Prescribing in the Elderly - PowerPoint Presentation

Slide1

Prescribing in the Elderly

Karen Birmingham, PharmD, BCPS

Specialty Clinical Pharmacy Services

Group HealthSlide2

“Quote”worthy Definitions

Aging

“Progressive accumulation

of random changes”“Time-related loss of functional units”“Better than the alternative”

Elderly“Age nearing or surpassing the average life span”“Age 65 years and older”“Always 15 years older than me”Slide3

A Global “Gray Tsunami”

By the year 2006:

almost 500 million people worldwide had reached or exceeded age 65

By the year 2030:Total world population estimated to reach over 9 billionElderly population in developing countries projected to increase 140%World population of people ≥ 65 years old expected to reach 1 billionBy the year 2050:

20% of all elderly patients will be ≥ 80 years oldSlide4

U.S. Elderly

Constitute 13% of the population

Consume 34% of all prescription medications

Use 40% of all over-the-counter drugsUp to 50% of elderly take multiple medicationsMedicare population analysis in 1999 (n=1.2 million)82% had at least one chronic condition24% had at least four chronic conditionsSlide5

Prescription Drug Use by Elderly

www.cdc.gov

%Slide6

Prescription $ Per Chronic Condition

www.cdc.gov

$Slide7

Drugs Most Used by Elderly Patients

Clinical Pharmacology and Therapeutics 2007Slide8

ADE, ADR and ME

Annals of Internal Medicine 2004Slide9

Adverse Drug Events

Occur in 20% of elderly patients

Account for 5-10% of hospitalizations

Nearly 20% ranked as severeFatal outcomes in 6% of casesRepeat hospitalizations in 30% of ADEsPrevalence of 5-37% in hospitalized patients

Interventions required in ~30% of patientsAffect ~ 350,000 long-term care patients annuallySlide10

Adverse Drug Events and Death

“If medication-related problems were ranked as a disease by cause of death,

it would be the 5

th leading cause of death in the United States.”Archives of Internal Medicine 2003Slide11

Risk Factors For Adverse Drug Events

Inappropriate prescribing

Polypharmacy

Misuse of OTC productsLack of appropriate drug monitoringComplicated dosing instructionsLanguage or educational barriersNonadherenceSlide12

How a Drug Does What It Does

The Pharmacologic Basis of Therapeutics, 11

th

ed.Slide13

Changes Due to Aging

Adapted from Journal of the American College of Cardiology 2010

↓

glomerular filtration rate

↓ renal circulation↓ renal clearance↓ hepatic circulation↓ hepatic mass↓ first-pass metabolism↓ activation of prodrug

↑ bioavailability

↑ gastric pH

↓ absorption surface

↓ GI mobility

Altered drug absorption

↑ body fat

↑ volume of distribution

of lipophilic drugs

↑ half-life

↑ time to steady-state

concentration

↓ lean body mass

↓ total body water

↓ volume of distribution

of water-soluble drugs

cognitive changes

↑ sensitivity to anticholinergics

Altered HPA axisSlide14

Cytochrome P450 Enzyme System

Fifty human CYP450 genes

Estimated 8-10 isoforms responsible for drug metabolism

Large range of activity in healthy humans (6-fold difference in rates)

Weight-adjusted CYP3A clearance more rapid in womenCurrently no predictive data for effects of age on CYP2CFaster clearance of CYP2D6 in men; decrease doses of drugs ~10-20% for women, decrease ~20% more in elderly womenRenal impairment may affect CYP P450 due to decreased gene expression

Adapted from

The Pharmacological Basis of Therapeutics 1996

CYP3A

CYP2E9

CYP1A2

CYP2C

CYP2D6Slide15

Drug Metabolism: Older vs. Younger

Adapted from Bressler and Bahl, Mayo Clinic Proceedings 2003Slide16

P-Glycoprotein and Drug Disposition

Efflux transporter

Found in hepatocytes, intestinal mucosal cells, and blood-brain barrier

Conflicting results from small studies:Animal studies suggest differences between male and female, not yet observed in humansOne study showed no significant difference in leukocyte P-glycoprotein in comparisons of young healthy adults vs. elderly healthy and frail adultsAnother study suggested decreased blood-brain barrier P-glycoprotein activity, possibly exposing brain to higher levels of drugsSlide17

Age Effects on Hemostasis

Coagulation Proteins

Fibrinolytic Proteins

Anticoagulant Proteins

↑ Factor V

↑ Factor VII

↑ Factor VIII

↑ Factor IX

↑ Factor XIII

↑ Fibrinogen

↑ kininogen

↑ prekallikrein

↑ D-dimer

↑ PAI-1

↓ plasmin

Antithrombin III

♂ ↓ ♀ ↓

Protein C

♂ ↔ ♀

↑

Protein S

♂ ↔ ♀

↑

TFPI

♂ ↓ ♀

↑

Adapted from Journal of the American College of Cardiology 2010Slide18

Pharmacodynamics in the Elderly

Drug Name

Drug Action

Drug Effect

diltiazem

antihypertensive

PR interval prolongation

furosemide

diuretic

scopolamine

cognitive function

morphine

analgesia

diazepam

sedation

verapamil

antihypertensive

warfarin

anticoagulant

Adapted from British Journal of Pharmacology 2004Slide19

Effect of Illness on Drug Actions

absorption

gastrointestinal pH

gastrointestinal motility

gastric contents

distribution

serum albumin

changes in binding sites

increased endogenous inhibitors

metabolism

renal impairment

hepatic impairment

drug interactions

excretion

renal impairment

gastrointestinal motility

receptor interaction

changes in number

changes in sensitivity

altered target site

Drug Response

1) Altered:

-metabolism

-cell environment

-concentrations

2) Tolerance

3) Resistance

4) Interactions

=Slide20

Congestive Heart Failure Effects

Parameter

Alteration

bioavailability

bowel edema

reduces

drug absorption of oral drugs

first pass metabolism altered by hepatic congestion

peripheral edema decreases

absorption

of topical/subcutaneous/intramuscular agents

distribution

unpredictable due to changes in total body water

and tissue perfusion

metabolism

reduced

liver perfusion alters drug metabolism

excretion

impaired renal function may inhibit drug elimination

pharmacodynamic

increased risk of radiocontrast nephropathy

increased sensitivity to antiarrhythmic medication

Adapted from Clinics in Chest Medicine 2003Slide21

High Risk Drugs Assessment Tools

Year

Country

Tool

1991

1997

2000

2007

2008

2008

2009

2010

USA

Canada

Canada

France

Ireland

Japan

Norway

Italy

Beers (updated in 1997 and 2003)

Canadian Criteria

IPET - Improving Prescribing in Elderly Tool

French Consensus Panel List

STOPP – Screening Tool of Older Persons’ Prescriptions

START – Screening Tool to Alert to Right Treatment

Japanese Beers Criteria

NORGEP – Norwegian General practice

Unnamed

Adapted from Annals of Pharmacotherapy 2010Slide22

Medication Appropriateness Index

Criterion

Standard Weight

Modified Weight

Drug-drug interactions?

2

2

Drug-disease interactions?

2

2

Is the drug indicated?

3

1

Is the drug effective?

3

1

Unnecessary drug duplication?

1

1

Appropriate therapy duration?

1

1

Correct dosage?

2

0

Correct directions?

2

0

Practical directions?

1

0

Cost effective compared with other drugs of equal efficacy?

1

0

Adapted from Annals of Pharmacotherapy 2010Slide23

Anticholinergic Risk Scale

3 points

2 points

1 point

amitriptyline

amantadine

carbidopa-levodopa

atropine

baclofen

entacapone

carisoprodol

cetirizine

haloperidol

chlorpheniramine

cimetidine

methocarbamol

chlorpromazine

clozapine

metoclopramide

cyproheptadine

cyclobenzaprine

mirtazapine

dicyclomine

desipramine

paroxetine

diphenhydramine

loperamide

pramipexole

hydroxyzine

loratadine

quetiapine

imipramine

nortriptyline

ranitidine

promethazine

olanzapine

risperidone

meclizine

prochlorperazine

selegiline

promethazine

tolterodine

trazodone

Adapted from Archives of Internal Medicine 2008Slide24

Drug Burden Index (DBI)

Total drug burden = B

AC

+ BS

E=

__

D

__



+ D

↑ DBI = ↓ physical performance and cognition

DBI:

Equations from Archives of Internal Medicine 2007Slide25

The Big Issues

Cognition, sedation, falls

GI toxicity

Cardiopulmonary effectsBleeding/clottingRenal impairmentLiver toxicitySlide26

High Risk For Falls

Anticholinergics

scopolamine pentobarbital hyoscyamine

atropine phenobarbital secobarbital

belladonna propantheline dicyclomine

Muscle

Relaxants

carisoprodol methocarbamol cyclobenzaprine

chlorzoxazone meprobamate metaxalone

Tricyclic

Antidepressants

amoxapine doxepin protriptyline

amitriptyline imipramine clomipramine

Antihistamines

diphenhydramine, hydroxyzine, cyproheptadine

Antiemetics

promethazine, trimethobenzamide

Benzodiazepines

diazepam, flurazepam, triazolam, chlordiazepoxide

Narcotics

meperidine, propoxypheneSlide27

Recommendations for Screening

Perform fall risk screening on all elderly patients, including:

History of falls or problems with gait/balance

Complete medication review, including prescriptions, over-the-counter drugs, herbal products, nutritional supplements, etc.Chronic condition risk factors, e.g. osteoporosis, cardiovascular disease, visual impairment, etc.Assessment of vitamin D deficiencySlide28

NSAIDS and GI Risk

Most

Meclofenamate

Indomethacin

Fenoprofen

Piroxicam

Flurbiprofen

Naproxen

Aspirin

Ketoprofen

Ibuprofen

Diclofenac

Sulindac

Salsalate

Etodolac

Least

Nabumetone

Relative GI Toxicity of Select NSAIDs

Adapted from Carman, EBRx Newsletter 2009Slide29

Other Adverse Effects of NSAIDs

Renal

GI

Coagulation

salt/H

2

0 retention

edema

hyperkalemia

↓ antihypertensive effects

↓ diuretic effects

↓ urate excretion

abdominal pain

anorexia

gastric erosions

hemorrhage

anemia

perforation

diarrhea

inhibit platelet activation

hemorrhage

bruisingSlide30

ADEs After Start of Pain Prescriptions

Adapted from Solomon, Archives of Internal Medicine 2010Slide31

Acetaminophen

Present in multiple OTC products and prescription pain medications

Maximum daily dose often exceeded in community and in hospitals

Increasing reports of severe hepatotoxicityHigher risk in patients who abuse alcohol and/or exceed dose recommendationsBy 2014, all acetaminophen prescription products must have no more than 325 mg acetaminophen per dosage unit New dose limit set by FDA in January 2011Slide32

Risk of Respiratory Depression

+

morphine, hydromorphone

meperidine, hydrocodone

fentanyl

GI Drugs

promethazine

cimetidine

promethazine

aprepitant

antimicrobials

macrolides

azole antifungals

protease inhibitors

psychotropics

benzodiazepines

tricyclic antidepressants

MAOIs

benzodiazepines

tricyclic antidepressants

MAOIs

analgesics

skeletal muscle relaxants

skeletal muscle relaxants

antihistamines

diphenhydramine

hydroxyzine

diphenhydramine

hydroxyzineSlide33

High Risk Drugs in Illness

Condition

Medications

Effect

Seizures

clozapine, bupropion, chlorpromazine

lowered seizure threshold

Clotting

Disorders

aspirin, NSAIDS, ticlopidine,

dipyridamole, clopidogrel,

prolonged clotting time, inhibited platelet aggregation

Parkinsonism

metoclopramide, antipsychotics

antidopaminergic and cholinergic effects

Arrhythmias

tricyclic antidepressants

proarrhythmic effects and QT interval changes

Obesity

olanzapine

weight gain

COPD

sedatives/hypnotics

respiratory depression

Benign prostatic hypertrophy

anticholinergics, narcotics, muscle relaxants

urinary hesitancySlide34

High Risk For Cardiovascular Disease

High Sodium Drugs

sodium polystyrene sulfate

piperacillin, ticarcillin

ranitidine

fluid retention

heart failure exacerbation

Stimulants

amphetamines diethylpropion

methylphenidate phentermine

↑ blood pressure

CV Drugs

short-acting nifedipine

short-acting dipyridamole

disopyramide

rapid

↓

in blood pressure,

↑ risk of syncope, stroke

↑ risk of heart failure

Oral

Estrogens

conjugated estrogen

esterified estrogen-methyltestosterone

estropipate

↑ risk of strokeSlide35

Drug Interactions

Drug interactions and polypharmacy

Two drugs = DDI occurrence in ~ 13% of patients

Six drugs = DDI occurrence in ~ 80% of patientsHospitalizations within one week of interactionsGlyburide + cotrimoxazole= 35/909 patientsDigoxin + clarithromycin = 27/1051 patientsACE inhibitors + diuretics = 43/523 patientsConcomitant alcohol use by 20% of elderlyMany patients report use of nutritional or herbal supplements.Slide36

Watch Out For These InteractionsSlide37

Watch Out For These InteractionsSlide38

Drug Interactions With Herbals

gingko

ginseng

garlic

ginger

echinacea

St. John’s wort

antithrombotic

X

X

X

X

X

ACEI/ARB

X

X

X

X

Ca blockers

X

X

X

X

X

-blockers

X

X

X

statins

X

X

X

X

X

amiodarone

X

X

X

X

digoxin

X

X

X

warfarin

X

X

X

X

X

XSlide39

ADEs: Drug Shortages and Recalls

Shortage of IV

sulfamethoxazole/ trimethoprim) led to refractory cases of pneumocystis pneumonia from alternative treatment with clindamycin and primaquineChemotherapy treatments delayed in a patient with a high potential for remission while attempting

to find a source of the needed drugUnintended intraoperative awareness occurred when a patient was given too little propofol based on weight in an attempt to conserve supplies

Cancellations of surgeries and procedures

Wrong dose of morphine administered after 4 mg/mL

prefilled syringes were replaced with 5 mg/mL vials

Pre-diluted methotrexate was unavailable;

a vial of dry powder was reconstituted incorrectly

and the patient received less than the prescribed doseSlide40

Prevention of ADEs

Frequent medication review and reconciliation

Evaluation of indications, benefits, side effects

Review of preprinted orders or prescription padsEnsure medication literacyPharmacologic “debridement”Utilization of online drug evaluation toolsRoutine pharmacist consultation