Geriatric Polypharmacy: A Pill for Every ill

Geriatric Polypharmacy:

A Pill for Every ill

Amelie Hollier, DNP, FNP-BC, FAANPPresident, APEA

Geriatric Patients

• Women: 80 years• Men: 75 years

US Life Expectancy

Natl Vital Stat Rep. 2010;58:1-136

Geriatric Patients

• The “Baby Boomers” turned 65 years old in 2011• Elderly population increases

by 30% each year from now until 2050!!!

2011

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

• Inter-individual variability• Polypharmacy• Concomitant diseases• Physiological changes

associated with aging (renal, hepatic dysfunction)• Multiple Prescribers!

It is MORE difficult to prescribe medications in Elderly Patients

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?

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 Drug? (or do we even need a drug?)

Second Question?

Example: Pain in Older Adults

Nonpharmacologic Management• Ice• Heat• Massage• Relaxation• Biofeedback• PT interventions: exercise, splints, braces

What Drug?

Second Question?

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 MedicationsAnti-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 peeI can’t spitI 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.

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 PanelJ AM Geriatr Soc. 2012;60(4):616-631

Anti-HistaminesWhat’s the Problem with these?• They are highly anti-cholinergic• Clearance reduced with advanced

age• Tolerance develops when used as

hypnotic2012 Beers Criteria Update Expert PanelJ AM Geriatr Soc. 2012;60(4):616-631

High Risk MedicationsDiphenhydramine: 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

2nd Gen Anti-Histamine Sedative Effect

Cetirizine ++Loratadine +

Fexofenadine 0Levocetirizine ++Desloratadine +

Good Rule of ThumbChoose 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. Her CrCl is 50 mL/min.

Which anti-infective should be avoided in her because of inadequate drug concentration in the urine?1. Sulfa drug2. Ciprofloxacin3. Amoxicillin4. Nitrofurantoin2012 Beers Criteria Update Expert PanelJ AM Geriatr Soc. 2012;60(4):616-631

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


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 creatinineLess muscle mass, less serum creatinine

What affects serum Cr?Diet

Meat Eater Vegetarian Diet

Creatinine Increasesbut 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?

a. Increases Crb. Decreases Crc. 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/1.73m2

• 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. Her CrCl is < 50 mL/min.

Which anti-infective should be avoided in her because of inadequate drug concentration in the urine?1. Sulfa drug (none as long as CrCl > 30 mL/min)2. Ciprofloxacin (none as long as CrCl > 30

mL/min)3. Amoxicillin (none as long as CrCl > 30 mL/min)4. 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 ThumbBe 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?

a. 20 year oldb. 40 year oldc. 60 year oldd. 80 year old

Benign Prostatic Hyperplasia• What medication class do we prescribe

to improve urinary flow?• What’s the most common side effect?

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 CarduraPrazosin MinipressTerazosin Hytrin

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 ThumbChoose an agent that is most specific in the medication class for the problem you are treating.

“Mrs. Dash”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 PanelJ 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 RxOmeprazole 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 clopidogrelantiplatelet activity

• Do not use esomeprazole (Nexium)• Use dexlansoprazole, lansoprazole,

pantoprazole, or HD famotidine

PPI Use

Increases pH• 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 HarmsInfection• 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”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 PPIIF CV risks high….

AHA Recommends for Pain

1. Acetaminophen2. Aspirin3. Tramadol4. Opioids5. Nonacetylated salicylates (Diflunisal)6. NSAIDs with low COX-2 selectivity7. NSAIDs with some COX-2 selectivity8. COX-2 selective agents

CV disease or risk factors for ischemic heart disease

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 dailyHigher doses associated with no additional

benefit and may increase toxicity


Age Related Change in Pharmacokinetics

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

DistributionDecrease 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. Boudreaux78 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?

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.

DistributionDecrease 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?

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.

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 agent2012 Beers Criteria Update Expert PanelJ AM Geriatr Soc. 2012;60(4):616-631

BenzodiazepinesAgent Brand Duration

Alprazolam Xanax Short/intermediate

Lorazepam Ativan Short/Intermediate

Oxazepam Serax Short/Intermediate

Clonazepam Klonopin LongDiazepam Valium Long

Flurazepam Dalman Long

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

Potentially harmful drugs in the elderly: Beers list and more. Pharmacist's Letter/Prescriber's Letter 2007;23(9):230907.

Ottawa (ON): Canadian Pharmacists Association; c2011. Benzodiazepine monograph [October 2009]. http://www.e-therapeutics.ca. (Accessed February 8, 2013).

Sleep Changes in Older Adults

• Take longer to fall asleep• Have less total nighttime sleep• Increased nighttime wakefulness• Daytime sleepiness• Awaken early


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 StepsNon-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 PanelJ AM Geriatr Soc. 2012;60(4):616-631


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

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

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!)

BisphosphonatesFLEX 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

Take Home Points!Consider ADEs for ANY NEW

symptom in an elderly patient!!!

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 [email protected]

Geriatric Polypharmacy: A Pill for Every ill

Documents

Transcript of Geriatric Polypharmacy: A Pill for Every ill