Prescribing Medications for the Elderly
APN Pharmacology Update Conference
March 28, 2014
Patricia M. Curtin, MD, FACP, CMD
Section Chief, Geriatric Medicine
Member, Pharmacy and Therapeutics Committee
Clinical Assistant Professor, Jefferson Medical College
OBJECTIVES
Know and understand:
•The pathophysiology of aging related to
processing medications in older adults
•Strategies for prescribing medications in older
adults in order to avoid adverse drug events
•Medications that should be avoided in older
adults and why
TOPICS COVERED
• Challenges in geriatric pharmacotherapy
• Key issues in geriatric pharmacology
• Principles of prescribing for older patients
• Risk factors for adverse drug events for older patients/mitigate
• AGS 2012 Updated Beers Criteria for Potentially Inappropriate
Medication (PIM) Use
• AGS “Choosing Wisely” Campaign: What physicians/patients
should question (related to medications)
• Hot off the press: JNC 8, ADA, FDA, CCHS Wish Lists
Sources and Resources
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CCHS Pharmacy ADR reports
Medication Safety Committee Wish List
AGS Beers Criteria (article, pocket card-$1)
ABIM Choosing Wisely Campaign—AGS List
Geriatric Dosage Handbook (Semla)
CCHS Formulary (Lexicomp)-Geriatric Considerations
CCHS Nurse-Pharmacist Referral (Powerchart)
WISH Website (References>Staff references>WISH)
Epocrates www.epocrates.com
iGeri app (iPhone, iPad)-($2.99)
WHY GERIATRIC PHARMACOTHERAPY
IS IMPORTANT
Now, people age 65+ are 13% of US population, buy 33% of prescription drugs
By 2040, will be 25% of population, will buy 50% of prescription drugs
Geriatrics Review Syllabus 8th Edition, 2013, Chapter 11, Pharmacotherapy, Semla, PharmD
WHY GERIATRIC PHARMACOTHERAPY
IS CHALLENGING
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More drugs are available each year
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FDA and off-label indications are expanding
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Formularies change frequently; substitutions made
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Drugs change from prescription to OTC-easier access
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“Nutraceuticals” (herbal preparations, nutritional supplements)
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Multiple Providers and Prescribers
- 20% of Medicare beneficiaries have 5 or more chronic
conditions and 50% receive 5 or more medications
- Guideline based therapy
• Data on medication efficacy and dosing come from clinical trials:
• Older adults are excluded from many randomized controlled trials
• Studies that include older adults often are not representative
– Exclude multiple chronic illnesses
• We don’t know what we don’t know
What we do know:
Age Related Changes in Physiology
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Increased Body fat
Decreased lean body mass
Decreased total body water
Decreased serum albumin (protein)
Decreased hepatic cell mass
Decreased liver blood flow
Decreased metabolism
Decreased renal mass
Decreased renal blood flow
PHARMACOKINETICS
• Absorption
• Distribution
• Metabolism
• Elimination
FACTORS THAT AFFECT
DRUG ABSORPTION
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Absorption (bioavailability) is not changed much by aging
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Route of administration
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What is taken with the drug (meds/tube feeds)
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Gastric pH may increase or decrease absorption of some drugs
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GI motility and enzymes
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Peak serum concentrations may be lower OR higher-variable
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Co-morbid illnesses
GRS 8; Pharmacotherapy
EFFECTS OF AGING ON
VOLUME OF DISTRIBUTION (VD)
• Age-associated changes in body composition can alter drug
distribution (where a drug penetrates and time to do so)
•  body water  lower VD for hydrophilic (likes water) drugs
•  lean body mass  lower VD for drugs that bind to muscle
(digoxin-  lean body mass, increase concentrations of dig)
•  plasma protein (albumin)  higher percentage of drug
that is unbound (active) (phenytoin)
•  fat stores  higher VD for lipophilic (likes fat) drugs
(benzos, phenytoin, valproic acid, lidocaine)
GRS 8; Pharmacotherapy
AGING AND METABOLISM
• The liver is the most common site of drug metabolism
• Aging decreases liver blood flow, size and mass
• Metabolic clearance of a drug by the liver may be
reduced
GRS 8; Pharmacotherapy
KEY CONCEPTS ABOUT
DRUG ELIMINATION
• Half-life: Time for serum concentration of drug to
decline by 50%
• Clearance: Volume of serum from which the drug is
removed per unit of time (eg, L/hour or mL/minute)
GRS 8; Pharmacotherapy
KIDNEY FUNCTION IS CRITICAL
FOR DRUG ELIMINATION
• Most drugs exit the body via the kidney
• Reduced elimination  drug accumulation and
toxicity
• Aging and common geriatric disorders can impair
kidney function
GRS 8; Pharmacotherapy
THE EFFECTS OF AGING
ON THE KIDNEY
 kidney size
 renal blood flow
 number of functioning nephrons
 renal tubular secretion
Result: Lower glomerular filtration rate (GFR)
GRS 8; Pharmacotherapy
SERUM CREATININE DOES NOT REFLECT CREATININE
CLEARANCE
 lean body mass  lower creatinine production
and
 glomerular filtration rate (GFR)
Result: In older people, serum creatinine may stay in
normal range, masking change in creatinine clearance
(CrCl)
Normal Creatinine Clearance: >60ml/min (age dependent)
GRS 8; Pharmacotherapy
TWO WAYS TO DETERMINE CREATININE CLEARANCE
Measure
• Requires 24-hour urine collection
• Time-consuming
Estimate
• Usually done with the Cockroft-Gault equation*
(*one of the most important equations to know)
(140 – age)(Ideal weight in kg) x (0.85 if female)=ml/min
72 X Creatinine (mg/dL)
Which of these meds need to be renally dosed
for reduced Creatinine clearance?
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Ultram (Tramadol)
Zantac (Ranitidine)
Neurontin (Gabapentin)
Claritin (Loratadine)
Levaquin (Levofloxacin)
Tenormin (Atenolol)
Zyloprim (Allopurinol)
Bactrim (Trimethoprim-Sulfa)
PHARMACODYNAMICS
• Definition: Physiologic effects of the drug
• May change with aging, for example:
 Benzodiazepines may cause more sedation and poorer
psychomotor performance in older adults (likely cause:
reduced clearance of the drug and resultant higher
plasma levels)
 Older patients may experience longer pain relief with
morphine
SUCCESSFUL PHARMACOTHERAPY
• Uses the correct drug
• Prescribes the correct dosage
• Targets the correct condition
• Is appropriate for the patient
Failure in any one of these
can result in adverse drug events (ADEs)
(75% of ADEs are dose related)
Geriatric Pharmacotherapy Principle:
Start low, Go slow, but Go
and
Avoid starting 2 drugs at same time
(if possible)
Adverse Drug Effects (ADEs)
Incidence of ADEs in
hospitals: 26/1000 beds
(2.6%)
ADEs are responsible for 5% to 28% of
acute geriatric hospital admissions
ADEs occur in 35% of
community-dwelling
older adults
MEDICATIONS MOST
COMMONLY INVOLVED IN ADEs
• Cardiovascular drugs, diuretics, NSAIDs,
hypoglycemics, antipsychotics, and anticoagulants
• Medications with a narrow margin of safety
(synthroid, phenytoin, lithium, valproic acid,
aminoglycosides, anticoagulants, digoxin,
hypoglycemic agents, etc)
• CCHS….same, except add opioids/benzodiazepines
Geriatrics Review Syllabus, Pharmacotherapy, Semla et al
Adverse Drug Events After Hospital Discharge in Older Adults: Types, Severity, and Involvement of Beers Criteria
Medications J Am Geriatr Soc. 2013; 61: 1894-1899
RISK FACTORS FOR ADEs
• Age 85 or older
• Female
• Low body weight or low BMI
• Estimated CrCl < 50 mL/min
• 5-9 or more medications
• 12 or more doses of drugs/day
• 6 or more concurrent chronic conditions
• Prior adverse drug event
ADE PRESCRIBING CASCADE
Drug 1
Adverse drug effect—
misinterpreted as a new medical condition
Drug 2
Adverse drug effect—
misinterpreted as a new medical condition
OPTIMIZING PRESCRIBING
• Achieve balance between over and under prescribing of
beneficial therapies
• >20% of ambulatory older adults receive at least one
potentially inappropriate medication
• Nearly 4% of office visits and 10% of hospital admissions
result in prescription of medications classified as never or
rarely appropriate
AGS UPDATED 2012 BEERS CRITERIA
FOR POTENTIALLY INAPPROPRIATE
MEDICATION USE IN OLDER ADULTS
Mark H Beers, MD 1954-2009
“A ballet-dancing opera
critic who hiked the Alps
and took up rowing after
diabetes cost him his legs”
 MD, Univ of Vermont
 First med student to do a
geriatrics elective at Harvard‘s
new Division on Aging
 Geriatric Fellowship, Harvard
 Faculty, UCLA/RAND
 Co-editor, Merck Manual of
Geriatrics
 Editor in Chief, Merck Manuals
BEERS CRITERIA
• Originally developed in 1991, 1997, 2003 and updated in 2012
by the American Geriatrics Society (by 11 member panel)
• Intend to improve drug selection and reduce exposure to
potentially inappropriate medications (PIM) in older adults
• Recommendations are evidence-based and in 3 categories:
 Drugs to avoid
 Drugs to avoid in patients with specific diseases or syndromes
 Drugs to use with caution
• Available at AGS web site: www.americangeriatrics.org
American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate
Medication Use in Older Adults. J Am Geriatr Soc. 2012;60:616–631.
BEERS CRITERIA
• Potentially inappropriate medications include
medications that:
– Have limited effectiveness in older adults
– Are associated with poor outcomes
• Delirium
• GI bleeding
• Falls
– Have safer alternatives available
American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate
Medication Use in Older Adults. J Am Geriatr Soc. 2012;60:616–631.
Table 1: Designations of Quality and Strength of
Evidence:
ACP Guideline Grading System, GRADE
Quality of Evidence
 High
• Consistent results from well-designed, well-conducted studies that directly assess effects
on health outcomes (2 consistent, higher-quality RCTs or multiple, consistent
observational studies with no significant methodological flaws showing large effects)
 Moderate
• Sufficient to determine effects on health outcomes, but the number, quality, size, or
consistency of included studies, generalizability , indirect nature of the evidence on
health outcomes (1 higher-quality trial with > 100 participants; 2 higher-quality trials
with some inconsistency, or 2 consistent, lower-quality trials; or multiple, consistent
observational studies with no significant methodological flaws showing at least moderate
effects) limits the strength of the evidence
 Low
• Insufficient to assess effects on health outcomes because of limited number or power of
studies, large and unexplained inconsistency between higher-quality studies; important
flaws in study design or conduct, gaps in the chain of evidence
• Or lack of information on important health outcomes
Table 1: Designations of Quality and Strength of
Evidence:
ACP Guideline Grading System, GRADE
Strength of Recommendation
Strong
Benefits clearly > risks and burden OR risks and burden
clearly > benefits
Weak
Benefits finely balanced with risks and burden
Insufficient
Insufficient evidence to determine net benefits or risks
What can Prescribers and other
interdisciplinary team members do?
 Collaborate with other team
members/disciplines using AGS POCKETCARDS
Tables (*pocket card limited to first 3 tables)
 Table 2 – PIMs (organ system/therapeutic category)
 Table 3 – PIMs due to Drug – Disease/Syndrome
Interaction
 Table 4 – Medications to be used with caution
 Table 5 – Medications moved or modified
 Table 6 – Medications removed
 Table 7 – Medications added
 Table 8 – Antipsychotics
 Table 9 – Drugs with strong anticholinergic
properties
(Tables 2,3,4 in article=Tables 1,2,3 in pocket card)
Table 9: Drugs with strong “anticholinergic” properties?
What’s the problem?
• May reduce acetylcholine levels in patients
who already have reduced levels: those who
are elderly, have dementia and/or delirium
• Increased risk of anticholinergic side
effects=confusion/delirium, constipation,
urine retention, orthostasis, paradoxical
excitement, tachycardia, visual disturbances,
dry mouth
Over 600 drugs with Anticholinergic Activity
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Furosemide (Lasix)
Triamterene/HCTZ
Digoxin
Dipyridamole (Persantine)
Theophylline anhydrous
Warfarin (Coumadin)
Prednisolone
Nifedipine (Procardia)
Isosorbide Dinitrate
Codeine
Diphenhydramine
Olanzapine
Paroxetine
Promethazine
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Tune, L.E. , Egell, S. Dementia. Geriatric Cognitive Disorders 1999. Courtesy
of Susan Scanland, MSN, APRN, GNP
AGS Beers Criteria, 2012
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Captopril
Imipramine/Desipramine
Amitriptyline (Elavil)
Cimetidine (Tagamet)
Ranitidine (Zantac)
Tobra/clinda/gentamycin
Ampicillin
Hydralazine
Diazepam (Valium)
• Oxybutynin (Ditropan)
Table 2 (Table 1 in pocket guide): Drugs to Avoid
Organ System/
TC/Drug
Rationale
Recommend. Quality of
Evidence
Strength of
Recommend.
Anticholinergics:
First generation
antihistamines/
antispasmodics
Highly
anticholinergic;
clearance
reduced with
age; may use in
Avoid
High/
Moderate
Strong
severe allergic rxn
Antiparkinson
Not rec for EPS
Avoid
Moderate
Strong
Nitrofurantoin
Pulmonary tox
Alternatives
Lack of efficacy
<60 mL/min
Avoid long
term use;
avoid if CrCl
<60 mL/min
Moderate
Strong
Alpha blockers
High Risk of
orthostasis
Avoid use as
BP med
Moderate
Strong
Digoxin
>0.125mg/d
High doses-no
benefit/toxicity
in HF
Avoid
Moderate
Strong
DIGOXIN
Digoxin itself or Digoxin toxicity can cause:
 Confusion
 nausea
 loss of appetite
 lethargy
 bradycardia
 heart block
DIGOXIN
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0.125 mg. dose effective; rarely use 0.25 mg
Half-life is 30-40 hours; up to 70 hrs in elderly
May be able to dose 2-3x/week
Therapeutic “range”-.7-2.0.
Patients don’t need to always be “in the
range”. Lower levels may be better (.5-.8)
(DIG trial, elderly CHF patients)
Table 2: Drugs to Avoid
Organ System/
TC/Drug: CNS
Rationale
Recommend.
Quality of Strength of
Evidence Recommend.
Tertiary TCAs
Highly
anticholinergic,
sedating,
orthostasis
Avoid
High
Strong
Antipsychotics,
conventional
and atypicals
Increase CVA and Avoid unless
mortality in
danger to
dementia pts
self/others
Nonpharm fail
Moderate
Strong
Non
Benzodiazepine
Hypnotics (“z”)
Ineffective at
tolerated doses,
antichol SE, falls
Avoid
Moderate
Strong
Benzodiazepine
Short,
intermediate,
and long acting
Risk cognitive
effects and injury
(fall/MVA/fx);
rare use
appropriate:
seizures, etoh/
Avoid for
treatment of
insomnia,
agitation, or
delirium
High
Strong
Sedatives/Hypnotics
What Benzodiazepines should we use in elderly?
• NONE - but if necessary (pre-med, COPD, etc):
• Ativan (Lorazepam)-(0.25mg. - 0.5 mg. q 8 hr. PRN (po/IM/IV)
(half-life 10-16 hrs); (maximum daily dose 2 mg) Peaks at 1 hr.
OR
• Serax (Oxazepam) 10 mg. q 8-12 hr. po prn (half-life 5-20 hrs);
(max dose 30mg/d)
• For Sleep—refer to CCHS Sleep Protocol, WISH Website
Organ System/ TC
/Drug: Misc
Rationale
Recommend.
Quality of
Evidence
Strength of
Recommend.
Megestrol
Minimal effect on
weight; risk of
thrombosis/death
Avoid
Moderate
Strong
Chlorpropamide
Glyburide
SIADH; both with
Hypoglycemia risk
Avoid
High
Strong
Insulin, sliding
scale
Hypoglycemia risk
w/o benefit
Avoid
Moderate
Strong
Metoclopramide
EPS and Tardive
Dyskinesia
Avoid, unless
gastroparesis
Moderate
Strong
Non-COX NSAIDs/
Indomethacin
Ketorolac
GI bleeding;
Protection w/ PPIs
or misoprostol
Avoid chronic
use
Moderate
Strong
Skeletal muscle
relaxants
Anticholinergic,
sedation,
fall/fracture;
effectiveness at
tolerated doses-?
Avoid
High
Moderate
Strong
Table 3: PIMs to Avoid due to Drug-Disease or
Drug-Syndrome Interactions
Disease/Syndrome Drug
Heart Failure
NSAIDS
CCBS
Delirium
All TCAs, Antichol
Benzos, hypnotics
H2 Antagonists
Dementia
Antichol, Benzos
H2Antagonists
Zolpidem,
Antipsychotics
Falls
Anticonvulsants,
Antipsychotics,
Benzos, Hypnotics
TCAs, SSRIs
Recommend/Rationale/QOE/SR
Avoid, Moderate, Strong
(fluid retention)
Avoid, Moderate, Strong
(adverse CNS effects)
Avoid, High, Strong
(adverse CNS effects)
(increased risk of CVA/mortality)
Avoid, High, Strong
(ataxia, impaired psychomotor fcn,
syncope)
Take homes: AGS 2012 Beers Criteria
 Don’t let the perfect be the enemy of the good
 Beers PIMs are only part of appropriate prescribing
 Target initiatives to high prevalence/high severity
meds (based on local data, where possible)
 Stopping meds should be done with same
consideration as starting
 Not meant to supersede clinical judgment or
individual patient values or needs
AGS Beers Criteria Website
Criteria
Full Article
Editorial
Perspective
Beers Criteria Pocket Card
Beers Criteria App
Public Education Resources for Patients & Caregivers
AGS Beers Criteria Summary
10 Medications Older Adults Should Avoid
Avoiding Overmedication and Harmful Drug Reactions
What to Do and What to Ask Your Healthcare Provider if a Medication You Take is
Listed in the Beers Criteria
My Medication Diary - Printable Download
Eldercare at Home: Using Medicines Safely - Illustrated PowerPoint Presentation
ABIM: CHOOSING WISELY CAMPAIGN
AGS: Top Ten Things Physicians and Patients Should Question
Medications (2013)
1.
2.
3.
4.
5.
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Don’t recommend percutaneous feeding tubes in patients
with advanced dementia; instead offer oral assisted feeding
Don’t use antipsychotics as first choice to treat behavioral
and psychological symptoms of dementia
Avoid using medications to achieve Hgb A1C <7.5% in most
adults age 65 and older: moderate control is better
Don’t use benzodiazepines or other sedative-hypnotics in
older adults as first choice for insomnia, agitation, delirium
Don’t use antimicrobials to treat bacteriuria in older
patients unless specific urinary tract symptoms are present
www.choosingwisely.org/doctor-patient-lists/american-geriatrics-society
ABIM: CHOOSING WISELY CAMPAIGN
AGS: Top Ten Things Physicians and Patients Should Question
Medications (2014)
6. Don’t prescribe cholinesterase inhibitors for dementia
without periodic assessment for perceived cognitive
benefits and adverse GI effects
7. Don’t recommend screening for breast or colorectal cancer,
nor prostate cancer (w PSA test) without considering life
expectancy and the risks of testing, overdiagnosis and over
treatment
8. Avoid using prescription appetite stimulants or highcalorie supplements for treatment of anorexia or cachexia
in older adults; instead, optimize social supports, provide
feeding assistance and clarify patient goals and
expectations.
9. Don’t prescribe a medication without conducting a drug
regimen review.
10. Avoid physical restraints to manage behavioral symptoms of
hospitalized older adults with delirium
CCHS Pharmacists’ “Choosing Wisely”
WISH LIST
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Hold parameters for antihypertensives
Add STOP dates to Antibiotic orders
Appropriate use of PPIs (pantoprazole, etc)
Add senna/docusate when starting opioids
Avoid antipsychotic use for acute delirium
Try to avoid concomitant use-opioids/benzos
Anticoagulants-new, bridging, reversals
Speaker’s “Choosing Wisely” Wish List
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Reconcile and validate list/how pt takes meds
Provide an indication for each medication
Calculate Creatinine Clearance on every pt.
DO NOT start dementia medications as an
inpatient (donepezil, memantine, etc)-no
benefit in hospital, risk of ADEs
• Watch acetaminophen dosing 3000-4000mg
• Consider new JNC8 goal of >60yo, BP<150/90
CASE (1 of 4)
• A 77-year-old man comes to the office because he has had
increased difficulty with urination, including straining to
void and occasional urinary incontinence.
• History includes benign prostatic hyperplasia, depression,
seasonal allergies, type 2 diabetes mellitus, and peripheral
neuropathy.
• Medications include tamsulosin 0.4 mg at bedtime,
metformin 1,000 mg q12h, fluticasone inhaler 2 sprays in
each nostril daily, diphenhydramine 25 mg q12h as
needed, and aspirin 81 mg/day.
CASE (2 of 4)
• His peripheral neuropathy improved with initiation 3
weeks ago of duloxetine 60 mg/day; he had experienced
intolerable adverse effects with gabapentin and
pregabalin.
• His allergies have been worse over the past month, and he
has been taking a dose of diphenhydramine at bedtime
with excellent symptom control.
• On physical examination, the prostate is not enlarged.
Urinary analysis is normal.
CASE (3 of 4)
Which of the following is the most appropriate
management for this patient?
A.Discontinue diphenhydramine.
B.Discontinue duloxetine.
C.Begin extended-release tolterodine.
D.Obtain postvoid residual urine level.
CASE (4 of 4)
Which of the following is the most appropriate
management for this patient?
A.Discontinue diphenhydramine.
B.Discontinue duloxetine.
C.Begin extended-release tolterodine.
D.Obtain postvoid residual urine level.
Prescribing Principles
for Older Adults
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Reconcile/validate how pt really takes meds
Try nonpharmacological interventions first
Balance risk vs. benefit
Start low and go slow
Avoid inappropriate medications
Discontinue unnecessary medications
Monitor for side effects; avoid prescribing cascade
Consider patient’s goals of care
Zwicker D. Nursing Standard of Practice Protocol: Reducing Adverse Drug Events.
Available at: http://consultgerirn.org/topics/medication/want_to_know_more