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POLYPHARMACY Wendolyn Gozansky , MD, MPH Associate Professor Division of Geriatric Medicine University of Colorado Denver. AGS. THE AMERICAN GERIATRICS SOCIETY Geriatrics Health Professionals. Leading change. Improving care for older adults. CONTENTS. Drugs and the elderly
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POLYPHARMACYWendolynGozansky, MD, MPHAssociate ProfessorDivision of Geriatric MedicineUniversity of Colorado Denver AGS THE AMERICAN GERIATRICS SOCIETY Geriatrics Health Professionals. Leading change. Improving care for older adults.
CONTENTS • Drugs and the elderly • Pharmacodynamic and pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing
12% of the population is aged 65+ Drug Use in the Elderly
12% of the population is aged 65+ 30% of all prescription drug use is among those aged 65+ Drug Use in the Elderly
12% 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+ Drug Use in the Elderly
ADVERSE DRUG REACTIONS (ADRs) • 106,000 deaths in 1994
ADVERSE DRUG REACTIONS (ADRs) • 106,000 deaths in 1994 • $177 billion in 2000
ADVERSE DRUG REACTIONS (ADRs) • 106,000 deaths in 1994 • $177 billion in 2000 • For every $1 spent on drugs, $1 spent on ADRs
ADVERSE DRUG REACTIONS (ADRs) • 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
ADVERSE DRUG REACTIONS (ADRs) • 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
Exponential Relation Between Polypharmacy and ADRs Nolan L. JAGS. 1988;36(2):142-149.
CONTENTS • Drugs and the elderly • Pharmacodynamic and pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing
Pharmacodynamics Response that occurs when a drug interacts at its receptor
Pharmacodynamic Changeswith Aging Increased response (eg, opiates)
Pharmacodynamic Changeswith Aging Increased response (eg, opiates) Decreased response (eg, beta-agonists)
Pharmacokinetics Drug concentration at the site of action
Pharmacokinetics • Drug concentration at the site of action • 4 determinants: • Absorption • Distribution • Metabolism • Elimination
PK Changes with Aging: ABSORPTION gastric pH gastric emptying splanchnic blood flow intestinal motility Minimal clinical importance
PK Changes with Aging: DISTRIBUTION fat mass muscle mass total body water albumin (binds acidic drugs) alpha-1 glycoprotein (binds basic drugs) Clinically important
20-year-old woman Rosenberg, I. J Nutr. 1997. 127(5):990-991S. Published with permission.
64-year-old woman 20-year-old woman Rosenberg, I. J Nutr. 1997. 127(5):990-991S. Published with permission.
64-year-old woman 20-year-old woman Rosenberg, I. J Nutr. 1997. 127(5):990-991S. Published with permission.
64-year-old woman 20-year-old woman Rosenberg, I. J Nutr. 1997. 127(5):990-991S. Published with permission.
PK Changes with Aging:METABOLISM 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:ELIMINATION 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
Pharmacokinetic Changeswith Aging What is the best formula for estimating GFR in older adults? • Cockcroft-Gault (CG) • Modification of Diet in Renal Disease (MDRD)
Biology of the Patient • Limited functional reserve
Biology of the Patient Disease Compensatory severitymechanisms Symptomatic Asymptomatic Resnick N.M, Marcantonio E.R. The Lancet. 1992;350(9085):1157-1158. Published with permission.
Biology of the Patient • Limited functional reserve • Drug-disease interactions
CONTENTS • Drugs and the elderly • Pharmacodynamic & pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing
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?
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!!!
Altered Compliance • Under-utilization • Over-utilization • Enforced compliance
Methods to Improve Compliance • # of drugs, prescribers, and pharmacies • Once-daily or twice-daily dosing • Pill boxes • Medication reminder charts • frequency of clinic visits
CONTENTS • Drugs and the elderly • Pharmacodynamic & pharmacokinetic changes with aging • Drug knowledge and compliance • Prudent prescribing
Avoid the Prescribing Cascade Drug 1 BMJ. 1997;315:1096-1099.
Avoid the Prescribing Cascade Drug 1 Adverse effect misinterpreted as new medical condition Rochon, P. BMJ. 1997;315:1096-1099. Published with permission.
Avoid the Prescribing Cascade Drug 1 Adverse effect misinterpreted as new medical condition Drug 2 Rochon, P. BMJ. 1997;315:1096-1099. Published with permission.
Avoid the Prescribing Cascade • HCTZ – Allopurinol • NSAIDs – Antihypertensives • Metoclopramide – Carbidopa/levodopa • Cholinesterase inhibitors – Tolterodine
Beware of Drug-Drug Interactions (DDIs) • 100% chance of DDIs with 8 drugs
Beware of Drug-Drug Interactions (DDIs) • 100% chance of DDIs with 8 drugs • Nearly 50% of community-dwelling geriatric patients had at least one DDI
Beware of Drug-Drug Interactions (DDIs) • 100% chance of DDIs with 8 drugs • Nearly 50% of community-dwelling geriatric patients had at least one DDI • DDIs can result in ADRs or suboptimal dosing
Prudent Prescribing Principles • Know your patients and their drug cabinets
Prudent Prescribing Principles • Know your patients and their drug cabinets • Educate yourself and your patients
Prudent Prescribing Principles • Know your patients and their drug cabinets • Educate yourself and your patients • Understand biases in clinical trials