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POLYPHARMACY
Wendolyn Gozansky, MD, MPHAssociate Professor
Division of Geriatric MedicineUniversity of Colorado Denver
THE AMERICAN GERIATRICS SOCIETY
Geriatrics Health Professionals.
Leading change. Improving care for older adults.
AGS
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 ELDERLY12% 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 polypharmacyChanges in pharmacodynamics/pharmacokineticsDrug-disease interactions
Slide 10
EXPONENTIAL RELATION BETWEEN POLYPHARMACY AND ADRs
Nolan L. JAGS. 1988;36(2):142-149.
# of Drugs Taken
Per
cen
t o
f P
atie
nts
wit
h
an A
DR
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 CHANGESWITH AGING
Increased response(eg, opiates)
Slide 14
PHARMACODYNAMIC CHANGESWITH 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:AbsorptionDistributionMetabolismElimination
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):990-991S. Published with permission.
64-year-old woman
20-year-old woman
Rosenberg, I. J Nutr. 1997. 127(5):990-991S. Published with permission.
64-year-old woman
20-year-old woman
Rosenberg, I. J Nutr. 1997. 127(5):990-991S. Published with permission.
64-year-old woman
20-year-old woman
Rosenberg, I. J Nutr. 1997. 127(5):990-991S. Published with permission.
hepatic mass
hepatic blood flow
first-pass metabolism
Clinically important: Longer half-life of drugs undergoing phase I metabolism (eg, diazepam vs lorazepam)
PK CHANGES WITH AGING:METABOLISM
Slide 24
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
PK CHANGES WITH AGING:ELIMINATION
Slide 25
PHARMACOKINETIC CHANGESWITH 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
Slide 27
CG VERSUS MDRD
Slide 28
BIOLOGY OF THE PATIENT
• Limited functional reserve
Slide 29
BIOLOGY OF THE PATIENT
Disease Compensatory severity mechanisms
Symptomatic 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
RELATION BETWEEN POLYPHARMACYAND NUMBER OF PRESCRIBERS
# of Drugs Prescribed
# o
f P
resc
rib
ers
Slide 37
RELATION BETWEEN POLYPHARMACYAND COMPLIANCE
# of Drugs Prescribed
% C
om
pli
an
ce
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
Slide 43Rochon, P. BMJ. 1997;315:1096-1099. Published with permission.
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 age-related change that causes clinically
significant alterations in drug pharmacokinetics?
1 2 3 4
0% 0%0%0%
A. Decreased fat mass
B. Increased gastric pH
C. Decreased glomerular filtration rate
D. Increased total body water
:10Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
Which of the following does not contribute to adverse drug reactions
(ADRs) in the elderly?
1 2 3 4
0% 0%0%0%
A. All prescriptions written by one provider
B. Comorbid illness
C. Hospitalization
D. Increasing numbers of medications
:10Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
Which of the following is associated with improved medication
compliance?
1 2 3 4 5
0% 0% 0%0%0%
A. Increasing numbers of medications
B. Clinic visit in the previous 48 hours
C. TID dosing
D. Drug side effects
E. Expensive medications
:10Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
Which of the following is a principle of prudent prescribing?
1 2 3 4
0% 0%0%0%
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
:10Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
Which of the following effects of aging contributes to an increased risk of
ADRs related to benzodiazepine use?
1 2 3
0% 0%0%
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
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
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 2
0%0%
1. True
2. False
:10Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
A patient with a serum creatinine of 0.5 mg/dL (within the normal range) will also
have a normal creatinine clearance
1 2
0%0%
1. True
2. False
:10Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
Older adults uniformly exhibit exaggerated pharmacodynamic responses compared
with younger adults.
1 2
0%0%
1. True
2. False
:10Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
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.
0% 0% 0% 0% 0%0%0%0%0%
A. Amiodarone (Cordarone)
B. Amitriptyline (Elavil)
C. Cyclobenzaprine (Flexeril)
D. Diazepam (Valium)
E. Diphenhydramine (Benadryl)
F. Indomethacin (Indocin)
G. Ketorolac (Toradol)
H. Nitrofurantoin (Macrodantin)
I. All of the above
:10Fick D.M, et al. Arch Intern Med. 2003;163(22):2716-2724.
Mark H. Beers, MD
19542009
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.
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Slide 65