1. POLYPHARMACY Wendolyn Gozansky, MD, MPH Associate Professor Division of Geriatric Medicine University of Colorado Denver
AGS
THE AMERICAN GERIATRICS SOCIETY
Geriatrics Health Professionals.
Leading change. Improving care for older adults.
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2. CONTENTS Drugs and the elderly
Pharmacodynamic and pharmacokinetic changes with aging
Drug knowledge and compliance
Prudent prescribing
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3. Drug Use in the Elderly
12% of the population is aged 65+
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4. Drug Use in the Elderly 12% of the population is aged 65+
30% of all prescription drug use is among those aged 65+
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5. 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+
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6. ADVERSE DRUG REACTIONS (ADRs)
106,000 deaths in 1994
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7. ADVERSE DRUG REACTIONS (ADRs)
106,000 deaths in 1994
$177 billion in 2000
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8. 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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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
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10. 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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11. Exponential Relation Between Polypharmacy and ADRs
Nolan L. JAGS. 1988;36(2):
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12. CONTENTS Drugs and the elderly
Pharmacodynamic and pharmacokinetic changes with aging
Drug knowledge and compliance
Prudent prescribing
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13. Pharmacodynamics
Response that occurs when a drug interacts at its receptor
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14. Pharmacodynamic Changes with Aging
Increased response
(eg, opiates)
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15. Pharmacodynamic Changes with Aging
Increased response
(eg, opiates)
Decreased response
(eg, beta-agonists)
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16. Pharmacokinetics
Drug concentration at the site of action
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17. Pharmacokinetics Drug concentration at the site of action
4 determinants:
Absorption
Distribution
Metabolism
Elimination
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18. PK Changes with Aging: ABSORPTION
 gastric pH
 gastric emptying
 splanchnic blood flow
 intestinal motility
Minimal clinical importance
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19. 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. 20-year-old woman
Rosenberg, I. J Nutr (5): S. Published with permission.
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21. 64-year-old woman 20-year-old woman
Rosenberg, I. J Nutr (5): S. Published with permission.
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22. 64-year-old woman 20-year-old woman
Rosenberg, I. J Nutr (5): S. Published with permission.
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23. 64-year-old woman 20-year-old woman
Rosenberg, I. J Nutr (5): S. Published with permission.
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24. 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)
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25. 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
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26. 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)
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27. Healthy – no DM, CAD, CHF, CRI
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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28. Healthy – no DM, CAD, CHF, CRI
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
MDRD
Overestimated GFR
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29. Biology of the Patient
Limited functional reserve
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30. Disease Compensatory severity mechanisms
Biology of the Patient
Disease Compensatory severity mechanisms
Symptomatic Asymptomatic
Resnick N.M, Marcantonio E.R. The Lancet. 1992;350(9085): Published with permission.
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31. Biology of the Patient Limited functional reserve
Drug-disease interactions
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32. CONTENTS Drugs and the elderly
Pharmacodynamic & pharmacokinetic changes with aging
Drug knowledge and compliance
Prudent prescribing
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33. 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?
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34. Topic

35. 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!!!
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36. Altered Compliance Under-utilization Over-utilization
Enforced compliance
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37. Relation Between Polypharmacy and Number of Prescribers
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38. Relation Between Polypharmacy and Compliance
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39. 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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40. CONTENTS Drugs and the elderly
Pharmacodynamic & pharmacokinetic changes with aging
Drug knowledge and compliance
Prudent prescribing
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41. Avoid the Prescribing Cascade
Drug 1
BMJ. 1997;315:
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42. Avoid the Prescribing Cascade
Drug 1
Adverse effect misinterpreted as new medical condition
Rochon, P. BMJ. 1997;315: Published with permission.
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43. Avoid the Prescribing Cascade
Drug 1
Adverse effect misinterpreted as new medical condition
Drug 2
Rochon, P. BMJ. 1997;315: Published with permission.
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44. Avoid the Prescribing Cascade
HCTZ – Allopurinol
NSAIDs – Antihypertensives
Metoclopramide – Carbidopa/levodopa
Cholinesterase inhibitors – Tolterodine
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45. Beware of Drug-Drug Interactions (DDIs)
100% chance of DDIs with 8 drugs
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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
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47. 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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48. Prudent Prescribing Principles
Know your patients and their drug cabinets
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49. Prudent Prescribing Principles
Know your patients and their drug cabinets
Educate yourself and your patients
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50. Prudent Prescribing Principles
Know your patients and their drug cabinets
Educate yourself and your patients
Understand biases in clinical trials
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51. 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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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
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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
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54. 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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55. Which of the following is an age-related change that causes clinically significant alterations in drug pharmacokinetics?
Decreased fat mass
Increased gastric pH
Decreased glomerular filtration rate
Increased total body water
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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56. Which of the following does not contribute to adverse drug reactions (ADRs) in the elderly?
All prescriptions written by one provider
Comorbid illness
Hospitalization
Increasing numbers of medications
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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57. Which of the following is associated with improved medication compliance?
Increasing numbers of medications
Clinic visit in the previous 48 hours
TID dosing
Drug side effects
Expensive medications
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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58. Which of the following is a principle of prudent prescribing?
Only inquire about prescribed medications
Ask the patient, “What could possibly be so hard about taking pills every day?”
Do not begin treatment without a diagnosis
Use drugs before a trial of non-pharmacologic therapy
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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59. Which of the following effects of aging contributes to an increased risk of ADRs related to benzodiazepine use?
Increased body fat mass causing a greater volume of distribution and decreasing drug half-life
Increased hepatic volume resulting in increased production of active metabolites
Decreased renal function causing delayed renal excretion
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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60. 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.
True
False
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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61. A patient with a serum creatinine of 0
A patient with a serum creatinine of 0.5 mg/dL (within the normal range) will also have a normal creatinine clearance
True
False
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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62. Older adults uniformly exhibit exaggerated pharmacodynamic responses compared with younger adults.
True
False
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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63. Which of the following drugs is/are listed as “high-severity” potentially inappropriate medications for patients aged 65+?
Amiodarone (Cordarone)
Amitriptyline (Elavil)
Cyclobenzaprine (Flexeril)
Diazepam (Valium)
Diphenhydramine (Benadryl)
Indomethacin (Indocin)
Ketorolac (Toradol)
Nitrofurantoin (Macrodantin)
All of the above
:10
Fick D.M, et al. Arch Intern Med. 2003;163(22):
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64. 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):
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