Geriatrics 2024 PDF - ACCP Updates in Therapeutics Preparatory Review

Geriatrics Jessica A. Bente, Pharm.D., BCPS, BCGP Cooperman Barnabas Medical Center Livingston, New Jersey  Geriatrics Geriatrics Jessica A. Bente, Pharm.D., BCPS, BCGP Cooperm...

Geriatrics Jessica A. Bente, Pharm.D., BCPS, BCGP Cooperman Barnabas Medical Center Livingston, New Jersey  Geriatrics Geriatrics Jessica A. Bente, Pharm.D., BCPS, BCGP Cooperman Barnabas Medical Center Livingston, New Jersey ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-315  Geriatrics Learning Objectives Self-Assessment Questions Answers and explanations to these questions can be 1. Evaluate the impact of pharmacokinetic and pharmaco- found at the end of this chapter. dynamic changes in older adults on risk and benefit of medications. Questions 1 and 2 pertain to the following case. 2. Assess inappropriate medication prescribing in older A.B., an 85-year-old man, presents to the primary care adults using accepted tools. 3. Recommend appropriate pharmacotherapy for patients clinic 1 month after his spouse’s death. His medical with dementia, including appropriate interventions for history is significant for hypertension, hyperlipidemia, patients with behavioral and psychological symptoms benign prostatic hyperplasia (BPH), and major depres- of dementia. sive disorder. His current medications include metopr- 4. Recommend appropriate pharmacotherapy for urinary olol extended release (ER) 25 mg daily, atorvastatin 20 incontinence and benign prostatic hyperplasia. mg daily, tamsulosin 0.4 mg daily, diazepam 5 mg at 5. Evaluate the risks, benefits, safety, and efficacy of med- bedtime as needed for sleep, and escitalopram 10 mg ication classes used in the treatment of osteoarthritis, daily. His daughter reports that he has been more lethar- rheumatoid arthritis, and gout. gic and unsteady during walking over the past 3 days. The patient reports trouble sleeping, necessitating the use of diazepam every night this past week. His blood Abbreviations in This Chapter pressure is 135/72 mm Hg and heart rate is 76 beats/ minute. Urinalysis is unremarkable, thyrotropin (TSH) AD Alzheimer disease is within the reference range, and Geriatric Depression ADLs Activities of daily living Scale (GDS) score is 6/15. AUASI American Urological Association Symptom Index 1. Which medication is most contributing to A.B.’s BPH Benign prostatic hyperplasia lethargy and confusion? BPSD Behavioral and psychological symptoms of dementia A. Diazepam. CI Cholinesterase inhibitor B. Metoprolol. CKD Chronic kidney disease C. Atorvastatin. CV Cardiovascular D. Escitalopram. CVD Cardiovascular disease DMARD Disease-modifying antirheumatic drug 2.  Which age-related change in pharmacokinetics IADLs Instrumental activities of daily living most likely underlies A.B.’s medication-related LUTS Lower urinary tract symptoms problem? MCI Mild cognitive impairment MMSE Mini-Mental State Examination A. Delayed oral absorption. OA Osteoarthritis B. Decreased renal excretion. PD Parkinson disease C. Slowed metabolism in the liver. PSA Prostate-specific antigen D. Decreased volume of distribution. PVR Postvoid residual RA Rheumatoid arthritis Questions 3 and 4 pertain to the following case. RF Rheumatoid factor B.C., a 76-year-old woman, was recently admitted to SU Serum urate a long-term care facility for rehabilitation after sev- TNF Tumor necrosis factor eral falls at home. Her medical history is significant UI Urinary incontinence for hypertension, hypothyroidism, Alzheimer disease ULT Urate-lowering therapy (AD), hyperlipidemia, and osteoarthritis (OA) of the XOI Xanthine oxidase inhibitor knee. She takes metoprolol succinate 50 mg daily, levothyroxine 75 mcg daily, atorvastatin 10 mg daily, and donepezil 10 mg daily. Her blood pressure is 126/80 mm Hg and heart rate is 66 beats/minute. Basic ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-316  Geriatrics metabolic panel results are all within reference ranges; B. Galantamine ER 24 mg daily. 25-hydroxyvitamin D concentration is 20 ng/mL, TSH C. Memantine 10 mg twice daily. is 1.89 mU/L, TC is 180 mg/dL, LDL is 140 mg/dL, D. Rivastigmine patch 4.6 mg daily. HDL is 35 mg/dL, and TGs are 176 mg/dL. Her Mini- Mental State Examination (MMSE) score is 16/30 and 6. Which intervention would be most appropriate to GDS score is 2/15. prevent an adverse drug reaction in C.S.? 3. Which recommendation would be most appropri- A. Discontinue glipizide. ate to reduce B.C.’s risk of falls? B. Discontinue lisinopril. A. Initiate memantine 5 mg daily. C. Reduce carvedilol to 6.25 mg twice daily. B. Initiate vitamin D 1000 units daily. D. Reduce potassium chloride to 10 mEq daily. C. Initiate aducanumab 1 mg/kg infusion every 4 weeks. 7. One year later, C.S. returns to the clinic. She has moved in with her daughter. Lately, she wanders D. Initiate calcium carbonate 500 mg twice daily. around the house continuously. She often changes clothes, cries out, grimaces, and asks repetitive 4. Which would be most appropriate for B.C.’s OA questions. Her current medication regimen includes knee pain? a rivastigmine 9.5-mg transdermal patch daily, A. Ibuprofen 200 mg four times daily. which she has been taking for the past 6 months. B. Acetaminophen 650 mg three times daily. Which would be most appropriate for C.S.’s new C. Tramadol 50 mg three times daily as needed behavioral symptoms? for pain. A. Initiate olanzapine 5 mg daily. D. Diclofenac 1% topical gel 4 g applied to knee B. Initiate risperidone 0.5 mg twice daily. four times daily. C. Initiate pimavanserin 34 mg daily. D.  Change acetaminophen to 650 mg every 6 Questions 5–7 pertain to the following case. hours around-the-clock. C.S., an 80-year-old woman, presents to your clinic accompanied by her daughter, who no longer feels com- 8.  An 80-year-old woman had a total right knee fortable leaving her mother alone because of her moth- replacement 3 days ago after conservative strate- er’s “increasing forgetfulness.” The patient’s medical gies for OA failed. Her medical history is signif- history is significant for type 2 diabetes, hypertension, icant for hypothyroidism, osteoporosis, OA, and coronary artery disease, congestive heart failure, and hyperlipidemia. Her current medications include OA. She takes the following medications: acetamino- simvastatin 20 mg daily, risedronate 35 mg weekly, phen 650 mg every 6 hours as needed for pain, lisin- levothyroxine 75 mcg daily, and oxycodone/acet- opril 20 mg daily, furosemide 20 mg daily, potassium aminophen 5/325 mg 1 tablet every 4 hours as chloride 20 mEq daily, carvedilol 12.5 mg twice daily, needed for moderate pain. She is in the hospital and glipizide 5 mg daily. Her MMSE score is 18/30. preparing for discharge. As the pharmacist coun- Blood tests obtained last week showed a normal basic sels the patient on her discharge medication, the metabolic panel, except for a fasting plasma glucose of patient reports a new onset of “losing her water” 65 mg/dL. Her A1C is 5.6%. A urinalysis is unremark- the day before and again overnight. Which inter- able. No nutritional deficiencies are noted. The patient’s vention would be most appropriate for this patient? blood pressure is 130/80 mm Hg and heart rate is 60 beats/minute. She is diagnosed with AD. A. Urinalysis. B. Pelvic floor exercises. 5. Which initial intervention would be most appropri- C. Mirabegron 25 mg daily. ate to help with C.S.’s cognitive function? D. Duloxetine 20 mg daily. A. Donepezil 10 mg daily. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-317  Geriatrics Questions 9 and 10 pertain to the following case. 850 mg twice daily, levothyroxine 100 mcg daily, P.L., a 69-year-old man, is admitted to the hospital after folic acid 1 mg daily, methotrexate 15 mg weekly, a motorcycle collision. He had serious injuries resulting naproxen 500 mg twice daily, calcium 600 mg in a left leg above-the-knee amputation and has under- twice daily, and vitamin D 1000 units twice daily. gone several surgical procedures and rehabilitation Her laboratory tests show a positive rheumatoid in the past 2 weeks. His current medications include factor (RF) and positive anti–cyclic citrullinated tamsulosin 0.4 mg daily, atenolol 25 mg daily, amlodip- peptides. The physician determines that this is a ine 10 mg daily, senna/docusate 8.6/50 mg twice daily, flare of severe disease. Which would be the most oxycodone controlled release 10 mg every 12 hours, appropriate intervention for maintenance treat- and hydromorphone 4 mg every 3 hours as needed for ment of this patient’s RA? breakthrough pain (uses 1 or 2 tablets daily). His blood A. Change naproxen to prednisone 20 mg daily. pressure is 155/88 mm Hg, heart rate is 84 beats/min- B. Change methotrexate to 25 mg intramuscularly. ute, and postvoid residual (PVR) volume is 400 mL after voiding 110 mL. His chronic medical conditions C. Change methotrexate to leflunomide 20 mg are unremarkable except for hypertension, BPH, and daily. gastroesophageal reflux disease. D. Administer infliximab 3 mg/kg 9.  Which intervention would be most appropriate 12. A 66-year-old man is initiated on allopurinol 100 for P.L.? mg once daily and naproxen 500 mg twice daily A. Change tamsulosin to alfuzosin 10 mg once for the treatment of an acute gout flare. On diag- daily. nosis, no tophi were present, serum urate (SU) was 10.9 mg/dL, and glomerular filtration rate (GFR) B. Increase atenolol to 50 mg daily. was 78 mL/minute/1.73 m 2. His allopurinol dose is C. Change tamsulosin to doxazosin 1 mg daily. increased 2 weeks after initial presentation to 200 D. Reduce hydromorphone to 2 mg every 3 hours mg, and at his 1-month follow-up, the allopurinol as needed for breakthrough pain. dose was further increased to 300 mg once daily. Naproxen was discontinued because his symptoms 10. One year later, P.L. returns for concerns related to had resolved; SU was 8.7 mg/dL and GFR was 84 BPH. His blood pressure is 118/74 mm Hg, heart mL/minute/1.73 m2. He is seen 2 weeks later for an rate is 78 beats/minute, and PVR volume is 220 emergency follow-up because he has developed a mL after voiding 150 mL. His current medications new rash; SU is 7.4 mg/dL and GFR is 72 mL/min- include doxazosin 4 mg daily, atenolol 25 mg daily, ute/1.73 m2. Which is best for managing his gout at and amlodipine 10 mg daily. Which is the most this time? appropriate intervention for P.L.? A. Increasing allopurinol to 400 mg daily. A. Initiate tadalafil 5 mg daily. B. Reinitiating naproxen 500 mg twice daily. B. Initiate finasteride 5 mg daily. C.  Changing allopurinol to febuxostat 40 mg C. Initiate alfuzosin 10 mg daily. daily. D. Initiate saw palmetto supplement daily 40 mg D.  Changing allopurinol to pegloticase 8 mg injected into affected joint. intravenously every 2 weeks. 11. A 72-year-old woman (height 66 inches, weight 82 kg) whose medical history is significant for rheumatoid arthritis (RA), type 2 diabetes, gas- troesophageal reflux disease, and hypothyroidism presents to the clinic with inflammation of the joints of the hands and stiffness lasting 1–2 hours in the morning. She smokes. Her current medica- tions include pantoprazole 40 mg daily, metformin ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-318  Geriatrics BPS Pharmacotherapy Specialty Examination Content Outline This chapter covers the following sections of the Pharmacotherapy Specialty Examination Content Outline, tested during the Spring 2024 window: 1. Patient-Centered Pharmacotherapy a. 1.1. Develop patient-centered, evidence-based pharmacotherapy plans. Subtasks: 1.1.1–1.1.3, 1.1.6, 1.1.8, 1.1.9, 1.1.11, 1.1.13 b. 1.2. Monitor the patient to ensure safe and effective pharmacotherapy. Subtasks: 1.2.2, 1.2.4 c. 1.3. Modify pharmacotherapy plans through ongoing patient assessment. Subtasks: 1.3.1, 1.3.2 This chapter covers the following sections of the Pharmacotherapy Specialty Examination Content Outline, tested starting Fall 2024: 1. Patient Care Specialty Areas a. 1A. Primary Pharmacotherapy Specialty Areas. Subtask: 1A4 b. 1B. Secondary Pharmacotherapy Specialty Areas. Subtask: 1B2 c. 1C. Tertiary Pharmacotherapy Specialty Areas. Subtasks 1C4, 1C7 2. Therapeutics and Patient Management a. 2A. Treatment Planning. Subtasks: 2A1–2A3, 2A5 b. 2B. Therapeutic Implementation. Subtasks: 2B1, 2B2 c. 2C. Treatment Outcomes and Monitoring. Subtasks: 2C1–2C3 3. Professional Practice a. 3A. Quality of Care. Subtask: 3A4 b. 3C. Practice Management. Subtask: 3C1 ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-319  Geriatrics I. OPTIMIZING PHARMACOTHERAPY IN OLDER ADULTS A. Aging 1. Aging is a normal process whereby the human body declines after peak growth and development. In general, aging results as the body responds to environmental stressors according to the person’s health and lifestyle factors together with genetic makeup. If environmental stressors are severe enough or indi- viduals have too small a reserve capacity, aging causes frailty, disability, and increased vulnerability to disease and death. 2. Currently, 54.1 million of Americans (16%) (U.S. Census Bureau 2022) are 65 and older. This is pro- jected to increase to 95 million (23%) by 2060. Older adults constitute about 16% of the population but are responsible for: a. 34% of medication costs b. 36% of hospital stays c. 40% of medication-related hospitalizations d. 50% of medication-related deaths 3. At least $30 billion/year is spent on medication-related morbidity. 4. There is large heterogeneity in older adults: Racial and ethnic diversity among older adults is increas- ing, and incomes have a wide range; some people live independently into their 90s and beyond, whereas others become frail and dependent at a younger age. Measurement of aging with years of life is insen- sitive to the differences between older adults. a. If an individual survives to age 65, he or she will likely live an additional 13–20 years. b. If an individual survives to age 85, he or she will likely live an additional 6–7 years. B. Pharmacokinetic Changes Associated with Aging (Table 1) 1. Common physiologic changes occur in most older adults, but they are highly variable because of differ- ences in genetics, lifestyle, and environment. Table 1. Common Physiologic Changes with Age That May Change Drug Pharmacokinetics Organ System Physiologic Change with Aging Effect on Pharmacokinetics GI ↑ Or no change in stomach pH ↓ Absorption of some drugs and nutrients requiring ↓ GI blood flow acidic environment Slowed gastric emptying Absorption rate may be prolonged Slowed GI transit Skin Thinning of dermis ↓ Or no change to drug reservoir formation with Loss of subcutaneous fat transdermal formulation Body ↓ Total body water ↑ Volume of distribution and accumulation of lipid- composition ↓ Lean body mass soluble drugs ↑ Body fat ↓ Volume of distribution of water-soluble drugs ↓ Or unchanged serum albumin ↑ Free fraction of highly protein-bound drugs ↑ α1-Acid glycoprotein Liver ↓ Liver mass ↓ First-pass extraction and metabolism ↓ Blood flow to the liver ↑ Half-life depending on the drug’s volume of ↓ Or no change in CYP enzymes distribution ↓ Clearance of drugs with a high first-pass extraction and metabolism ↓ Or no change in phase I metabolism No change in phase II drug metabolism ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-320  Geriatrics Table 1. Common Physiologic Changes with Age That May Change Drug Pharmacokinetics (Cont’d) Organ System Physiologic Change with Aging Effect on Pharmacokinetics Renal ↓ GFR ↓ Renal elimination of many medications ↓ Renal blood flow ↑ Half-life of renally eliminated drugs and metabolites ↓ Tubular secretion ↓ Renal mass 2. Absorption a.  Iron, vitamin B12, antifungals, and calcium are decreased with hypochlorhydria or achlorhydria. b. Slower gastric emptying may increase the risk of ulceration from aspirin, NSAIDs, bisphospho- nates, or potassium chloride tablets. c. Most drugs are absorbed by passive diffusion without significant age-related changes. d. Transdermal formulations usually require a subcutaneous fat layer to form a drug reservoir for absorption. Use with caution in patients who are thin or who have cachexia. 3. Distribution a. Lipid-soluble medications (e.g., diazepam) have an increased half-life in older adults. b. Highly albumin-bound drugs (e.g., phenytoin) may have a larger fraction of free (active) drug. c. P-glycoprotein, an efflux transporter for several organs including the brain, decreases with aging, which may lead to higher brain concentrations of medications (e.g., opioid analgesics). 4. Metabolism a. Morphine and propranolol bioavailability is substantially increased because of a reduction in first- pass metabolism. Expect other drugs with high first-pass metabolism to be similarly affected. b. Changes in metabolism through phase I (oxidative) reactions catalyzed by CYP enzymes are vari- able and confounded by age, sex, concomitant drugs, and genetics. c. Lorazepam, oxazepam, and temazepam depend solely on phase II metabolism and are less affected by age-related changes in metabolism. 5. Excretion a. Drugs eliminated through glomerular filtration must be dosed according to individual estimated renal function. b. The Cockcroft-Gault equation is a validated method for estimating CrCl for drug dosing in older adults. Note the exceptions (e.g., dabigatran, dofetilide, rivaroxaban) that used actual body weight in the Cockcroft-Gault equation during drug development, rather than ideal body weight, which is reflected in the labeled dosing. In addition, clinicians may use adjusted weight for patients with obesity with formulas used for younger adults, though evidence in older adults is lacking. c. Some clinicians round the SCr concentration up to 1 mg/dL because older adults have lower muscle mass, which produces less creatinine, and an extremely low SCr would overestimate renal function with these formulas. This rounding is not supported by evidence and remains controversial. C. Pharmacodynamic Changes Common with Aging 1. Central nervous system: Increased permeability of blood-brain barrier leads to increased sensitivity and adverse effects. a. Anticholinergic agents: Confusion, agitation, hallucinations b. Benzodiazepines and opioids: Somnolence, confusion, agitation c. Antipsychotics and metoclopramide: Extrapyramidal effects and tardive dyskinesia d. Tricyclic antidepressants, α-blockers, α2-agonists: Orthostatic hypotension, drowsiness, confusion ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-321  Geriatrics 2. Gastrointestinal a. Increased pH can lead to decreased vitamin or drug absorption (vitamin B12). b. Increased risk of bleeding because of NSAIDs 3. Cardiovascular (CV): Increased catecholamine concentrations lead to down-regulation of β1-receptors. a. Blunted effect of β-blockers b. Increased sensitivity to QT-prolonging agents: Antipsychotics, fluoroquinolones, azithromycin 4. Impaired homeostasis a. Diuretics, angiotensin-converting enzyme inhibitors: Sodium and electrolytes b. Diuretics: Hydration status Patient Case 1. An 85-year-old woman (weight 65 kg) who resides at home with her daughter has a medical history significant for type 2 diabetes and hypertension, and 1 year ago, she had a right hip fracture after a fall. Her regularly scheduled medications include glyburide 10 mg daily, lisinopril 10 mg daily, metformin 500 mg twice daily, and a multivitamin daily. Her as-needed medications include melatonin 6 mg at bedtime as needed for sleep, meclizine 25 mg ½ tablet three times daily as needed for dizziness, and docusate 100 mg twice daily. Her laboratory results show fasting plasma glucose 90 mg/dL, Na 138 mEq/L, K 4.5 mEq/L, Cl 102 mEq/L, CO2 25 mEq/L, BUN 30 mg/dL, SCr 1.8 mg/dL, and TSH 4.0 mU/L. Considering the potential for altered pharma- cokinetics and pharmacodynamics with aging, which pair of medications is most likely to place this patient at risk of an adverse drug event? A. Docusate and melatonin. B. Metformin and meclizine. C. Lisinopril and meclizine. D. Glyburide and metformin. D. Drug-Related Risk Assessment for Older Adults 1. Medication overuse a. Unnecessary drugs: Use of more medications than clinically indicated and unneeded therapeutic duplication b. Common unnecessary drugs: GI agents, CNS agents, vitamins, minerals c. Etiology i. Prescribing cascade: When a drug is prescribed for treating another drug’s adverse effects ii. Several prescribers iii. Inadequate transitions of care 2. Medication underuse a. Omitted but necessary or indicated drug therapy or inadequate dosing b. Commonly underused drugs: Anticoagulants, statins, antihypertensives c. Medications considered appropriate according to guidelines may be omitted because the prescriber or patient is overly wary of adverse drug effects. 3. Nonadherence a. Unintentional nonadherence caused by complex drug regimen b. Dementia or other cognitive impairment increases risk. c. Cost of medications d. Intentional nonadherence because of patient health beliefs or concerns ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-322  Geriatrics 4. Withdrawal syndromes a. Abrupt discontinuation of medication may cause rebound symptoms or delirium. b. Common culprits: Antihypertensives, antidepressants, anxiolytics, pain medications 5. Inappropriate medications a. Explicit tools: Objective statements that do not require clinical judgment for interpretation i. AGS Beers Criteria for potentially inappropriate medication use in older adults (a) Evidence-based list of drugs likely to disproportionately affect older adults (i.e., increased risk of falls, confusion, and death) (b) Adopted by many federal agencies and Part D plans (c) Arranged as drugs and drug classes to avoid, drugs to avoid in certain diseases or condi- tions, and drugs to be used with caution (d) Examples: Anticholinergics, benzodiazepines, sedative-hypnotics, select opioids, hypo- glycemics, NSAIDs, proton pump inhibitors, select anticoagulants, and aspirin for pri- mary prevention ii. The screening tool of an older person’s prescriptions and the screening tool to alert to right treatment (STOPP/START) criteria b. Implicit tools: Patient centered; interpretation requires clinical judgment and patient-specific infor- mation. Regarding the Medication Appropriateness Index: i. 10 questions to ask about each medication regarding indication, effect, dosing, directions, interactions, duration, and cost ii. Indication, effectiveness, and correct dosage carry the most weight. iii. Does not assess drug allergies, adverse drug reactions, or adherence 6. Choosing Wisely criteria a. 10 things to question in older adults b. 7 of the 10 items are drug related. i. Antipsychotics in patients with dementia should be avoided. ii. The target A1C in diabetes management is 7.5% or higher. iii. Avoid benzodiazepines and sedative-hypnotics for insomnia, agitation, or delirium. iv. Do not initiate antimicrobials for bacteriuria without symptoms. v. Assess the benefit-risk of cholinesterase inhibitors (CIs). vi. Appetite stimulants are not helpful for anorexia or cachexia. vii. Drug regimen review is necessary with every new prescription. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-323  Geriatrics Patient Case 2. A 70-year-old woman (height 66 inches, weight 71.7 kg [158 lb]) is in the clinic for an evaluation by the clinical pharmacist for polypharmacy. She has concerns of fatigue, light-headedness, constipation, and “too many medicines.” Her medical history is significant for hypertension, chronic obstructive pulmonary disease, diabetes, frequent UTIs, depression, and moderate dementia. Her vital signs include blood pressure 160/82 mm Hg, heart rate 49 beats/minute, respiratory rate 16 breaths/minute, and Sao2 99% on room air. Her current medications are as follows: fluticasone/salmeterol 250/50 1 puff twice daily, aspirin 81 mg daily, acetamin- ophen 650 mg three times daily, clopidogrel 75 mg daily, donepezil 10 mg daily, glipizide 5 mg twice daily, lisinopril 10 mg daily, loratadine 10 mg daily, metoprolol 50 mg twice daily, paroxetine 40 mg daily, famoti- dine 10 mg twice daily, and simvastatin 40 mg at bedtime. Nitrofurantoin 100 mg twice daily for 10 days was initiated 3 days ago. Laboratory values from her physician visit 3 days before are as follows: Na 130 mg/ dL, K 4.2 mEq/dL, Cl 99 mg/dL, CO2 24 mEq/dL, BUN 24 mg/dL, SCr 1.6 mg/dL, fasting glucose 67 mg/ dL, A1C 6.3%, urinalysis unremarkable except for blood-small, pH 7.5, RBCs 11–25/high-power field (HPF), white blood cells 0–2/HPF, and bacteria 168/HPF. Which medication list best depicts the medications with the greatest potential to harm this patient, according to the AGS 2023 Beers Criteria? A. Paroxetine, donepezil, aspirin. B. Donepezil, glipizide, simvastatin. C. Glipizide, donepezil, nitrofurantoin. D. Metoprolol, aspirin, famotidine. F. Changes in Function Associated with Aging 1. Quality of life, place of residence, and social and physical function may become more important than duration of life. 2. Instrumental activities of daily living (IADLs): Examples: Doing housekeeping, using telephone, man- aging medications, shopping, cooking, managing money 3. Activities of daily living (ADLs): Examples: Feeding, dressing, bathing, toileting, transferring 4. Cognitive screening 5. Mood: Geriatric Depression Scale a. More sensitive to older adults b. Validated in various settings (e.g., home, long-term care) and in patients with various cognition c. The long form is composed of 30 questions; the 15-question tool (GDS-15) is more commonly used. A score of 5 or higher on the GDS-15 suggests depression. 6. Gait and balance G. Geriatric Syndromes 1. Geriatric syndromes follow a concentric model, with many risk factors and several etiologies con- tributing to a clinical presentation, rather than the linear model with one etiology following a defined pathogenesis. 2. Falls a. Possible etiologies: Psychoactive medications, polypharmacy, orthostatic hypotension, hypoglyce- mia, hyponatremia, myocardial infarction, UTI b. Examples of contributing risk factors: Vitamin D deficiency, poor balance, deconditioning/muscle weakness, poor vision, environment ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-324  Geriatrics 3. Delirium a. A disturbance in attention and awareness developing over hours to days, with fluctuation b. Possible etiologies: Psychoactive medications, polypharmacy, hypoglycemia, hyponatremia, myo- cardial infarction, infection c. Examples of contributing risk factors: Dementia, stroke, vitamin B12 deficiency, poor hearing, lack of sleep, constipation, pain, thyroid disorder 4. Hazards of hospitalization a. Immobilization leads to deconditioning, which increases risk of falls and fractures. Regaining what was lost takes longer in older adults. b. Immobilization and “tethers” (e.g., intravenous lines, oxygen lines, catheters) necessitate nursing assistance to bathroom. Unavoidable delay may lead to incontinence, catheters, infections, falls, and pressure sores. c. Sensory deprivation from isolation and inaccessibility to glasses or hearing aids can lead to delirium. d. Prescribed diets or nothing-by-mouth status can lead to an increased risk of dehydration, decreased plasma volume, malnutrition, insertion of feeding tubes, and aspiration pneumonia. e. Preventable adverse drug events are common contributors to increased morbidity and mortality in older hospitalized adults. f. Early mobility, adequate nutrition, reduced polypharmacy, and early discharge planning may reduce functional disability and length of stay. Patient Case 3. A 70-year-old woman is admitted to the hospital with a broken arm after a fall. While in the hospital, she is on bedrest most of the time, loses 2 kg (current weight 63 kg), and has trouble sleeping. She is to be discharged to a rehabilitation facility for 2–3 weeks of therapy. Her medications at discharge are glipizide 5 mg daily, lisinopril 10 mg daily, aspirin 81 mg daily, a multivitamin daily, mirtazapine 15 mg at bedtime, calcium 500 mg twice daily, and tramadol 25 mg every 8 hours as needed for pain. To maintain and improve function in this patient, which intervention is best to implement? A. Add atorvastatin 10 mg daily. B. Increase lisinopril to 20 mg daily. C. Add vitamin D 1000 units twice daily. D. Change tramadol to naproxen 500 mg twice daily as needed for pain. II. DEMENTIA A. Epidemiology 1. Affects 4–5 million people in the United States 2. Of people 65 and older, 6% have dementia, increasing to 30%–50% of those 85 and older. B. Dementia Definition: Cognitive decline in complex attention, executive function, learning and memory, language, and/or perceptual-motor or social cognition AND interferes with work or social functions 1. Delirium should be ruled out and reversible causes corrected first. 2. Mild cognitive impairment (MCI) is the condition of people with some deficits in cognition who do not meet the criteria for dementia. 3. AD is the most common and most studied type of dementia. 4. Theories of pathogenesis include cholinergic, β-amyloid plaques, tau protein (neurofibrillary tangles), genetics (apolipoprotein E4 ), and inflammation (cytokines, prion). ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-325  Geriatrics Table 2. Comparisons of Memory Impairment and Dementias with AD Disease Differences from AD Treatment Notes Common Irreversible Causes MCI No interference with work or social functions Eliminate or control risk factors for One in five patients progress to AD dementia May use CIs, which reduced risk of progression by 40% in one study Vascular Includes focal neurologic signs and symptoms Control of cardiac and vascular risk factors dementia Radiologic evidence of stroke CIs and memantine not effective Onset within 3–6 mo of stroke Abrupt deterioration followed by stepwise progression Lewy body Fluctuating cognition with pronounced variation in Especially avoid typical antipsychotics, dementia attention and alertness which may worsen motor symptoms Recurrent visual hallucinations May use CIs Motor features of PD Dementia of PD onset predates cognitive impairment Especially avoid typical antipsychotics, advanced PD Usually at latter stages of PD which may worsen motor symptoms May use CIs Frontotemporal Affects personality, behavior, self-care, and CIs may worsen behavior and cause agitation dementia language SSRIs or trazodone may be beneficial Onset in ages 45–65 with a 2- to 10-yr course Reversible Causes Vitamin B12 Progressive memory loss Replace vitamin B12 according to standard deficiency Vitamin B12 serum concentration < 300 pg/mL protocols May be anemic also, but folic acid may disguise the anemia Hypothyroidism Deficient or inadequate replacement of thyroxine Levothyroxine replacement according to standard protocols Depression Trouble with concentration and memory Treatment of depression according to Apathy and “I don’t care” responses standard protocols NPH Triad of progressive memory loss, Surgical placement of ventricular shunt incontinence, and gait abnormality Symptoms improve after lumbar puncture Medications Anticholinergics, muscle relaxants, opioids, Decrease dose or deprescribe as appropriate antiseizure medications, benzodiazepines, and tricyclic antidepressants may increase memory loss and confusion mimicking symptoms of dementia AD = Alzheimer disease; CI = cholinesterase inhibitor; MCI = mild cognitive impairment; NPH = normal pressure hydrocephalus; PD = Parkinson disease; SSRI = selective serotonin reuptake inhibitor. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-326  Geriatrics C. Assessment Tools 1. Cognitive assessment tools a. Mini-Mental State Examination (Table 3) i. 30-point scale; higher score indicates better function ii. Untreated AD: Score usually decreases by 3 or 4 points a year. iii. Heavily relies on verbal and language skills, so is less accurate if education is poor iv. Requires fee to administer examination b. SLUMS examination i. 30-point scale; higher score indicates better function ii. Includes adjustment of scores for lower educational status c. Montreal Cognitive Assessment i. 30-point scale; higher score indicates better function ii. Less reliant on verbal or language skills iii. Requires training and fee to use assessment d. Mini-Cog assessment i. 5-point scale; higher score indicates better function, but does not stage disease ii. Easiest to administer; takes 3 minutes 2. Functional assessment tools: Reisberg Functional Assessment Staging (FAST) scale (Table 4) a. 16-item scale correlating with activity limitations and decline associated with AD b. Stage 7 associated with prognosis of 6 months or less life expectancy D. Diagnostic Guidelines 1. Recognizes three phases: a. Preclinical, asymptomatic phase b. Symptomatic, predementia phase (MCI) c. Dementia phase 2. Diagnosis may be identified for research purposes by: a. Biomarkers of increased tau or decreased β-amyloid concentrations in CSF b. Reduced glucose uptake in brain on positron emission tomography scanning using florbetapir F18 or flutemetamol F18 c. Atrophy of specific brain areas on MRI 3. Preclinical and predementia phases are targets for investigational studies to halt progression. 4. For clinicians, diagnosis is typically made without these biomarkers or imaging. E. Clinical Presentation and Classification Table 3. Stages of Alzheimer Disease MMSE Score Examples of Cognitive Loss Examples of Functional Loss (out of 30) Mild 20–24 Some short-term memory loss; Loss of IADLs such as laundry, housekeeping, word-finding problems and managing medications; may get lost in familiar places Moderate 10–19 Disorientation to time and place, Needs assistance with ADLs such as bathing, inability to engage in activities and dressing, and toileting conversation Severe < 10 Loss of speech and ambulation, Dependency in basic ADLs such as feeding incontinence of bowel and bladder oneself; often needs around-the-clock care ADLs = activities of daily living; IADLs = instrumental activities of daily living; MMSE = Mini-Mental State Examination. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-327  Geriatrics Table 4. Activity Limitation with AD FAST Scale Item Activity Limitation with AD Stage 1 No difficulty Stage 2 Subjective work difficulties; forgetting location of objects Stage 3 Work difficulties evident to coworkers; difficulty traveling to new locations Stage 4 Difficulty performing complex tasks (finances, planning) Stage 5 Requires assistance choosing proper clothing (season or occasion) Stage 6 Decreased ability to independently bathe, dress, and toilet 6a Difficulty dressing properly 6b Unable to bathe properly 6c Unable to toilet properly (forget flushing, improper wiping) 6d Urinary incontinence 6e Fecal incontinence Stage 7 Loss of speech, ambulation, and consciousness 7a Speech limited to 1–5 words per day 7b Intelligible vocabulary lost 7c Nonambulatory 7d Unable to sit up 7e Unable to smile 7f Unable to hold head up AD = Alzheimer disease. F. Management 1. Goals are to maintain function and cognition. 2. Nonpharmacologic therapy a. Education, especially with caregiver b. Physical exercise and mental exercise c. Management of comorbid conditions d. Avoid alcohol and medications that worsen mentation. Patient Case 4. An 84-year-old widow lives at home alone. She can perform ADLs and most IADLs with her daughter’s assistance. Her current medications are hydrochlorothiazide 12.5 mg daily for hypertension, tolterodine long acting 4 mg daily for incontinence, escitalopram 20 mg daily for depression, acetaminophen 650 mg as needed for arthritis, and calcium/vitamin D for prevention of osteoporosis. The patient’s physician administers the MMSE, and her score is 23/30. On physical examination, no cogwheel rigidity or tremor is noted. Which recommendation would be best at this time? A. Add donepezil 5 mg daily. B. Discontinue tolterodine and reassess the patient. C. Add a vitamin B12 1000-mg injection monthly. D. Change hydrochlorothiazide to lisinopril 5 mg daily. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-328  Geriatrics 3. Pharmacologic therapy (Table 5) a. Controversy over significance of clinical response b. Mild to moderate AD: Initiate CI. i. No evidence that one agent is superior to others ii. Titrate to recommended maintenance dose as tolerated. iii. May increase to maximum dose if tolerated and maintenance dose no longer effective, or try alternative CI, but clinically meaningful improvement unlikely c. Moderate to severe AD: May initiate N-methyl-d-aspartate (NMDA) receptor antagonist (meman- tine), CI, or combination: Slight or no benefit with combination therapy in systematic reviews d.  Disease-modifying immunotherapies i.  Anti–amyloid monoclonal antibody treatments (a) Directed against aggregated β-amyloid, thus reducing β-amyloid plaques (b) Indicated for MCI or mild dementia of AD ii. Anti-tau monoclonal antibody therapies under phase II and phase III clinical trials Table 5. Comparison of Drugs for AD Treatment Starting Maintenance Dosage Adverse Effects Drug Dose Dose Forms Comments Cholinesterase Inhibitors Donepezil 5 mg daily 10 mg daily Tablets GI: Nausea, vomiting, May increase Orally diarrhea to 23 mg/day disintegrating CNS: Headache, tablets insomnia, dizziness Rivastigmine 1.5 mg 3–6 mg twice Capsules Cardiac: Bradycardia, Highest rate of GI effects twice daily daily orthostatic Oral solution Labeled for dementia with hypotension, syncope 4.6-mg 9.5-mg patch Transdermal Parkinson disease as well (AGS Beers Criteria patch daily daily; may patch Monitor for skin reactions for patients with increase to with patch syncope) 13.3-mg patch daily Long-term risks: Falls, hip fracture, Galantamine 4 mg twice 8–12 mg twice Tablets Preferable to administer pacemaker placement daily daily Oral solution with food 8 mg ER 8–24 mg ER ER capsules Renal dosing adjustment once daily once daily necessary NMDA Receptor Antagonist Memantine 5 mg once 10 mg twice Tablets CNS: Headache, Usually well tolerated daily daily Oral solution dizziness, 7 mg ER 28 mg ER confusion, agitation, ER capsules once daily once daily hallucinations GI: Diarrhea, vomiting Combination Product Donepezil/ 10/28 mg 10/28 mg once ER capsule See above Use after stabilized on memantine once daily daily donepezil and memantine in the separately evening Renal dosing adjustment necessary ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-329  Geriatrics Table 5. Comparison of Drugs for AD Treatment (Cont’d) Starting Maintenance Dosage Adverse Effects Drug Dose Dose Forms Comments Disease-Modifying Immunotherapies (anti–amyloid monoclonal antibodies) Aducanumab 1 mg/ 10 mg/kg IV infusion Diarrhea, confusion, Dose based on actual kg every every 4 wk for altered mental status body weight 4 wk for infusions 7–12 MRI brain within 1 yr infusions 1 before initiation required; Serious: ARIA-H and 2, then additional MRIs if (micro-hemorrhage), titrate patient experiences signs/ ARIA-E (brain edema, headache), seizure symptoms of ARIA Lecanemab 10 mg/kg 10 mg/kg IV infusion Headache, infusion Dose is based on actual every 2 wk every 2 wk reaction body weight; MRI Serious: ARIA-E, brain before initiation ARIA-H, anaphylaxis, and before 5th, 7th, decreased lymphocytes and 14th infusions. Additional MRIs if patient experiences signs/ symptoms of ARIA AD = Alzheimer disease; ARIA-E = amyloid-related imaging abnormalities-edema; ARIA-H = amyloid-related imaging abnormalities-hemo- siderin deposition; IV = intravenous(ly); MCI = mild cognitive impairment. 4.Therapy duration a. The Choosing Wisely criteria recommend evaluating with objective tools at 12 weeks and consid- ering discontinuation if the goals of therapy are not met. b. Studies investigating long-term efficacy beyond 1 year are limited, but many patients receive the drug for years. c. Recommend to discontinue at advanced stages of disease (FAST stage 7) i. Tapering is recommended if the patient is taking a high dose. ii. Rebound agitation may occur. Patient Case 5. A 75-year-old woman with AD who lives at home with her husband has been treated with donepezil 10 mg daily for about 3 years. When she began therapy, her MMSE score was 21/30; her present MMSE score is 17/30. The patient cannot perform most IADLs but can perform most ADLs with cueing. About 2 months ago, her donepezil dose was increased to 23 mg, but she could not tolerate it, and it was reduced back to 10 mg daily. Her husband asks about changing her drug treatment to help maintain her function. Which is the next best course of action? A. Retry donepezil 23 mg daily. B. Initiate memantine 5 mg daily. C. Initiate an aducanumab 1-mg/kg infusion every 4 weeks. D. Change donepezil to a rivastigmine 9.5-mg patch daily. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-330  Geriatrics III. BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA A. Epidemiology 1. As disease progresses from mild to moderate, behavioral and psychological symptoms of dementia (BPSD) occur. These tend to wane as the disease progresses to severe. 2. Up to 90% of patients with dementia have BPSD at some point in disease progression. 3. Associated with high rate of disability, functional decline, poor health outcomes, physical injury, nurs- ing home placement, and emergency services 4. Behaviors commonly peak during late afternoon or early evening and are thus called “sundowning.” B. Assessment 1. Scales are rarely used in nursing homes or clinical practice, but it is important to identify the target behavior, how often it is occurring, and how severe it is in order to assess the treatment response. 2. Assess for a medical reason that may precipitate the target behavior and treat it, if found. a. Delirium precipitated by medical illness or medication should be ruled out. b. Often, patients cannot communicate issues like pain, constipation, or sleep. Treat with scheduled regimens instead of as needed (e.g., scheduled acetaminophen, bowel regimens, or melatonin). C. Nonpharmacologic Treatment: Cornerstone of Therapy 1. The theory is that behavior is the communication of unmet need. 2. Eliminate antecedents and triggers. 3. Person-centered interventions: Consider patient’s longstanding habits, values, and beliefs; use distrac- tion, music, aromatherapy, and pet therapy. 4. Symptoms likely to respond: Wandering, hoarding, hiding objects, repetitive questioning, withdrawal, social inappropriateness, apathy D. Pharmacologic Treatment: Many of these DO NOT have FDA-labeled indications for BPSD (Table 6). 1. Agency for Healthcare Research and Quality has published a summary on the use of atypical antipsy- chotic agents for off-label indications. Atypical antipsychotics improve behavioral symptoms of demen- tia, but effect sizes are small and adverse effects are significant. 2. Antipsychotic medications may increase the risk of death when used in older adult patients with dementia-related psychosis (black box warning). 3. In May 2023, brexpiprazole was the first and only antipsychotic to receive FDA approval for treatment of agitation caused by dementia of AD. a. Still carries black box warning (see earlier) b. Studies examined participants with established agitation (at least 2 weeks) and assessed response over 12 weeks. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-331  Geriatrics Table 6. Drug Treatment for BPSD Symptom Presentation Treatment Options After Nonpharmacologic Efforts Ineffective Anxiety Part of this is because they Buspirone or SSRI/SNRI or gabapentin cannot remember things Limit benzodiazepines Apathy One of the earliest symptoms CIs Nonpharmacologic treatment Methylphenidate effective in small, short-term studies tailored to patient’s activities Depression Up to 80% of patients with AD SSRI or mirtazapine have depression Insomnia Sleep-wake cycle is disrupted Melatonin Mirtazapine can be considered if concomitant depression Wandering Walk so much they begin to lose No drug will stop patients from wandering weight Paranoia, They may think that because they Risperidone, olanzapine, quetiapine, and aripiprazole hallucinations, cannot find something, you stole it have been tried. Use very low doses. ADEs may offset sundowning, Often accuse spouse of infidelity any benefit agitation For patients with parkinsonian symptoms, quetiapine is If psychosis and delusions do not bother anyone, do not use drugs preferred because of decreased dopaminergic activity and EPS Pimavanserin can be used for PD-related psychosis. Aggression, Most difficult and best response is Valproic acid products commonly used despite resistance to care to treat nonpharmacologically controversial evidence that benefits outweigh risk. Drugs under investigation for agitation include prazosin, dextromethorphan/quinidine, and citalopram AD = Alzheimer disease; ADE = adverse drug effect; BPSD = behavioral and psychological symptoms of dementia; CI = cholinesterase inhibitor; EPS = extrapyramidal symptoms; PD = Parkinson disease; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-332  Geriatrics Patient Case Questions 6 and 7 pertain to the following case. You are evaluating the medication profile of an 87-year-old woman who resides in a secure advanced dementia unit. Her medical history includes dementia (likely AD), Parkinson disease (PD), and OA. She needs assistance with all ADLs, including total assistance with bathing and dressing, as well as help with feeding. She transfers with minimal help to using a wheelchair. Her medication regimen includes donepezil 10 mg daily, memantine 10 mg twice daily, carbidopa/levodopa 25/100 mg four times daily, and a multivitamin supplement daily. The patient’s most recent MMSE score is 5/30. When reviewing the nursing notes, you see several references to the patient’s continuously crying out, “Help me, help me,” beginning around 5 p.m. On medical evaluation, revers- ible causes of her hypervocalization are ruled out. 6. Which initial approach is most appropriate for this patient? A. Initiate ibuprofen 400 mg every 8 hours. B. Order haloperidol 1 mg every 6 hours as needed for agitation. C. Begin music therapy with songs the patient enjoyed when younger. D. Move the patient to a private room to minimize social contacts after 3 p.m. 7. After 2 months, the patient’s agitation increases such that the nursing staff cannot bathe or feed her. Assuming nonpharmacologic approaches are ineffective, which is the best pharmacologic approach to treat her behavioral symptoms? A. Increase donepezil to 23 mg daily. B. Begin melatonin 6 mg at bedtime. C. Add quetiapine 25 mg at 4 p.m. daily. D. Add citalopram 10 mg daily. IV. URINARY INCONTINENCE A. Epidemiology 1. Prevalence in community-dwelling older adult women is 38%. 2. Less common in older adult men: 17% 3. Up to 75% of nursing home residents have urinary incontinence (UI). 4. Transient incontinence can occur because of DRIP: D = Drugs, Delirium R = Retention, Restricted Mobility I = Impaction, Infection, Inflammation P = Polyuria, Prostatitis B. Physiology 1. During filling, β3-adrenergic stimulation relaxes detrusor muscle to increase capacity. 2. α-Adrenergic stimulation tightens the internal bladder sphincter. 3. Acetylcholine (M3 receptors) mediates involuntary and volitional bladder contractions. 4. Normal bladder emptying occurs with a decrease in urethral resistance and contraction of the bladder muscle. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-333  Geriatrics 5. Aging effects include decreased bladder elasticity and capacity, more frequent voiding, decline in blad- der outlet and urethral resistance in women with loss of estrogen, and decrease in flow rate in men with prostatic enlargement. C. Types of UI Table 7. Common Types of UI and Drug-Induced Causes Type of Description Drug-Induced Causes Incontinence Urge or overactive Loss of a moderate amount of urine with an Cholinergic agents that stimulate the bladder bladder increased need to void such as bethanechol and CIs Common in patients with AD, PD, MS, and stroke Stress incontinence Loss of small amounts of urine with increased α-Blockers such as prazosin decrease abdominal pressure (e.g., sneezing, coughing) urethral sphincter tone Stress UI is more common in postmenopausal women Overflow Loss of urine because of excessive bladder Anticholinergic agents, calcium channel incontinence volume caused by outlet obstruction or an blockers, and opioids decrease detrusor acontractile detrusor muscle contractions PVR is often high (> 300 mL), indicating incomplete emptying Functional Inability to reach the toilet because of mobility Sedating drugs that cause confusion incontinence constraints Diuretics increase voiding Mixed incontinence UI that has more than one cause, usually stress and overactive bladder AD = Alzheimer disease; CI = cholinesterase inhibitor; MS = multiple sclerosis; PD = Parkinson disease; PVR = postvoid residual; UI = urinary incontinence. D. Nonpharmacologic Interventions: First-line Therapy 1. Lifestyle modifications a. Weight loss for patients with a BMI greater than 25–30 kg/m 2 b. Limit/avoid caffeine and alcohol c. Quit smoking d. Limit fluid intake before bedtime 2. Stress incontinence a. Pelvic floor exercises (Kegel exercises) are first line for stress. b. Biofeedback may be needed to teach pelvic floor exercises. c. Pessaries (a prosthetic vaginal insertion device) or bulking agent injections also help stress incontinence. 3. Urge incontinence a. Pelvic floor exercises in combination with medication for urge or mixed UI b. Bladder training to increase time between voiding in urge incontinence c. Peripheral tibial nerve stimulation or sacral neuromodulation techniques are third line after life- style and pharmacologic treatments. 4. Scheduled and timed voiding may be helpful for patients with dementia. 5. Prostatectomy in men or self-catheterization for severe overflow incontinence ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-334  Geriatrics E. Pharmacologic Treatment (Table 8) Table 8. Recommended Pharmacologic Treatment by Type of Incontinence Type of Drug Treatment Comments Incontinence Urge or overactive Antimuscarinic agents Magnitude of clinical efficacy is modest bladder Oxybutynin, tolterodine, Strong anticholinergic effects (on Beers Criteria) fesoterodine, trospium, Long-acting formulations preferred because of modest solifenacin, darifenacin decreased adverse effect profile β3-Agonist Minimal anticholinergic effects Mirabegron, vibegron Cost is commonly a barrier for patients Can be used in combination with antimuscarinic agents if monotherapy fails Avoid in hypertension OnabotulinumtoxinA Prevents stimulation of detrusor muscle Intradetrusor or injections Must be able to perform self-catheterization Stress α-Adrenergic agonists Efficacy evidence is limited Pseudoephedrine, phenylephrine Topical estrogens Use if other symptoms of estrogen deficiency Conjugated estrogen vaginal Vaginal estrogens may improve severity of stress cream or estradiol vaginal insert incontinence or ring Serotonin-norepinephrine Not FDA labeled for stress UI; may reduce the severity reuptake inhibitor of incontinence Duloxetine Adverse effects may limit its usefulness Overflow α-Adrenergic antagonists Adverse effects vary depending on selectivity to Alfuzosin, tamsulosin, silodosin, receptors in the bladder or prostate (alfuzosin, silodosin, doxazosin, terazosin, prazosin and tamsulosin are more specific and preferred in older adults) 5-α-Reductase inhibitors To slow progression Finasteride, dutasteride Reduce the size of the prostate and alter PSA values Cholinomimetics Stimulates the detrusor muscle but also has systemic Bethanechol cholinomimetic effects Phosphodiesterase type 5 5 mg once daily approved for BPH inhibitors Tadalafil Functional No drug treatments Consider interventions to remove any potential cause, barriers, or obstacles; provide schedules or prompted toileting; assistance may be required to transfer on and off commode Mixed Focus on predominating Consider treatments for individual components symptoms (i.e., stress and urge) BPH = benign prostatic hyperplasia; PSA = prostate-specific antigen; UI = urinary incontinence. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-335  Geriatrics Patient Case 8. A 75-year-old woman reports urinary urgency, frequency, and loss of urine when she cannot get to the bath- room in time. She also wears a pad at night that she changes two or three times because of incontinence. Her medical history is significant for MCI (MMSE score 25/30), OA, and hypothyroidism. A urinalysis is negative for leukocyte esterase and nitrites. Physical examination is normal, and her PVR is normal (less than 100 mL). Which therapy would be best to initiate for this patient at this time? A. Mirabegron. B. Darifenacin. C. Pelvic floor exercises and solifenacin. D. Pelvic floor exercises and tolterodine immediate release. V. BENIGN PROSTATIC HYPERPLASIA A. Epidemiology 1. BPH usually develops after age 40. 2. By age 60, 50% of all men have BPH; by age 85, 90% have BPH. B. Pathophysiology and Clinical Presentation 1. Type II 5-α-reductase facilitates conversion of testosterone to dihydrotestosterone, resulting in prostate growth. 2. Lower urinary tract symptoms (LUTS) occur in 25% of men. a. Voiding (obstructive) symptoms: Decreased force, hesitancy, dribbling b. Storage (irritative) symptoms: Urinary urgency, frequency, nocturia, dysuria 3. The American Urological Association Symptom Index (AUASI) score can help determine severity and appropriate treatment. The index consists of seven questions evaluating the severity of LUTS on a 0–5 scale. Higher numbers indicate more severe symptoms. C. Evaluation 1. Medical history, digital rectal examination, BUN, SCr, and urinalysis 2. If prostate cancer is suspected, prostate-specific antigen (PSA) 3. If significant urinary retention is suspected, need to assess PVR. If PVR is greater than 50 mL, patients have an increased risk of infection. 4. Assess for medications that may exacerbate BPH symptoms. a. α-Adrenergic agonists (decongestants) can stimulate smooth muscle contraction in the prostate and urethra, obstructing urinary flow through the urethra. b. Anticholinergic drugs (urinary and GI antispasmodics, antihistamines, tricyclic antidepressants, phenothiazines) can reduce the ability of the bladder detrusor muscle to contract and empty the bladder. c. Diuretics can increase urinary frequency and volume. d. Testosterone replacement can stimulate prostate growth. 5. If the AUASI score is 0–7 (mild), use watchful waiting. 6. Patients with high AUASI scores of 20 and more (severe disease) should be assessed for prostatectomy. 7. Patients with moderate disease (scores 8–19) are candidates for medical treatment. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-336  Geriatrics D. Pharmacologic Treatment (Table 9) 1. α-Adrenergic blockers: These relieve LUTS in men with moderate or severe AUASI scores by reducing smooth muscle contractions in the urethra and surrounding tissues. a. Nonspecific α-adrenergic blockers such as doxazosin and terazosin also lower blood pressure significantly. b. Newer agents are uroselective antagonists of α1-adrenergic receptors (tamsulosin, silodosin) and selective antagonists of postsynaptic α1-adrenergic receptors (alfuzosin) in the prostate and blad- der. They may have less associated hypotension. c. All α-blockers can cause hypotension. d. Compared with placebo, α-blockers lower the AUASI score by 4–6 points in patients with LUTS and BPH. e. All α-blockers are metabolized through the CYP3A4 pathway and have drug interactions with strong CYP3A4 inhibitors and inducers. f. Intraoperative floppy iris syndrome is a concern with α-blockers, especially tamsulosin. Men with LUTS being offered α-blockers should be asked about planned cataract surgery. Men with planned cataract surgery should avoid starting α-blockers until their cataract surgery is completed. If already taking an α-blocker, patients need to inform his surgeon so that precautions can be taken. 2. 5-α-Reductase inhibitors a. These agents prevent the conversion of testosterone to dihydrotestosterone, 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 dihydrotestoster- one by 80%–90%. ii. Dutasteride is a nonselective inhibitor of both type I and II 5-α-reductase. Prostatic dihydro- testosterone production is quickly suppressed with this agent. iii. Despite these pharmacologic differences, finasteride and dutasteride did not differ in trials; both reduced prostate size. b. 5-α-Reductase inhibitors do not immediately reduce LUTS and should be reserved for use in men with a large prostate (more than 30 mL in volume or 40 g in weight). At least 6 months of therapy is usually needed for clinical benefit. Prostate size may be reduced by about 25% during this interval. c. PSA concentrations are used to monitor for prostate cancer. Because these agents lower PSA con- centrations, a baseline PSA test is recommended before initiating α-reductase inhibitors. d. Long-term therapy with an α-reductase inhibitor can increase the risk of high-grade tumors of the prostate in healthy men without a history of prostate cancer. 3. Phosphodiesterase type 5 inhibitors a. Tadalafil 5 mg once daily is approved for use in BPH. b. Mechanism is thought to be caused by phosphodiesterase-induced smooth muscle relaxation in the bladder, urethra, and prostate. c. Studied as monotherapy; the FDA does not recommend use in combination with α-blockers because the combination has not been adequately studied for BPH, and there is a risk of lowering the blood pressure. May be used in practice to treat both BPH and erectile dysfunction 4. Combination therapy a. May be needed in men with LUTS, a larger prostate size, and an elevated PSA or in men with co-occurring symptoms of erectile dysfunction b. Finasteride and doxazosin are the best studied; dutasteride is FDA label approved for use with tamsulosin in symptomatic men having an enlarged prostate. c. Two large clinical trials (Medical Therapy of Prostatic Symptoms [MTOPS] and the Combination of Avodart and Tamsulosin studies [CombAT]) comparing monotherapy with combination therapy concluded that in men with LUTS and an enlarged prostate, further benefit can be achieved using the two drugs in combination. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-337  Geriatrics 5. Supplements a. Saw palmetto plant extract (Serenoa repens) i. Conflicting evidence about the efficacy of saw palmetto in relieving LUTS; 2012 systematic review suggested no benefit over placebo ii. Using this agent with 5-α-reductase inhibitors may reduce the efficacy of the reductase inhibitors. b. β-Sitosterol, Pygeum africanum show some benefit, but short-term studies 6. Management of storage (irritative) symptoms a. Anticholinergic or β3-agonist agents can be appropriate and effective alternatives in men when LUTS are predominantly storage (irritative) symptoms, regardless of PVR. 7. Surgery is preferred in men with severe symptoms and in those with moderate symptoms who lack adequate response to medical options. Table 9. Comparison of Pharmacologic Agents Used for Benign Prostatic Hyperplasia Medication Dose Range Select Adverse Effects Comments Terazosin 1–10 mg daily Orthostatic hypotension Initiate at low dose; can titrate Doxazosin 1–8 mg daily every 2–7 days Start at bedtime Alfuzosin ER 10 mg daily Orthostatic hypotension No need to titrate Take after a meal Tamsulosin 0.4–0.8 mg daily May cause less orthostasis Start at bedtime modified release Causes ejaculatory dysfunction Silodosin 8 mg daily Causes ejaculatory dysfunction; Contraindicated if CrCl < 30 4 mg daily if CrCl 30–50 appears less sedating mL/min/1.73 m2 mL/min/1.73 m2 Take with food Finasteride 5 mg daily Decreased libido Onset of action is usually 6 mo Dutasteride 0.5 mg daily Monitor PSA Dutasteride/ 0.5/0.4 mg daily Pregnancy category X tamsulosin Tadalafil 5 mg daily Orthostatic hypotension Avoid use with α-blockers No data in combination or with long-term use PSA = prostate-specific antigen. Patient Case 9. An 85-year-old man with LUTS visits his physician, who determines his AUASI score is 15. His blood pres- sure is 118/70 mm Hg sitting. A digital rectal examination confirms the diagnosis of BPH, and the physician schedules a further workup including a prostate ultrasound, which shows a prostate volume of 31 g. Which therapy is best at this time? A. Terazosin. B. Finasteride plus saw palmetto. C. Tamsulosin. D. Finasteride plus tamsulosin. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-338  Geriatrics VI. OSTEOARTHRITIS A. Epidemiology 1. OA is the most prevalent form of arthritis, affecting more than 46 million Americans. 2. Highly associated with aging: Large weight-bearing joints (e.g., hip and knee) are commonly affected. B. Etiology and Pathophysiology 1. Risk factors include age, female sex, obesity, genetics, sports activities, occupation, previous injury, acromegaly, and other chronic illnesses. 2. Loss of cartilage occurs in the joint as the balance of chondrocyte function shifts from formation to destruction. Secondary inflammation and production of cytokines play a role. 3. Subchondral bone and the synovium are damaged, and the joint space narrows. 4. Single injuries or repeated micro-injuries may initiate or accelerate process. 5. Symptoms of pain result from activation of nociceptive nerve endings in the damaged joint. 6. Therapy goals: Relieve pain and swelling, maintain or improve joint function, prevent loss of function, and maintain or improve quality of life C. Nonpharmacologic Treatment 1. Patient education: Lifestyle, expectations, when to seek care, and behavioral, psychosocial, and physi- cal interventions, including self-efficacy and self-management programs to reduce pain and disability 2. Weight loss decreases the biomechanical load on large weight-bearing joints; even a small amount of weight loss helps decrease pain and disability. 3. Exercise, including yoga, tai chi, weight bearing 4. Physical and occupational therapy 5. Surgery D. Drug Therapy 1. NSAIDs are first line; topical agents are preferred, particularly for knee OA, to reduce systemic expo- sure and adverse effects. a. Avoid chronic use, or if necessary, use a cyclooxygenase 2 (COX-2) selective NSAID or add a pro- ton pump inhibitor to reduce the risk of GI bleeding. This recommendation is especially important for older adults. b. If one NSAID is not effective, change to others. c. Monitor for adverse effects: Rash, abdominal pain, GI bleeding, renal impairment, hypertension, heart failure, and drug-drug interactions d. Patients taking aspirin (for cardiac disease) should be educated to take aspirin at least 30 minutes before their first daily NSAID dose in the morning to avoid any interactions or reductions in aspirin efficacy. Naproxen appears to be safest with respect to cardiac risk. e. Monitor in chronic users: CBC, BUN, SCr, and AST at least annually 2. Topical agents: Topical NSAIDs are preferred for knee OA or smaller joints near surface of skin. Limited efficacy for widespread joint pain a. Diclofenac 1% gel (or patch is FDA labeled for minor trauma): Four short-term trials showed a 50% reduction in pain in 40% of subjects (number needed to treat was 5); longer-term trials had number needed to treat of 10. Comparative trials with oral administration showed no difference in the pro- portion of patients who received pain relief. b. Topical capsaicin is conditionally recommended for knee OA and conditionally recommended against for hand OA; usually dosed four times daily on a scheduled basis, not as-needed; difficult to administer: Wear gloves, avoid contact with eyes, and do not skip doses. Local irritation occurs in 40% of patients. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-339  Geriatrics c. Use of topical rather than oral NSAIDs for patients 75 and older who have hand or knee OA may be preferred to reduce systemic absorption and adverse effects. 3. Intra-articular glucocorticoid injections: a. Methylprednisolone or triamcinolone 10- to 40-mg injection depending on size of joint; may be repeated every 3 months b. Primary adverse effects are risk of septic arthritis, synovitis 4. Acetaminophen: a. Alternative to NSAIDs or when NSAID use is contraindicated; very small effect sizes in clinical trials, few of those treated experience important benefit b. Maximum dosage of 3 g daily in divided doses should be considered in older adults with frailty or those 75 and older. c. Ensure the patient knows to watch for “hidden” acetaminophen in other products. d. Monitor for hepatotoxicity in patients with an elevated risk of liver disease (previous liver prob- lems, heavy alcohol consumption) with periodic liver function tests. May consider limiting dosage to 2 g daily 5. Duloxetine a. Most of the evidence is in OA of knee, but conditionally recommended for patients with OA of knee, hip, or hand b. Can be used alone or in combination with NSAIDs c. Concerns about patient tolerability; use shared decision-making before initiation 6. Dietary supplements: Glucosamine-containing supplements are commonly used for relief of OA pain. a. 2019 American College of Rheumatology (ACR) guidelines strongly recommend against use of glucosamine supplements for relief of knee, hip, and/or hand OA. b. Chondroitin sulfate or combination glucosamine/chondroitin use is recommended against for knee and/or hip OA but is conditionally recommended for hand OA. c. Evidence to support treatment is contradictory; many studies are low quality. d. The adverse effect profile of glucosamine/chondroitin is similar to that of placebo. 7. Opioids a. Tramadol is an alternative when NSAIDs are ineffective or contraindicated; conditionally recom- mended for patients with knee, hand, and/or hip OA b. Non-tramadol opioids are conditionally recommended against in patients with knee, hand, and/or hip OA. However, they can be used in certain circumstances when non-opioid alternatives have been exhausted. c. Monitor and anticipate opioid adverse effects, and treat accordingly. Patient Case 10. An 85-year-old man presents with pain from OA of the knee. He has hypertension, coronary artery disease, and BPH. For OA, he has been taking acetaminophen 650 mg three times daily. He reports that acetamino- phen helps but that the pain persists and limits his ability to walk. Which is the best next step for this patient? A. Change acetaminophen to celecoxib. B. Add diclofenac gel to knee. C. Change acetaminophen to ibuprofen. D. Add duloxetine. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-340  Geriatrics 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 1%–2%, with women predominating until after age 60, when preva- lence becomes equal. 3. RA can occur at any age but increases in prevalence up to age 70. 4. RA is an autoimmune disease with a strong genetic predisposition. B. Pathophysiology and Clinical Presentation 1. Chronic inflammation of the synovium leads to proliferation and development of a pannus. 2. The pannus invades joint cartilage and eventually causes erosion of the bone and 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 inflammatory symptoms. Symptoms also include warmth, redness, and swelling of the joints, usually with symmetrical distribution. 5. Laboratory tests often show a positive RF, an elevated sedimentation rate, CRP, anti–cyclic citrulli- nated peptide antibodies, and normochromic normocytic anemia. 6. RA can also affect other organs, causing pulmonary fibrosis, vasculitis, and dry eyes. C. Treatment 1. The treatment goal is to control the inflammatory process so that disease remission occurs. This leads to relief of pain, maintenance of function, and improved quality of life. Treatment response can be measured by: a. Reduction in the number of affected joints and in joint tenderness and swelling b. Improvement in pain c. Decreased amount of morning stiffness d. Reduction in serologic markers such as RF e. Improvement in quality-of-life scales 2. Nonpharmacologic treatment: Concurrent with pharmacologic 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 d. Assistive devices, if needed e. Surgery for tendons or joints 3. Disease-modifying antirheumatic drugs (DMARDs) a. Initiate a DMARD within 3 months of diagnosis. b. Treatment strategies i. Treat-to-target (a) Frequent monitoring of disease activity using validated measures and modification of treatment to minimize disease activity (b) Initial goal is low disease activity, then remission (c) Based on optimization of methotrexate before adding or changing other DMARDs ii. Tapering/discontinuing DMARDs (a) Continuation of all DMARDs at current doses is recommended over a dose reduction or discontinuation, regardless of remission. ACCP Updates in Therapeutics® 2024: The Pharmacotherapy Preparatory Review and Recertification Course 2-341  Geriatrics (b) Dose reduction or discontinuation may be considered on the basis of shared decision-mak- ing and patient preferences if the patient is at target (low disease activity or remission) for at least 6 months. Gradual dose reduction/taper is preferred to abrupt discontinuation. c. Nonbiologic DMARDs are first line. i. For DMARD-naive patients with moderate to high disease activity: (a) Methotrexate preferred first line: Oral methotrexate preferred to subcutaneous because of ease of administration and similar bioavailability at starting doses (b) Leflunomide can be considered alternative first line: Efficacy similar to methotrexate, but less long-term data and increased cost compared with methotrexate (c) Hydroxychloroquine and sulfasalazine second line ii. For DMARD-naive patients with low disease activity: (a) Hydroxychloroquine recommended first line because of low adverse effect profile (b) Sulfasalazine recommended over methotrexate and leflunomide: Sulfasalazine preferred in pregnancy iii. Some patients with poor prognostic indicators such as functional limitation, extra-articular disease, positive RF, anti–cyclic citrullinated peptide antibodies, or bony erosions on radiog- raphy may be candidates for combination DMARD therapy. d. Biologic DMARDs are used in combination with methotrexate for severe disease or as alternatives if nonbiologic DMARDs are ineffective or contraindicated. i. Tumor necrosis factor (TNF) inhibitors: Etanercept, infliximab, adalimumab, certolizumab, golimumab ii. Non-TNF biologics: Abatacept, anakinra, rituximab, tocilizumab, sarilumab iii. Biologic kinase inhibitor: Tofacitinib, baricitinib, upadacitinib iv. An FDA boxed warning was added in September 2021 for tofacitinib regarding increased risk of serious cardiac-related events such as a myocardial infarction or stroke, cancers, blood clots, and death according to the review of clinical trial safety results that compared tofacitinib with TNF inhibitors in patients with RA. Boxed warnings were also added to baricitinib and upadacitinib. Avoid in patients who currently smoke or formerly smoked, those with CV risk factors, and those with a known malignancy. v. Most often used: Etanercept, infliximab, abatacept, or rituximab 4. Glucocorticosteroid and NSAID use in RA a. Glucocorticosteroids have often been used as bridge therapy to provide anti-inflammatory effects while waiting for the DMARDs to take effect; however, this is no longer recommended because of the risk of adverse effects associated with glucocorticosteroids (osteoporosis, infection risk, CV disease [CVD]). i. Initiation/addition/changing of DMARD without glucocorticosteroids is recommended over use of concomitant glucocorticosteroids. ii. If glucocorticosteroids are required on the basis of patient-specific factors, short-term use (less than 3 months) is pr