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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

JAGS. 1988;36:142-149.


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

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


64-year-old woman

20-year-old woman

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


64-year-old woman

20-year-old woman

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


64-year-old woman

20-year-old woman

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


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)


CG vERSUS MDRD


CG VERSUS MDRD


Biology of the Patient

  • Limited functional reserve


Biology of the Patient

Disease Compensatory severitymechanisms

SymptomaticAsymptomatic

Lancet. 1997;350:1157-1158.


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


Relation Between Polypharmacyand Number of Prescribers


Relation Between Polypharmacyand 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

BMJ. 1997;315:1096-1099.


Avoid the Prescribing Cascade

Drug 1

Adverse effect misinterpreted as new medical condition

Drug 2

BMJ. 1997;315:1096-1099.


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


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 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 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 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


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?

  • All prescriptions written by one provider

  • Comorbid illness

  • Hospitalization

  • Increasing numbers of medications

:10


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?

  • 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


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


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


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.

  • True

  • False

:10


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


Mark H. Beers, MD

19542009

DM Fick et al. Arch Intern Med.

2003;163:2716-2724.


Thank you for your time!

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