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?
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
Confusion, anorexia
Menstrual changes,
constipation,
changes in hair and
skin
Burning, frequency,
urgency
UTI
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
First Question?
What Diagnosis?
What Disease?
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.
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
2nd Gen Anti-Histamine
Sedative Effect
Cetirizine
Loratadine
Fexofenadine
Levocetirizine
Desloratadine
++
+
0
++
+
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. 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
2. Ciprofloxacin
3. Amoxicillin
4. 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. 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?
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/1.73m2
• 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, antiarrhythmics
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?
a.
b.
c.
d.
20 year old
40 year old
60 year old
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
Prazosin
Terazosin
Cardura
Minipress
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
*Uroxatral
*Flomax
(generic)
*Rapaflo
Comments
Alfuzosin (needs renal and hepatic dose
adjustments)
Tamsulosin (no renal or hepatic
precautions); sulfa allergy precaution
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”
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
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 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”
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
1.
2.
3.
4.
5.
6.
7.
8.
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
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?
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)
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 agent
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):616-631
Benzodiazepines
Agent
Alprazolam
Brand
Xanax
Lorazepam
Ativan
Oxazepam
Serax
Clonazepam
Diazepam
Flurazepam
Klonopin
Valium
Dalman
Duration
Short/intermedi
ate
Short/Intermedi
ate
Short/Intermedi
ate
Long
Long
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
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
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!)
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
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 Associates
amelie@apea.com