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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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slide1

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
CONTENTS
  • Drugs and the elderly
  • Pharmacodynamic and pharmacokinetic changes with aging
  • Drug knowledge and compliance
  • Prudent prescribing
drug use in the elderly1

12% of the population is aged 65+

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

Drug Use in the Elderly
drug use in the elderly2

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 adr s
ADVERSE DRUG REACTIONS (ADRs)
  • 106,000 deaths in 1994
adverse drug reactions adr s1
ADVERSE DRUG REACTIONS (ADRs)
  • 106,000 deaths in 1994
  • $177 billion in 2000
adverse drug reactions adr s2
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 adr s3
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 adr s4
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
contents1
CONTENTS
  • Drugs and the elderly
  • Pharmacodynamic and pharmacokinetic changes with aging
  • Drug knowledge and compliance
  • Prudent prescribing
pharmacodynamics
Pharmacodynamics

Response that occurs when a drug interacts at its receptor

pharmacodynamic changes with aging
Pharmacodynamic Changeswith Aging

Increased response

(eg, opiates)

pharmacodynamic changes with aging1
Pharmacodynamic Changeswith Aging

Increased response

(eg, opiates)

Decreased response

(eg, beta-agonists)

pharmacokinetics
Pharmacokinetics

Drug concentration at the site of action

pharmacokinetics1
Pharmacokinetics
  • Drug concentration at the site of action
  • 4 determinants:
    • Absorption
    • Distribution
    • Metabolism
    • Elimination
pk changes with aging absorption
PK Changes with Aging: ABSORPTION

 gastric pH

 gastric emptying

 splanchnic blood flow

 intestinal motility

Minimal clinical importance

pk changes with aging distribution
PK Changes with Aging: DISTRIBUTION

 fat mass

 muscle mass

 total body water

 albumin (binds acidic drugs)

 alpha-1 glycoprotein (binds basic drugs)

Clinically important

slide20

20-year-old woman

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

slide21

64-year-old woman

20-year-old woman

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

slide22

64-year-old woman

20-year-old woman

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

slide23

64-year-old woman

20-year-old woman

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

pk changes with aging metabolism
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
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 changes with aging
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
Biology of the Patient
  • Limited functional reserve
biology of the patient1
Biology of the Patient

Disease Compensatory severitymechanisms

Symptomatic Asymptomatic

Lancet. 1997;350:1157-1158.

biology of the patient2
Biology of the Patient
  • Limited functional reserve
  • Drug-disease interactions
contents2
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
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 cabinet1
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
Altered Compliance
  • Under-utilization
  • Over-utilization
  • Enforced compliance
methods to improve 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
contents3
CONTENTS
  • Drugs and the elderly
  • Pharmacodynamic & pharmacokinetic changes with aging
  • Drug knowledge and compliance
  • Prudent prescribing
avoid the prescribing cascade
Avoid the Prescribing Cascade

Drug 1

BMJ. 1997;315:1096-1099.

avoid the prescribing cascade1
Avoid the Prescribing Cascade

Drug 1

Adverse effect misinterpreted as new medical condition

BMJ. 1997;315:1096-1099.

avoid the prescribing cascade2
Avoid the Prescribing Cascade

Drug 1

Adverse effect misinterpreted as new medical condition

Drug 2

BMJ. 1997;315:1096-1099.

avoid the prescribing cascade3
Avoid the Prescribing Cascade
  • HCTZ – Allopurinol
  • NSAIDs – Antihypertensives
  • Metoclopramide – Carbidopa/levodopa
  • Cholinesterase inhibitors – Tolterodine
beware of drug drug interactions ddi s
Beware of Drug-Drug Interactions (DDIs)
  • 100% chance of DDIs with 8 drugs
beware of drug drug interactions ddi s1
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 ddi s2
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
Prudent Prescribing Principles
  • Know your patients and their drug cabinets
prudent prescribing principles1
Prudent Prescribing Principles
  • Know your patients and their drug cabinets
  • Educate yourself and your patients
prudent prescribing principles2
Prudent Prescribing Principles
  • Know your patients and their drug cabinets
  • Educate yourself and your patients
  • Understand biases in clinical trials
prudent prescribing principles3
Prudent Prescribing Principles
  • Know your patients and their drug cabinets
  • Educate yourself and your patients
  • Understand biases in clinical trials
  • Ask about compliance
prudent prescribing principles4
Prudent Prescribing Principles
  • 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
prudent prescribing principles5
Prudent Prescribing Principles
  • 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
  • Try non-pharmacologic strategies
prudent prescribing principles6
Prudent Prescribing Principles
  • 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
  • Try non-pharmacologic strategies
  • Offer drug therapy when indicated
slide55
Which of the following is an age-related change that causes clinically significant alterations in drug pharmacokinetics?
  • Decreased fat mass
  • Increased gastric pH
  • Decreased glomerular filtration rate
  • Increased total body water

:10

which of the following does not contribute to adverse drug reactions adrs in the elderly
Which of the following does not contribute to adverse drug reactions (ADRs) in the elderly?
  • All prescriptions written by one provider
  • Comorbid illness
  • Hospitalization
  • Increasing numbers of medications

:10

which of the following is associated with improved medication compliance
Which of the following is associated with improved medication compliance?
  • Increasing numbers of medications
  • Clinic visit in the previous 48 hours
  • TID dosing
  • Drug side effects
  • Expensive medications

:10

which of the following is a principle of prudent prescribing
Which of the following is a principle of prudent prescribing?
  • Only inquire about prescribed medications
  • Ask the patient, “What could possibly be so hard about taking pills every day?”
  • Do not begin treatment without a diagnosis
  • Use drugs before a trial of non-pharmacologic therapy

:10

slide59
Which of the following effects of aging contributes to an increased risk of ADRs related to benzodiazepine use?
  • Increased body fat mass causing a greater volume of distribution and decreasing drug half-life
  • Increased hepatic volume resulting in increased production of active metabolites
  • Decreased renal function causing delayed renal excretion

:10

slide60

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.

  • True
  • False

:10

slide61
A patient with a serum creatinine of 0.5 mg/dL (within the normal range) will also have a normal creatinine clearance
  • True
  • False

:10

older adults uniformly exhibit exaggerated pharmacodynamic responses compared with younger adults
Older adults uniformly exhibit exaggerated pharmacodynamic responses compared with younger adults.
  • True
  • False

:10

slide63
Which of the following drugs is/are listed as “high-severity” potentially inappropriate medications for patients aged 65+?
  • Amiodarone (Cordarone)
  • Amitriptyline (Elavil)
  • Cyclobenzaprine (Flexeril)
  • Diazepam (Valium)
  • Diphenhydramine (Benadryl)
  • Indomethacin (Indocin)
  • Ketorolac (Toradol)
  • Nitrofurantoin (Macrodantin)
  • All of the above

:10

slide64

Mark H. Beers, MD

19542009

DM Fick et al. Arch Intern Med.

2003;163:2716-2724.

thank you for your time
Thank you for your time!

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www.americangeriatrics.org

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