Geriatric Polypharmacy: A Pill for Every ill? Speaker has no relationship to disclose. Objectives. Amelie Hollier, DNP, FNP BC, FAANP President, APEA

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1 Geriatric Polypharmacy: A Pill for Every ill? Amelie Hollier, DNP, FNP BC, FAANP President, APEA Speaker has no relationship to disclose. Objectives 1. Assess medications for elder appropriateness prior to prescribing 2. Develop strategies to prescribe/discontinue medications for elderly patients who are seen in primary care 3. Apply principles of safe geriatric prescribing when managing elderly patients 1

2 Fact # 1 Geriatric Patients US Life Expectancy Women: 81.0 years Men: 76.2 years Fact # 2 Geriatric Patients 2011 Elderly population increases by 30% each year from now until 2050!!! The Baby Boomers turned 65 years old in 2011! It is MORE difficult to prescribe medications in Elderly Patients Inter individual variability Polypharmacy Concomitant diseases Physiological changes associated with aging (renal, hepatic dysfunction) Multiple prescribers! 2

3 A Reasonable Approach: Always ask and answer these 3 questions before prescribing First: What is the Diagnosis? Second: What drug? Third: What dose? First Question? What s the Diagnosis? There are TWO critical considerations! First Consideration Unrecognized ADEs Adverse Drug Events In older adults, drug induced symptoms are commonly mistaken for a new disease or worsening of an existing disease Some drug induced symptoms are indistinguishable from common older adult illnesses 3

4 Second Consideration Diagnosis in the Elderly New onset of disease in an elderly patient usually affects an organ that has been weakened by a different disease process Harrison s Principles of Internal Medicine Diagnosis in Elderly Elderly Adults have atypical presentation of diseases Disease Elderly Presentation Non Elderly Presentation Anemia SOB, Angina, Fatigue Fatigue Hypothyroidism Cardiac conduction defects, cognitive changes, looks depressed Menstrual changes, constipation, changes in hair and skin UTI Confusion, anorexia Burning, frequency, urgency Take Home Point New onset of disease in an elderly patient usually affects an organ that has been weakened by a different disease process. Harrison s Principles of Internal Medicine 4

5 First Question? What s the Diagnosis? Second Question? What Drug? (or do we even need a drug?) Example: Pain in Older Adults Non pharmacologic Management Patient education Ice/Heat Massage/stretching Relaxation Biofeedback PT interventions: exercise, splints, braces 5

6 American Geriatrics Society Beers Criteria 2015 What Drug? Beers Criteria Most widely used criteria (since 1991) to assess inappropriate drug prescribing in elderly AGS Updated 2012 Beers Criteria for Potentially Inappropriate Medication (PIMS) Use in Older Adults J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs : Beers Updates Lists potentially harmful drug drug interactions List of meds to avoid or have dosage reduced based on renal function List of alternatives for the Avoid List or on the potentially harmful drug disease interactions list J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs

7 Beers Criteria Goal is to improve care of older adults by reducing exposure to PIMs What Makes a Drug Potentially Inappropriate for an Elderly Patient? Inappropriate Medications Anti cholinergic Side Effects Memory impairment, confusion, hallucinations, dry mouth, blurred vision, urinary retention, constipation, tachycardia, acute angle glaucoma 7

8 An Ode to an Anticholinergic Med Oh this drug, it makes me pink, Sometimes, I can t think or even blink. I can t see, I can t pee I can t spit I can t defecate (**it) Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 30 ml/min. Which anti infective should be avoided in her for long term suppression (because of pulmonary toxicity)? 1. Sulfa drug 2. Ciprofloxacin 3. Amoxicillin 4. Nitrofurantoin J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 30 ml/min. Beers Criteria recommends nitrofurantoin avoidance: For long term suppression 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4): J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs

9 Beers 2015: New Recommendation Beers Criteria recommends nitrofurantoin use if Cr Cl > 30 ml/min 2012 Beers Criteria recommended avoidance of nitrofurantoin if Cr Cl < 60 ml/min 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4): J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs What about drugs that need dose adjustment due to renal insufficiency? Excretion Age related changes in kidney function Decreases in renal mass Decreases in renal blood flow (1 2% decline/year after age 40) 9

10 Measure of Kidney Function Creatinine production is related to muscle mass Creatinine production decreases with advancing age & loss of muscle mass. This produces decreased serum Cr levels So..Normal serum Cr, but impaired renal function At what age was his serum creatinine higher? 60 years old 90 years old What Affects Creatinine Levels? What you look like What you eat Who you are 10

11 What affects serum Cr? Muscle Mass More Less More muscle mass, more serum creatinine Less muscle mass, less serum creatinine What affects serum Cr? Diet Meat Eater Vegetarian Diet Creatinine Increases but may be temporary Creatinine decreases What affects serum Cr? Age and Gender Creatinine decreases as you age (due to less muscle mass) Creatinine greater in males due to greater muscle mass 11

12 How does obesity affect serum creatinine? a. Increases Cr b. Decreases Cr c. Has no effect So. Many Factors Affect Creatinine Levels A better measure of kidney function is CrCl (ml/min) Most accurate CrCl is collected over a 24 hour period, but it s a major drag to collect!! GFR (Glomerular filtration rate = ml/min) can be used to estimate CrCl (Not Perfect, but it s pretty good!) GFR is usually estimated by Labs: egfr egfr Normal Range > 60mL/min/1.73m 2 About 38% of individuals aged 70 years or older without HTN or DM, had GFRs of < 60mL/min/1.73m 2 Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Am J Kidney Dis. 2003;41(1):1. 12

13 At what age was his GFR (or CrCl) greater? 60 years old 90 years old Excretion Decrease in GFR (50% decline between 50 and 90 years) Decrease in Creatinine Clearance Known Decreased Renal Clearance in Elderly Acetaminophen Anti arrhythmics Anti convulsants Anti depressants Anti psychotics Benzos, beta blockers, theophylline Warfarin Many, many others! 13

14 Good Rule of Thumb Be familiar with the medications you prescribe! Remember: Some drugs require renal dosing and hepatic dosing Mrs. Downs 77 year old female who relates feeling sad a lot of the time and having very low energy. She was screened for depression by her PCP using the PHQ 9. Her results indicate likely depression. She is not suicidal. How should she be managed? Assessment Many common ailments can masquerade as depression Hypo/hyperthyroidism Anemia, infection UTI Vitamin D deficiency 14

15 IF a medication is used to treat Mrs. Downs depression, which one is preferable? Which class? WHICH ONE? Where s the evidence? SSRIs SNRIs (watch CrCl for duloxetine <30 ml/min) TCAs How do you Choose an SSRI? Some Considerations: Primarily metabolized by the CYP 450 system, 2D6 enzymes Citalopram, escitalopram, sertraline have least effect on these enzymes How do you Choose an SSRI? Some Other Considerations: Safety: unsteady gait, hx of falls Ease of discontinuing treatment Safety in fragile elders Side effect profile 15

16 What abnormality is common in older patients who take SSRIs? a. Hyponatremia b. Hypokalemia c. Hyperkalemia d. Hyperglycemia Hyponatremia and SSRIs WHY? SIADH=syndrome of inappropriate secretion of antidiuretic hormone Incidence in elders: 10 40% Andreescu C, Reynolds, CF 3 rd. Late life depression: Evidence based treatment and promising new directions for research and clinical practice. Psychiatr Clin North Am 2011; 34(2): ,vii iii. Review. Hyponatremia and SSRIs What else increases risk? Older age Female gender Low body weight Diuretic, NSAID use 16

17 Hyponatremia and SSRIs How to monitor? Onset within 2 weeks Consider checking sodium level before starting or changing dose Most common symptoms: fatigue, anorexia, confusion Least common: seizures, coma, death Mrs. Downs Suppose Mrs. Downs has atrial fibrillation and takes warfarin daily? Any worries with prescribing an SSRI? What other side effects and SSRIs? Increased Bleeding risks Especially if aspirin or NSAIDs are on board 17

18 Increased Bleeding and SSRIs Mechanism??? Impaired platelet aggregation Depletion of serotonin in platelets Increased gastric acidity Increased Bleeding and SSRIs How common is this and When??? Risk is low of upper GI bleed Within 4 weeks up to many months Median time of bleeding: 25 weeks Increased Bleeding and SSRIs Reduction of Risks PPIs reduce the risk of bleeding If on warfarin, check INR more frequently Avoid concomitant use of aspirin, NSAIDs 18

19 TCAs Tricyclic Antidepressants Most extensively studied in elderly patients! Shows good efficacy! What s the problem??? Tricyclic Antidepressants Potent anticholinergic side effects!!! Sedation Orthostatic hypotension, unsteady gait, psychomotor impairment Tricyclic Antidepressants Cardiac effects: bradycardia, slowed conduction, orthostatic hypotension Monitor EKG before and during use Monitor orthostatic BP measurements Monitor pulse 19

20 Tricyclic Antidepressants Best safety profile is Secondary amines: Nortriptyline (Pamelor) Desipramine (Norpramin) Secondary Amines Here s why! Can measure levels with lab studies Use therapeutic window to guide dosing Mrs. Dash 83 year old female who has osteoarthritis in both knees. She is still mobile but complains of daily pain in her knees. She is not a surgical candidate at this time. 20

21 Mrs. Dash She self medicates with ibuprofen and she reports good pain control using 400 mg ibuprofen 2 3 times daily. Is this a Problem? Mrs. Dash She self medicates with ibuprofen and she reports good pain control using 400 mg ibuprofen 2 3 times daily. Age >75 years is a risk factor for chronic NSAID use! 2015 Beers: NSAIDs Avoid any use of indomethacin Avoid any use of ketorolac If no heart failure or renal failure and use is unavoidable, choose ibuprofen, naproxen with gastroprotection if used > 7 days J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs

22 Pain Med Considerations Acetaminophen PRN or scheduled PRN first, then scheduled up to 3 grams daily Non-acetylated salicylate, capsaicin, lidocaine patch, topical NSAID, SNRI J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs COX 2 NSAIDs Beers Criteria Avoid : NSAIDs Avoid in heart failure or CrCl <30 ml/min J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs Gastrointestinal Risk Treat with PPI if NSAID use > 7 days 22

23 Topical NSAIDs? GI Risk? No study demonstrates greater safety with topical vs oral NSAIDs but seems unlikely There have been GI bleeds with topical NSAIDs FDA requires same standard NSAID warning on oral and topical agents???efficacy beyond 2 weeks Cost: $ /month Cardiovascular Risk COX 1 and COX 2 NSAIDs inhibit the Cyclooxygenase pathway and thus, prostaglandins COX 1 normally expressed in all tissues COX 2 usually undetectable but are present during inflammatory states 23

24 AHA Recommends for Pain CV disease or risk factors for ischemic heart disease 1. Acetaminophen 2. Aspirin 3. Tramadol 4. Opioids 5. Nonacetylated salicylates (Diflunisal) 6. NSAIDs with low COX 2 selectivity 7. NSAIDs with some COX 2 selectivity 8. COX 2 selective agents Aspirin/NSAID Interaction CV Risk: Increased risk of MI Aspirin irreversibly inhibits platelets NSAIDs reversibly bind to platelets If NSAID and Aspirin are taken together, NSAID blocks aspirin s ability to inhibit platelets Advice: Patient should take aspirin at least an hour prior to taking an NSAID! NSAID Use after MI Risk of reinfarction or death is increased if NSAID taken after recent MI Risk of reinfarction or death increased YEARS after MI CV risk after MI DOES NOT decline over time! Avoid NSAIDs indefinitely after an MI! Schjerning Olsen AM, Fosbol EL, Lindhardsen J, et al. Long term cardiovascular risk of NSAID use according to time passed after first time myocardial infarction: a nationwide cohort study. Circulation 2012 Sep 10 24

25 Proton Pump Inhibitors Commonly used to reduce risk of GI Bleeds One of the most widely used drug classes in 2009, 2010, 2011, 2012 (3 rd highest class in sales) Estimates that 69% are inappropriately prescribed PPI Harms 1. Infection Pneumonia/C. difficile: R/T gastric acid suppression may allow bacterial growth Care in use with patients with COPD, asthma, increased age, immunosuppression PPI Use 2. Increases ph Alters the absorption of many drugs Calcium, Fe, Vitamin D, Vitamin B12, others 25

26 PPI Harms Fracture Risk in patients > 50 years, high doses, or use > 1 year 25% increase in all fractures 47% increase in spinal fractures FDA requires fracture risk info added to labeling in OTC and Rx PPIs PPI OTC and Rx 3. Omeprazole and Na bicarb (Zegerid) Na bicarb = baking soda Allows omeprazole to be absorbed a little bit faster Each cap contains 300 mg Na Avoid in HTN, HF, or other patients in whom Na should be restricted Beers: Avoid Drug Disease or Drug Syndrome Interactions Heart Failure Syncope Dementia and Cognitive Impairment Falls and Fractures Insomnia Constipation 26

27 Beers Criteria Avoid : Heart Failure Digoxin > mg daily Higher doses associated with no additional benefit and may increase toxicity 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4): Age Related Change in Pharmacokinetics As aging occurs, there is a DECREASE in total body water (10 15%) Distribution Decrease in total body water (10 15%) So, smaller distribution of water soluble drugs 27

28 Increased Drug Concentration! Serum levels increase due to decreased volume of distribution Examples: Digoxin Beers Criteria Avoid : Heart Failure Digoxin > mg daily Higher doses associated with no additional benefit and may increase toxicity 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4): Mrs. Boudreaux 78 year old female who is very active and enjoys playing cards with her friends one evening per week. During the card game she has dinner and a couple of glasses of wine. She states that this has been her habit for several years but now she becomes dizzy before finishing her second glass of wine. She has had no change in weight, medications (or wine). 28

29 What is going on with Mrs. Boudreaux? a. The wine glasses are getting bigger. b. She just can t hold her liquor anymore. c. This is an age related change with EtOH metabolism. Distribution Decrease in total body water (10 15%) So, smaller distribution of water soluble (EtOH) drugs 1. Increased EtOH Concentration! Serum levels increase due to decreased volume of distribution Examples: EtOH (Mrs. Boudreaux wine) 29

30 2. Changes in EtOH Metabolism Liver mass decreases Hepatic blood flow decreases First pass metabolism decreases 3. Decreased Production of CYP 450 enzymes Can decrease up to 30% in elderly! Lots of variability (even in young, middle adults) More studies needed but, decreases in 1A2, 2C19 Decrease or no change in 3A4, 2C9 No change in 2D6 2 glasses of wine Age 48 years EtOH CYP 450: 2E1 enzymes Complete Metabolism 2E1 Enzymes Undetectable Concentrations of EtOH in blood 30

31 2 glasses of wine Age 78 years EtOH CYP 450: 2E1 enzymes Incomplete Metabolism 2E1 Enzymes Higher Concentrations of EtOH in blood What is going on with Mrs. Boudreaux? a. The wine glasses are getting bigger. b. She just can t hold her liquor anymore. c. This is an age related change with EtOH metabolism. Anti Coagulants 31

32 Speaking of warfarin. Mr. Thibodeaux takes warfarin 2 mg daily. His INR has been therapeutic. For the past 3 weeks, he has had tooth abscess with extraction and hasn t been able to eat because his dentures don t fit. He has lost 7 pounds. Considerations? Mr. Thibodeaux What important safety issue must be addressed by the NP? a. Falls precautions instituted. b. Monitor for decreased CrCl. c. Check INR. d. Check albumin level. Why? Speaking of warfarin. Warfarin is protein bound Must assume serum albumin levels decreased Mr. Thibodeaux 32

33 So if Plasma protein decreases. Patient takes 100 mg of Drug A daily. Drug A is 90% bound, that means 10 mg of drug is active. Decrease in protein of 10% IF Protein decreases by 10% (90 x.10 = 9 mg), then 19 mg free drug. Greater effect of from the drug! Drug A 10 mg Free 90 mg Bound 10% Decrease in Protein Drug A 19 mg Free 81 mg Bound What important safety issue must be addressed by the NP? a. Falls precautions instituted. b. Monitor for decreased CrCl. c. Check INR. d. Check albumin level. Why? Speaking of warfarin. More circulating warfarin! INR will be increased! Risk of bleeding increased! Mr. Thibodeaux 33

34 Take Home Point Until Mr. Thibodeaux gets his teeth back Third Question? What Dose? What dose? Most drug studies do not include geriatric patients in clinical trials 34

35 What dose? No one knows! Start low and go slow Wrap Up! Consider ADEs for ANY NEW symptom in an elder!!! Take Home Point Follow the Beers List to keep elders from unintended harm! And PIMs! 35

36 Take Home Points! Do we really need a drug? Can a safer drug be used instead? Thank you! Amelie Hollier, DNP, FNP BC, FAANP Advanced Practice Education Associates amelie@apea.com References cdc.gov Harrison s Principles of Internal medicine, Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4): J Am Geriatr Soc. 2015; Oct 8. doi: 10:1111/jgs Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Am J Kidney Dis. 2013;41(1):1. Andreescu C, Reynolds, CF 3 rd. Late life depression: Evidence based treatment and promising new directions for research and clinical practice. Psychiatr Clin North Am 2011; 34(2): ,vii iii. Review. Am College of Rheumatology Guidelines for Management of Osteoarthrtis, 2012 Schjerning Olsen AM, Fosbol EL, Lindhardsen J, et al. Long term cardiovascular risk of NSAID use according to time passed after first time myocardial infarction: a nationwide cohort study. Circulation 2012 Sep 10 Ottawa (ON): Canadian Pharmacists Association; c2011. Benzodiazepine monograph [October 2009]. therapeutics.ca. (Accessed August 8, 2015). Potentially harmful drugs in the elderly: Beers list and more. Pharmacist's Letter/Prescriber's Letter 2014;23(9):