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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

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DRUG USE IN THE ELDERLY
12% of the population is aged 65+

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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 .

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.

ADVERSE DRUG REACTIONS (ADRs) • 106. $1 spent on ADRs • 95% of ADRs considered to be predictable Slide 9 .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 .ADVERSE DRUG REACTIONS (ADRs) • 106.000 deaths in 1994 • $177 billion in 2000 • For every $1 spent on drugs.

1988.36(2):142-149. Slide 11 . JAGS.EXPONENTIAL RELATION BETWEEN POLYPHARMACY AND ADRs Nolan L.

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 .

opiates) Slide 14 .PHARMACODYNAMIC CHANGES WITH AGING Increased response (eg.

opiates) Decreased response (eg.PHARMACODYNAMIC CHANGES WITH AGING Increased 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 .

1997. .20-year-old woman Rosenberg. J Nutr. Published with permission. 127(5):990991S. I.

64-year-old woman 20-year-old woman Rosenberg. I. J Nutr. . 127(5):990991S. 1997. Published with permission.

64-year-old woman 20-year-old woman Rosenberg. 1997. Published with permission. 127(5):990991S. . I. J Nutr.

1997. I. . 127(5):990991S. J Nutr. Published with permission.64-year-old woman 20-year-old woman Rosenberg.

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 Slide 27 .

CG VERSUS MDRD Slide 28 .

BIOLOGY OF THE PATIENT • Limited functional reserve Slide 29 .

BIOLOGY OF THE PATIENT Disease severity Symptomatic Compensatory mechanisms Asymptomatic Resnick N.350(9085):11571158. Marcantonio E. Published with permission.M. Slide 30 . The Lancet.R. 1992.

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 .

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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 POLYPHARMACY AND NUMBER OF PRESCRIBERS Slide 37 .

RELATION BETWEEN POLYPHARMACY AND COMPLIANCE Slide 38 .

and pharmacies • Once-daily or twice-daily dosing • Pill boxes • Medication reminder charts •  frequency of clinic visits Slide 39 .METHODS TO IMPROVE COMPLIANCE •  # of drugs. prescribers.

CONTENTS • Drugs and the elderly • Pharmacodynamic & pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing Slide 40 .

1997.315:1096-1099.AVOID THE PRESCRIBING CASCADE Drug 1 BMJ. Slide 41 .

Slide 42 .AVOID THE PRESCRIBING CASCADE Drug 1 Adverse effect misinterpreted as new medical condition Rochon. Published with permission.315:1096-1099. P. BMJ. 1997.

Published with permission. 1997.AVOID THE PRESCRIBING CASCADE Drug 1 Adverse effect misinterpreted as new medical condition Drug 2 Rochon. P.315:1096-1099. BMJ. 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

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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 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 .

2003. Decreased glomerular filtration rate D.M. :10 . Decreased fat mass B. Increased total body water Fick D. Arch Intern Med.Which of the following is an agerelated change that causes clinically significant alterations in drug pharmacokinetics? A. et al. Increased gastric pH C.163(22):2716-2724.

Hospitalization D. .Which of the following does not contribute to adverse drug reactions (ADRs) in the elderly? A. Arch Intern Med. 2003.M. Comorbid illness C.163(22):2716-2724. Increasing numbers of medications :10 Fick D. All prescriptions written by one provider B. et al.

et al. Arch Intern Med. Clinic visit in the previous 48 hours C. Drug side effects E. Expensive medications Fick D. TID dosing D.M.Which of the following is associated with improved medication compliance? A. Increasing numbers of medications B.163(22):2716-2724. :10 . 2003.

Which of the following is a principle of prudent prescribing? A. Use drugs before a trial of non-pharmacologic therapy Fick D. Do not begin treatment without a diagnosis D. :10 . Arch Intern Med. “What could possibly be so hard about taking pills every day?” C. et al.163(22):2716-2724. Ask the patient.M. Only inquire about prescribed medications B. 2003.

2003.Which of the following effects of aging contributes to an increased risk of ADRs related to benzodiazepine use? A. Decreased renal function causing delayed renal excretion Fick D.163(22):2716-2724. Arch Intern Med.M. Increased hepatic volume resulting in increased production of active metabolites C. :10 . Increased body fat mass causing a greater volume of distribution and decreasing drug half-life B. et al.

True 2. Arch Intern Med.163(22):2716-2724. et al. 2003.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.M. . 1. False :10 Fick D.

A patient with a serum creatinine of 0. False Fick D. et al.163(22):2716-2724. True 2.M. :10 . Arch Intern Med.5 mg/dL (within the normal range) will also have a normal creatinine clearance 1. 2003.

Older adults uniformly exhibit exaggerated pharmacodynamic responses compared with younger adults. True 2. False Fick D. 2003. Arch Intern Med. et al.163(22):2716-2724. 1.M. :10 .

C. 2003. G. H. B.163(22):2716-2724. D.M. Amiodarone (Cordarone) Amitriptyline (Elavil) Cyclobenzaprine (Flexeril) Diazepam (Valium) Diphenhydramine (Benadryl) Indomethacin (Indocin) Ketorolac (Toradol) Nitrofurantoin (Macrodantin) All of the above Fick D. F. Arch Intern Med.Which of the following drugs is/are listed as “high-severity” potentially inappropriate medications for patients aged 65+? A. E. I. et al. :10 .

163(22):2716-2724.Mark H. 2003. et al. RN." Donna M. Fick. . Arch Intern Med. 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. Beers. PhD.

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