THE AMERICAN GERIATRICS SOCIETY Geriatrics Health Professionals.

POLYPHARMACY

Wendolyn Gozansky, MD, MPHAssociate Professor

Division of Geriatric MedicineUniversity of Colorado Denver

THE AMERICAN GERIATRICS SOCIETYGeriatrics 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 ELDERLY12% of the population is aged 65+

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DRUG USE IN THE ELDERLY12% of the population is aged 65+

30% of all prescription drug use is among those aged 65+

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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+

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ADVERSE DRUG REACTIONS (ADRs)

• 106,000 deaths in 1994

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

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

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• 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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• 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

JAGS. 1988;36:142-149.

# of Drugs Taken

Perc

ent o

f Pat

ient

s w

ith

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

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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

J Nutr. 1997. 127:990-991S.

64-year-old woman

20-year-old woman

J Nutr. 1997; 127:990-991S.

64-year-old woman

20-year-old woman

J Nutr. 1997. 127:990-991S.

64-year-old woman

20-year-old woman

J Nutr. 1997. 127:990-991S.

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

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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

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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 alMean 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 alMean 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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Disease Compensatory severity mechanisms

Symptomatic Asymptomatic

Lancet. 1997;350:1157-1158.Slide 30


• Limited functional reserve

• Drug-disease interactions

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CONTENTS


• Pharmacodynamic & pharmacokinetic changes with aging



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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?

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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!!!

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ALTERED COMPLIANCE

• Under-utilization

• Over-utilization

• Enforced compliance

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RELATION BETWEEN POLYPHARMACYAND NUMBER OF PRESCRIBERS

# of Drugs Prescribed

# of

Pre

scrib

ers

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RELATION BETWEEN POLYPHARMACYAND COMPLIANCE

# of Drugs Prescribed

% C

ompl

ianc

e

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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


• Pharmacodynamic & pharmacokinetic changes with aging



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AVOID THE PRESCRIBING CASCADE

Drug 1

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


Drug 1

Adverse effect misinterpreted as new medical condition

BMJ. 1997;315:1096-1099.Slide 42


Drug 1

Adverse effect misinterpreted as new medical condition

BMJ. 1997;315:1096-1099.

Drug 2

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• 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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• 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

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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 massB. Increased gastric pHC. Decreased

glomerular filtration rate

D. Increased total body water

:10

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 illnessC. HospitalizationD. Increasing numbers

of medications

:10

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 dosingD. Drug side effectsE. Expensive

medications

:10

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

:10

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

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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 2

0%0%

1. True2. False

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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 2

0%0%

1. True2. False

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Older adults uniformly exhibit exaggerated pharmacodynamic responses compared

with younger adults.

1 2

0%0%

1. True2. False

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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

:10

Mark H. Beers, MD

19542009

DM Fick et al. Arch Intern Med.

2003;163:2716-2724.

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THE AMERICAN GERIATRICS SOCIETY Geriatrics Health Professionals.

Documents

prescription drug use

adverse drug reactions

aging drug knowledge

otc drug use

adrs slide

receptor slide

predictable slide

site of action slide