementia who received AP treatment
Schneider, JAMA 2005

Wang, N Engl J Med
2006

Ballard, Lancet 2009
(DART-AD)

Meta-analysis of 15 randomized trials

Overall odds ratio of death of 1.54

3353 patients with
Alzheimer’s disease with agitation were randomly assigned to placebo or AP
Retrospective cohort evaluation of more than
22,000 older people who received either conventional or atypical APs
A double-blind trial of 165 patients in long-term care who were receiving an AP were randomized to discontinue the
AP or to continue with their
AP therapy

(confidence interval 1.06–
2.23)

Increase in mortality was observed for aripiprazole, quetiapine, olanzapine, and risperidone. Trial duration was from 8 to 22 weeks

p=0.02
The relative risk of death after Both types of APs are associated
AP drug administration was with an increased risk of death for higher with conventional APs older people vs. atypical APs
At 12 months, the cumulative Most patients were receiving either risperidone or haloperidol survival was 70% in those who remained on APs vs. 77% treatment in those who were randomized to placebo. The survival difference in the placebo group was more pronounced at 24 and 36 months

AP = antipsychotic; CIs = cholinesterase inhibitors.

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IV. Urinary Incontinence
A. Epidemiology
1. In community-dwelling elderly individuals, UI affects about 38% of women and 17% of men.
2. More than half of nursing home residents suffer from UI.
3. Although the prevalence of UI is correlated with age, UI is not caused by aging.
4. UI is a costly condition, with estimates of more than $5 billion annually spent by long-term care institutions.

B. Physiology of the Genitourinary System and Urination
1. Successful urination is accomplished through a complex system involving the central nervous system, spinal cord, peripheral nerves, and lower urinary tract.
a. In the lower urinary tract, the bladder is regulated by the sympathetic nervous system through acetylcholine interactions with muscarinic receptors.
i. Stimulation of the sympathetic nervous system allows detrusor muscle relaxation and bladder filling. ii. The M3 receptor is the predominant muscarinic receptor in the bladder, and its stimulation results in bladder contraction to enable emptying.
b. The internal urethral sphincter is regulated by the parasympathetic nervous system.
i. During bladder filling, the urethral sphincter is contracted through inhibition of the parasympathetic nervous system. ii. When the bladder is full, signals from the brain result in parasympathetic stimulation, and urethral sphincter relaxation occurs.
c. Urination results when the bladder intravesical pressure exceeds resistance from the urethra and urethral sphincter.
2. Aging effects on the genitourinary system
a. Decrease in bladder elasticity
b. Reduction in bladder capacity
c. More frequent voiding
d. Genitourinary changes related to sex
i. Women have a decline in bladder outlet and urethral resistance because of a loss of estrogen, which weakens the pelvic musculature. ii. Men may experience a decrease in urine flow rate and instability of the detrusor muscle from prostatic enlargement.
3. Causes/risk factors for UI: An evaluation of UI is important to correct any reversible underlying conditions. The following mnemonic is sometimes used, spelling the word diapers: Delirium, Infection, Atrophic vaginitis and urethritis, Psychiatric disorders,
Excessive urine output, Restricted mobility, and Stool impaction.
4. Types of UI

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Table 8. Common Types of UI, Drug-Induced Causes, and Treatment
Type of
Incontinence
Urge or overactive bladder

Drug-Induced
Causes
Cholinergic agents that stimulate the bladder such as bethanechol and cholinesterase inhibitors

Loss of urine with increased abdominal pressure (sneezing, coughing, etc.). Stress
UI is more common in postmenopausal women and in men s/p prostatectomy

α-Blockers such as prazosin decrease urethral sphincter tone Drug Treatment
Antimuscarinic/
anticholinergic agents
Darifenacin, oxybutynin, solifenacin, tolterodine, trospium Comments
Anticholinergic agents are first-line therapy. Differences in muscarinic receptor–blocking exist, but clinical efficacy between these agents has not been shown. Oxybutynin appears to have highest risk of CNS effects

Tricyclic antidepressants
Imipramine, doxepin, nortriptyline, desipramine
Stress
incontinence

Description
Loss of moderate amounts of urine with an increase in need to void. Detrusor instability can result from CNS damage from a stroke

TCAs are not preferred for use in the elderly because of their nonspecific anticholinergic profile
Efficacy evidence is limited with the α-adrenergic agonists and estrogen for stress UI. Surgery to support the bladder and bladder neck is highly effective α-Adrenergic agonists
Pseudoephedrine,
phenylephrine
Topical estrogens
Conjugated estrogen vaginal cream or estradiol vaginal insert/ring Serotonin/norepinephrine reuptake inhibitor
Duloxetine

Overflow incontinence Loss of urine because of excessive bladder volume caused by outlet obstruction or an acontractile detrusor Anticholinergic agents, calcium channel blockers, and opioids decrease detrusor muscle contractions α-Adrenergic antagonists:
(outlet obstruction)
Alfuzosin, tamsulosin, doxazosin, terazosin, prazosin Not FDA approved for stress UI; adverse effects (including nausea, dry mouth, and fatigue) may limit its usefulness Adverse effects vary depending on selectivity to receptors in the bladder and/or prostate (alfuzosin and tamsulosin are more specific)

Add-on therapy with
5-hydroxy reductase inhibitors or bladder antispasmodics: Finasteride, dutasteride, tolterodine, oxybutynin

Functional incontinence Inability to reach the toilet because of mobility constraints

Mixed incontinence UI that has more than one cause; usually stress and overactive bladder Sedative hypnotics and other sedating drugs that may cause confusion; diuretics may increase voiding

For advanced BPH or refractory symptoms Cholinomimetics:
Bethanechol
Remove barriers and obstacles, provide schedules or prompted toileting; assistance may be required to transfer on/off commode
Focus on symptoms that dominate Stimulates the detrusor muscle
Consider interventions to remove any potential cause

Consider treatments for individual components (i.e., stress and urge)

BPH = benign prostatic hypertrophy; CNS = central nervous system; FDA = U.S. Food and Drug Administration; s/p = status post; TCA = tricyclic antidepressant; UI = urinary incontinence.

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Patient Case
11. A 65-year-old woman reports worsening problems with stress incontinence. She is unable to participate in physical activities, and she has decreased social engagements. She has hypertension and has been advised not to take α-agonists. Which one of the following is the best course of action at this time?
A.
B.
C.
D.

A trial of topical estrogens.
Instruction in exercises to improve pelvic floor muscle strength.
Referral to a urogynecologic surgeon for evaluation.
Administration of tolterodine.

V. Benign prostatic hypertrophy
A. Epidemiology
1. Prostatic hypertrophy usually develops after age 40.
2. By age 60, half of all men have BPH; by age 85, 90% have BPH.
3. Growth of the prostate gland leads to narrowing of the urethra and obstruction of urinary flow.
B. Pathophysiology and Signs and Symptoms
1. Not entirely understood; however, type II 5-α-reductase facilitates the conversion of testosterone to dihydrotestosterone (DHT), resulting in prostate growth.
2. Symptoms caused by bladder outlet obstruction occur, including urinary hesitancy, frequency, urgency, nocturia, urinary stream weakness, and an inability to completely empty the bladder. These symptoms are referred to as lower urinary tract symptoms (or LUTS) and are characterized to determine severity and the need for treatment.
3. The American Urological Association Symptom Index (AUASI) can help determine severity and treatment options. The index consists of seven questions evaluating the severity of LUTS on a 0–5 scale. Higher numbers indicate severer symptoms.
C. Evaluation of BPH
1. All patients should undergo a medical history, digital rectal examination, and urinalysis.
2. Selected individuals should be further assessed with the prostate-specific antigen (PSA) test.
3. Patients with mild symptoms on the AUASI (total score of 0–7) should undergo watchful waiting. 4. Patients with moderate LUTS on the AUASI (8–19) can consider medical therapy.
5. Patients with severe LUTS (20 or higher on the AUASI) and those with the following problems should be assessed for surgery.
a. Persistent gross hematuria
b. Bladder stones
c. Recurrent urinary tract infections
d. Renal insufficiency
D. Treatment of BPH
1. α-Adrenergic blockers: Relieve LUTS in men with AUASI scores that are moderate or severe by reducing smooth muscle contraction in the urethra and surrounding tissues.
a. Nonspecific α-adrenergic blockers such as doxazosin, prazosin, and terazosin also lower BP.

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b. Newer agents are selective antagonists of α1a-adrenergic receptors (tamsulosin) and selective antagonists of postsynaptic α1-adrenergic receptors (alfuzosin) in prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra tissues.
c. All the α-blockers can produce hypotension.
d. Compared with placebo, the α-blockers have been shown to be effective in improving
LUTS in patients with BPH. A 4- to 6-point reduction in the AUASI can be expected.
e. Differences between the agents are related to their adverse effect profile. Although the newer agents are more specific antagonists, all agents can produce hypotension.
2. α-Reductase inhibitors
a. DHT is a hormone that stimulates prostate growth.
b. α-Reductase inhibitors prevent the conversion of testosterone to DHT; these agents have been shown to modify the disease course and may reduce the risk of urinary retention and surgical interventions.
i. Finasteride competitively inhibits type II 5-α-reductase and lowers prostatic DHT by
80%–90%.
ii. Dutasteride is a nonselective inhibitor of both type I and II 5-α-reductase. Prostatic
DHT production is quickly suppressed with this agent. iii. Despite these pharmacologic differences, no differences between these two agents were observed in trials; both reduce prostate size.
c. α-Reductase inhibitors do not immediately reduce LUTS and should be reserved for use in men with large prostate volume (more than 40 g). At least 6 months of therapy is usually needed to achieve clinical benefit. Prostate size may be reduced by about 25% in this time frame.
d. PSA concentrations are used to monitor for prostate cancer. Because these agents lower
PSA concentrations, a baseline PSA test is recommended before initiating treatment with α-reductase inhibitors.
3. Combination therapy
a. May be needed in men with LUTS, a larger prostate size, and an elevated PSA.
b. Finasteride and doxazosin most studied; dutasteride is FDA approved for use with tamsulosin in symptomatic men with an enlarged prostate
c. Two large clinical trials (MTOPS and CombAT) have evaluated monotherapy versus combination therapy and have concluded that, in men with LUTS and an enlarged prostate, further benefit can be achieved by use of the two drugs in combination.
4. Supplements
a. Saw palmetto plant extract (Serenoa repens)
b. Conflicting evidence regarding the efficacy of saw palmetto in relieving LUTS
c. Use of this agent with 5-α-reductase inhibitors may reduce the efficacy of the reductase inhibitors. 5. Surgery – Preferred in men with severe symptoms and in those with moderate symptoms who have not adequately responded to medical options

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Patient Case
12. A.W. is an 85-year-old man who presents to his physician with LUTS. A digital rectal examination confirms the diagnosis of BPH, and the physician schedules a further work-up including a prostate ultrasound, which indicates his prostate volume is 31 g. A.W.’s score on the AUASI is 15. Which one of the following therapies is best at this time?
A. Watchful waiting.
B. Finasteride.
C. Tamsulosin.
D. Finasteride plus tamsulosin.

Table 9. Comparison of Drugs for the Treatment of Benign Prostatic Hypertrophy
Medication
Terazosin/ doxazosin Alfuzosin
Tamsulosin

Dose Range
1–10 mg po QHS
1–8 mg po QHS
10 mg po DAILY
0.4–0.8 mg po QHS

Finasteride/ dutasteride 5 mg po DAILY
0.5 mg po DAILY

Adverse Effects
Orthostatic hypotension
Orthostatic hypotension
May cause less orthostasis, but has higher rate of ejaculatory dysfunction Decreased libido

Comments
Initiate at low dose; can titrate up every 2–7 days
No need to titrate
Recommended for patients who cannot tolerate α1-blockers
Onset of action is usually 6 months

po = orally; QHS = every night.

VI. Arthritis
A. Osteoarthritis
1. Epidemiology
a. OA is the most prevalent form of arthritis, affecting more than 46 million Americans.
b. Highly associated with aging
c. Women are afflicted more often than men and often live to old age with disability from
OA.
d. Large weight-bearing joints, such as the hip and knee, are commonly affected.
2. Etiology and pathophysiology
a. Several concomitant conditions can greatly increase the likelihood of developing OA.
i. Obesity ii. Joint damage from repetitive movements and certain sports iii. Genetics and family history
b. Loss of cartilage occurs in the joint as the balance of chondrocyte function shifts from formation to destruction.
c. Subchondral bone is damaged, and the joint space narrows.
d. Symptoms of pain result from activation of nociceptive nerve endings within the damaged joint.

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B. Therapy goals are to relieve pain, maintain or improve joint function, prevent loss of function, and maintain or improve quality of life.
C. Nonpharmacologic Treatment
1. Patients need education to understand the chronic nature of OA.
2. Weight loss will decrease the biomechanical load on large weight-bearing joints; even small amounts of weight loss help decrease pain and disability.
3. Physical and occupational therapy
4. Exercise
5. Surgery
D. Drug Therapy (analgesics are summarized in a table at the end of the Rheumatoid Arthritis section)
1. Acetaminophen is the analgesic of choice to treat pain from OA. Early research in the treatment of OA of the knee recommended 1 g taken 4 times/day. This dose of acetaminophen can lead to liver failure.
a. The FDA estimates 400 people die every year of liver failure related to unintentional acetaminophen overdose.
b. Patients often take different combination products containing acetaminophen, leading to excessive dosages.
c. The FDA is reviewing the data regarding the appropriate dose of acetaminophen and recommends 650 mg every 4–6 hours.
d. The FDA is considering lowering the maximal total daily dosage of acetaminophen from all sources to 3250 mg.
e. Individuals with liver disease should receive doses of acetaminophen that are less than
2600 mg/day.
2. In older people with OA, NSAIDs should seldom be used.
a. In selected patients, cyclooxygenase-2 (COX-2) inhibitors and NSAIDs may be used with extreme caution when other therapies have failed and when the benefit of treatment outweighs the risk.
b. For those using a nonselective NSAID, some authorities recommend that a proton pump inhibitor be used for gastric protection.
c. For patients using celecoxib and aspirin (for cardiac disease), a proton pump inhibitor may be recommended for gastric protection, provided the patient is not taking clopidogrel. d. Older patients receiving treatment with NSAIDs or COX-2 inhibitors should be closely monitored for gastric and renal toxic reactions, hypertension, heart failure, and drug-drug interactions. 3. Opioids
a. Patients with persistent pain from OA that is moderate or severe are candidates for treatment with opioids.
b. Monitor and anticipate opioid adverse effects and treat accordingly.
c. Do not exceed acetaminophen daily dosage guidelines when using combination products.
d. Patients should be reassessed in an ongoing fashion to ensure that treatment goals are being met.
4. Adjuvant drug therapy
a. Use appropriate medications, such as gabapentin, in patients with neuropathic pain from OA.
b. Avoid the use of tricyclic antidepressants in older patients because of the increased risk of anticholinergic adverse effects.
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c. Avoid the use of skeletal muscle relaxants such as cyclobenzaprine and carisoprodol because of the high risk of anticholinergic adverse effects and lack of efficacy. In patients with muscle spasms related to OA, the use of baclofen could be considered.
d. There is limited efficacy for topical agents such as capsaicin, diclofenac gel, and lidocaine patch 5% for OA.
e. Short-term relief of pain may be achieved with intra-articular hyaluronic acid or glucocorticosteroid injections.
5. Alternative dietary supplements
a. Glucosamine sulfate, 500 mg taken 3 times/day, with or without chondroitin, may be considered for chronic therapy to prevent joint degradation and relieve pain.
i. Evidence to support treatment is contradictory. ii. The adverse effect profile of glucosamine is similar to that of placebo and includes gastrointestinal complaints.

Patient Case
13. W.F. is an 85-year-old man who presents to his physician with pain from hip OA. He also has hypertension, coronary artery disease, and BPH. For his OA, W.F. has been taking acetaminophen 650 mg 3 times/day.
W.F. reports that acetaminophen helps, but he still experiences pain that limits his ability to walk. Which one of the following is the best next step in analgesic therapy for W.F.?
A.
B.
C.
D.

Change the analgesic to celecoxib.
Add hydrocodone.
Change the analgesic to ibuprofen.
Add glucosamine.

VII. Rheumatoid Arthritis
A. Epidemiology
1. A systemic disease characterized by a bilateral inflammatory arthritis that usually affects the small joints of the hands, wrists, and feet
2. The prevalence is estimated to be between 1% and 2%, with women being afflicted 3 times more often than men.
3. Rheumatoid arthritis can occur at any age; it is often seen in younger people.
4. Rheumatoid arthritis is an autoimmune disease with a strong genetic predisposition.
B. Pathophysiology and Clinical Presentation
1. Chronic inflammation of the synovium leads to proliferation and the development of a pannus.
2. The pannus invades joint cartilage and eventually causes erosion of the bone as well as joint destruction. 3. The cause of the initial inflammatory activation is unknown, but once activated, the immune system produces antibodies and cytokines that accelerate cartilage and joint destruction.
4. Patients present with joint pain and stiffness, fatigue, and other signs of chronic disease.
Symptoms also include warmth, redness, and swelling of the joints.
5. Laboratory tests often reveal a positive rheumatoid factor (RF), elevated sedimentation rate,
C-reactive protein, and normochromic normocytic anemia.
6. Rheumatoid arthritis can also affect other organs such as the lung.
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C. Treatment
1. The goal of treatment is to control the inflammatory process so that disease remission occurs.
This should lead to relief of pain, maintenance of function, and improved quality of life.
a. Measurement of treatment response:
i. Reduction in the number of affected joints and in joint tenderness and swelling ii. Improvement in pain iii. A decreased amount of morning stiffness iv. Reduction in serologic markers such as RF
v. Improvement in quality-of-life scales
2. Disease-modifying antirheumatic drugs (DMARDs)
a. DMARD therapy should be initiated within the first few months of diagnosis.
i. Methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide are commonly used as first-line agents. ii. Biologic agents that inhibit tumor necrosis factor and interleukin receptor antagonists are often used in patients who do not respond to a first-line agent such as methotrexate. iii. DMARDs generally require about 3 months of use before an effect is seen.
b. NSAIDs and/or glucocorticosteroids should be used for the immediate treatment of pain and inflammation.
i. NSAIDs do not affect disease progression in rheumatoid arthritis; their antiinflammatory effect is seen within 1–2 weeks of daily dosing, whereas the analgesic effect begins within several hours of administration. ii. Glucocorticosteroids are not recommended for long-term use because of their high number of adverse effects and long-term complications. They are often used as bridge therapy to provide anti-inflammatory effects while waiting for the DMARDs to take effect. c. The order of use of disease-modifying therapy is unclear. Often, methotrexate is used as first-line therapy. If the treatment response is not optimal, combination DMARDs may be tried, or a biologic agent can be added to methotrexate.
d. Published guidelines provide summary information to help guide therapy. Patients are categorized by their history of disease response and severity of disease indicators to determine the appropriate use of biologic agents.
3. Nonpharmacologic treatment
a. Rest during periods of disease exacerbation
b. Occupational and physical therapy to support mobility and maintain function
c. Maintenance of a normal weight (avoid overweight and obesity) to reduce biomechanical stress on joints

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Patient Case
14. F.A. is a 55-year-old woman with rheumatoid arthritis. On diagnosis 1 year ago, F.A. had an RF titer of 1:64, signs and symptoms of inflammation in the joints of both hands, and about 45 minutes of morning stiffness.
She began therapy with methotrexate, and she is presently receiving 15 mg every week, folic acid 2 mg/day, ibuprofen 800 mg 3 times/day, and omeprazole 20 mg/day. At today’s clinic visit, F.A. reports a recurrence of her symptoms. Radiographic evaluation of her hand joints shows progression of joint space narrowing and bone erosion. Which one of the following is the next step in therapy for F.A.?
A.
B.
C.
D.

Administer etanercept.
Administer hydroxychloroquine.
Add prednisone bridge therapy.
Change to leflunomide.

Table 8. Selected Drug Therapy for Osteoarthritis and Rheumatoid Arthritis
Drug
Starting Dose
Comments
Preferred Nonopioid Analgesics for Osteoarthritis
Acetaminophen
650 mg every 4–6 hours
First-line therapy. Maximal daily dose from all sources should not exceed 3250 mg
Celecoxib
100 mg/day
For patients also receiving antiplatelet therapy for cardiac disease, gastric protection should be employed
Tramadol
25 mg every 4–6 hours
An extended-release form is available; mixed opioid and
SSRI effects may lead to serotonin syndrome in patients also receiving antidepressant therapy
Selected Opioid Analgesics for Osteoarthritis
Hydrocodone
2.5–5 mg every 4–6 hours
Daily dose limited by the other analgesic components of most products
Oxycodone
2.5–5 mg every 4–6 hours
As above for the combination products; sustained-release preparation is usually used every 12 hours, but dosing can vary from every 8–24 hours
Morphine
2.5–10 mg every 4–6 hours
A variety of dosage forms are available including extended- and immediate-release forms
Hydromorphone
1–2 mg every 3–4 hours
Short duration of action
Fentanyl
12–25 mcg/hour patch every Not recommended in opioid-naïve patients; peak effects
72 hours from the transdermal system usually occur 18–24 hours after the first dose, with steady state achieved after 1–2 weeks of therapy
Selected NSAIDs for Rheumatoid Arthritis
Anti-inflammatory Dose
Ibuprofen
1.2–3.2 g/day
Monitor for GI ulceration, bleeding, and renal toxicity;
Meloxicam
7.5–15 mg/day anti-inflammatory effect may take 1–2 weeks; do not use
Nabumetone
1–2 g/day in patients with heart failure
Naproxen
0.5–1.5 g/day

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Drug
Starting Dose
Selected DMARDs for Rheumatoid Arthritis
Customary Dose
Methotrexate
7.5–15 mg every week

Comments

Probably first-line DMARD; monitor for myelosuppression, liver dysfunction, and pulmonary fibrosis; a teratogen
Leflunomide
10–20 mg/day
Similar to methotrexate; an initial loading dose may give
(Arava)
therapeutic response within the first month
Hydroxychloroquine 200–300 mg 2 times/day
Must routinely monitor for ocular toxicity; however, this
(Plaquenil)
agent has a better adverse effect profile overall
Sulfasalazine
500–1000 mg 2 times/day
GI adverse effects often limit the use of this agent
Etanercept
50 mg SC weekly
Binds to TNF, inactivating this cytokine; generally well
(Enbrel)
tolerated; usually used in those whose methotrexate therapy fails; monitor for infection; check baseline PPD
Infliximab
3 mg/kg IV at 0, 2, and 6
A mouse/human chimeric antibody to TNF; used in
(Remicade)
weeks and then every 8 combination with methotrexate to prevent formation of weeks thereafter antibodies to this protein; monitor for infection; check baseline PPD
Adalimumab
40 mg SC every 2 weeks
Human antibody to TNF; less antigenic than other TNF
(Humira)
antibodies; monitor for infection; check baseline PPD
Anakinra
100 mg SC daily
IL-1 receptor antagonist; avoid combination therapy with
(Kineret)
TNF agents because of increased risk of infection
Rituximab
Two infusions of 1000 mg
Chimeric antibody to CD20 protein on B lymphocytes;
(Rituxan)
given 2 weeks apart corticosteroid infusions help reduce infusion reactions; used in combination with methotrexate to improve response Abatacept
Weight-based dose every
Inhibits interactions between antigens and T cells; may
(Orencia)
2 weeks for two doses and be useful in those who do not respond to TNF inhibitors; then monthly (i.e., 750 mg for monitor for infusion reactions those weighing 60–100 kg)
Golimumab
50 mg SC every month
Monoclonal antibody against TNF. Intended for use in
(Simponi)
combination with methotrexate. Monitor for infections
Certolizumab pegol 400 mg SC at 0, 2, and 4
Monoclonal antibody against TNF; may have best
(Cimzia)
weeks, then 200 mg every response when used in combination with methotrexate. other week
Monitor for infections
Tocilizumab
4 mg/kg IV infusion every 4 Anti-human IL-6 receptor monoclonal antibody; indicated
(Actemra)
weeks; can increase to 8 mg/ for patients who have not responded to TNF inhibitors. kg based on clinical response Monitor for infections
DMARD = disease-modifying antirheumatic drug; GI = gastrointestinal; IL = interleukin; IV = intravenously; NSAID
= nonsteroidal anti-inflammatory drug; PPD = purified protein derivative; SC = subcutaneously; SSRI = selective serotonin reuptake inhibitor; TNF = tumor necrosis factor.

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References
REFERENCES

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Medication Use in Older People

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005593. DOI: 10.1002/14651858.CD005593.

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Pathophysiologic Approach. New York: McGrawHill, 2008:57–66.

4. Gill SS, Anderson GM, Fischer HD, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors. Arch Intern Med
2009;169:867–73.

2. Schwartz JB. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clin Pharmacol Ther 2007;82:87–96.

5. Grimmer T, Kurz A. Effects of cholinesterase inhibitors on behavioural disturbances in Alzheimer’s disease: a systematic review. Drugs Aging
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3. Elliott DP. Pharmacokinetics and pharmacodynamics in the elderly. In: Schumock G, Brundage
D, Chapman M, et al, eds. Pharmacotherapy SelfAssessment Program, 5th ed. Lenexa, KS: American College of Clinical Pharmacy, 2004:115–30.

6. Qaseam A, Snow V, Cross JT, et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of
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4. Lamb EJ, Webb MC, Simpson DE, Coakley AJ,
Newman DJ, O’Riordan SE. Estimation of glomerular filtration rate in older patients with chronic renal insufficiency: is the modification of diet in renal disease formula an improvement? J Am
Geriatr Soc 2003;51:1012–7.

Behavioral Symptoms of Dementia
1. Howard RJ, Juszczak E, Ballard CG, et al. Donepezil for the treatment of agitation in Alzheimer’s disease. N Engl J Med 2007;357:1382–92.

5. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults. Arch Intern Med
2003;163:2716–24.

2. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia. Meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934–43.

6. Higashi T, Shekelle PG, Solomon DH, et al. The quality of pharmacologic care for vulnerable older patients. Ann Intern Med 2004;140:714–20.

3. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med
2005;353:2335–41.

7. Handler SM, Wright RM, Ruby CM, Hanlon
JT. Epidemiology of medication-related adverse events in nursing homes. Am J Geriatr Pharmacother 2006;4:264–72.

4. Schneider LS, Tariot PN, Dagerman KS, et al.
Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med
2006;355:1525–38.

8. Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the Food and Drug
Administration, 1998–2005. Arch Intern Med
2007;167:1752–9.
Dementia

5. Yury CA, Fisher JE. Meta-analysis of the effectiveness of atypical antipsychotics for the treatment of behavioural problems in persons with dementia. Psychother Psychosom 2007;76:213–8.

1. Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia. 2. Diagnosis.
CMAJ 2008;178:825–36. (Part 2 of a 5-part series on dementia).

6. Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia. A review of the evidence. JAMA
2005;293:596–8.

2. Slattum PW, Swerdlow RH, Massey Hill A. Alzheimer disease. In: DiPiro JT, Talbert RL,

7. Ballard C, Hanney ML, Theodoulou M, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a

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Osteoarthritis and Rheumatoid Arthritis

randomized placebo-controlled trial. Lancet Neurol 2009;8:151–7 [Epub 2009 Jan 8].

1. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc 2009;57:1331–46.

8. Ballard CG, Waite J, Birks J. Atypical antipsychotics for aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst Rev
2006;1:CD003476. DOI:
10.1002/14651858.
CD003476.pub2.

2. ACR Subcommittee on Osteoarthritis Guidelines.
Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update.
Arthritis Rheum 2000;43:1905–15.

9. Sutor, B, Rummans TA, Smith GE. Assessment and management of behavioral disturbances in nursing home patients with dementia. Mayo Clin
Proc 2001;76:540–50.

3. U.S. Food and Drug Administration. Acetaminophen Information. www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm.
Accessed February 28, 2011.
4. Saag KG, Teng GG, Patkar NM, et al. American
College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic diseasemodifying anti-rheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008;59:762–84.

Urinary Incontinence and Benign
Prostatic Hypertrophy
1. Yamaguchi O, Nishizawa O, Takeda M, et al. Clinical guidelines for overactive bladder. Int J Urol
2009;16:126–42.

5. Bruce SP. Rheumatoid arthritis. In: Richardson M,
Chant C, Cheng JWM, et al, eds. Pharmacotherapy Self-Assessment Program, 6th ed. Chronic Illness II. Lenexa, KS: American College of Clinical
Pharmacy, 2009:73–90.

2. Chughtai B, Levin R, De E. Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin. Clin Interv Aging
2008;3:503–9.

6. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J
Med 2006;354:795–808.

3. Rogers R. Urinary stress incontinence in women.
N Engl J Med 2008;358:1029–36.
4. Edwards JL. Diagnosis and management of benign prostatic hyperplasia. Am Fam Physician
2008;77:1403–10.

7. McAlindon TE, LaValley MP, Gulin JP, et al.
Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA 2000;283:1469–75.

5. Kaplan SA, Roehrborn CG, McConnell JD, et al.
Long-term treatment with finasteride results in a clinically significant reduction in total prostate volume compared to placebo over the full range of baseline prostate sizes in men enrolled in the
MTOPS trial. J Urol 2008;180:1030–3.
6. Roehrborn CG, Siami P, Barkin J, et al. The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study.
J Urol 2008;179:616–21.
7. American Urological Association. Guideline on the management of benign prostatic hyperplasia
(2006 update). Available at www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm?sub=bph. Accessed October 1, 2010.
8. Sherman JJ. Health issues in older men. In: Dunsworth T, Richardson M, Chant C, et al, eds. Pharmacotherapy Self-Assessment Program, 6th ed.
Women’s and Men’s Health. Lenexa, KS: American College of Clinical Pharmacy, 2008:163–80.

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Answers and Explanations to Patient Cases
1. Answer C
This patient is typical of an older person in a nursing home with many chronic diseases requiring drug management. At this time, she has several risk factors for falls including a history of fall with hip fracture; diseases such as diabetes, dementia, and hypertension; dizziness; and use of several drugs. An assessment for gait and balance would help determine the severity of her risk.

of her Parkinson disease.
6. Answer D
Rivastigmine is a potent inhibitor of acetyl and butyl cholinesterase, leading to significant cholinergic adverse effects such as nausea, vomiting, and diarrhea.
These adverse effects can be diminished by a slow-dosage titration of the drug. In addition, when a patient is at his/her full therapeutic dose, use of the transdermal delivery system will generate even plasma concentrations and lessen the incidence of cholinergic adverse effects. Based on the maintenance dose achieved of 12 mg of rivastigmine, this man can be changed to the 18mg patch that delivers 9.5 mg/day.

2. Answer D
Renal elimination is usually the most significantly changed pharmacokinetic parameter in older people.
In this patient, her advanced age and diseases will also add to her loss of renal function. Using the CockcroftGault equation, N.H.’s estimated creatinine clearance is
24 mL/minute.
Creatinine clearance = [(140 − 85)65/(72 × 1.8)] × 0.85

7. Answer C
Over 3 years, R.A. has declined 4 points on her MMSE, which suggests a treatment response to donepezil. Furthermore, R.A. is still able to live at home with her husband, and she has maintained some function in her basic ADLs. Because she has benefited from acetylcholinesterase inhibitor use, it should not be abruptly discontinued. Evidence from clinical trials with memantine shows that an additional treatment response can be observed when memantine is added to donepezil therapy. Memantine should be initiated at 5 mg/day and increased every 2 weeks until the full therapeutic dose is achieved (10 mg 2 times/day).

3. Answer A
The diabetes treatment should be addressed promptly.
Because N.H. has considerable renal insufficiency, she does not meet the prescribing guidelines for metformin.
Use of metformin in individuals with impaired renal function increases the likelihood of lactic acidosis. In addition, glyburide is partly eliminated in the kidney, has duration of effect of about 24 hours, and is not recommended for elderly patients with poor renal elimination. N.H. could be experiencing periods of hypoglycemia that contribute to her dizziness.

8. Answer C
This patient has several issues related to her medication regimen. Patients in late stages of dementia (as evidenced by an MMSE of 5/30) will develop a functional incontinence caused by their loss of cognition and inability to recognize toileting needs. Oxybutynin is an anticholinergic agent useful in treating overactive bladder rather than functional incontinence, and it also has pharmacologic properties that oppose the action of donepezil. A review of the patient’s incontinence history will help determine whether this drug is efficacious in the treatment of her UI.

4. Answer A
Efforts to maintain bone and muscle strength are important for N.H. Most people who are older do not consume a diet rich in calcium or vitamin D. In addition, because N.H. resides in a nursing home, she will have less sun exposure and is more likely to be deficient in vitamin D.
5. Answer C
This patient has mild-moderate dementia in addition to
Parkinson disease. Although some patients with Parkinson disease develop dementia, many do not. This patient has been stable for some years. When evaluating her cognitive loss, it is important to limit the use of any drug that could contribute to confusion. Anticholinergics such as trihexyphenidyl can cause confusion. Because this drug is likely part of the patient’s Parkinson disease treatment, the dose should be slowly reduced, and the patient should be monitored for exacerbations

9. Answer B
Discontinue oxybutynin. This drug is classified as an inappropriate drug on the basis of Beers consensus criteria. In addition, oxybutynin is highly anticholinergic and may lead to confusion in older patients. If the patient does have overactive bladder (rather than functional incontinence), alternative medications can be used that more specifically target the bladder muscle

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renal disease) does not outweigh the potential benefit.
Glucosamine can be added to this patient’s medication regimen; however, if effective, it will not provide immediate relief of pain.

with less potential for central nervous system effects.
10. Answer A
Hyper-vocalization is a difficult behavior to address.
In general, medications are not very efficacious in this case. Increasing the dose of quetiapine would likely result in increased sedation in the patient. Although the behavior might decrease during periods of sedation, the behavior often returns when the patient adjusts or develops a tolerance to the sedative properties. The other drug choices, adding valproic acid or citalopram, do not have much evidence of effectiveness in the literature.
A behavioral approach is the best method to try in this patient. Types of interventions that could be effective include those that create a soothing, serene environment for the patient, such as soft music. Activities appropriate to the patient’s level of cognition might also be helpful as a distracting mechanism as well as a way to improve interactions. Reassurance by staff is also particularly helpful so that the patient feels more comforted – often, moving a patient from his/her room and closer to the nurses’ station will help a patient feel less alone and less afraid.

14. Answer A
This is an example of a young woman with indicators of poor prognosis with rheumatoid arthritis (positive RF, young age, many symptoms) who has not responded to therapy with methotrexate. Although the next treatment step is not entirely clear, her best choices would be between combination DMARD therapy and a biologic agent. Leflunomide would not be preferred because its efficacy is similar to methotrexate. Hydroxychloroquine would not be recommended as sole therapy for someone who has not responded to methotrexate. Etanercept has a response in 60%–75% of patients whose therapy with methotrexate has failed. Glucocorticosteroids are used as adjunctive therapy for the first several months of treatment with a disease-modifying agent.

11. Answer C
In a postmenopausal woman, stress incontinence that affects daily function should be evaluated by a surgeon with expertise in urogynecology. Data showing the efficacy of available drug therapy for stress incontinence are limited. Kegel exercises can be helpful in improving the strength of muscles in the pelvic floor, but they are seldom sufficient to treat stress incontinence.
12. Answer C
Pharmacologic therapy targeted at reducing urethral sphincter pressure has proved effective in reducing
BPH symptoms. Tamsulosin is an α-adrenergic blocker with more specific activity for the genitourinary system. Postural hypotension can still occur with all α-adrenergic blockers, so patients should be monitored when therapy is initiated. Finasteride, an α-reductase inhibitor, and combination therapy with these agents are recommended when there is evidence of large prostate size.
13. Answer B
The American Geriatrics Society recommends treatment with opioids for OA when older patients do not respond to initial therapy with acetaminophen. The
NSAIDs and COX inhibitors are seldom considered when a thorough assessment of the patient shows that the risk of treatment (gastrointestinal bleeding and

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Answers and Explanations to Self-Assessment Questions
1. Answer B
Amitriptyline is highly anticholinergic and can cause confusion in the elderly. A worsening of this patient’s dementia could lead to confusion, but it would not likely occur in such a short time and would not be the assessment until a full medication review and medical work-up could be performed. Although confusion could be a symptom of depression, citalopram 20 mg/ day is an adequate dose to treat depression. There is no reason to repeat a urinalysis.

5. Answer d
Appropriateness of the dose of metoprolol can be ensured by evaluating patient parameters such as BP and
HR; metoprolol undergoes about a 50% first-pass effect and is metabolized by the CYP2D6 isoenzyme system.
Based on W.G.’s estimated creatinine clearance of 46 mL/minute, he may not meet the prescribing guidelines for metformin; a discontinuation of the drug rather than a dosage reduction may be warranted. Glipizide is also eliminated by metabolism. Gabapentin, Answer D, is correct because this drug is eliminated renally. Based on this patient’s creatinine clearance, his dosage should not exceed 1400 mg/day.

2. Answer B
All the choices presented for this question might reduce the risk of falls in J.T. However, Answer B is best because a great deal of literature documents the association between the use of benzodiazepines with long elimination half-lives and hip fracture. Furthermore, no diagnosis exists that warrants a benzodiazepine for J.T.
If a diagnosis were added that required a benzodiazepine, a better choice would be lorazepam. Parkinson disease is a risk factor for falls. Exercise can reduce the likelihood of falls. Avoiding postural hypotension from antihypertensive medications will also help reduce falls. However, of all four choices, use of diazepam is
(apparently) unnecessary as well as inappropriate because of its pharmacokinetic profile.

6. Answer B
The use of several medications is the strongest variable associated with adverse drug reactions. Although one might suspect that older patients are more sensitive to drugs because of the pharmacokinetic and pharmacodynamic changes that occur with aging, age is not as important as polypharmacy when the data showing a correlation between age and adverse drug reactions are controlled for the number of drugs taken.
7. Answer C
The FDA is considering changes in combination products that contain acetaminophen and in the over-thecounter available doses of acetaminophen. About 400 deaths occur annually because of unintentional overdose with acetaminophen because many consumers do not know the ingredients of combination drug products.
W.G. could easily be consuming more than 4 g of acetaminophen per day (the “old” maximal dosage).

3. Answer C
Although we do not know the specific type of J.T.’s incontinence that requires tolterodine treatment, her description of her present symptoms suggests that she cannot ambulate well enough to get to the bathroom.
Her ambulation problems could be attributable to worsening Parkinson disease. This type of incontinence is referred to as “functional.” One intervention that could help J.T. with her functional incontinence is the adoption of a toileting program so that she voids on a schedule. This would help reduce her need to ambulate to the bathroom because of an urge to void.

8. Answer A
Tylenol PM contains diphenhydramine, a strong anticholinergic antihistamine. Anticholinergic medications can block bladder contractions, which can lead to an inability to void. This potential adverse effect is of particular concern in a man with BPH who may have some baseline amount of outlet obstruction because of an enlarged prostate gland.

4. Answer A
Older patients have several age-related physiologic changes in the gastrointestinal tract that can alter absorption of medications. A decrease in stomach acidity occurs, and drugs that require an acidic environment to dissolve and/or be absorbed will be affected. In this question, iron would be affected by this change. Fortunately, most drugs are absorbed through passive diffusion, and this does not change appreciably in the older patient. 9. Answer A
The best evidence for use of the cholinesterase inhibitors is in patients with mild-moderate Alzheimer’s disease because they can often help slow disease progression. A patient scoring a 10/30 on the MMSE would be classified as having severe dementia, where benefit

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15. Answer C
Although prednisone is not a long-term solution to treat
S.C.’s rheumatoid arthritis, it would be appropriate to treat her pain for the short term. She would not likely be a candidate for etanercept so close to her hospitalization for sepsis. Nonsteroidal anti-inflammatory drugs would be contraindicated with her renal function and age. Patients receiving golimumab have not responded to other therapies, and the drug is to be used in combination with methotrexate.

would not be as pronounced. The NPI helps assess psychiatric symptoms in a patient. The data are conflicting about whether cholinesterase inhibitors benefit a patient with neuropsychiatric symptoms.
10. Answer D
Cholinesterase inhibitors prevent the breakdown of acetylcholine, resulting in increased cholinergic activity. The initiation of cholinesterase inhibitors in older people with dementia can worsen incontinence through the increase in acetylcholine stimulation of the bladder.
This type of incontinence would be classified as urge incontinence. 11. Answer A
Drugs often increase sedation and somnolence in older people. In L.M., lorazepam and quetiapine have the greatest likelihood of causing sedation. There is no diagnosis for the use of quetiapine, and this drug should be titrated down and discontinued.
12. Answer C
There is a small, but consistently increased, risk of death in older patients when APs are initiated. Analysis of the literature that documents this risk shows that death usually occurs within the first 6 months of prescribing an AP and is attributable to many causes. The increased risk has been observed with all the APs. This has led to black box labeling requirements by the FDA.
13. Answer d
Patients should be assessed for reversible causes of behavior when a change in their status occurs. This evaluation should include assessment of the patient for signs and symptoms of hunger, dehydration, depression, pain, delirium, sleep deprivation, infection, and drug adverse effects. Any reversible causes for the combative behavior should be corrected and a behavioral approach implemented to achieve proper hygiene and personal care.
14. Answer B
L.M. is 95 years old, so extra caution must be taken in prescribing analgesics when the risk of treatment may exceed the benefit. Acetaminophen is recommended as first-line therapy for the treatment of OA, and a lower dose should be used in this patient. Nonsteroidal antiinflammatory drugs are not recommended because of the increased risk of gastrointestinal bleeding and renal toxicity. L.M. is receiving aspirin 81 mg/day, which is another contraindication to the use of NSAIDs in older patients. Updates in Therapeutics: The Pharmacotherapy Preparatory Review and Recertification Course
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