POLYPHARMACY
AGS
Wendolyn Gozansky, MD, MPH
Associate Professor
Division of Geriatric Medicine
University of Colorado Denver
THE AMERICAN GERIATRICS SOCIETY
Geriatrics Health Professionals.
Leading change. Improving care for older adults.
CONTENTS
• Drugs and the elderly
• Pharmacodynamic and pharmacokinetic
changes with aging
• Drug knowledge and compliance
• Prudent prescribing
Slide 2
DRUG USE IN THE ELDERLY
12% of the population is aged 65+
Slide 3
DRUG USE IN THE ELDERLY
12% of the population is aged 65+
30% of all prescription drug
use is among those aged 65+
Slide 4
DRUG USE IN THE ELDERLY
12% of the population is age 65+
30% of all prescription drug use
is among those aged 65+
50% of all OTC drug use is
among those aged 65+
Slide 5
ADVERSE DRUG REACTIONS (ADRs)
• 106,000 deaths in 1994
Slide 6
ADVERSE DRUG REACTIONS (ADRs)
• 106,000 deaths in 1994
• $177 billion in 2000
Slide 7
ADVERSE DRUG REACTIONS (ADRs)
• 106,000 deaths in 1994
• $177 billion in 2000
• For every $1 spent on drugs, $1 spent on ADRs
Slide 8
ADVERSE DRUG REACTIONS (ADRs)
• 106,000 deaths in 1994
• $177 billion in 2000
• For every $1 spent on drugs, $1 spent on ADRs
• 95% of ADRs considered to be predictable
Slide 9
ADVERSE DRUG REACTIONS (ADRs)
• 106,000 deaths in 1994
• $177 billion in 2000
• For every $1 spent on drugs, $1 spent on ADRs
• 95% of ADRs considered to be predictable
• 7-fold increased risk in the elderly
 Related to polypharmacy
 Changes in pharmacodynamics/pharmacokinetics
 Drug-disease interactions
Slide 10
Percent of Patients with
an ADR
EXPONENTIAL RELATION BETWEEN
POLYPHARMACY AND ADRs
# of Drugs Taken
Nolan L. JAGS. 1988;36(2):142-149.
Slide 11
CONTENTS
• Drugs and the elderly
• Pharmacodynamic and pharmacokinetic changes
with aging
• Drug knowledge and compliance
• Prudent prescribing
Slide 12
PHARMACODYNAMICS
Response that occurs when a drug interacts at
its receptor
Slide 13
PHARMACODYNAMIC CHANGES
WITH AGING
Increased response
(eg, opiates)
Slide 14
PHARMACODYNAMIC CHANGES
WITH AGING
Increased response
(eg, opiates)
Decreased response
(eg, beta-agonists)
Slide 15
PHARMACOKINETICS
Drug concentration at the site of action
Slide 16
PHARMACOKINETICS
• Drug concentration at the site of action
• 4 determinants:
 Absorption
 Distribution
 Metabolism
 Elimination
Slide 17
PK CHANGES WITH AGING:
ABSORPTION
 gastric pH
 gastric emptying
 splanchnic blood flow
 intestinal motility
Minimal clinical importance
Slide 18
PK CHANGES WITH AGING:
DISTRIBUTION
 fat mass
 muscle mass
 total body water
 albumin (binds acidic drugs)
 alpha-1 glycoprotein (binds basic drugs)
Clinically important
Slide 19
20-year-old
woman
Rosenberg, I. J
Nutr. 1997.
127(5):990991S.
Published with
permission.
64-year-old
woman
20-year-old
woman
Rosenberg, I. J
Nutr. 1997.
127(5):990991S.
Published with
permission.
64-year-old
woman
20-year-old
woman
Rosenberg, I. J
Nutr. 1997.
127(5):990991S.
Published with
permission.
64-year-old
woman
20-year-old
woman
Rosenberg, I. J
Nutr. 1997.
127(5):990991S.
Published with
permission.
PK CHANGES WITH AGING:
METABOLISM
 hepatic mass
 hepatic blood flow
 first-pass metabolism
Clinically important: Longer half-life of drugs
undergoing phase I metabolism (eg, diazepam vs
lorazepam)
Slide 24
PK CHANGES WITH AGING:
ELIMINATION
 renal mass
 renal blood flow
 glomerular filtration rate
Most clinically important
•  concentration of drugs dependent on renal clearance
• Serum creatinine alone does not provide adequate
information to guide dosing
Slide 25
PHARMACOKINETIC CHANGES
WITH AGING
What is the best formula for estimating GFR in
older adults?
• Cockcroft-Gault (CG)
• Modification of Diet in Renal Disease (MDRD)
Slide 26
CG VERSUS MDRD
Verhave et al
Lamb et al
71
80
Mean measured GFR,
mL/min/1.73m2
79.4
53.3
Subject characteristics
Healthy – no DM,
CAD, CHF, CRI
Comorbidities and
CRI
Mean age, yr
Slide 27
CG VERSUS MDRD
Verhave et al
Lamb et al
71
80
Mean measured GFR,
mL/min/1.73m2
79.4
53.3
Subject characteristics
Healthy – no DM,
CAD, CHF, CRI
Comorbidities and
CRI
CG
Underestimated GFR
Underestimated
GFR
MDRD
Underestimated GFR
Overestimated GFR
Mean age, yrs
Slide 28
BIOLOGY OF THE PATIENT
• Limited functional reserve
Slide 29
BIOLOGY OF THE PATIENT
Disease
severity
Symptomatic
Compensatory
mechanisms
Asymptomatic
Resnick N.M, Marcantonio E.R. The Lancet.
1992;350(9085):1157-1158. Published with permission.
Slide 30
BIOLOGY OF THE PATIENT
• Limited functional reserve
• Drug-disease interactions
Slide 31
CONTENTS
• Drugs and the elderly
• Pharmacodynamic & pharmacokinetic
changes with aging
• Drug knowledge and compliance
• Prudent prescribing
Slide 32
DO YOU KNOW WHAT’S IN YOUR
PATIENT’S MEDICINE CABINET?
~20% of drugs found on home inventory were
not revealed by physician interview
Most frequently unreported class of drugs?
Slide 33
Slide 34
DO YOU KNOW WHAT’S IN YOUR
PATIENT’S MEDICINE CABINET?
~20% of drugs found on home inventory were
not revealed by physician interview
Most frequently unreported class of drugs?
BENZODIAZEPINES!!!
Slide 35
ALTERED COMPLIANCE
• Under-utilization
• Over-utilization
• Enforced compliance
Slide 36
# of Prescribers
RELATION BETWEEN POLYPHARMACY
AND NUMBER OF PRESCRIBERS
# of Drugs Prescribed
Slide 37
% Compliance
RELATION BETWEEN POLYPHARMACY
AND COMPLIANCE
# of Drugs Prescribed
Slide 38
METHODS TO IMPROVE COMPLIANCE
•  # of drugs, prescribers, and pharmacies
• Once-daily or twice-daily dosing
• Pill boxes
• Medication reminder charts
•  frequency of clinic visits
Slide 39
CONTENTS
• Drugs and the elderly
• Pharmacodynamic & pharmacokinetic
changes with aging
• Drug knowledge and compliance
• Prudent prescribing
Slide 40
AVOID THE PRESCRIBING CASCADE
Drug 1
BMJ. 1997;315:1096-1099.
Slide 41
AVOID THE PRESCRIBING CASCADE
Drug 1
Adverse effect
misinterpreted as new
medical condition
Rochon, P. BMJ. 1997;315:1096-1099. Published with
permission.
Slide 42
AVOID THE PRESCRIBING CASCADE
Drug 1
Adverse effect
misinterpreted as new
medical condition
Drug 2
Rochon, P. BMJ. 1997;315:1096-1099. Published with
permission.
Slide 43
AVOID THE PRESCRIBING CASCADE
• HCTZ – Allopurinol
• NSAIDs – Antihypertensives
• Metoclopramide – Carbidopa/levodopa
• Cholinesterase inhibitors – Tolterodine
Slide 44
BEWARE OF DRUG-DRUG
INTERACTIONS (DDIs)
• 100% chance of DDIs with 8 drugs
Slide 45
BEWARE OF DRUG-DRUG
INTERACTIONS (DDIs)
• 100% chance of DDIs with 8 drugs
• Nearly 50% of community-dwelling geriatric
patients had at least one DDI
Slide 46
BEWARE OF DRUG-DRUG
INTERACTIONS (DDIs)
• 100% chance of DDIs with 8 drugs
• Nearly 50% of community-dwelling geriatric
patients had at least one DDI
• DDIs can result in ADRs or suboptimal dosing
Slide 47
PRUDENT PRESCRIBING PRINCIPLES
• Know your patients and their drug cabinets
Slide 48
PRUDENT PRESCRIBING PRINCIPLES
• Know your patients and their drug cabinets
• Educate yourself and your patients
Slide 49
PRUDENT PRESCRIBING PRINCIPLES
• Know your patients and their drug cabinets
• Educate yourself and your patients
• Understand biases in clinical trials
Slide 50
PRUDENT PRESCRIBING PRINCIPLES
• Know your patients and their drug cabinets
• Educate yourself and your patients
• Understand biases in clinical trials
• Ask about compliance
Slide 51
PRUDENT PRESCRIBING PRINCIPLES
• Know your patients and their drug cabinets
• Educate yourself and your patients
• Understand biases in clinical trials
• Ask about compliance
• Always include ADRs in the differential
diagnosis of a new problem
Slide 52
PRUDENT PRESCRIBING PRINCIPLES
• Know your patients and their drug cabinets
• Educate yourself and your patients
• Understand biases in clinical trials
• Ask about compliance
• Always include ADRs in the differential
diagnosis of a new problem
• Try non-pharmacologic strategies
Slide 53
PRUDENT PRESCRIBING PRINCIPLES
• Know your patients and their drug cabinets
• Educate yourself and your patients
• Understand biases in clinical trials
• Ask about compliance
• Always include ADRs in the differential
diagnosis of a new problem
• Try non-pharmacologic strategies
• Offer drug therapy when indicated
Slide 54
Which of the following is an agerelated change that causes clinically
significant alterations in drug
pharmacokinetics?
A. Decreased fat mass
B. Increased gastric pH
C. Decreased
glomerular filtration
rate
D. Increased total body
water
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
0%
1
0%
2
0%
3
0%
4
:10
Which of the following does not
contribute to adverse drug reactions
(ADRs) in the elderly?
A. All prescriptions
written by one
provider
B. Comorbid illness
C. Hospitalization
D. Increasing numbers
of medications
0%
1
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
0%
2
0%
3
0%
4
:10
Which of the following is associated
with improved medication
compliance?
A. Increasing numbers
of medications
B. Clinic visit in the
previous 48 hours
C. TID dosing
D. Drug side effects
E. Expensive
medications
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
0%
1
0%
0%
2
3
0%
0%
4
:105
Which of the following is a principle of
prudent prescribing?
A. Only inquire about
prescribed medications
B. Ask the patient, “What
could possibly be so hard
about taking pills every
day?”
C. Do not begin treatment
without a diagnosis
D. Use drugs before a trial
of non-pharmacologic
therapy
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
0%
1
0%
2
0%
3
0%
:10
4
Which of the following effects of aging
contributes to an increased risk of
ADRs related to benzodiazepine use?
A. Increased body fat mass
causing a greater volume
of distribution and
decreasing drug half-life
B. Increased hepatic
volume resulting in
increased production of
active metabolites
C. Decreased renal function
causing delayed renal
excretion
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
0%
1
0%
2
0%
3
:10
Patients who think they are taking too
many medications report lower quality
of life than patients who think they are
taking the right number of
medications.
1. True
2. False
0%
1
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
0%
2
:10
A patient with a serum creatinine of 0.5
mg/dL (within the normal range) will also
have a normal creatinine clearance
1. True
2. False
0%
1
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
0%
2
:10
Older adults uniformly exhibit exaggerated
pharmacodynamic responses compared
with younger adults.
1. True
2. False
0%
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
1
0%
2
:10
Which of the following drugs is/are listed as
“high-severity” potentially inappropriate
medications for patients aged 65+?
A.
B.
C.
D.
E.
F.
G.
H.
I.
Amiodarone (Cordarone)
Amitriptyline (Elavil)
Cyclobenzaprine (Flexeril)
Diazepam (Valium)
Diphenhydramine (Benadryl)
Indomethacin (Indocin)
Ketorolac (Toradol)
Nitrofurantoin (Macrodantin)
All of the above
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
0%
0%
0%
0%
0%
0%
0%
A.
B.
C.
D.
E.
F.
G.
0%
H.
0%
I.
:10
Mark H. Beers, MD
19542009
Data from "Updating the Beers Criteria for Potentially Inappropriate
Medication Use in Older Adults: Results of a US Consensus Panel
of Experts." Donna M. Fick, PhD, RN, et al. Arch Intern Med.
2003;163(22):2716-2724.
THANK YOU FOR YOUR TIME!
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Slide 65