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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 Patterns of Prescription Drug Use among Older Adults Prescription Drug Use in the Elderly – Pharmacoepidemiology Medication-Related Problems and Adverse Events – Why the elderly are especially at risk Suboptimal Prescribing – Scope of the Problem Inappropriate Prescribing – Drugs to Avoid Summary and Questions Prescription Drug Use in the Elderly: Pharmacoepidemiology Drug Use in the Elderly Benefits Major advances in pharmacotherapeutics. Effective and appropriate use of medications can – reduce the risk of premature mortality,functional decline, and disability. – improve quality of life. Drug Use in the Elderly-Benefits Examples Antihypertensives – Reduce risk of heart failure and stroke ß-blockers and aspirin – Reduce risk of mortality and recurrent heart attack after a myocardial infarction Angiotensin Converting Enzyme (ACE) Inhibitors – Reduce mortality and risk of hospitalization in heart failure Biphosphonates – Reduce risk of hip and vertebral fractures in osteoporosis Prescription Drug Use 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. Nursing home residents commonly receive an average of 6 concurrent medications and 20% receive 10 or more. Use of Medications During the Preceding Week 100 90 94 91 81 80 Use, % 70 57 60 Any Use ≥ 5 Drugs 44 50 ≥ 10 Drugs 40 30 25 20 12 12 5 10 0 Total Men (≥ 65 yrs old) Women (≥ 65 yrs old) Kaufman, JAMA 2002 Use of Prescription Drugs During the Preceding Week 100 90 81 71 80 Use, % 70 60 50 Any Use 50 ≥5 Drugs 40 30 19 20 23 7 10 0 Total Men (≥ 65 yrs old) Women (≥ 65 yrs old) Kaufman, JAMA 2002 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 Drug Use in Community Dwelling Elderly* 58.8 Cardiovascular Agents 33.9 Anti-infective Agents Analgesics 28.3 23.9 Hormones Psychotherapeutic Agents 18 Respiratory Agents 18 13.1 Central Nervous System Agents Coagulation Modifiers 9.9 Anti-hyperlipidemic Agents 9.4 Diabetic Agents 8.6 0 10 20 30 Percentage (%) 40 50 60 *1996: N=27,285,988 Moxey, Health Care Financing Review 2003 Prescription Drug Use: Harms 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. 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. In nursing home residents, 51% of ADEs were found to be preventable. Medication-Related Problems Why the elderly are at risk Why the elderly are at risk 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 – Fragmentation of care (Poly-doctoring) – Inadequate training in principles of geriatric practice 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 – Absorption – Distribution – Clearance: elimination (renal), metabolism (liver) 2004: Cusack, Amer. J of Geriatric Pharmacotherapy Volume of Distribution (Vd) 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 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 Protein Binding 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 albumin include ceftriaxone,diazepam, phenytoin, warfarin. Elimination: Heterogeneity of Physiology and Organ Function 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%. Reduced renal clearance of active metabolites may enhance therapeutic effect or increase risk of toxicity. 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 Hepatic Metabolism 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. 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. Environmental effects: smoking stimulates monoxygenase enzymes and increases clearance of theophylline. 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. 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 . Suboptimal Prescribing in the Elderly Suboptimal Prescribing Polypharmacy Underuse of Effective Medications Drug-Drug Interactions Drug-Disease Interactions Inadequate Monitoring Inappropriate Dosing Inappropriate Duration Drugs to Avoid Suboptimal Quality Typology of Quality Problems – Overuse (Polypharmacy) – Underuse – Misuse (Inappropriate Prescribing ) – Errors The Prescribing Cascade 1997: Rochon, BMJ 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. 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. Metabolism through the hepatic cytochrome P 450 system is an important cause of DDIs. Polypharmacy 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. 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 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. 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 3year mortality risk. 2004: Ko, JAMA Inappropriate Prescribing in the Elderly Inappropriate Prescribing in the Elderly 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. Inappropriate prescribing increases risk for falls, hip fractures, cognitive impairment, diminished independence, and death. Anticholinergics Many potentially inappropriate drugs have anticholinergic properties. Acetylcholine neurotransmitter with key role in both sympathetic and parasympathetic nervous systems. Side effects include dry mouth, constipation, urinary retention, blurred vision, confusion. Summary: Drugs in the Elderly A Double-Edged Sword Questions 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? Which elders are at higher risk and how can these risks be mitigated?