POLYPHARMACY Wendolyn Gozansky, MD, MPH Associate Professor Division of Geriatric Medicine University of Colorado Denver THE AMERICAN GERIATRICS SOCIETY.

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

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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


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

Slide 7


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

Slide 8


• 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


• 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


• Pharmacodynamic and pharmacokinetic changes with aging



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


64-year-old woman

20-year-old woman


64-year-old woman

20-year-old woman


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


Disease Compensatory severity mechanisms

Symptomatic Asymptomatic

Resnick N.M, Marcantonio E.R. The Lancet. 1992;350(9085):1157-1158. Published with permission.

Slide 30


• Limited functional reserve

• Drug-disease interactions

Slide 31

CONTENTS


• Pharmacodynamic & pharmacokinetic changes with aging



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

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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

Slide 39

CONTENTS


• Pharmacodynamic & pharmacokinetic changes with aging



Slide 40

AVOID THE PRESCRIBING CASCADE

Drug 1

BMJ. 1997;315:1096-1099.Slide 41


Drug 1

Adverse effect misinterpreted as new medical condition

Rochon, P. BMJ. 1997;315:1096-1099. Published with permission.

Slide 42


Drug 1

Adverse effect misinterpreted as new medical condition

Drug 2

Slide 43Rochon, P. BMJ. 1997;315:1096-1099. Published with permission.


• 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

Slide 45



• Nearly 50% of community-dwelling geriatric patients had at least one DDI

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

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

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

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• 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



diagnosis of a new problem• Try non-pharmacologic strategies

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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 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


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


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


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


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


Older adults uniformly exhibit exaggerated pharmacodynamic responses compared

with younger adults.

1 2

0%0%

1. True

2. False


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


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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POLYPHARMACY Wendolyn Gozansky, MD, MPH Associate Professor Division of Geriatric Medicine University of Colorado Denver THE AMERICAN GERIATRICS SOCIETY.

Documents

adrs slide

compliance slide

metabolism slide

important slide

predictable slide

receptor slide

ags slide

site of action slide