Geriatric Polypharmacy: A Pill for Every ill Amelie Hollier, DNP, FNP-BC, FAANP President, APEA

Geriatric Patients US Life Expectancy Women: 80 years Men: 75 years Natl Vital Stat Rep. 2010;58:1-136

Geriatric Patients 2011 The “Baby Boomers” turned 65 years old in 2011 Elderly population increases by 30% each year from now until 2050!!!

Geriatric Patients 20% of people aged > 65 years take at least 10 medications Termed: the “P” word Patterns of medication use in the United States, 2006. A report from the Slone Survey. www.bu.edu/slone/SloneSurvey/ AnnualRpt/ SloneSurveyWebReport2006.pdf. Accessed February 1, 2013.

Geriatric Patients As the number of medications increases, so does the risk of adverse drug events (ADEs) ADEs: weight loss, falls, changes in cognition, loss of independence, hospitalization

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!

A Reasonable Approach: Always answers these 3 Questions before Prescribing First: What is the Diagnosis? Second: What drug? Third: What dose?

What Diagnosis? What Disease? First Question? What Diagnosis? What Disease?

Unrecognized ADEs 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

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 Ex: Elderly adult develops anemia Harrison’s Principles of Internal Medicine

Example 1: Mr. Smith 80 year old male who is mostly independent; he has a number of chronic diseases that are stable. He has developed iron deficiency anemia over the last 3 months from a “slow bleeding” polyp in large intestine.

How does an older adult with anemia present? In older adults we see: Shortness of breath Chest pain (angina) Fatigue (“I’m getting older”)

Example 2: Mrs. Jones 80 year old female who is very independent; she has several chronic diseases that are stable with medications. She has developed hypothyroidism over the last 4 months.

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

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

What Diagnosis? What Disease? First Question? What Diagnosis? What Disease?

What Drug? (or do we even need a drug?) Second Question? What Drug? (or do we even need a drug?)

Example: Pain in Older Adults Nonpharmacologic Management Ice Heat Massage Relaxation Biofeedback PT interventions: exercise, splints, braces

Second Question? 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

Beers Criteria Goal is to improve care of older adults by reducing exposure to PIMs

Inappropriate Medications Anti-cholinergic Side Effects Memory impairment, confusion, hallucinations, dry mouth, blurred vision, urinary retention, constipation, tachycardia, acute angle glaucoma

“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 (**it) (“defecate”)

Mrs. Thomas 80 year old female who is completely independent; she has a several chronic diseases that are stable with medications. She complains of difficulty sleeping when her arthritic knee aches. She takes an OTC medication with diphenhydramine for sleep.

Is this harmful if she uses this only three times weekly? Mrs. Thomas Is this harmful if she uses this only three times weekly?

Potentially Inappropriate Medications AVOID Antihistamines (First Generations) Brompheniramine (Bromfed) Carbinoxamine (Chlor-Trimeton) Diphenhydramine (Benadryl) Hydroxyzine (Atarax, Vistaril) Promethazine (Phenergan) Others 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4):616-631

Anti-Histamines What’s the Problem with these? They are highly anti-cholinergic Clearance reduced with advanced age Tolerance develops when used as hypnotic 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4):616-631

High Risk Medications Diphenhydramine: impaired cognition, urinary retention (next day sedation, impaired driving)

Good Rule: “Avoid First Generation Anti-histamines” Suppose Mrs. Thomas had an acute allergic reaction after eating boiled crawfish in South Louisiana?

Anti-Histamines Cetirizine ++ Loratadine + Fexofenadine Levocetirizine 2nd Gen Anti-Histamine Sedative Effect Cetirizine ++ Loratadine + Fexofenadine Levocetirizine Desloratadine

Good Rule of Thumb Choose an agent from a different generation; or the least potent in the medication class “Hay Fever”: Consider a topical nasal anti-histamine {Asteline (Azelastine)}

Good Rule of Thumb Consider a different class of medication What about a topical nasal steroid?

Mrs. Jones is 75 years old. She is diagnosed with a UTI Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 50 mL/min. Which anti-infective should be avoided in her because of inadequate drug concentration in the urine? Sulfa drug Ciprofloxacin Amoxicillin Nitrofurantoin 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4):616-631

Mrs. Jones is 75 years old. She is diagnosed with a UTI Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 50 mL/min. Beers Criteria recommends nitrofurantion avoidance: CrCl < 60 mL/min For long-term suppression 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4):616-631

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)

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

What Affects Creatinine Levels? What you look like What you eat Who you are

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

How does obesity affect serum creatinine? Increases Cr Decreases Cr Has no effect Copyright 1998 Advanced Practice Education Associates

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/1.73m2 About 38% of individuals aged 70 years or older without HTN or DM, had GFRs of < 60mL/min/1.73m2 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.

Excretion Decrease in GFR (50% decline between 50 and 90 years) Decrease in Creatinine Clearance

Mrs. Jones is 75 years old. She is diagnosed with a UTI Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is < 50 mL/min. Which anti-infective should be avoided in her because of inadequate drug concentration in the urine? Sulfa drug (none as long as CrCl > 30 mL/min) Ciprofloxacin (none as long as CrCl > 30 mL/min) Amoxicillin (none as long as CrCl > 30 mL/min) Nitrofurantoin (AVOID!)

Known Decreased Renal Clearance in Elderly Acetaminophen Anti-arrhythmics Anti-convulsants Anti-depressants Anti-psychotics Benzos, beta blockers, theophylline Warfarin Many, many others!

Excretion Many drugs with dosage adjustments: allopurinol, many antibiotics, digoxin, lithium, gabapentin, H2 blockers, anti-arrhythmics

Good Rule of Thumb Be familiar with the medications you prescribe! Remember: Some drugs require renal dosing and hepatic dosing

What patient is most likely to present with benign prostatic hyperplasia? 20 year old 40 year old 60 year old 80 year old Copyright 1998 Advanced Practice Education Associates

Benign Prostatic Hyperplasia What medication class do we prescribe to improve urinary flow? What’s the most common side effect?

Non-selective Alpha Blocker Beers Criteria Recommends “Avoid” alpha blockers for routine treatment of hypertension OK to use alpha blockers for BPH with education and precautions Non-selective Alpha Blocker Medications Doxazosin Cardura Prazosin Minipress Terazosin Hytrin 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4):616-631

Alpha Blockers for treatment of BPH or Urinary outflow problems Uro-specific Alpha Blockers Comments *Uroxatral Alfuzosin (needs renal and hepatic dose adjustments) *Flomax (generic) Tamsulosin (no renal or hepatic precautions); sulfa allergy precaution *Rapaflo Silodosin (needs renal and hepatic dose adjustments) *Possible intraoperative floppy iris syndrome (IFIS) during cataract surgery

Good Rule of Thumb Choose an agent that is most specific in the medication class for the problem you are treating.

“Mrs. Dash” Is this a Problem? 73 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. She self-medicates with ibuprofen and she reports good pain control using 400 mg ibuprofen 2-3 times daily. Is this a Problem?

Beers Criteria “Avoid”: NSAIDs Non-COX selective NSAIDs, oral Aspirin > 325 mg daily Ibuprofen Diclofenac, Etodolac Meloxicam Naproxen Ketorolac, Indomethacin (most adverse GI effects) 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4):616-631

Gastrointestinal Risk Treated 3-6 months: 1% risk of Upper GI ulcers, bleeding or perforation Treated 1 year: 2-4%

Proton Pump Inhibitors Very effective at preventing ulcers Once daily Usually better tolerated than misoprostol; slightly less effective Hooper L, Brown TJ, Elliott R, et al. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ 2004; 329:948.

PPI OTC and Rx 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

PPI plus clopidogrel Absolutely not omeprazole (inh 2C19 activity)! Reduces conversion of clopidogrelantiplatelet activity Do not use esomeprazole (Nexium) Use dexlansoprazole, lansoprazole, pantoprazole, or HD famotidine

Increases pH PPI Use Alters the absorption of many drugs Calcium, Fe, Vitamin B12

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 Harms Fracture Risk in patients > 50 years, high doses, or use > 1 year WHY???

PPI Harms Possible decreased calcium absorption caused by PPIs Inconclusive relationship between PPIs and bone density

PPI Harms Infection Pneumonia/C. difficile: R/T gastric acid suppression may allow bacterial growth Care in use with patients with COPD, asthma, increased age, immunosuppression

What about Vitamin B12 Deficient Patients on PPIs? Consider using a different mucus membrane Sublingual, intranasal

…Back to “Mrs. Dash” IF GI risks high: consider PPI IF CV risks high…. 73 year old female who has osteoarthritis in both knees. She self-medicates with ibuprofen and she reports good pain control using 400 mg ibuprofen 2-3 times daily. IF GI risks high: consider PPI IF CV risks high….

AHA Recommends for Pain CV disease or risk factors for ischemic heart disease Acetaminophen Aspirin Tramadol Opioids Nonacetylated salicylates (Diflunisal) NSAIDs with low COX-2 selectivity NSAIDs with some COX-2 selectivity COX-2 selective agents

Beers: Aspirin for Primary Prevention of cardiac events Lack of evidence of benefit versus risk in individuals aged > 80 years FYI: Strength of recommendation is “weak” Quality of Evidence is Low

Beers: “Avoid” Drug-Disease or Drug Syndrome Interactions Heart Failure Syncope Dementia and Cognitive Impairment Falls and Fractures Insomnia Constipation

Beers Criteria “Avoid”: Heart Failure Digoxin > 0.125 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):616-631

Age Related Change in Pharmacokinetics As aging occurs, there is a DECREASE in total body water (10-15%)

Distribution So, smaller distribution of water soluble drugs Decrease in total body water (10-15%) So, smaller distribution of water soluble drugs

Increased Drug Concentration! Serum levels increase due to decreased volume of distribution Examples: Digoxin

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).

What is going on with Mrs. Boudreaux? The wine glasses are getting bigger. She just can’t hold her liquor anymore. This is an age related change with EtOH metabolism. Copyright 1998 Advanced Practice Education Associates

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)

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!

What is going on with Mrs. Boudreaux? The wine glasses are getting bigger. She just can’t hold her liquor anymore. This is an age related change with EtOH metabolism. Copyright 1998 Advanced Practice Education Associates

Beers: “Avoid” Drug-Disease or Drug Syndrome Interactions Heart Failure Syncope Dementia and Cognitive Impairment Falls and Fractures Insomnia Constipation

Sleep Complaints in Older Adults 50% of older adults complain of at least one sleep complaint Impairs functional ability Increases risk of accidents and falls 1/3 of elderly patients in North America receive a benzo hypnotic for insomnia (or non-benzo)

Beers Criteria “Avoid”: Benzos Hypnotics Benzodiazepines: Avoid for insomnia, agitation, or delirium Avoid in dementia (worsens symptoms) Increased sensitivity to these and slower metabolism Increased risk of falls, cognitive impairment A short acting agent can behave like an intermediate or long acting agent 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4):616-631

Benzodiazepines Agent Brand Duration Alprazolam Xanax Short/intermediate Lorazepam Ativan Short/Intermediate Oxazepam Serax Clonazepam Klonopin Long Diazepam Valium Flurazepam Dalman

But if you just have to use one for anxiety… Generally speaking, consider 1/3 to ½ adult dose for elderly, titrate Lorazepam (Ativan): Pharmacokinetics are not significantly affected by age Avoid doses over 3 mg Ottawa (ON): Canadian Pharmacists Association; c2011. Benzodiazepine monograph [October 2009]. http://www.e-therapeutics.ca. (Accessed February 8, 2013). Potentially harmful drugs in the elderly: Beers list and more. Pharmacist's Letter/Prescriber's Letter 2007;23(9):230907.

Sleep Changes in Older Adults Take longer to fall asleep Have less total nighttime sleep Increased nighttime wakefulness Daytime sleepiness Awaken early

Sleep Changes in Older Adults Common Causes Arthritic pain Depression Shortness of breath (HF, COPD, angina) Parkinson’s (nightmares, night terrors, levodopa) Medications: SSRIs, SNRIs, theophylline, cimetidine, phenytoin, steroids, bronchodilators Dementia: nighttime wandering

First Steps Non-Pharmacologic Avoidance of nicotine, alcohol, and caffeine Increasing daytime exercise and light exposure Limit or eliminate daytime napping Reduce light and noise Comfortable room temperature Meals > 2-3 hours before bedtime

Beers Criteria “Avoid”: Non-benzo Hypnotics (aka: Z-drugs) Benzodiazepine Receptor Agonists: Less rebound insomnia, tolerance, and dependence than benzos Eszopiclone (Lunesta), Zolpidem (Ambien), Zaleplon (Sonata) Elderly patients have same side effects as with benzos (delirium, falls, fractures) 2012 Beers Criteria Update Expert Panel J AM Geriatr Soc. 2012;60(4):616-631

Sleep Changes in Older Adults Pharmacologic Melatonin No serious adverse events Interacts with warfarin, ASA, clopidogrel, ticlopidine, antidiabetic agents (decreased glucose tolerance and insulin sensitivity)

High Risk Medications Insulin and SUs: Aggressive glycemic control often yields more harm than good

Endocrine Target A1C A1C: goal is <7% in most patients (but not all elderly!) >7% for some patients with many co-morbids or too abbreviated a lifespan to benefit from intensive therapy Copyright 1998 Advanced Practice Education Associates

What do these drugs all have in common? Macrolides, quinolones, telithromycin, sulfonamides Amitriptyline, citalopram, paroxetine, sertraline, venlafaxine, fluoxetine Albuterol, levalbuterol, salmeterol Phenylephrine, pseudoephedrine Cocaine

QT Prolongation Long QT Syndrome (LQTS) Increased risk of ventricular tachycardia

Torsades de Pointes Polymorphic V-tach Many drugs are culprits, but often it is combo of drugs

What increases the risk? Low potassium, magnesium Bradycardia Anything that prolongs myocardial repolarization

What DRUGS increase the risk? Quinolones Risk is additive with other drugs or conditions that increase risk

WHO is at risk? Elderly Psychiatric patients Patients with eating disorders (electrolyte imbalances)

Osteoporosis

Bisphosphonates Osteoporosis Efficacy wanes with time What’s optimal duration? New labeling from FDA (no consensus what it should say!)

Bisphosphonates FLEX Trial Compared bisphos with stopping after 5 years of continuous use Alendronate > 5 years did not provide much additional protection against fractures Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment. The Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006;296:2927-38

What dose? Most drug studies do not include geriatric patients in clinical trials

Underprescribing “Unintended underutilization” Example: Patient with MI: BB, ACE, ASA, statin plus other meds Don’t underprescribe to improve compliance

Consider ADEs for ANY NEW symptom in an elderly patient!!! Take Home Points! Consider ADEs for ANY NEW symptom in an elderly patient!!!

Follow the Beers list to keep elders from unintended harm! And PIMs! Take Home Points! Follow the Beers list to keep elders from unintended harm! And PIMs!

Final Take Home Points! Do we really need a drug? Can a safer drug be used instead?

Questions??? Amelie Hollier, DNP, FNP-BC, FAANP Advanced Practice Education Associates amelie@apea.com