1. Patterns of Prescription Drug Use among Older Adults Arlene S. Bierman, MD, MS Ontario Women’s Health Council Chair in Women’s Health Centre for Research in Inner City Health St. Michael’s Hospital June 15, 2005

2. Patterns of Prescription Drug Use among Older Adults Prescription Drug Use in the Elderly Prescription Drug Use in the Elderly – Pharmacoepidemiology Medication-Related Problems and Adverse Events Medication-Related Problems and Adverse Events – Why the elderly are especially at risk Suboptimal Prescribing Suboptimal Prescribing – Scope of the Problem Inappropriate Prescribing Inappropriate Prescribing – Drugs to Avoid Summary and Questions Summary and Questions

3. Prescription Drug Use in the Elderly: Pharmacoepidemiology

4. Drug Use in the Elderly Benefits Major advances in pharmacotherapeutics. Major advances in pharmacotherapeutics. Effective and appropriate use of medications can Effective and appropriate use of medications can – reduce the risk of premature mortality,functional decline, and disability. – improve quality of life.

5. Drug Use in the Elderly-Benefits Examples Antihypertensives Antihypertensives – Reduce risk of heart failure and stroke ß-blockers and aspirin ß-blockers and aspirin – Reduce risk of mortality and recurrent heart attack after a myocardial infarction Angiotensin Converting Enzyme (ACE) Inhibitors Angiotensin Converting Enzyme (ACE) Inhibitors – Reduce mortality and risk of hospitalization in heart failure Biphosphonates Biphosphonates – Reduce risk of hip and vertebral fractures in osteoporosis

6. Prescription Drug Use Persons age 65 and older 15% US population but use 33% of all prescription drugs. Persons age 65 and older 15% US population but use 33% of all prescription drugs. Community-dwelling elders take an average of 3-4 prescriptions concurrently. Community-dwelling elders take an average of 3-4 prescriptions concurrently. Nursing home residents commonly receive an average of 6 concurrent medications and 20% receive 10 or more. Nursing home residents commonly receive an average of 6 concurrent medications and 20% receive 10 or more.

7. Use of Medications During the Preceding Week Use, % Kaufman, JAMA 2002

8. Use of Prescription Drugs During the Preceding Week Use, % Kaufman, JAMA 2002

9. Vitamins/Minerals & Herbals/Supplements Use: 1-Week Prevalence* ≥ 65 years old Men(n=243)Women(n=351)Total(N=2590) Any vitamin/mineral use 47%59%40% Any herbal/supplement use 11%14%14% Type * Percentages weighted according to household size Kaufman, JAMA 2002

10. Drug Use in Community Dwelling Elderly* *1996: N=27,285,988 Moxey, Health Care Financing Review 2003 Percentage (%)

11. Prescription Drug Use: Harms Medications have the potential for harm as well as benefit and adverse drug events (ADE) are common. Medications have the potential for harm as well as benefit and 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 experienced an ADE, 29% required health care services. Annually 35% of community-dwelling elders experienced an ADE, 29% required health care services. Adverse drug events responsible for 5-28% of acute hospitalizations among geriatric patients. Adverse drug events responsible for 5-28% of acute hospitalizations among geriatric patients. In nursing home residents, 51% of ADEs were found to be preventable. In nursing home residents, 51% of ADEs were found to be preventable.

12. Medication-Related Problems Why the elderly are at risk

13. Patient-level factors Patient-level factors – Age-associated changes in pharmacokinetics – Age-associated changes in pharmacodynamics – Comorbidity: drug-disease interactions – Polypharmacy: drug-drug interactions – Less physiologic reserve – Frailty System level factors System level factors – Fragmentation of care (Poly-doctoring) – Inadequate training in principles of geriatric practice

14. Changes in Pharmacokinetics Age-associated changes in physiology and organ function result in changes in pharmacokinetics Age-associated changes in physiology and organ function result in changes in pharmacokinetics Pharmacokinetics is the time course of a drug and its metabolites through the body Pharmacokinetics is the time course of a drug and its metabolites through the body – Absorption – Distribution – Clearance: elimination (renal), metabolism (liver) 2004: Cusack, Amer. J of Geriatric Pharmacotherapy

15. Volume of Distribution (Vd) Volume of Distribution (Vd) Vd is the extent of distribution in the plasma relative to the amount in the body. Vd is the extent of distribution in the plasma relative to the amount in the body. The elderly have an increased proportion body fat and decreased muscle mass that changes the Vd The elderly have an increased proportion body fat and decreased muscle mass that changes the Vd Increased volume of distribution for fat soluble drugs increases longer half life-e.g., diazepam Increased volume of distribution for fat soluble drugs increases longer half life-e.g., diazepam Decreased volume of distribution for water soluble drugs increases drug plasma concentration-e.g., ethanol Decreased volume of distribution for water soluble drugs increases drug plasma concentration-e.g., ethanol

16. Protein Binding Decreased albumin associated with chronic disease: e.g.,malnutrition, liver or kidney conditions. Decreased albumin associated with chronic disease: e.g.,malnutrition, liver or kidney conditions. Drugs that bind to plasma proteins will have increased bioavailability due to a higher proportion of unbound (active) agent. Drugs that bind to plasma proteins will have increased bioavailability due to a higher proportion of unbound (active) agent. Drugs that bind to albumin include ceftriaxone,diazepam, phenytoin, warfarin. Drugs that bind to albumin include ceftriaxone,diazepam, phenytoin, warfarin.

17. Elimination: Heterogeneity of Physiology and Organ Function Decreased renal function results in decreased elimination of drugs excreted by the kidney. Decreased renal function results in decreased elimination of drugs excreted by the kidney. Even in the absence of kidney disease renal clearance may be reduced 35-50%. Even in the absence of kidney disease renal clearance may be reduced 35-50%. Reduced renal clearance of active metabolites may enhance therapeutic effect or increase risk of toxicity. Reduced renal clearance of active metabolites may 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 healthy elderly had no decline in renal function, and small number actually improved-risk of subtherapeutic dosing However, Baltimore Longitudinal Study of Aging 1/3 of healthy elderly had no decline in renal function, and small number actually improved-risk of subtherapeutic dosing

18. Hepatic 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 40-45% compared to a 25 year old. Regional blood flow to the liver at age 65 is reduce by 40-45% compared to a 25 year old. Metabolic clearance of drugs by the liver may be reduced. Metabolic clearance of drugs by the liver may be reduced. Disease effects: liver congestion from heart failure decreases warfarin metabolism and an increased pharmacologic response. Disease effects: liver congestion from heart failure decreases warfarin metabolism and an increased pharmacologic response. Environmental effects: smoking stimulates monoxygenase enzymes and increases clearance of theophylline. Environmental effects: smoking stimulates monoxygenase enzymes and increases clearance of theophylline.

19. Changes in Pharmacodynamics Age-associated changes in pharmacodynamics (the time course and intensity of pharmacolgic effect) place elderly at increased risk for adverse drug events. Age-associated changes in pharmacodynamics (the time course and intensity of pharmacolgic effect) place elderly at increased risk for adverse drug events. Older patients may have more sedation and impaired function after a single dose of benzodiazepines than younger persons. Older patients may have more sedation and impaired function after a single dose of benzodiazepines than younger persons. After single dose of nitrazepam older patients made more mistakes on psychomotor testing compared to placebo while younger patients had no impairment. After single dose of nitrazepam older patients made more mistakes on psychomotor testing compared to placebo while younger patients had no impairment.

20. Suboptimal Prescribing in the Elderly

21. Suboptimal Prescribing Polypharmacy Polypharmacy Underuse of Effective Medications Underuse of Effective Medications Drug-Drug Interactions Drug-Drug Interactions Drug-Disease Interactions Drug-Disease Interactions Inadequate Monitoring Inadequate Monitoring Inappropriate Dosing Inappropriate Dosing Inappropriate Duration Inappropriate Duration Drugs to Avoid Drugs to Avoid

22. Suboptimal Quality Typology of Quality Problems Typology of Quality Problems – Overuse (Polypharmacy) – Underuse – Misuse (Inappropriate Prescribing) – Errors

23. The Prescribing Cascade 1997: Rochon, BMJ

24. Drug-Drug Interactions Drug-Drug Interaction (DDI) is the pharmacologic or clinical response to a drug combination that differs from the effect of the two agents when given alone. Drug-Drug Interaction (DDI) is the pharmacologic or clinical response to a drug combination that differs from the effect of the two agents when given alone. DDIs increase with the number of drugs used and are associated with an increased risk of adverse drug events. DDIs increase with the number of drugs used and are associated with an increased risk of adverse drug events. Most common effects neuropsychologic (confusion) or cognitive impairment, hypotension, renal failure. Most common effects neuropsychologic (confusion) or cognitive impairment, hypotension, renal failure. Metabolism through the hepatic cytochrome P 450 system is an important cause of DDIs. Metabolism through the hepatic cytochrome P 450 system is an important cause of DDIs.

25. Polypharmacy Polypharmacy is the administration of more medications than are clinically indicated. Polypharmacy is the administration of more medications than are clinically indicated. Lipton found 59%of elderly outpatients taking drugs that had no indication or were less than optimal. Lipton found 59%of elderly outpatients taking drugs that had no indication or were less than optimal. Schmader found 55% of outpatients to be taking drugs with no indication, 32.7% were taking ineffective drugs, and 16.8% were taking drugs with therapeutic duplication. Schmader found 55% of outpatients to be taking drugs with no indication, 32.7% were taking ineffective drugs, and 16.8% were taking drugs with therapeutic duplication. 2001: Hanlon, JAGS

26. Underuse Among patients elderly patients with cardiovascular disease and diabetes, only 19.1% of patients were prescribed statins. In patients 66 to 74 years old, the adjusted probabilities of statin prescription were 37.7%, 26.7%, and 23.4% in the categories of low, intermediate, and high baseline risk, respectively. Among patients elderly patients with cardiovascular disease and diabetes, only 19.1% of patients were prescribed statins. In patients 66 to 74 years old, the adjusted probabilities of statin prescription were 37.7%, 26.7%, and 23.4% in the categories of low, intermediate, and high baseline risk, respectively. The likelihood of statin prescription was 6.4% lower (adjusted 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 mortality risk. The likelihood of statin prescription was 6.4% lower (adjusted 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 mortality risk. 2004: Ko, JAMA

27. Inappropriate Prescribing in the Elderly

28. Inappropriate Prescribing in the Elderly Inappropriate prescribing is a major patient safety concern in the aged population. Inappropriate prescribing is a major patient safety concern in the aged population. Studies consistently find that 20-27% of older Americans receive drugs identified as inappropriate. Studies consistently find that 20-27% of older Americans receive drugs identified as inappropriate. Inappropriate prescribing increases risk for falls, hip fractures, cognitive impairment, diminished independence, and death. Inappropriate prescribing increases risk for falls, hip fractures, cognitive impairment, diminished independence, and death.

29. Anticholinergics Many potentially inappropriate drugs have anticholinergic properties. Many potentially inappropriate drugs have anticholinergic properties. Acetylcholine neurotransmitter with key role in both sympathetic and parasympathetic nervous systems. Acetylcholine neurotransmitter with key role in both sympathetic and parasympathetic nervous systems. Side effects include dry mouth, constipation, urinary retention, blurred vision, confusion. Side effects include dry mouth, constipation, urinary retention, blurred vision, confusion.

30. Summary: Drugs in the Elderly A Double-Edged Sword

31. Questions How do age-related changes in physiology mediate the health effects effect of environmental exposures in the elderly? How do age-related changes in physiology mediate the health effects effect of environmental exposures in the elderly? What do we need to know about potential interactions between environmental exposures and medications and/or specific diseases? What do we need to know about potential interactions between environmental exposures and medications and/or specific diseases? Which elders are at higher risk and how can these risks be mitigated? Which elders are at higher risk and how can these risks be mitigated?