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Geriatric PharmacologyWhen More is Not Better
Nathan R. Harmon, DO,CMD,
CAQ- Geriatrics, Hospice and
Palliative Medicine
Disclosures
• No Financial Disclosures
Goals
• Review elements unique to Geriatric Pharmacology
• Define Polypharmacy
• Discuss medications potentially to avoid
– Beers List
– STOPP and START
• Discuss a methodology in approaching medication use in
Geriatrics
• Review a case related to geriatric pharmacology
Factors Influencing Drug Effects in
the Elderly
• Multiple Co-existing illnesses, medications
may worsen other conditions
– CHF (diuretics)  CKD  AKI
• Increased sensitivity to dosing/adverse effects
• Pharmacologic changes with aging
Pharmacokinetics
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What the Body does to the drug
Absorption
Distribution
Metabolism
Excretion
Body Composition Changes with
Aging
Age Group
Body Wt (kg)
Body Fat (kg)
Muscle Mass (kg)
20-29
80
15
24
30-49
81
19
20
60-69
79
23
17
70-79
80
25
13
Volume of Distribution (Vd)
• We lose muscle (water) as we age
– Water soluble medications (digoxin) are not stored, but
enter bloodstream quicker
– Reach steady state faster; higher serum concentration for a
given dose
• We gain adipose as we age
– Lipid soluble medications (diazepam) are stored, less than
expected initial serum concentration, but leach out over
greater time
• Protein (albumin) bound medications (phenytoin)  higher
serum concentration with malnourishment
Vd of Diazepam
Age
Volume of Distribution
Hepatic Metabolism
• Phase I – oxidative (cytochrome P450 family)
– Declines with aging
• Medications take longer to be metabolized
• More susceptible to multiple medications
competing for metabolism
Renal Function
• Due to decreased muscle mass, Cr alone is not
a good predictor of renal function
• MDRD not validated in patients > 70
• Renal dosing of medications should be done
using Cockroft-Gault
Half Life
• t ½ ~ Vd / Clearance
• Aging
– Increased Vd (for lipophilic medications)
– Decreased Clearance
– Longer half-life
Pharmacodynamics
• What the Drug does to the body
• In general, more sensitive to effects of
medications
– Lower than normal doses may be therapeutic
The “Physics” of Geriatric
Pharmacotherapy
• Therapeutic Inertia – drugs continued in the
absence of clear benefit
– “De-prescribing”
• Therapeutic Momentum – drugs added for
questionable indications
– Insomnia
• The Prescribing Cascade – Drugs added to
treat side effects from other drugs
Gurwitz, J., “Drug Therapy in Older Persons: Beliefs, Myths and Challenges”, Harvard 31st
Annual Review of Geriatric Medicine, 2015.
Prescribing Cascade
Metoclopramide (Reglan)
Extrapyramidal Effects
Levodopa treatment
Gurwitz, J., “Drug Therapy in Older Persons: Beliefs, Myths and Challenges”, Harvard 31st
Annual Review of Geriatric Medicine, 2015.
Prescribing Cascade
Nifedipine for HTN
Increased Edema, Impaired bladder emptying,
Constipation
Over active Bladder
Antimuscarinic Added
Laxative Added
Gurwitz, J., “Drug Therapy in Older Persons: Beliefs, Myths and Challenges”, Harvard 31st
Annual Review of Geriatric Medicine, 2015.
Prescribing Cascades
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NSAIDs  HTN  Anti-hypertensives
Thiazides  Gout  Gout therapy
Glucocorticoids  Hypoglycemics
Cholinesterase inhibitors  Anticholinergics
for urinary incontinence
I think you may be challenged by polypharmacy.
Polypharmacy Defined
• Use of ‘multiple’ drugs
• More than 5 (9) medications
– >50% Medicare beneficiaries have 3 or more chronic medical
conditions
– 36-37% Community dwelling elders on 5 or more medications
– 50% vitamin and/or dietary supplement
– 40% NH patients on 9 or more medications
• Use of more drugs than are Medically Necessary
– Not indicated, not effective, or therapeutic duplication
– Used to treat complication of another drug of marginal benefit
• “Extreme polypharmacy” (20 or more)
Expert Opin Drug Saf. 2014 (Jan);13(1). (NIH Public Access)
Polypharmacy -- How did we get
here?
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Great and important changes in medicine.
– New tools which are quite powerful
• Cancer medications
• Beta blockers and ace inhibitors
• Control of metabolic disorders
– Lipids
– Diabetes
– osteoporosis
– Attempts to standardize our care
• Guidelines
Aging population
– Multiple chronic illnesses
– Living longer
Increased specialization
– Multiple prescribers.
Consequences of Polypharmacy
• DDI’s
– Hospitalized patients
• 5-9 meds50% risk of DDI
• 20 or more meds100% risk of DDI
• Community Dwelling elderly 50%
• Non adherence
– 43-100% in Community Dwelling elderly
– 4 or more medications  35%
– Patients over 65 only 40% had 100% concordance
between Brown Bag and Pharmacy Records.
• Caskie et al. Exp Aging Res. 2006;32(1):79-103
Consequences of Polypharmacy
• Observational Studies suggest it is a bad thing
• Associated with multiple co-morbidities and
frailty
– Meds are of value
– There is some under-prescribing
– We do not have a robust science
“BAD” Drugs
• Beers List
• STOPP/START Criteria
Beers Criteria: History and Utilization
 Original 1991 – Nursing home pts
 PIMs – Potentially Inappropriate Medications
 QA/QI
 Updates
1997
All elderly; adopted by CMS in 1999 for nursing
home regulation
2003
Era of generalization to Med D
2012
Further adoption into quality
measures
2015
Updated recommendations with drugs to avoid
d/t renal function, and select drug-drug
interactions
Designations of Quality and Strength of Evidence:
ACP Guideline Grading System, GRADE
Quality
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High Evidence
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Moderate Evidence
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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)
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
Low Evidence
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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
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
Beers List
• Only 40% of the categories of medications
listed have High Quality evidence
• Alternatives to medications are not given
• Medications may be appropriate in certain
clinical situations
– Digoxin, Spironolactone for CHF
• Does give medications to avoid for certain
clinical situations
STOPP/START Criteria
• The STOPP (Screening Tool of Older Persons’ potentially
inappropriate Prescriptions) and START (Screening Tool to
Alert doctors to Right Treatment)
• STOPP might work better than Beers to identify meds that
result in negative outcomes, such as hospital admission.
• But as with Beers criteria, there is no convincing evidence that
using the START/STOPP criteria reduces morbidity, mortality,
or cost.
• Use these lists to identify red flags that might require
intervention, not as the final word on medication
appropriateness; look at the total patient picture.
Gallagher P, O’Mahony D. STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions): application to acutely ill
elderly patients and comparison with Beers’ criteria. Age Ageing 2008;37:673-9.
Barry PJ, Gallagher P, Ryan C, O’Mahony D. START (screening tool to alert doctors to the right treatment)―an evidence-based
screening tool to detect prescribing omissions in elderly patients. Age Ageing 2007;36:632-8.
ADE’S-Common Drug Classes
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Cardiovascular drugs
NSAIDs
Hypoglycemics
2nd Gen Antipsychotics
Anticoagulants and Antiplatelet agents
Antihistamines (medications “PM”)
Anticholinergics
Drug Comparison Charts RxFiles 10th Ed., 2014.
ADE’s-Risk Factors
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Age>84
Low BMI
6 or more Chronic Illnesses
CrCl <50 mL/min
9 or more medications
12 or more medication doses/day
Prior ADE
Drug-Drug Interactions
• http://www.uptodate.com
• Example of medications – See Case later
De-prescribing
• Stopping Wisely
•“…as complicated as
starting a new medication”
An Approach
• Patient goals
• Safety
– Any possible ADE’s
– DDI
– High risk medications
• Anticholinergics
• Efficacy
– Medical goals in relation to time to benefit and prognosis
– Evidence base for elderly
• Complexity and cost
– Compliance
Case
• 85 y/o WF presents to establish care
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Alzheimer’s disease diagnosed two years ago
COPD
CAD (40% RCA in FL after presenting with dyspnea and edema)
HLD
HTN (160/90 on 2 ED visits)
CHF
UI
Depression
DJD
Constipation
Case
• PMH
– Ex-smoker
• Lives alone
– Housekeeper for heavy cleaning and laundry
– Daughter helps with checkbook and shopping
Case
• BP 130/60 sitting
• Height 62 inches
• Weight 137 lbs
120/55 standing
– BMI 25.1
• Mildly antalgic gait and uses cane
• Bright alert, slightly vague
A Patient
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FEV1 55% Pred, SpO2 92%
Cr 1.1/K+ 5.0
EF 45%
LDL 85
Brown Bag Meds (21)
• Amlodipine 10 mg q AM
• Atorvastatin 10 mg q PM
• Fluticasone/salmeterol 100/50
bid
• Oxybutynin 15 mg q AM
• Donepezil 10 mg q AM
• Fluoxetine 20 mg qAM + 10
mg (1/2) prn agitation and
stress
• Meloxicam 7.5 mg qAM
• Ranitidine 150 mg bid
• Ibuprofen 200 mg q hrs prn
• ASA 81 mg daily
• Proventil HFA prn
• Ipratropium/Albuterol neb 2-4
times a day
• Multi Vit qAM
• Vit C qAM
• Miralax 1 tsp/8 oz H2O qAM
• Hydrocodone/Acetaminophen
5/325 tid
• Lisinopril 40 mg daily
• Metoprolol 25 mg bid
• Lasix 40 mg daily
• KCL 20 meq daily
• Tylenol PM qhs
Comments
Brown Bag Meds Re-organized
Category
Category
CV/HTN
--Amlodipine
--Lisinopril
--Metoprolol
--Lasix
--Atorvastatin
--Aspirin
Psychiatric
--Fluoxetine
--Donepezil
Respiratory
--Fluticasone/Salmeterol
--Proventil HFA
--Ipratroprium/Albuterol
GI
--Ranitidine
--Miralax
Musculoskeletal
--Ibuprofen
--Hydrocodone/Acetominophen
--Meloxicam
--Tylenol PM
Misc
--Oxybutynin
--MVI
--Vit C
--KCL
Comments
Safety
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Any possible ADE’s
DDI
High risk medications
Anticholinergics
Patient goals
• Atorvastatin
– Time to benefit 2 years
– Safe to discontinue with LE < 1 year and improve
QOL
• JAMA Intern Med 2015;175:691-700.
Drug-Drug Interactions
• http://www.uptodate.com
Summary
• Geriatric Pharmacology
– Physiological changes affect distribution, metabolism and
clearance
– Consider Polypharmacy
• Redundant Medications
• Group by system or condition
– Beers list, STOPP/START, Common ADEs/DDIs
– Make use of outpatient lists, pharmacy consultation
– Deprescribing – Patient preference, Goals of Care, Life
Expectancy, Medication Efficacy, DDI’s, ADE’s
Questions
References
• As cited in presentation