Patterns of Prescription Drug Use Patterns of Prescription Drug Use among Older Adultsamong Older Adults

Arlene S. Bierman, MD, MSArlene S. Bierman, MD, MSOntario Women’s Health Council Chair in Women’s HealthOntario Women’s Health Council Chair in Women’s Health

Centre for Research in Inner City HealthCentre for Research in Inner City HealthSt. Michael’s HospitalSt. Michael’s Hospital

June 15, 2005June 15, 2005

Patterns of Prescription Drug Use Patterns of Prescription Drug Use among Older Adultsamong Older Adults

Prescription Drug Use in the ElderlyPrescription Drug Use in the Elderly– PharmacoepidemiologyPharmacoepidemiology

Medication-Related Problems and Adverse EventsMedication-Related Problems and Adverse Events– Why the elderly are especially at risk Why the elderly are especially at risk

Suboptimal PrescribingSuboptimal Prescribing– Scope of the ProblemScope of the Problem

Inappropriate PrescribingInappropriate Prescribing– Drugs to AvoidDrugs to Avoid

Summary and QuestionsSummary and Questions

Prescription Drug Use Prescription Drug Use

in the Elderly:in the Elderly:

PharmacoepidemiologyPharmacoepidemiology

Drug Use in the ElderlyDrug Use in the ElderlyBenefitsBenefits

Major advances in pharmacotherapeutics.Major advances in pharmacotherapeutics. Effective and appropriate use of medications Effective and appropriate use of medications

can can – reduce the risk of premature mortality,functional reduce the risk of premature mortality,functional

decline, and disability.decline, and disability.– improve quality of life. improve quality of life.

Drug Use in the Elderly-BenefitsDrug Use in the Elderly-BenefitsExamplesExamples

AntihypertensivesAntihypertensives– Reduce risk of heart failure and strokeReduce risk of heart failure and stroke

ß-blockers and aspirinß-blockers and aspirin– Reduce risk of mortality and recurrent heart attack Reduce risk of mortality and recurrent heart attack

after a myocardial infarctionafter a myocardial infarction Angiotensin Converting Enzyme (ACE) InhibitorsAngiotensin Converting Enzyme (ACE) Inhibitors

– Reduce mortality and risk of hospitalization in heart failureReduce mortality and risk of hospitalization in heart failure BiphosphonatesBiphosphonates

– Reduce risk of hip and vertebral fractures in osteoporosisReduce risk of hip and vertebral fractures in osteoporosis

Prescription Drug UsePrescription Drug Use

Persons age 65 and older 15% US population Persons age 65 and older 15% US population but use 33% of all prescription drugs.but use 33% of all prescription drugs.

Community-dwelling elders take an average of Community-dwelling elders take an average of 3-4 prescriptions concurrently.3-4 prescriptions concurrently.

Nursing home residents commonly receive an Nursing home residents commonly receive an average of 6 concurrent medications and 20% average of 6 concurrent medications and 20% receive 10 or more.receive 10 or more.

Use of Medications During the Preceding WeekUse of Medications During the Preceding Week

81

25

5

91

44

12

94

57

12

0

10

20

30

40

50

60

70

80

90

100

Total Men (≥ 65 yrs old) Women (≥ 65 yrs old)

Any Use

≥ 5 Drugs

≥ 10 DrugsUse

, %U

se, %

Kaufman, JAMA 2002Kaufman, JAMA 2002

Use of Prescription Drugs During the Preceding WeekUse of Prescription Drugs During the Preceding Week

50

7

71

19

81

23

0

10

20

30

40

50

60

70

80

90

100

Total Men (≥ 65 yrs old) Women (≥ 65 yrs old)

Any Use

≥5 DrugsUse

, %

Use

, %

Kaufman, JAMA 2002Kaufman, JAMA 2002

Vitamins/Minerals & Herbals/Supplements Use: Vitamins/Minerals & Herbals/Supplements Use: 1-Week Prevalence*1-Week Prevalence*

≥ ≥ 65 years old65 years old

MenMen(n=243)(n=243)

WomenWomen(n=351)(n=351)

Total Total

(N=2590)(N=2590)

Any Any vitamin/mineral vitamin/mineral useuse

47%47% 59%59% 40%40%

Any Any herbal/supplement herbal/supplement useuse

11%11% 14%14% 14%14%

TypeType

* Percentages weighted according to household size* Percentages weighted according to household size

Kaufman, JAMA 2002Kaufman, JAMA 2002

Drug Use in Community Dwelling Elderly*Drug Use in Community Dwelling Elderly*

13.1

18

18

8.6

9.4

9.9

23.9

28.3

33.9

58.8

0 10 20 30 40 50 60

Diabetic Agents

Anti-hyperlipidemic Agents

Coagulation Modifiers

Central Nervous System Agents

Respiratory Agents

Psychotherapeutic Agents

Hormones

Analgesics

Anti-infective Agents

Cardiovascular Agents

*1996: N=27,285,988*1996: N=27,285,988Moxey, Health Care Financing Review 2003Moxey, Health Care Financing Review 2003

Percentage (%)Percentage (%)

Prescription Drug Use: HarmsPrescription Drug Use: Harms

Medications have the potential for harm as well as Medications have the potential for harm as well as benefit andbenefit and adverse drug events (ADE) are common. adverse drug events (ADE) are common.

An ADE is an injury from a medication.An ADE is an injury from a medication. Annually 35% of community-dwelling elders Annually 35% of community-dwelling elders

experienced an ADE, 29% required health care experienced an ADE, 29% required health care services.services.

Adverse drug events responsible for 5-28% of acute Adverse drug events responsible for 5-28% of acute hospitalizations among geriatric patients.hospitalizations among geriatric patients.

In nursing home residents, 51% of ADEs were found In nursing home residents, 51% of ADEs were found to be preventable.to be preventable.

Medication-Related ProblemsMedication-Related ProblemsWhy the elderly are at riskWhy the elderly are at risk

Why the elderly are at riskWhy the elderly are at risk

Patient-level factorsPatient-level factors– Age-associated changes in pharmacokineticsAge-associated changes in pharmacokinetics– Age-associated changes in pharmacodynamicsAge-associated changes in pharmacodynamics– Comorbidity: drug-disease interactionsComorbidity: drug-disease interactions– Polypharmacy: drug-drug interactionsPolypharmacy: drug-drug interactions– Less physiologic reserveLess physiologic reserve– FrailtyFrailty

System level factorsSystem level factors– Fragmentation of care (Poly-doctoring)Fragmentation of care (Poly-doctoring)– Inadequate training in principles of geriatric practiceInadequate training in principles of geriatric practice

Changes in PharmacokineticsChanges in Pharmacokinetics

Age-associated changes in physiology and Age-associated changes in physiology and organ function result in changes in organ function result in changes in pharmacokineticspharmacokinetics

Pharmacokinetics is the time course of a drug Pharmacokinetics is the time course of a drug and its metabolites through the body and its metabolites through the body

– AbsorptionAbsorption

– Distribution Distribution

– Clearance: elimination (renal), metabolism (liver) Clearance: elimination (renal), metabolism (liver) 2004: Cusack, Amer. J of Geriatric Pharmacotherapy 2004: Cusack, Amer. J of Geriatric Pharmacotherapy

Volume of Distribution (Vd)Volume of Distribution (Vd)

Vd is the extent of distribution in the plasma relative to Vd is the extent of distribution in the plasma relative to the amount in the body.the amount in the body.

The elderly have an increased proportion body fat and The elderly have an increased proportion body fat and decreased muscle mass that changes the Vddecreased muscle mass that changes the Vd

Increased volume of distribution for fat soluble drugs Increased volume of distribution for fat soluble drugs increases longer half life-e.g., diazepamincreases longer half life-e.g., diazepam

Decreased volume of distribution for water soluble Decreased volume of distribution for water soluble drugs increases drug plasma concentration-e.g., drugs increases drug plasma concentration-e.g., ethanolethanol

Protein BindingProtein Binding

Decreased albumin associated with chronic Decreased albumin associated with chronic disease: e.g.,malnutrition, liver or kidney disease: e.g.,malnutrition, liver or kidney conditions.conditions.

Drugs that bind to plasma proteins will have Drugs that bind to plasma proteins will have increased bioavailability due to a higher increased bioavailability due to a higher proportion of unbound (active) agent.proportion of unbound (active) agent.

Drugs that bind to albumin include Drugs that bind to albumin include ceftriaxone,diazepam, phenytoin, warfarin.ceftriaxone,diazepam, phenytoin, warfarin.

Elimination: Heterogeneity of Elimination: Heterogeneity of Physiology and Organ FunctionPhysiology and Organ Function

Decreased renal function results in decreased Decreased renal function results in decreased elimination of drugs excreted by the kidney.elimination of drugs excreted by the kidney.

Even in the absence of kidney disease renal Even in the absence of kidney disease renal clearance may be reduced 35-50%.clearance may be reduced 35-50%.

Reduced renal clearance of active metabolites may Reduced renal clearance of active metabolites may enhance therapeutic effect or increase risk of toxicity.enhance therapeutic effect or increase risk of toxicity.

Need to reduce dose and/or increase dosing intervals.Need to reduce dose and/or increase dosing intervals. However, Baltimore Longitudinal Study of Aging 1/3 of However, Baltimore Longitudinal Study of Aging 1/3 of

healthy elderly had no decline in renal function, and healthy elderly had no decline in renal function, and small number actually improved-risk of subtherapeutic small number actually improved-risk of subtherapeutic dosingdosing

Hepatic MetabolismHepatic Metabolism

Decreased liver size and hepatic blood flow.Decreased liver size and hepatic blood flow. Regional blood flow to the liver at age 65 is reduce by Regional blood flow to the liver at age 65 is reduce by

40-45% compared to a 25 year old.40-45% compared to a 25 year old. Metabolic clearance of drugs by the liver may be Metabolic clearance of drugs by the liver may be

reduced.reduced. Disease effects: liver congestion from heart failure Disease effects: liver congestion from heart failure

decreases warfarin metabolism and an increased decreases warfarin metabolism and an increased pharmacologic response.pharmacologic response.

Environmental effects: smoking stimulates Environmental effects: smoking stimulates monoxygenase enzymes and increases clearance of monoxygenase enzymes and increases clearance of theophylline. theophylline.

Changes in PharmacodynamicsChanges in Pharmacodynamics

Age-associated changes in pharmacodynamics (the Age-associated changes in pharmacodynamics (the time course and intensity of pharmacolgic effect) place time course and intensity of pharmacolgic effect) place elderly at increased risk for adverse drug events.elderly at increased risk for adverse drug events.

Older patients may have more sedation and impaired Older patients may have more sedation and impaired function after a single dose of benzodiazepines than function after a single dose of benzodiazepines than younger persons. younger persons.

After single dose of nitrazepam older patients made After single dose of nitrazepam older patients made more mistakes on psychomotor testing compared to more mistakes on psychomotor testing compared to placebo while younger patients had no impairment .placebo while younger patients had no impairment .

Suboptimal Prescribing Suboptimal Prescribing

in the Elderlyin the Elderly

Suboptimal PrescribingSuboptimal Prescribing

PolypharmacyPolypharmacy Underuse of Effective MedicationsUnderuse of Effective Medications Drug-Drug InteractionsDrug-Drug Interactions Drug-Disease InteractionsDrug-Disease Interactions Inadequate MonitoringInadequate Monitoring Inappropriate DosingInappropriate Dosing Inappropriate DurationInappropriate Duration Drugs to AvoidDrugs to Avoid

Suboptimal Quality Suboptimal Quality

Typology of Quality ProblemsTypology of Quality Problems– Overuse (Polypharmacy)Overuse (Polypharmacy)– UnderuseUnderuse– Misuse (Inappropriate PrescribingMisuse (Inappropriate Prescribing ))– ErrorsErrors

The Prescribing CascadeThe Prescribing Cascade

1997: Rochon, BMJ1997: Rochon, BMJ

Drug-Drug Interactions Drug-Drug Interactions

Drug-Drug Interaction (DDI) is the pharmacologic or Drug-Drug Interaction (DDI) is the pharmacologic or clinical response to a drug combination that differs clinical response to a drug combination that differs from the effect of the two agents when given alone.from the effect of the two agents when given alone.

DDIs increase with the number of drugs used and are DDIs increase with the number of drugs used and are associated with an increased risk of adverse drug associated with an increased risk of adverse drug events.events.

Most common effects neuropsychologic (confusion) or Most common effects neuropsychologic (confusion) or cognitive impairment, hypotension, renal failure.cognitive impairment, hypotension, renal failure.

Metabolism through the hepatic cytochrome P 450 Metabolism through the hepatic cytochrome P 450 system is an important cause of DDIs.system is an important cause of DDIs.

PolypharmacyPolypharmacy

Polypharmacy is the administration of more Polypharmacy is the administration of more medications than are clinically indicated.medications than are clinically indicated.

Lipton found 59%of elderly outpatients taking drugs Lipton found 59%of elderly outpatients taking drugs that had no indication or were less than optimal.that had no indication or were less than optimal.

Schmader found 55% of outpatients to be taking Schmader found 55% of outpatients to be taking drugs with no indication, 32.7% were taking ineffective drugs with no indication, 32.7% were taking ineffective drugs, and 16.8% were taking drugs with therapeutic drugs, and 16.8% were taking drugs with therapeutic duplication.duplication.

2001: Hanlon, JAGS2001: Hanlon, JAGS

UnderuseUnderuse Among patients elderly patients with cardiovascular disease Among patients elderly patients with cardiovascular disease

and diabetes, only 19.1% of patients were prescribed statins. In and diabetes, only 19.1% of patients were prescribed statins. In patients 66 to 74 years old, the adjusted probabilities of statin patients 66 to 74 years old, the adjusted probabilities of statin prescription were 37.7%, 26.7%, and 23.4% in the categories prescription were 37.7%, 26.7%, and 23.4% in the categories of low, intermediate, and high baseline risk, respectively. of low, intermediate, and high baseline risk, respectively.

The likelihood of statin prescription was 6.4% lower (adjusted The likelihood of statin prescription was 6.4% lower (adjusted odds ratio, 0.94; 95% confidence interval, 0.93-0.95) for each odds ratio, 0.94; 95% confidence interval, 0.93-0.95) for each year of increase in age and each 1% increase in predicted 3-year of increase in age and each 1% increase in predicted 3-year mortality risk.year mortality risk.

2004: Ko, JAMA2004: Ko, JAMA

Inappropriate Prescribing Inappropriate Prescribing

in the Elderlyin the Elderly

Inappropriate Prescribing in the ElderlyInappropriate Prescribing in the Elderly

Inappropriate prescribing is a major patient Inappropriate prescribing is a major patient safety concern in the aged population.safety concern in the aged population.

Studies consistently find that 20-27% of older Studies consistently find that 20-27% of older Americans receive drugs identified as Americans receive drugs identified as inappropriate. inappropriate.

Inappropriate prescribing increases risk for Inappropriate prescribing increases risk for falls, hip fractures, cognitive impairment, falls, hip fractures, cognitive impairment, diminished independence, and death. diminished independence, and death.

AnticholinergicsAnticholinergics

Many potentially inappropriate drugs have Many potentially inappropriate drugs have anticholinergic properties.anticholinergic properties.

Acetylcholine neurotransmitter with key role in Acetylcholine neurotransmitter with key role in both sympathetic and parasympathetic nervous both sympathetic and parasympathetic nervous systems.systems.

Side effects include dry mouth, constipation, Side effects include dry mouth, constipation, urinary retention, blurred vision, confusion.urinary retention, blurred vision, confusion.

Summary: Drugs in the ElderlySummary: Drugs in the ElderlyA Double-Edged SwordA Double-Edged Sword

QuestionsQuestions

How do age-related changes in physiology How do age-related changes in physiology mediate the health effects effect of mediate the health effects effect of environmental exposures in the elderly? environmental exposures in the elderly?

What do we need to know about potential What do we need to know about potential interactions between environmental exposures interactions between environmental exposures and medications and/or specific diseases?and medications and/or specific diseases?

Which elders are at higher risk and how can Which elders are at higher risk and how can these risks be mitigated?these risks be mitigated?