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Medication Use in the Older Patient Anthony J. Caprio, MD Kevin Biese, MD, MAT Ellen Roberts, PhD, MPH Jan Busby-Whitehead, MD Picture of pills The University of North Carolina at Chapel Hill With Support from The Donald W. Reynolds Foundation and The John A. Hartford Foundation © The University of North Carolina at Chapel Hill, Center for Aging and Health. All Rights Reserved. Objectives 1) Identify risk factors for Adverse Drug Events (ADEs) in older adults 2) Identify the physiologic changes associated with normal aging that influence pharmacokinetics and pharmacodynamics 3) Recognize ADEs when an older adult presents with a new clinical condition or complaint 4) Avoid potentially harmful medications for older adults 5) Utilize strategies for shortening medication lists and carefully introducing new medications 2 Mrs. Anderson • 87yo female from nursing home; fell last night with complaint of left hip and back pain • Unable to recall events, agitated; says “yes,” when asked if she is in pain. Seems very confused • Reportedly able to ambulate short distance with walker at baseline, needs assistance with dressing, bathing, toileting. Able to feed herself • Note from nursing home about rectal bleeding 2 days ago • Electronic medical record indicates that she was in the ED last month for a heavily bleeding laceration after a fall and supratherapeutic INR of 5.6 (while on antibiotics for a urinary tract infection) 3 Past Medical History 1) Dementia (MMSE 20/30) 12) Osteoarthritis, especially hips and knees 2) Parkinson’s disease 3) 13) Macular degeneration CVA with residual L-sided weakness 14) Type 2 DM 4) Osteoporosis 15) Peripheral neuropathy 5) Urinary incontinence 16) Chronic renal insufficiency 6) Recurrent UTIs 17) Anemia 7) Hypertension 18) Hypothyroidism 8) CAD s/p stent 2 years ago 19) COPD on oxygen 9) CHF (EF 30%) 20) Diverticulosis 10) Atrial Fibrilation 11) Hyperlipidemia 4 Medications Picture of pills 1) Donepezil (Aricept) 5mg po Daily 18) Docusate sodium 100mg po BID 2) Carbidopa/Levodopa 10/100 po TID 19) PEG powder (Miralax) 17g po Daily 3) Aspirin 325mg po Daily 20) 4) Warfarin (Coumadin) 5mg po qHS Tiotropium (Spiriva) 18mcg inhaled Daily 5) Tolterodine (Detrol) 2mg po BID 21) Montelukast (Singulair) 10mg po Daily 6) Atorvastatin (Lipitor) 40mg po qHS 22) Fluticasone/Salmeterol (Advair) 100/50 inhaled BID 7) Insulin (long-acting and sliding scale) 23) 8) Gabapentin (Neurontin) 300mg po TID Albuterol/Atrovent nebulizers prn wheezing 9) Iron sulfate 325mg po TID 24) Multivitamin one po Daily 10) Trazodone 50mg po qHS 25) Vitamin E 400 IU po Daily 11) Levothyroxine 50mcg po Daily 26) Calcium Carbonate 500mg po TID 12) Furosemide (Lasix) 60mg po BID 27) Vitamin D 800 units po Daily 13) Potassium Chloride 20meq po Daily 28) Nitrofurantoin (Macrodantin) 100mg po qHS 14) Metoprolol 100mg po BID 15) Lisinopril 20mg po Daily 16) Amlodipine 10mg po Daily 17) Acetaminophen 1000mg po TID 5 Challenges of Prescribing for Older Adults Multiple medical conditions Multiple medications Multiple prescribers Different metabolisms and responses Adherence and cost Supplements, herbals, and over-the-counter drugs Lancet. 1995;346(8966):32–36. 6 Lots of Medications and Little Evidence • 2/3 of older adults are on regular medications • Adults age >65 account for 1/3 of all prescriptions, but only represent 15% of the US population • Older adults are frequently not included in clinical trials, which makes it difficult to predict drug metabolism or drug effects Health Care Financ Rev. 1990;11:1-41. 7 Dangers of Multiple Medications: “Polypharmacy” • Adverse effects (side effects) • Drug-drug interactions • Duplication of drug therapy • Poor adherence » Cost » Decreased quality of life 8 Adverse Drug Events (ADEs) • Adverse symptoms • Adverse clinical outcomes » » » » » Doctor visits or hospitalizations Falls Functional decline Changes in cognition (delirium) Death • Poor adherence, poor quality of life • Increased cost 9 Most Common Medications Causing ADEs • • • • • • • • Antibiotics Analgesics Anticoagulants Antihistamines Anticonvulsants Antipsychotics Cardiovascular meds Diabetic meds JAMA 2006; 296:1858–1866 JAGS 2004;52:1349–1354 NEJM 2003;348:1556–64 10 Prevalence of ADEs • • • • 35% of community-dwelling older adults 5-28% of inpatient geriatric admissions 2/3 of nursing home patients (over 4 years) In the emergency department: » 2.0 per 1000 for adults under 65 » 4.9 per 1000 for aged 65 years or older » 6.8 per 1000 for aged 85 years or older JAGS 1997;45:945-948 JAGS 1996;44:194-197 Am Pharm Assoc 2002;42:847-857 JAMA 2006; 296:1858–1866 11 Potential Risk Factors for Adverse Drug Events (ADE) >6 chronic disease >12 doses/day ≥ 9 medications Low BMI (<22kg/m2) Age >85 years Creatinine clearance < 50 mL/min History of prior ADE 12 Consult Pharm 1997;12:1103–11. Is Mrs. Anderson at Risk for an ADE? 6 chronic disease >12 doses/day ≥ 9 medications Low BMI (<22kg/m2) likely Age >85 years Creatinine clearance < 50 mL/min possibly History of prior ADE Nursing home resident 13 Why is Mrs. Anderson at Risk? • Multiple drugs (high “exposure” ) » Risk of ADE is proportional to number of drugs » Increased probability of drug-drug interactions • Physiologic changes (increased susceptibility) » Associated with disease states » Associated with NORMAL AGING 14 Physiologic Changes with Normal Aging • Less water • More fat Picture of Jack LaLanne • Less muscle mass • Slowed hepatic metabolism • Decreased renal excretion • Decreased responsiveness and sensitivity of the baroreceptor reflex 15 Absorption • Not affected by the normal aging process • Can be altered by drug interactions » Antacids » Iron • Can be effected by disease » Lack of intrinsic factor (B12 absorption) » Delayed gastric emptying 16 Distribution • Less water = ↓ volume of distribution Higher concentration of water soluble drugs • More fat = ↑ volume of distribution Prolonged action of fat-soluble drugs (increased half-life) • Lower serum proteins (like albumin) increases the concentration of unbound (free or active) form of drugs 17 Metabolism • Slowed Phase I, cytochrome P450, reactions » Oxidation, reduction, dealkylation » Warfarin and phenytoin levels may be higher because of altered metabolism • Phase II reactions are essentially unchanged » Conjugation, acetylation, methylation • Drug-drug interactions » Increased risk with increased number of drugs 18 Excretion • Hepatic • Renal » Renal clearance may be reduced » Serum creatinine may not be an accurate reflection of renal clearance in elderly patients. (decreased lean body mass) • Active drug metabolites may accumulate » Prolonged therapeutic action » Adverse effects 19 Physiologic Changes Associated with Disease States • Cardiac disease » Impaired cardiac output (decreased absorption, metabolism, clearance) » Greater susceptibility to cardiac adverse effects • Kidney and liver disease » Decreased drug clearance and altered metabolism • Neurological diseases » Diminished neurotransmitter levels » Greater susceptibility to neurological effects 20 Why Did Mrs. Anderson Fall? • Functional status » Uses walker at baseline » Dependent in other ADLs (like bathing) • Sensory impairments » Macular degeneration » Peripheral neuropathy • Neurological diseases » Dementia » Parkinson’s Disease • Co-morbid diseases » Cardiovascular (syncope) » Diabetes mellitus (hypoglycemia) » Anemia (hypotension) 21 Orthostatic Hypotension, Falls, and Hip Fractures • Baroreceptor sensitivity decreases with age • Trazodone » New medication according to nursing home med record » Associated with orthostatic hypotension • Diuretic use can cause volume depletion and orthostatic hypotension • Falls and hip fractures are associated with significant morbidity and mortality in older adults 22 Why is Mrs. Anderson Confused? • Head injury? » Contusion on forehead » Recent history of supratherapeutic INR • Dementia » Moderate dementia by history » What is her baseline? • Delirium » Infection (history of UTIs) » Drugs (Adverse Drug Event) » Hospital (change in environment) 23 Delirium • More than confusion » Acute onset, fluctuating course » Inattention » Disorganized thinking or altered level of consciousness • Associated with low levels of acetylcholine » Low levels in patients with dementia at baseline » Risk with use of anticholinergic medications 24 Anticholinergic Medications • Drug classes • Antihistamines • Tricyclic antidepressants • Antispasmodics and muscle relaxants Diagram of the parasympatheic nervous system. • Adverse effects • • • • Dry Mouth Urinary retention Constipation Delirium 25 Pharmacologic Tug-of-War • Tolterodine (Detrol) » Potent anticholinergic » Relaxes detrusor muscle to treat urge incontinence (detrusor hyperactivity; “overactive bladder”) » Can worsen delirium, constipation • Donepezil (Aricept) » » » » • Acetylcholinesterase Inhibitor Higher levels of acetylcholine may help improve cognition Can cause detrusor hyperactivity and diarrhea Could cause symptomatic bradycardia and syncope (also on β-blocker) Incontinence and falls » Dementia is a risk factor for both incontinence and falls » Incontinence may be an ADE related to Donepezil » Diuretic use can worsen incontinence and cause orthostatic hypotension 26 Principle 1: “Think Drugs” Before Making a New Diagnosis • Consider adverse drug effect as etiology of new signs/symptoms • Consider discontinuing or dose-reducing medications • Avoid prescribing a new medication to treat an adverse drug effect (“Prescribing Cascade”) • Remember that over-the-counter drugs, supplements, and herbals can be the culprit 27 28 Slide courtesy of Anthony Caprio, MD Common Conditions Could Really Be Adverse Drug Effects Constipation Calcium Channel Blockers; Iron Incontinence α-blockers Memory loss Antihistamines Syncope Tricyclics, α-blockers Falls Benzodiazepines Weight loss Fluoxetine (Prozac) 29 Mrs. Anderson: Acute Management • Pain » Morphine 2mg iv x 2 doses for pain » More comfortable after the 2nd dose • Nausea and vomiting » Complains of “sick stomach” » Vomits repeatedly • Agitation » Increasingly agitated, trying to climb out of bed » Shouting “Veronica” repeatedly 30 What Do You Prescribe? •Pain •Nausea •Agitation 31 Beers Criteria • A consensus-based list of potentially inappropriate medications for older adults • The Beers criteria were published 1991 and revised in 1997, 2002, and 2012 • Statistical association with adverse drug events has been documented • Does not account for the complexity of the entire medication regimen J Am Geriatrics Society, 2012 Online link to this article is: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf Pharmacotherapy 2005;25(6):831–838 32 Beers Criteria: Potentially Inappropriate Medications for Older Adults • Table 2: Organ System or Therapeutic Category or Drug » Describes concern for prescribing certain drugs or classes of drugs for older adults » Rationale, recommendation, quality of evidence, and strength of recommendation • Table 3: Due to Drug-Disease or DrugSyndrome Interactions » Describes drugs or classes of drugs that can cause or worsen a particular disease or syndrome » Rationale, recommendation, quality of evidence, and strength of recommendation J Am Geriatrics Society, 2012 Tables available online at: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf 33 Pain Medications • Caution with non-steroidal anti-inflammatory drugs (NSAIDS) » Indomethacin has significant CNS side effects » Ketorolac (Toradol) can cause serious GI and renal effects • Meperidine (Demerol) has low oral efficacy, active metabolites and CNS effects • Morphine metabolites are renally cleared Beers criteria: J Am Geriatrics Society, 2012 Tables available online at: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf 34 Anti-Emetics • Antihistamines: promethazine (Phenergan) » Anticholinergic, may worsen delirium (↓acetylcholine) » Beers Criteria medication • Dopamine antagonists: metoclopramide (Reglan) » May worsen Parkinsonism (↓dopamine) » Beers Criteria medication • Serotonin (5-HT3) antagonists: odansetron (Zofran) » Expensive, but likely safest for this patient Beers criteria: J Am Geriatrics Society, 2012 Tables available online at: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf 35 Managing Agitated Delirium • Treat pain » Although opioids may cause confusion, untreated pain may precipitate and perpetuate delirium • Assess for other sources of discomfort » Hunger, thirst, cold » Urinary retention, fecal impaction; • Sensory » Eye glasses and hearing aids » Try to minimize sensory “overload” » Reorientation 36 Antipsychotic Medications • “Black Box” warning: increased risk stroke, death • Typical (ie. haloperidol) » » » » Potent antidopaminergic effects Can severely worsen Parkinsonism Beers Criteria medication Intravenous haloperidol associated with arrhythmias • Atypical (ie. risperidone, quetiapine, olanzepine) » Olanzepine may be best choice in setting of prolonged QTc » Quetiapine safest for Parkinson’s Disease but may not be as useful for acute management 37 Benzodiazepines for Agitated Delirium • Avoid if possible » Appropriate if being used to treat alcohol withdrawal » If necessary, use lowest dose possible » Beers Criteria medication • May cause a paradoxical reaction in older adults » Increased agitation and anxiety » May lead to prescribing cascade (ie. antipsychotic) • Avoid long-acting benzodiazepines » Prolonged half-life in older adults (days) » Sedation, aspiration, delirium » Increased risk of falls and fractures Beers criteria: J Am Geriatrics Society, 2012 Tables available online at: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf 38 Conclusion: Mrs. Anderson • Medicated with morphine for pain • One dose of odansetron (Zofran) for nausea • Evaluated by orthopedics and plan for operative repair for pain control and since patient ambulatory at baseline • Fecal disimpaction • Her family brings her eye glasses and hearing aids to the hospital Beers criteria: J Am Geriatrics Society, 2012 39 Clinical Case: Mr. Johnson Mr. Johnson is 83 years old. He complains of a “runny nose” during meals on a daily basis. He asks if there is a medication to stop his runny nose. Although inconvenient at mealtime, he is not bothered by this symptom at other times during the day. Question: Does he need a prescription? 40 Vasomotor Rhinitis • Likely diagnosis is vasomotor rhinitis • May respond to ipratropium (Atrovent) nasal spray. • Disposable facial tissues are available without a prescription and have few side effects • “Sedating” antihistamines can have significant anticholinergic effects. 41 Am Fam Physician 2005;72:1057-62. Principle 2: “Less is More” (Keep the Medication List Short) • • • • • Question the need for new medications Stop medications, whenever possible Prioritize treatments Weigh risks and benefits But, avoid undertreating older patients » Pain » Systolic hypertension (stroke, renal failure, heart disease) » Anticoagulation and atrial fibrillation (stroke prevention) Drugs Aging 2003; 20: 23-57. Lancet 2000; 355: 865–872. Ann Intern Med 1999;131:492-501. J Gen Intern Med 2005; 20:116–122. 42 Clinical Case: Mr. Jones Mr. Jones is 82 years old with a history of herpes zoster (shingles) 6 months ago. He continues to experience severe daily pain in the same dermatomal distribution as the original rash. • Question: What is the diagnosis? • Question: What is the treatment? 43 Post-Herpetic Neuralgia • Opioid medications • Capsaicin » OTC alternative » Topical (better than systemic) » May be poorly tolerated due to local effects • Tricyclic antidepressants » Effective, but have anticholinergic properties. Amitriptyline > nortriptyline > desipramine » Amitriptyline is a Beers Criteria medication • Gabapentin (Neurontin) » Clinical trials: 1800–3600mg/day divided doses. » Dose-reduce with renal insufficiency. Neurology 2002;59(7):1015–21. Pain 1988;33(3):333–40. Neurology 1998;51(4):1166–71. JAMA 1998;280(21):1837–42. 44 Principle 3: “Start Low and Go Slow…” • Start one medication at a time • Start with a low dose and increase gradually • Monitor for response and adverse effects • Once daily is usually best • Assess adherence with regimen 45 “…But, Go All The Way!” • Be conservative, but don’t miss the target! • What is your goal? Are you achieving it? • If you are not at goal, can the dose be increased or are you limited by side effects? • Are you observing a clinical benefit at lower doses? • Consider stopping if you can’t “go all the way” and the benefits at lower doses are not clear. 46 Physiologic Changes Associated with Normal Aging • Absorption usually does not change • ↑ concentrations of water soluble and free (unbound) drugs • Longer half-life for lipophilic drugs • Slower phase I metabolism • Impaired excretion • Decreased responsiveness of the baroreceptors 47 Prescribing for Older Adults 1) “Think drugs” before making a new diagnosis 2) “Less is more” (keep the med list short) 3) Use caution with Beers Criteria medications 4) “Start low and go slow”…when starting a new drug….“but go all the way.” 48 Acknowledgments and Disclaimers This project was supported by funds from The Donald W. Reynolds Foundation, the American Geriatrics Society/The John A. Hartford Foundation Geriatrics for Specialists Grant. This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by The Donald W. Reynolds Foundation and/or The John A. Hartford Foundation. The UNC Center for Aging and Health, the UNC Division of Geriatric Medicine, and the UNC Department of Emergency Medicine also provided support for this activity. This work was compiled and edited through the efforts of Carol Julian. 49 © The University of North Carolina at Chapel Hill, Center for Aging and Health. All Rights Reserved. 50