Geriatrics: Optimizing Pharmacotherapy in Older Adults PDF

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 to...

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 individuals 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 projected 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 increasing, 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 insensitive 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 differences in genetics, lifestyle, and environment. Table 1. Common Physiologic Changes with Age That May Change Drug Pharmacokinetics Organ System Physiologic Change with Aging GI ↑ Or no change in stomach pH ↓ GI blood flow Slowed gastric emptying Slowed GI transit Skin Thinning of dermis Loss of subcutaneous fat Body ↓ Total body water composition ↓ Lean body mass ↑ Body fat ↓ Or unchanged serum albumin ↑ α1-Acid glycoprotein Liver ↓ Liver mass ↓ Blood flow to the liver ↓ Or no change in CYP enzymes Effect on Pharmacokinetics • ↓ Absorption of some drugs and nutrients requiring acidic environment • Absorption rate may be prolonged • ↓ Or no change to drug reservoir formation with transdermal formulation • ↑ Volume of distribution and accumulation of lipidsoluble drugs • ↓ Volume of distribution of water-soluble drugs • ↑ Free fraction of highly protein-bound drugs • ↓ First-pass extraction and metabolism • ↑ Half-life depending on the drug’s volume of 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-308 Geriatrics Table 1. Common Physiologic Changes with Age That May Change Drug Pharmacokinetics (Cont’d) Organ System Physiologic Change with Aging Renal ↓ GFR ↓ Renal blood flow ↓ Tubular secretion ↓ Renal mass Effect on Pharmacokinetics • ↓ Renal elimination of many medications • ↑ Half-life of renally eliminated drugs and metabolites 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, bisphosphonates, 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 firstpass 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 variable 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. Chronic medication examples can be found in the 2019 American Geriatrics Society (AGS) Beers Criteria. 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-309 AL GRAWANY 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 Questions 1 and 2 pertain to the following case. 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, aspirin 81 mg 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. 1. Considering the potential for altered pharmacokinetics, which pair of medications is most likely to cause problems for the patient? A. Aspirin and melatonin. B. Lisinopril and meclizine. C. Lisinopril and metformin. D. Glyburide and metformin. 2. Considering the potential for increased pharmacodynamic sensitivity, which pair of medications is most likely to cause problems for the patient? A. Aspirin and melatonin. B. Lisinopril and meclizine. C. Lisinopril and metformin. 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 ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-310 Geriatrics 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 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 conditions, and drugs to be used with caution (d) Examples: Anticholinergics, benzodiazepines, sedative-hypnotics, older antipsychotics, select opioids, hypoglycemics, NSAIDs, and proton pump inhibitors ii. Another tool popular in European countries is 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 information. 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-311 Geriatrics 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, managing 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 contributing 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, hypoglycemia, hyponatremia, myocardial infarction, UTI b. Examples of contributing risk factors: Vitamin D deficiency, poor balance, deconditioning/muscle weakness, poor vision, environment 3. Delirium a. A disturbance in attention and awareness developing over hours to days, with fluctuation b. Possible etiologies: Psychoactive medications, polypharmacy, hypoglycemia, hyponatremia, myocardial 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. ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-313 Geriatrics Patient Case Questions 6 and 7 pertain to the following case. 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. 1. When recommending medication changes for this patient, which functional assessment is most important to evaluate? A. IADLs. B. Depression. C. Pressure sores. D. Gait and balance. 2. 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-314 Geriatrics Table 2. Comparisons of Memory Impairment and Dementias with AD Disease MCI Vascular dementia Differences from AD Treatment Notes Common Irreversible Causes No interference with work or social functions Eliminate or control risk factors for dementia One in five patients progress to AD Includes focal neurologic signs and symptoms May use CIs, which reduced risk of progression by 40% in one study Control of cardiac and vascular risk factors Radiologic evidence of stroke CIs and memantine not effective Onset within 3–6 mo of stroke Abrupt deterioration followed by stepwise progression Lewy body dementia Dementia of advanced PD Frontotemporal dementia Vitamin B12 deficiency Fluctuating cognition with pronounced variation in attention and alertness Especially avoid typical antipsychotics, which may worsen motor symptoms Recurrent visual hallucinations May use Cis Motor features of PD PD onset predates cognitive impairment Usually at latter stages of PD Especially avoid typical antipsychotics, which may worsen motor symptoms May use CIs Affects personality, behavior, self-care, and language CIs may worsen behavior and cause agitation SSRIs or trazodone may be beneficial Onset in ages 45–65 with a 2- to 10-yr course Reversible Causes Replace vitamin B12 according to standard Progressive memory loss 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 Depression Trouble with concentration and memory NPH Apathy and “I don’t care” responses Triad of progressive memory loss, incontinence, and gait abnormality Medications Symptoms improve after lumbar puncture Anticholinergics, muscle relaxants, opioids, antiseizure medications, benzodiazepines, and tricyclic antidepressants may increase memory loss and confusion mimicking symptoms of dementia Levothyroxine replacement according to standard protocols Treatment of depression according to standard protocols Surgical placement of ventricular shunt Decrease dose or deprescribe as appropriate 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-315 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 Mild MMSE Score (out of 30) 20–24 Moderate 10–19 Severe < 10 Examples of Cognitive Loss Examples of Functional Loss Some short-term memory loss; word-finding problems 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, incontinence of bowel and bladder Dependency in basic ADLs such as feeding 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-316 Geriatrics Table 4. Activity Limitation with AD FAST Scale Item Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Stage 6 6a 6b 6c 6d 6e Stage 7 7a 7b 7c 7d 7e 7f Activity Limitation with AD No difficulty Subjective work difficulties; forgetting location of objects Work difficulties evident to coworkers; difficulty traveling to new locations Difficulty performing complex tasks (finances, planning) Requires assistance choosing proper clothing (season or occasion) Decreased ability to independently bathe, dress, and toilet Difficulty dressing properly Unable to bathe properly Unable to toilet properly (forget flushing, improper wiping) Urinary incontinence Fecal incontinence Loss of speech, ambulation, and consciousness Speech limited to 1–5 words per day Intelligible vocabulary lost Nonambulatory Unable to sit up Unable to smile 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 8. 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-317 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 (memantine), CI, or combination: Slight or no benefit with combination therapy in systematic reviews d.  Disease-modifying immunotherapies i. Antiamyloid monoclonal antibody: Aducanumab (a) Accelerated FDA approval for MCI or mild dementia; safety and efficacy in later stages of AD not studied (b) Phase III trials showed reduction in amyloid plaques, but modest reduction in cognitive decline (c) Infusion every 4 weeks; around $28,200 per year (d)  In April 2022, the Centers for Medicare & Medicaid determined that aducanumab would only be covered for patients in clinical trials, making its role in therapy still to be determined. ii. Anti-tau monoclonal antibody therapies under phase II and phase III clinical trials Table 5. Comparison of Drugs for AD Treatment Starting Dose Maintenance Dose Drug Cholinesterase Inhibitors Donepezil 5 mg daily 10 mg daily Adverse Effects Tablets GI: Nausea, vomiting, diarrhea Comments May increase to 23 mg/day Orally disintegrating CNS: Headache, tablets insomnia, dizziness 3–6 mg twice daily Capsules Transdermal patch 4 mg twice daily 9.5-mg patch daily; may increase to 13.3-mg patch daily 8–12 mg twice daily 8 mg ER once daily 8–24 mg ER once daily Rivastigmine 1.5 mg twice daily 4.6-mg patch daily Galantamine Dosage Forms Oral solution Tablets Oral solution ER capsules Cardiac: Bradycardia, orthostatic hypotension, syncope (AGS Beers Criteria for patients with syncope) Long-term risks: Falls, hip fracture, pacemaker placement Highest rate of GI effects Labeled for dementia with Parkinson disease as well Monitor for skin reactions with patch Preferable to administer with food Renal dosing adjustment necessary ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-318 Geriatrics Table 5. Comparison of Drugs for AD Treatment (Cont’d) Starting Dose Maintenance Dose Drug NMDA Receptor Antagonist Memantine 5 mg once 10 mg twice daily daily 7 mg ER once daily Combination Product Donepezil/ 10/28 mg memantine once daily in the evening Dosage Forms Adverse Effects Comments Tablets CNS: Headache, Oral solution dizziness, 28 mg ER once ER capsules confusion, agitation, hallucinations daily Usually well tolerated 10/28 mg once daily Use after stabilized on donepezil and memantine separately GI: Diarrhea, vomiting ER capsule See above Renal dosing adjustment necessary Disease-Modifying Immunotherapies (anti–amyloid monoclonal antibodies) Aducanumab 1 mg/ 10 mg/kg IV infusion Diarrhea, confusion, kg every every 4 wk for altered mental status 4 wk for infusions 7–12 infusions 1 Serious: ARIA-H and 2, then (micro-hemorrhage), titrate ARIA-E (brain edema, headache), seizure Only therapy approved for MCI Dose based on actual body weight MRI brain within 1 yr before initiation required; 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-hemosiderin 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 considering 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. ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-319 AL GRAWANY Geriatrics Patient Cases 9. An 87-year-old man with AD receives rivastigmine 6 mg twice daily. His family notes improved functional ability but reports that he has nausea and vomiting that appear to be related to rivastigmine. Which recommendation is best for the patient at this time? A. Advise the patient to take rivastigmine with an antacid. B. Change rivastigmine to the patch that delivers 9.5 mg daily. C. Discontinue rivastigmine and initiate memantine 5 mg twice daily. D. Add prochlorperazine 25 mg by rectal suppository with each rivastigmine dose. 10. 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. 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, nursing home placement, and emergency services 4. Behaviors commonly peak during late afternoon or early evening and are thus called “sundowning.” ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-320 Geriatrics Table 6. Symptoms During Disease Progression MMSE Score Stage Symptoms 25 Mild Memory loss Mood swingsa Apathy Mild executive dysfunction Poor drawing Mild personality changesa Moderate Unable to learn Aggression, psychosisa Aphasia, apraxia Confusion, insomniaa Wandering, agitationa Need for assistance with ADLs Severe Gait changesa Loss of ADLs Incontinence Bed confinement 20 15 10 5 0 Noncognitive symptoms. ADLs = activities of daily living; MMSE = Mini-Mental State Examination. a 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. Pain is a common issue that patients cannot communicate. Treat with scheduled acetaminophen. b. Delirium precipitated by medical illness or medication should be ruled out. c. Constipation is a common geriatric syndrome and an issue patients cannot communicate. Treat with scheduled bowel regimen. 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 distraction, music, aromatherapy, and pet therapy. 4. Symptoms likely to respond: Wandering, hoarding, hiding objects, repetitive questioning, withdrawal, social inappropriateness, apathy D. Pharmacologic Treatment: None of these are FDA-labeled indications. (Table 7) 1. Agency for Healthcare Research and Quality has published a summary on the use of atypical antipsychotic agents for off-label indications. Atypical antipsychotics improve behavioral symptoms of dementia, but effect sizes are small and adverse effects are significant. 2. Retrospective case-control study of older veterans with dementia during a 180-day period indicated haloperidol number needed to harm (NNH) was 8, compared with atypical antipsychotics, with NNH of 14–31 for risk of death. 3. Antipsychotic medications may increase the risk of death when used in older adult patients with dementia-related psychosis (black box warning). ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-321 Geriatrics Table 7. Drug Treatment for BPSD Symptom Presentation Anxiety Part of this is because they cannot remember things Apathy One of the earliest symptoms Depression Nonpharmacologic treatment tailored to patient’s activities Up to 80% of patients with AD have depression Sleep-wake cycle is disrupted Insomnia Wandering Paranoia, hallucinations, sundowning, agitation Aggression, resistance to care Treatment Options After Nonpharmacologic Efforts Ineffective Buspirone or SSRI/SNRI or gabapentin Limit benzodiazepines CIs Methylphenidate effective in small, short-term studies SSRI or mirtazapine Melatonin Walk so much they begin to lose weight They may think that because they cannot find something, you stole it Often accuse spouse of infidelity If psychosis and delusions do not bother anyone, do not use drugs Most difficult and best response is to treat nonpharmacologically Mirtazapine can be considered if concomitant depression No drug will stop patients from wandering Risperidone, olanzapine, quetiapine, and aripiprazole have been tried. Use very low doses. ADEs may offset any benefit For patients with parkinsonian symptoms, quetiapine is preferred because of decreased dopaminergic activity and EPS Pimavanserin can be used for PD-related psychosis. Use of pimavanserin in AD is being studied Valproic acid products commonly used despite 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-322 Geriatrics Patient Case Questions 11 and 12 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, reversible causes of her hypervocalization are ruled out. 11. 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. 12. 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® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 2-323