POLYPHARMACY Wendolyn Gozansky, MD, MPH Associate Professor Division of Geriatric Medicine University of Colorado Denver

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POLYPHARMACYWendolyn Gozansky, MD,
MPHAssociate ProfessorDivision of Geriatric
MedicineUniversity of Colorado Denver
AGS
THE AMERICAN GERIATRICS SOCIETY Geriatrics Health
Professionals. Leading change. Improving care for
older adults.
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CONTENTS

• Drugs and the elderly
• Pharmacodynamic and pharmacokinetic changes with
  aging
• Drug knowledge and compliance
• Prudent prescribing

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Drug Use in the Elderly
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Drug Use in the Elderly
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Drug Use in the Elderly
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ADVERSE DRUG REACTIONS (ADRs)

• 106,000 deaths in 1994

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ADVERSE DRUG REACTIONS (ADRs)

• 106,000 deaths in 1994
• 177 billion in 2000

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ADVERSE DRUG REACTIONS (ADRs)

• 106,000 deaths in 1994
• 177 billion in 2000
• For every 1 spent on drugs, 1 spent on ADRs

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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

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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

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Exponential Relation Between Polypharmacy and ADRs
Nolan L. JAGS. 198836(2)142-149.
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CONTENTS

• Drugs and the elderly
• Pharmacodynamic and pharmacokinetic changes with
  aging
• Drug knowledge and compliance
• Prudent prescribing

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Pharmacodynamics

• Response that occurs when a drug interacts at its
  receptor

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Pharmacodynamic Changeswith Aging

• Increased response
• (eg, opiates)

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Pharmacodynamic Changeswith Aging

• Increased response
• (eg, opiates)
• Decreased response
• (eg, beta-agonists)

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Pharmacokinetics

• Drug concentration at the site of action

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Pharmacokinetics

• Drug concentration at the site of action
• 4 determinants
• Absorption
• Distribution
• Metabolism
• Elimination

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PK Changes with Aging ABSORPTION

• ? gastric pH
• ? gastric emptying
• ? splanchnic blood flow
• ? intestinal motility
• Minimal clinical importance

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PK Changes with Aging DISTRIBUTION

• ? fat mass
• ? muscle mass
• ? total body water
• ? albumin (binds acidic drugs)
• ? alpha-1 glycoprotein (binds basic drugs)
• Clinically important

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20-year-old woman
Rosenberg, I. J Nutr. 1997. 127(5)990-991S.
Published with permission.
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64-year-old woman
20-year-old woman
Rosenberg, I. J Nutr. 1997. 127(5)990-991S.
Published with permission.
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64-year-old woman
20-year-old woman
Rosenberg, I. J Nutr. 1997. 127(5)990-991S.
Published with permission.
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64-year-old woman
20-year-old woman
Rosenberg, I. J Nutr. 1997. 127(5)990-991S.
Published with permission.
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PK Changes with AgingMETABOLISM

• ? hepatic mass
• ? hepatic blood flow
• ? first-pass metabolism
• Clinically important Longer half-life of drugs
  undergoing phase I metabolism (eg, diazepam vs
  lorazepam)

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PK Changes with AgingELIMINATION

• ? 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

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Pharmacokinetic Changeswith Aging

• What is the best formula for estimating GFR in
  older adults?
• Cockcroft-Gault (CG)
• Modification of Diet in Renal Disease (MDRD)

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CG vERSUS MDRD
Verhave et al Lamb et al
Mean age, yr 71 80
Mean measured GFR, mL/min/1.73m2 79.4 53.3
Subject characteristics Healthy no DM, CAD, CHF, CRI Comorbidities and CRI
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CG VERSUS MDRD
Verhave et al Lamb et al
Mean age, yrs 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
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Biology of the Patient

• Limited functional reserve

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Biology of the Patient
Disease Compensatory severity mechanisms
Symptomatic Asymptomatic
Resnick N.M, Marcantonio E.R. The Lancet.
1992350(9085)1157-1158. Published with
permission.
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Biology of the Patient

• Limited functional reserve
• Drug-disease interactions

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CONTENTS

• Drugs and the elderly
• Pharmacodynamic pharmacokinetic changes with
  aging
• Drug knowledge and compliance
• Prudent prescribing

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Do you know whats in your patients medicine
cabinet?

• 20 of drugs found on home inventory were not
  revealed by physician interview
• Most frequently unreported class of drugs?

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(No Transcript)
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Do you know whats in your patients medicine
cabinet?

• 20 of drugs found on home inventory were not
  revealed by physician interview
• Most frequently unreported class of drugs?
• BENZODIAZEPINES!!!

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Altered Compliance

• Under-utilization
• Over-utilization
• Enforced compliance

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Relation Between Polypharmacyand Number of
Prescribers
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Relation Between Polypharmacyand Compliance
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Methods to Improve Compliance

• ? of drugs, prescribers, and pharmacies
• Once-daily or twice-daily dosing
• Pill boxes
• Medication reminder charts
• ? frequency of clinic visits

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CONTENTS

• Drugs and the elderly
• Pharmacodynamic pharmacokinetic changes with
  aging
• Drug knowledge and compliance
• Prudent prescribing

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Avoid the Prescribing Cascade
Drug 1
BMJ. 19973151096-1099.
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Avoid the Prescribing Cascade
Drug 1
Adverse effect misinterpreted as new medical
condition
Rochon, P. BMJ. 19973151096-1099. Published
with permission.
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Avoid the Prescribing Cascade
Drug 1
Adverse effect misinterpreted as new medical
condition
Drug 2
Rochon, P. BMJ. 19973151096-1099. Published
with permission.
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Avoid the Prescribing Cascade

• HCTZ Allopurinol
• NSAIDs Antihypertensives
• Metoclopramide Carbidopa/levodopa
• Cholinesterase inhibitors Tolterodine

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Beware of Drug-Drug Interactions (DDIs)

• 100 chance of DDIs with 8 drugs

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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

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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

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Prudent Prescribing Principles

• Know your patients and their drug cabinets

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Prudent Prescribing Principles

• Know your patients and their drug cabinets
• Educate yourself and your patients

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Prudent Prescribing Principles

• Know your patients and their drug cabinets
• Educate yourself and your patients
• Understand biases in clinical trials

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Prudent Prescribing Principles

• Know your patients and their drug cabinets
• Educate yourself and your patients
• Understand biases in clinical trials
• Ask about compliance

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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

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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

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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

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Which of the following is an age-related change
that causes clinically significant alterations in
drug pharmacokinetics?

1. Decreased fat mass
2. Increased gastric pH
3. Decreased glomerular filtration rate
4. Increased total body water

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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Which of the following does not contribute to
adverse drug reactions (ADRs) in the elderly?

1. All prescriptions written by one provider
2. Comorbid illness
3. Hospitalization
4. Increasing numbers of medications

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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Which of the following is associated with
improved medication compliance?

1. Increasing numbers of medications
2. Clinic visit in the previous 48 hours
3. TID dosing
4. Drug side effects
5. Expensive medications

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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Which of the following is a principle of prudent
prescribing?

1. Only inquire about prescribed medications
2. Ask the patient, What could possibly be so hard
   about taking pills every day?
3. Do not begin treatment without a diagnosis
4. Use drugs before a trial of non-pharmacologic
   therapy

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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Which of the following effects of aging
contributes to an increased risk of ADRs related
to benzodiazepine use?

1. Increased body fat mass causing a greater volume
   of distribution and decreasing drug half-life
2. Increased hepatic volume resulting in increased
   production of active metabolites
3. Decreased renal function causing delayed renal
   excretion

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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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

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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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

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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Older adults uniformly exhibit exaggerated
pharmacodynamic responses compared with younger
adults.

1. True
2. False

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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Which of the following drugs is/are listed as
high-severity potentially inappropriate
medications for patients aged 65?

1. Amiodarone (Cordarone)
2. Amitriptyline (Elavil)
3. Cyclobenzaprine (Flexeril)
4. Diazepam (Valium)
5. Diphenhydramine (Benadryl)
6. Indomethacin (Indocin)
7. Ketorolac (Toradol)
8. Nitrofurantoin (Macrodantin)
9. All of the above

Fick D.M, et al. Arch Intern Med.
2003163(22)2716-2724.
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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. 2003163(22)2716-2724.
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