Side Effect Burden in the
Elderly Population
Joshana K. Goga Pharm.D. BCPP
Sheppard Pratt Health System
University of Maryland School of Pharmacy
September 2013
Objectives
• Recognize high risk medications in the elderly
population
• Evaluate medications on Beer’s criteria
• Evaluate medications with anticholinergic load
• Evaluate STOPP approach
Aging Population
Based on online data from the U.S. Census Bureau’s 1
Physiological Changes in
Elderly
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Cardiac output decreases
Blood pressure increases and arteriosclerosis develops
Lungs show impaired gas exchange, a decrease in vital capacity and slower
expiratory flow rates
Creatinine clearance decreases with age although the serum creatinine level remains
relatively constant due to a proportionate age-related decrease in creatinine production
Slowing of gastrointestinal system with trophic gastritis and
altered hepatic drug metabolism
Progressive elevation of blood glucose occurs with age on a multifactorial basis
Osteoporosis is frequently seen due 'to a linear decline in bone mass after the fourth decade
Epidermis of the skin atrophies with age and due to changes in collagen and elastin the skin
loses its tone and elasticity
Lean body mass declines with age and this is primarily due to loss and atrophy of muscle cells
Degenerative changes occur in many joints and this, combined with the loss of muscle mass,
inhibits elderly patients locomotion
Liver function decline-patient variability
Prescription use in Elderly
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Elderly patients take about three times as many medications as younger patients do1
According to the Medicare, the average number of prescriptions per year, including refills, is
currently 28.5 per senior (up from 19.6 in 1992)
Greatest consumers of prescribed and non-prescribed medications2
Average cost per prescription has also jumped from $28.50 in 1992 to $42.30 in 2000, an
increase of 48%
In 2012, prescription drug prices rose 3.6%, twice the 1.7% inflation rate, Bureau of
Economic Analysis data
Since the elderly have less participation in drug trials, there is insufficient information on the
side effects and adverse reactions of drugs on the elderly
As a result, older patients have to rely on general guidelines with information extrapolated
from other age groups to make decisions regarding prescription drug use 1
1.Shaughnessy, F., Allen, Anderson, J., Robert, 1995. "Drug Prescribing for the Elderly." Family Practice Recertification VOL 17,
No. 11: 62-69.
2. United States Pharmacopeia, 2000. "Guiding Principles for Enhancing the Likelihood of Positive Medication Use Outcomes in
Geriatric Patients." The United States Pharmacopeial Convention.
Prescription Use in the Elderly
• Social circumstances such as living alone, difficulty in visiting
their primary physician
• Confusion resulting from the use of multiple medications,
memory problems and failing vision leading to impaired
functioning
• Failure to comply with the complicated drug treatment plan
and poor understanding of the drug treatment
Elderly :
Risk of Adverse Drug Events
• over 700,000 emergency department visits each year
• Nearly 120,000 pts each year need hospitalization for
further treatment after ER
• Older adults (65 years or older) are twice as likely as
others to come to emergency departments for adverse
drug events
• over 177,000 emergency visits each year and nearly
seven times more likely to be hospitalized after an
emergency visit
CDC 2013
National Action Plan
• The National Action Plan for Adverse Drug
Event Prevention has two key objectives:
identify common, clinically significant,
preventable, and measurable adverse drug
events (ADEs); and align the efforts of federal
health agencies to reduce patient harm from
these specific ADEs nationally.
National Action Plan
• Based on national ADE data from inpatient and
outpatient settings, three types of ADEs were
considered to be common, clinically significant,
preventable, and measureable, and therefore selected as
the high-priority targets of this Action Plan.
• The three initial targets of the Action Plan are:
• 1) Anticoagulants (primary ADE of concern: bleeding)
• 2) Diabetes agents (primary ADE of concern:
hypoglycemia)
• 3) Opioids (primary ADE of concern: accidental
overdoses/oversedation /respiratory depression)
National Action Plan
The Plan suggests a four–pronged approach to
reduce patient harms from these three ADEs:
Surveillance, Prevention, Incentives and
Oversight, and Research
Tool: Beer’s Criteria
History
• First introduced 1997, updated 2003, 2012
• Expert panel consisting of geriatrician, geriatric
psychiatrist, and pharmacist
• Identify “potentially inappropriate medications”
(PIMs) to avoid in the over 65 population
• Associated with poor patient outcomes
- limited efficacy in older adults
Fick DM Updating the Beer’s Criteria for Potentially Inappropriate Medication Use in Older Adults.
Archives of Internal Medicine. 2003;163:2716-2724
Tool: Beer’s Criteria
• Current update partnership with American
Geriatric Society
• PIMs categorized into two broad groups:
– Medications to avoid in older adults regardless
of diseases or conditions
– Medications considered potentially
inappropriate when used in older adults with
certain diseases or syndromes
• Third group added: medications that should be
used with caution
Beer’s Criteria for Potentially
Inappropriate Medication Use in Older
Adults
Drug
Rationale
Recc
Aspirin for primary prevention of
cardiac events
Lack of evidence of benefit vs. risk
in pts age >80
Use with caution
in adults >80
Dabigatran
(Pradaxa)
Greater risk of bleeding than with
warfarin in adults aged >75; lack of
evidence for efficacy and safety in
pts CrCl < 30 mL/min
Use with caution
in adults aged
>75 or if CrCL <
30 mL/min
Prasugrel
(Effient)
Greater risk of bleeding in older
Use with caution
adults; risk may be offset by benefit in adults age >
in highest-risk older adults (e.g. with 75
prior MI or DM)
Beer’s Criteria for Potentially
Inappropriate Medication Use in Older
Adults
Drug
Rationale
Recc
Antispychotics
Carbamazepine
Carboplatin
Cisplatin
Mirtazapine
SNRIs
SSRIs
TCAs
Vincristine
May exacerbate or cause syndrome
of inappropriate antidiuretic
hormone secretion or
hyponatremia; need to monitor
sodium level closely when starting
or changing dosages in older adults
due to increased risk
Use with caution
vasodilators
May exacerbate episodes of
syncope in individuals with history
of syncope
Use with caution
Beer’s Criteria for Potentially
Inappropriate Medication Use in Older
Adults
Drug
Indication Beers recc
Alternatives
Nitrofurantoin
Anti-infective,
often used for UTI
Gram(+)cocci, incl.
Staph,
enterococci;
Gram(-) bacilli but
variable activity
(need sensitivity
testing) vs
Klebsiella,
Enterobacter,
Proteus
Fluoroquinolones (best
penetration into prostate
gland)
-Levofloxacin*,
ciprofloxacin
Bactrim (women only)
Beta-lactams
-Carbenicillin indanyl
-3rd/4th gen
cephalosporins
-Ceftibuten
-Cefixime
Potential for pulmonary
toxicity; safer
alternatives available;
lack of efficacy in
patients with CrCl < 60
mL/min due to
inadequate drug
concentration in the
urine.
Moderate quality
evidence, strong
recommendation to
avoid for long-term
suppression; avoid in
patients with CrCl < 60
mL/min
Beer’s Criteria for Potentially
Inappropriate Medication Use in Older
Adults
Drug
Indication Beers recc
Alternatives
Clonidine
Hypertension
Thiazide diuretics
ACE inhibitors
Angiotensin receptor
blockers
Calcium channel
blockers
Beta blockers
High risk of adverse
CNS effects; may
cause bradycardia
and orthostatic
hypotension; not
recommended as
routine
treatment for
hypertension
Low quality evidence
but strong
recommendation to
avoid as 1st line
hypertensive
Beer’s Criteria for Potentially
Inappropriate Medication Use in Older
Adults
Drug
Indication Beers recc
Long-acting
sulfonulureas
-Chlorpropamide
Glyburide
Type 2 diabetes
Alternatives
Chlorpropamide: prolonged Glipizide
half-life in older adults; can
cause prolonged
hypoglycemia; causes
syndrome of inappropriate
antidiuretic hormone
secretion.
Glyburide: greater risk of
severe prolonged
hypoglycemia in older
adults.
High quality evidence,
strong recommendation to
avoid altogether
Anticholinergic Load
• Cumulative effect of several medications with
anticholinergic properties
• Risks =Dry eyes, dry mouth, urinary retention,
constipation, tachycardia, delirium
Tool: Anticholinergic Load
Rudolph JL. The Anticholinergic Risk Scale and Anticholinergic Adverse Effects in Older Person s.
Archives of Internal Medicine. 2008;168(5):508-513
Tool: STOPP
• newer criteria to identify potentially inappropriate
medications in elderly
• including drug–drug and drug–disease interactions,
drugs which increase risk of falls and drugs which
duplicate therapy
• They were developed by a panel of 18 experts in
geriatric pharmacotherapy including physicians,
pharmacologists, pharmacists and a psychiatrist.
• Unlike the Beers criteria, STOPP criteria have been
significantly associated with avoidable adverse drug
events in older people that cause or contribute to
hospitalization1
Tool: STOPP VS Beers
• STOPP criteria are organized according to physiological
systems, whereas Beers criteria are not
• STOPP criteria deal with drugs that are currently in
widespread use; Beers criteria include several drugs that are
no longer available in
• STOPP criteria place special emphasis on potential adverse
drug-drug interactions and duplicate drug class prescription,
whereas Beers criteria do not
• STOPP criteria contain several common instances of
potentially inappropriate prescribing that are not mentioned
in Beers criteria
Tool: STOPP
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Cardiovascular System
Digoxin > 0.125mg with impaired renal function (Clcr < 50ml/min)
Loop diuretic -for edema only,first line monotherapy for hypertension
Beta blocker with COPD with verapamil
Diltiazem or verapamil with NYHA Class III or IV heart failure
Calcium channel blockers with constipation
Aspirin and warfarin without H2 receptor antagonist or PPI
Dipyridamole as monotherapy for CV secondary prevention
Aspirin With history of PUD,Doses > 150mg/day,With no history of coronary, cerebral or
peripheral vascular disease,To treat dizziness not due to cerebrovascular disease
Warfarin
– > 6 mo. for first uncomplicated DVT
>12 mo. for first uncomplicated PE
Aspirin, clopidogrel, dipyridamole or warfarin with concurrent bleeding disorder
Tool: STOPP
Central Nervous System and Psychotropics
• TCA’s (Tricyclic Antidepressants)
• With dementia
• With glaucoma
• With cardiac conduction abnormalities
• With constipation
• With opiate or calcium channel blocker
• With prostatism or urinary retention
• Long term benzodiazepines (> 1 month)
• Long term neuroleptics
• With parkinson’s (> 1 month)
• As long term hypnotics
• Phenothiazines with epilepsy
• Anticholinergics to treat extra-pyramidal symptoms of neuroleptics
• SSRI’s with hyponatremia
• > 1 week use first generation antihistamines (diphenhydramine, chlorpheniramine,
promethazine, cyclizine)
Tool: STOPP
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Gastrointestinal
Respiratory
Musculoskeletal
Urogenital
Endocrine
Drugs that adversely affect those prone to falls (≥ 1 fall/3mo
Analgesics
Duplicate Drug class
Beers VS. STOPP
• STOPP criteria and Beers criteria have several
areas of overlap
• Both sets of criteria emphasize the higher risk of
adverse drug reactions and events in older people
with use of long-acting benzodiazepines, tricyclic
antidepressants, anticholinergic drugs, and non–
cyclooxygenase 2–selective nonsteroidal antiinflammatory drugs. Both sets of criteria also
focus on several common potential adverse drugdisease interactions in older people
Beers VS. STOPP
• OBJECTIVES: The purpose of this study was to utilize STOPP and Beers
Criteria to identify PIMs in geriatric patients at an inpatient psychiatric
facility, with the goal of implementing a formal process for assessing
medication regimens. This process would be expected to decrease adverse
outcomes
• METHODS: Both criteria were used by the pharmacist to identify PIMs and
recommendations were made to address the PIMs. A retrospective chart
review evaluated whether utilization of the two criteria led to a significant
change in number of PIMs and associated adverse outcomes
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The primary outcome was the change in number of PIMs for the Beers
Criteria versus the STOPP Criteria. Secondary outcomes included the
change in number of PIMs, falls, required referrals/transfers, and
medication-specific ADEs for each set of criteria assessed separately
M.Snyder etal. Application of STOPP Criteria and Beers Criteria in an Inpatient Psychiatric Facility and Impact on Utilization of Potentially
Inappropriate Medications and Adverse Outcomes, Poster presentation CPNP Annual Meeting 2012
Beers VS. STOPP
• RESULTS: Twenty-nine patients met inclusion criteria, and 76 treatment
recommendations were made. More PIMs per patient were identified at
baseline utilizing STOPP (mean±SD,3.9±2.3)versus Beers Criteria
(mean±SD, 2.2±1.3) (p<0.001)
• The number of PIMs decreased using STOPP (from 112 to 66; mean
decrease per patient -1.6±1.5, p<0.0001) and Beers Criteria (from 63 to
23; mean decrease per patient -1.4±1.1, p<0.0001), although the change
was not significant for STOPP vs. Beers (p=0.375). All secondary outcomes
decreased using both criteria
• CONCLUSIONS: Utilization of each set of criteria by the pharmacist led to a
significant decrease in PIMs and adverse outcomes decreased at follow-up
using both criteria. Implementation of a process for assessing medication
regimens of geriatric patients utilizing the Beers and/or STOPP Criteria
would likely be beneficial to this institution
Case
Side Effect Burden
• RS is an 83 year old white, widowed male
presenting to SPH with agitation, grabbing
staff by the throat, and being delusional. He
was transferred from Meritus Medical Center
ER.
Case
Side Effect Burden
• Pt behaviors are changed from baseline x 4 weeksbecoming increasingly agitated and threatening –such
as grabbing a nurse by the throat at his AL facility.
Also, he has been raising his fist to the staff and
peers. Patient is delusional thinking that the nurses
station is his home. He is impulsive and difficult to
redirect.
• Pt dementia has progressed rapidly, as he was on his
own until this past thanksgiving when he had a heart
attack.
• Pt claims to have been in A-fib for a long time and
was on blood thinners at one point. Denies
palpitations, diaphoresis, chest pain, and dizziness
Case
Side Effect Burden
• Past Medical History
– Bilateral Aortic Aneurysms
– Eczema
– Chronic A-fib
– CHF
– GERD s/p cholestectomy
– HTN
– Hx of MI, CABG
– DM
– Renal insufficiency
Allergies: “morphine” and “oxycodon
Case
Side Effect Burden
• Social History: RS is a high school graduate. Worked
on a railroad, owned a bar and bounced for it. Served
in the Navy during WWII. Wife died 15 years ago.
Sister describes patient has highly intelligent,
motivated, and having a good sense of humor prior to
illness. Currently resides in assisted living facility
• Family History: father was a railroader and farmer.
Mother was a homemaker. There were 10 siblings-2
others still living. 1 brother was an alcoholic
Outpatient Medication
Aspirin 81mg
Inpatient Medication
Aspirin 81 mg
Indication
CAD/DM
Lorazepam 1 mg q6h prn
Anxiety
Ambien 5 mg qhs
Insomnia
Furosemide 80 mg qam, 40 mg
qpm
Furosemide 80 mg qam, 40 mg
qpm
CHF
glyburide 5 mg qd
Glyburide 5 mg qam
DM
Imdur 30 mg qd
Isosorbide mononitrate 30 mg
qam
CAD
K-Dur 20 mEq tid
Potassium Chloride 20 mEq tid
Supplement
Vitamin D 1000 U qd
Supplement
Metoprolol 40 mg qhs
Metoprolol 25 mg bid
HTN
Donepezil 5 mg qd
Donepezil 5 mg qam
Dementia
Seroquel 25 mg bid
Clonidine 0.1 mg PRN
Agitation
Aspirin 81 mg qam
CAD/cardioprotection
Chlordiazepoxide 50 mg q6 prn
Alcohol Withdrawal
Enoxaparin 40 mg qd
DVT prophylaxis
Hydrocortisone 2.5% topical bid
Eczema
Sliding scale insulin
DM
Case
Side Effect Burden
Physical Exam
• HEENT normal
• Lungs- bilateral diminished bases
• Heart: irregular rate
• Abdominal- normal
• Extremities 2+ bilateral ankle edema
• Skin: thick flaking patches to skin on hands and arms.
Some open and abraised areas. Skin thin and bruised on
forearms. Abrasion to right lower shin, scabbed, no
erythema.
• Muscular: normal
• Neurological/motor exam: normal
Case
Side Effect Burden
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Weight=79.3 kg
Height=70 inches
Temp =98.3
RR= 18
HR=92
Sitting BP= 90-130’s/50-80’s
Standing BP= 112/70
Case
Side Effect Burden
• Atrial Fibrillation with Rapid Ventricular
Response
• 120 bpm
• No acute ST segment changes
Labs
Lab
Result
Lab
Result
Glucose
100 mg/cL
CrCl
38.5 mL/min
Na
145 mEq/L
HgA1c
6.7%
K
4.1 mEq/L
Cholesterol
129 mg/dL
Cl
106 mEq/L
Anion Gap
7.0
TG
74 mg/dL
Osmolality
305 mOSM/Kg
HDL
33.3 mg/dL
Ca
9.0 mg/dL
LDL
94 mg/dL
GFR
44 mL/min/1.73m^2
TSH
2.73 ulU/mL
B12
583.8 pg/mL
BUN
29 mg/dL
Cr
1.5 mg/dL
Case
Side Effect Burden
Assessment for: falls : Daily [minimum for score>17]
1. Age : Over 70
2. History of Falls : Fallen 1 to 2 times
3. Medication and Treatment : Antihypertensive, Antipsychotic
4. Cognition : Altered awareness of one's immediate Physcial environment, Impulsiveness, Impaired
Cognition
5. Physical Status : Fatigue and weakness
6. Orthostasis : Not Applicable
7. Gait and Balance - Get-up-and-go Test. : Pushes up, successful in one attempt, Balance problems
walking, decreased muscle coordination Jerking or instability when walking Gait pattern changes when
walking
8. Elimination : Unremarkable
Fall Risk Score Total : 21
Institute Fall Risk Precautions
Level of Interventions : Assessment Score 18 - 26 CATEGORY 2
Identified Fall Risk Interventions : Problem identified on MTP Routine observation checks and document
on rounds sheet Bed in low position Instruct pt to get up slowly Keep hallway clear of excess furniture,
equipment, supplies Adequate lighting\prompt cleanup spills\wet floors RN/MD review pt's medications
for fall related issues RN/MD review use of PRNs RN/MD review observation level Instruct pt to notify
staff of dizziness Encourage fluids, monitor standing BP once per day Notify MD of falls Get PT
Consult order if fall occurs/for gait/balance problem
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Case
Side Effect Burden
• Brainstorming
• Rate Control
– Are you concerned with a HR of 120?
– Aortic aneurysms?
• Rhythm Control?
• Do we anti-coagulate this patient?
– Fall risk?
– Dabigatran vs. Warfarin vs. clopidogrel plus aspirin
• Do we worry about this patient’s dementia?
• What concerns you about these medications?