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MEDICATION USE IN THEELDERLY ony J. Caprio, MDKevin Biese MD, MATEllen Roberts PhD, MPHJan Busby-Whitehead, MDUniversity of North Carolina Chapel HillDivision of Geriatric MedicineCenter for Aging and HealthDepartment of Emergency MedicineTHE AMERICAN GERIATRICS SOCIETYGeriatrics Health Professionals.Leading change. Improving care for older adults.

OBJECTIVES Identify the physiologic changes associated withnormal aging in relation to drug absorption,distribution, neurological effects, metabolism, andexcretion Identify risk factors for adverse drug events in olderadults Recognize adverse drug events when an older adultpatient presents with a common clinical condition orcomplaint Identify and avoid potentially harmful medications forolder adultsSlide 2

CASE STUDY: “MRS. ANDERSON” 87-year-old woman from nursing home; fell last night andcomplains of left hip and back pain Unable to recall events; agitated; says “yes” when asked ifshe is in pain Reportedly able to ambulate short distance with walker atbaseline; needs assistance with dressing, bathing,toileting; able to feed herself Note from nursing home about rectal bleeding 2 days ago Electronic medical record (WebCIS) indicates that shewas in ED last month for a heavily bleeding lacerationafter a fall and supratherapeutic INR of 5.6 (while onantibiotics for a urinary tract infection)Slide 3

CASE STUDY: PAST MEDICAL HISTORY(From WebCIS)1) Dementia (MMSE 20/30)2) Parkinson’s disease3) CVA with residualL-sided weakness4) Osteoporosis5) Urinary incontinence6) Recurrent UTIs7) Hypertension8) CAD; stent 2 years ago9) CHF (EF 30%)10) Atrial fibrillation11) Hyperlipidemia12) Osteoarthritis, especiallyhips and knees13) Macular degeneration14) Type 2 DM15) Peripheral neuropathy16) Chronic renal insufficiency17) Anemia18) Hypothyroidism19) COPD on oxygen20) DiverticulosisSlide 4

CASE STUDY: PHYSICAL EXAM (1 of 2) Vitals: T: 38.0; BP: 150/95; HR: 110; RR: 20; O2 sat:89% on RA, 96% on 2L General: very thin, frail, agitated elderly female;appears uncomfortable; inattentive and able to answeronly simple questions HEENT: quarter-sized contusion on L forehead;EOMI; PERRLA; moist mucous membranes CVS: S1, S2 irregularly irregular; unable to assessJVP due to agitation Chest: poor effort; faint crackles at bilateral basesSlide 5

CASE STUDY: PHYSICAL EXAM (2 of 2) Abdomen: mildly distended; diminished bowel sounds;diffusely tender; no rebound Rectal: large amount of hard stool, guaiac negative Extremities: L leg shortened and externally rotated;pain with movement; groin tenderness; 2 edema inbilateral LE; pulses intactSlide 6

CASE STUDY: MEDICATIONS1)Donepezil (Aricept) 5 mg PO daily16) Amlodipine 10 mg PO daily2)Carbidopa/Levodopa 10/100 PO TID17) Acetaminophen 1,000 mg PO TID3)Aspirin 325 mg PO daily18) Docusate sodium 100 mg PO BID4)Warfarin (Coumadin) 5 mg PO qHS5)Tolterodine (Detrol) 2 mg PO BID19) Polyethylene glycol powder (Miralax) 17 g POdaily6)Atorvastatin (Lipitor) 40 mg PO qHS7)Insulin (long-acting and sliding scale)8)Gabapentin (Neurontin) 300 mg PO TID9)Iron sulfate 325 mg PO TID10) Trazodone 50 mg PO qHS11) Levothyroxine 50 mcg PO daily12) Furosemide (Lasix) 60 mg PO BID13) Potassium chloride 20 mEq PO daily14) Metoprolol 100 mg PO BID20) Tiotropium (Spiriva) 18 mcg inhaled daily21) Montelukast (Singulair) 10 mg PO daily22) Fluticasone/salmeterol (Advair) 100/50 inhaledBID23) Albuterol/Atrovent nebulizers PRN for wheezing24) Multivitamin one PO daily25) Vitamin E 400 IU PO daily26) Calcium carbonate 500 mg PO TID27) Vitamin D 800 units PO daily28) Nitrofurantoin (Macrodantin) 100 mg PO qHS15) Lisinopril 20 mg PO dailySlide 7

CHALLENGES OF PRESCRIBINGFOR OLDER ADULTS Multiple medical conditions Multiple medications Multiple prescribers Different metabolisms and responses Lack of evidence for use in elderly Adherence and cost Supplements, herbals, and over-the-counter drugsLancet. 1995;346(8966):32-36.Slide 8

POLYPHARMACY 2/3 of older adults are on regular medications People aged 65 account for 1/3 of allprescriptions written, but they represent only 15%of the US population Dangers of multiple medications (“polypharmacy”) Adverse effects Drug-drug interactions Duplication of drug therapy Poor adherence Cost Decreased quality of lifeSlide 9

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 costSlide 10

ADEs AND OLDER ADULTS (1 of 2) 35% of community-dwelling older adultsexperience an ADE annually ADEs 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 olderJAMA. 2006; 296:1858-1866.JAGS. 1997;45:945-948.JAGS. 1996;44:194-197.Am Pharm Assoc. 2002;42:847-857.Slide 11

ADEs AND OLDER ADULTS (2 of 2) 2/3 of nursing home patients experience anADE over a 4-year period 1.6 per 1000 older adults require hospitaladmission because of an ADE (7 times therate in younger adults) Nearly 1/3 of all geriatric hospital admissionsare due to ADEsJAMA. 2006; 296:1858-1866.JAGS. 1997;45:945-948.JAGS. 1996;44:194-197.Am Pharm Assoc. 2002;42:847-857.Slide 12

MOST COMMONLY ASSOCIATEDWITH ADEs IN OLDER ADULTSOutpatient ADEs Antibiotics Analgesics Anticoagulants Antihistamines Anticonvulsants Antipsychotics Cardiovascular medications Diabetes medicationsJAMA. 2006; 296:1858-1866.JAGS. 2004;52:1349-1354.N Engl J Med. 2003;348:1556-1564.Ann Intern Med. 2007;147:755-765.ADEs in theEmergency Department Warfarin (17.3%) Insulin (13%) Digoxin (3.2%)Slide 13

POTENTIAL RISK FACTORSFOR ADEs 6 chronic diseases 12 doses/day 9 medications Low BMI ( 22 kg/m2) Age 85 years Creatinine clearance 50 mL/min History of prior ADEConsult Pharm. 1997;12:1103-1111.Slide 14

CASE STUDY: IS MRS. ANDERSONAT RISK OF AN ADE? 6 chronic diseases — yes 12 doses/day— yes 9 medications — yes Low BMI ( 22 kg/m2) — likely Age 85 years — yes Creatinine clearance 50 mL/min — possibly History of prior ADE — yes Nursing home resident — yesSlide 15

CASE STUDY: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 agingSlide 16

PHYSIOLOGIC CHANGESASSOCIATED WITH DISEASE STATES Cardiac diseases Impaired cardiac output (decreased absorption,metabolism, clearance) Greater susceptibility to cardiac adverse effects Kidney and liver diseases Decreased drug clearance Neurological diseases Diminished neurotransmitter levels Impaired cerebral blood flow Greater sensitivity to neurological effectsSlide 17

PHYSIOLOGIC CHANGESASSOCIATED WITH NORMAL AGING Less water More fat Less muscle mass Slowed hepatic metabolism Decreased renal excretion Decreased responsiveness of the baroreceptorsSlide 18

ABSORPTION Not affected by the normal aging process Can be altered by drug interactions Antacids Iron Can be affected by disease Lack of intrinsic factor (Vitamin B12 absorption) Delayed gastric emptyingSlide 19

DISTRIBUTION Less water volume of distribution higherconcentration of water-soluble drugs More fat volume of distribution prolongedaction of fat-soluble drugs (increased half-life) Lower level of serum proteins (eg, albumin)increases the concentration of the unbound(free or active) form of drugsSlide 20

METABOLISM Slowed phase I (including cytochrome P450) reactions Oxidation, reduction, dealkylation Warfarin and phenytoin levels may be higherbecause of altered metabolism Phase II reactions are essentially unchanged Conjugation, acetylation, methylation Drug-drug interactions Increased risk with increased number of drugsSlide 21

EXCRETION Hepatic Renal Renal clearance may be reduced Serum creatinine may not be an accuratereflection of renal clearance in elderly patients(decreased lean body mass) Active drug metabolites may accumulate Prolonged therapeutic action Adverse effectsSlide 22

CASE STUDY: WHY DID MRS. A FALL? Functional status Uses walker at baseline Dependent in other ADLs (like bathing) Sensory impairments Macular degeneration Peripheral neuropathy CNS diseases Dementia Parkinson’s disease Comorbid diseases Cardiovascular (syncope) Diabetes mellitus (hypoglycemia) Anemia (hypotension)Slide 23

ORTHOSTATIC HYPOTENSION, FALLS,AND HIP FRACTURES Baroreceptor sensitivity decreases with age Trazodone New medication according to nursing home record Associated with orthostatic hypotension Diuretic use can cause volume depletion and orthostatichypotension Falls and hip fractures are associated with significantmorbidity and mortality in older adultsSlide 24

CASE STUDY: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)Slide 25

DELIRIUM More than confusion Acute onset, fluctuating course Inattention Disorganized thinking or altered level ofconsciousness Associated with low levels of acetylcholine Low levels in patients with dementia at baseline Use of anticholinergic medications is a risk factorSlide 26

ANTICHOLINERGIC MEDICATIONS Drug classes Antihistamines Tricyclic antidepressants Antispasmodics and muscle relaxants Adverse effects Dry mouth Urinary retention Constipation Confusion, deliriumSlide 27

PHARMACOLOGIC TUG-OF-WAR Tolterodine (Detrol) Potent anticholinergic Relaxes detrusor muscle to treat urge incontinence (detrusor hyperactivity;“overactive bladder) Can worsen constipation Donepezil (Aricept) Acetylcholinesterase inhibitorRaises levels of acetylcholine to help improve cognitionCan cause detrusor hyperactivity and diarrheaCould cause symptomatic bradycardia, syncope (Mrs. A is also on β-blocker) Incontinence and falls Dementia is a risk factor for both incontinence and falls May be adverse drug events related to donepezil Diuretic use can worsen incontinence and cause orthostatic hypotensionSlide 28

“THINK DRUGS” BEFOREMAKING A NEW DIAGNOSIS Consider adverse drug effect as etiology of newsigns/symptoms Remember that an over-the-counter drug,supplement, or herbal remedy can be the culprit Consider discontinuing or dose-reducingmedications Avoid prescribing a new medication to treat anadverse drug effect (“prescribing cascade”)Slide 29

COMMON CONDITIONS COULDREALLY BE ADVERSE DRUG EFFECTSConditionConstipationCould be caused by: Calcium channel blocker IronIncontinenceMemory loss α-blocker AntihistaminesSyncope FallsWeight lossTricyclic antidepressantα-blockerBenzodiazepineFluoxetine (Prozac)Slide 30

CASE STUDY (continued) Labs Hb/Hct 10/30.1 (baseline) INR 1.9 Creatinine 2.0 (baseline 1.5) Trop T 0.090 (ref 0.000-0.034); normal CK and CK-MB UA negative EKG: unchanged; anterior T-wave flattening CT of head Atrophy, chronic small-vessel ischemic disease No acute bleedSlide 31

CASE STUDY:PELVIS AND LEFT HIP X-RAYSSlide 32

CASE STUDY: ACUTE MANAGEMENT Pain Already given morphine 2 mg IV2 doses for pain Nausea and vomiting Complains of “sick stomach” Emesis after morphine Agitation Increasingly agitated, trying to climb out of bed Shouting “Veronica” repeatedlySlide 33

CASE STUDY:WHAT DO YOU ORDER? Pain Nausea AgitationSlide 34

POTENTIALLY INAPPROPRIATEMEDICATION USE IN OLDER ADULTS:Beers Criteria (1 of 2) A consensus-based list of medications that arepotentially inappropriate for the elderly The Beers criteria were published in 1991, revised in1997 and 2002 Statistical association with adverse drug events hasbeen documented Does not account for the complexity of the entiremedication regimenArch Intern Med. 2003;163:2716-2724.Pharmacotherapy. 2005;25(6):831-838.Slide 35

POTENTIALLY INAPPROPRIATEMEDICATION USE IN OLDER ADULTS:Beers Criteria (2 of 2) Table 1: Independent of disease or condition Describes concern for prescribing certain drugs orclasses of drugs for older adults Gives severity rating (low or high) Table 2: Considering diagnosis or condition Describes drugs or classes of drugs that can cause orworsen a particular disease or condition Gives severity rating (low or high)Arch Intern Med. 2003;163:2716-2724.Slide 36

PAIN MEDICATIONS Propoxyphene (Darvon) has limited efficacy andsignificant side effects (has been withdrawn from themarket) Caution with nonsteroidal anti-inflammatory drugs Indomethacin has significant CNS side effects Ketorolac (Toradol) can cause serious GI and renal effects Meperidine (Demerol) has low oral efficacy, activemetabolites and CNS effects Morphine metabolites are renally clearedArch Intern Med. 2003;163:2716-2724.Slide 37

ANTI-EMETICS Antihistamines: promethazine (Phenergan) Anticholinergic, may worsen delirium ( acetylcholine) Included on Beers list (Table 1) Dopamine antagonists: metoclopramide (Reglan) May worsen parkinsonism ( dopamine) Included on Beers list (Table 2) Serotonin (5-HT3) antagonists: odansetron (Zofran) Expensive, but likely safest for this patientArch Intern Med. 2003;163:2716-2724.Slide 38

MANAGING AGITATED DELIRIUM Treat pain Opioids may cause confusion, but untreated pain mayprecipitate and perpetuate delirium Assess for other sources of discomfort Hunger, thirst, cold Fecal impaction; urinary retention Address sensory impairment Eye glasses and hearing aids Try to minimize sensory “overload” ReorientationSlide 39

ANTIPSYCHOTIC MEDICATIONS Blac