Download Prescribing in the Elderly - Benton Franklin County Medical Society

Prescribing in the Elderly
Karen Birmingham, PharmD, BCPS
Specialty Clinical Pharmacy Services
Group Health
Objectives
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Review pharmacokinetic
changes due to aging.
Summarize effects of illness
on drug action.
Present assessment tools
and discuss high risk drug
classes.
List some major drug-drug
and drug-herbal
interactions.
Identify actions to help
prevent adverse drug
events in the elderly.
“Quote”worthy Definitions
Aging
Elderly
“Progressive accumulation
of random changes”
“Age nearing or surpassing
the average life span”
“Time-related loss of
functional units”
“Age 65 years and older”
“Better than the alternative”
“Always 15 years older than
me”
A Global “Gray Tsunami”

By 2006:
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By 2030:
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Almost 500 million people
worldwide ≥ 65 years old
Total world population
over 9 billion
Elderly in developing
countries ↑ by 140%
World population ≥ 65
years old ~ 1 billion
By 2050:
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20% of all elderly patients
will be ≥ 80 years old
U.S. Elderly
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Constitute 13% of the population
Consume 34% of all prescription medications
Use 40% of all over-the-counter drugs
Up to 50% of elderly take multiple medications
Medicare population analysis in 1999
(n=1.2 million)
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
82% had at least one chronic condition
24% had at least four chronic conditions
Prescription Drug Use by Elderly
%
www.cdc.gov
Prescription $ Per Chronic Condition
$
www.cdc.gov
Drugs Most Used by Elderly Patients
Clinical Pharmacology and Therapeutics 2007
ADE, ADR and ME
Annals of Internal Medicine 2004
Adverse Drug Events
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Occur in 20% of elderly patients
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Account for 5-10% of hospitalizations
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Prevalence of 5-37% in hospitalized patients
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Nearly 20% ranked as severe
Fatal outcomes in 6% of cases
Repeat hospitalizations in 30% of ADEs
Interventions required in ~30% of patients
Affect ~ 350,000 long-term care patients annually
Adverse Drug Events and Death
“If medication-related problems were
ranked as a disease by cause of death,
it would be the 5th leading cause of death
in the United States.”
Archives of Internal Medicine 2003
Risk Factors For Adverse Drug Events
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Inappropriate prescribing
Polypharmacy
Misuse of OTC products
Lack of appropriate drug monitoring
Complicated dosing instructions
Language or educational barriers
Nonadherence
How a Drug Does What It Does
The Pharmacologic Basis of Therapeutics, 11th ed.
Changes Due to Aging
↓ lean body mass
↓ total body water
↓ volume of distribution
of water-soluble drugs
↑ body fat
↑ volume of distribution
of lipophilic drugs
↑ half-life
↑ time to steady-state
concentration
↑ gastric pH
↓ absorption surface
↓ GI mobility
Altered drug absorption
cognitive changes
↑ sensitivity to anticholinergics
Altered HPA axis
↓ hepatic circulation
↓ hepatic mass
↓ first-pass metabolism
↓ activation of prodrug
↑ bioavailability
↓ glomerular filtration rate
↓ renal circulation
↓ renal clearance
Adapted from Journal of the American College of Cardiology 2010
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 women
• Currently no predictive data for
effects of age on CYP2C
• Faster clearance of CYP2D6 in men;
decrease doses of drugs ~10-20%
for women, decrease ~20% more in
elderly women
• Renal impairment may affect CYP
P450 due to decreased gene
expression
The Pharmacological Basis of Therapeutics 1996
Drug Metabolism and Aging
Adapted from Bressler and Bahl, Mayo Clinic Proceedings 2003
P-Glycoprotein and Drug Disposition
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Efflux transporter
Found in hepatocytes, intestinal mucosal cells,
and blood-brain barrier
Conflicting results from small studies:
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Animal studies suggest differences between male and
female, not yet observed in humans
One study showed no significant difference in
leukocyte P-glycoprotein in comparisons of young
healthy adults vs. elderly healthy and frail adults
Another study suggested decreased blood-brain
barrier P-glycoprotein activity, possibly exposing brain
to higher levels of drugs
Age Effects on Hemostasis
Coagulation
Proteins
↑
↑
↑
↑
↑
↑
↑
↑
Factor V
Factor VII
Factor VIII
Factor IX
Factor XIII
Fibrinogen
kininogen
prekallikrein
Fibrinolytic
Proteins
↑ D-dimer
↑ PAI-1
↓ plasmin
Anticoagulant
Proteins
Antithrombin III
Protein C
Protein S
TFPI
M
↓
↔
↔
↓
Adapted from Journal of the American College of Cardiology 2010
F
↓
↑
↑
↑
Pharmacodynamics in the Elderly
Drug Name
Drug Action
diltiazem
antihypertensive
PR interval prolongation
furosemide
diuretic
scopolamine
cognitive function
morphine
analgesia
diazepam
sedation
verapamil
antihypertensive
warfarin
anticoagulant
Drug Effect
Adapted from British Journal of Pharmacology 2004
Effect of Illness on Drug Actions
absorption
gastrointestinal pH
gastrointestinal motility
gastric contents
serum albumin
distribution changes in binding sites
increased endogenous inhibitors
renal impairment
metabolism hepatic impairment
drug interactions
excretion
receptor
interaction
renal impairment
gastrointestinal motility
changes in number
changes in sensitivity
altered target site
=
Drug Response
1) Altered:
-metabolism
-cell environment
-concentrations
2) Tolerance
3) Resistance
4) Interactions
Congestive Heart Failure Effects
Parameter
bioavailability
distribution
metabolism
Alteration
bowel edema reduces drug absorption of oral drugs
first pass metabolism altered by hepatic congestion
peripheral edema decreases absorption of
topical/subcutaneous/intramuscular agents
unpredictable due to changes in total body water
and tissue perfusion
reduced liver perfusion alters drug metabolism
impaired renal function may inhibit drug elimination
excretion
pharmacodynamic
increased risk of radiocontrast nephropathy
increased sensitivity to antiarrhythmic medication
Adapted from Clinics in Chest Medicine 2003
High Risk Drugs Assessment Tools
Year Country
1991
1997
2000
2007
2008
USA
Canada
Canada
France
Ireland
2008
2009
2010
Japan
Norway
Italy
Tool
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 2010
Medication Appropriateness Index
Criterion
Drug-drug interactions?
Standard Weight Modified Weight
2
2
2
3
2
1
3
1
1
1
1
2
1
0
Practical directions?
2
1
0
0
Cost effective compared with
other drugs of equal efficacy?
1
0
Drug-disease interactions?
Is the drug indicated?
Is the drug effective?
Unnecessary drug duplication?
Appropriate therapy duration?
Correct dosage?
Correct directions?
Adapted from Annals of Pharmacotherapy 2010
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 2008
Drug Burden Index (DBI)
Total drug burden = BAC +BS
DBI: E =

__D__
 + D
↑ DBI = ↓ physical performance and cognition
Equations from Archives of Internal Medicine 2007
The Big Issues
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Cognition, sedation, falls
GI toxicity
Cardiopulmonary effects
Bleeding/clotting
Renal impairment
Liver toxicity
High Risk For Falls
Anticholinergics
scopolamine
atropine
belladonna
pentobarbital
hyoscyamine
phenobarbital secobarbital
propantheline dicyclomine
Muscle
Relaxants
carisoprodol
methocarbamol cyclobenzaprine
chlorzoxazone meprobamate
metaxalone
Tricyclic
Antidepressants
amoxapine
amitriptyline
Antihistamines
diphenhydramine, hydroxyzine, cyproheptadine
Antiemetics
promethazine, trimethobenzamide
Benzodiazepines
diazepam, flurazepam, triazolam,
chlordiazepoxide
Narcotics
meperidine, propoxyphene
doxepin
imipramine
protriptyline
clomipramine
Recommendations for Screening
Perform fall risk screening on all elderly
patients, including:
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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 deficiency
Relative GI Toxicity of NSAIDs
Nabumetone
Etodolac
Salsalate
Sulindac
Diclofenac
Ibuprofen
Ketoprofen
Aspirin
Naproxen
Flurbiprofen
Piroxicam
Fenoprofen
Indomethacin
Meclofenamate
Least
Most
Adapted from Carman, EBRx Newsletter 2009
Other Adverse Effects of NSAIDs
Renal
GI
salt/H20 retention
abdominal pain
edema
anorexia
hyperkalemia
gastric erosions
↓ antihypertensive effects hemorrhage
↓ diuretic effects
anemia
↓ urate excretion
perforation
diarrhea
Coagulation
inhibit platelet
activation
hemorrhage
bruising
ADEs After Start of Pain Prescriptions
Adapted from Solomon, Archives of Internal Medicine 2010
Acetaminophen
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Present in multiple OTC products and
prescription pain medications
Maximum daily dose often exceeded in
community and in hospitals
Increasing reports of severe hepatotoxicity
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Higher risk in patients who abuse alcohol and/or
exceed dose recommendations
By 2014, all acetaminophen prescription products
must have no more than 325 mg acetaminophen
per dosage unit
 New dose limit set by FDA in January 2011
Risk of Respiratory Depression
+
morphine
hydromorphone
meperidine
hydrocodone
fentanyl
GI Drugs
promethazine
cimetidine
promethazine
aprepitant
macrolides
azole antifungals
protease inhibitors
antimicrobials
psychotropics
benzodiazepines
tricyclic antidepressants
MAOIs
benzodiazepines
tricyclic antidepressants
MAOIs
analgesics
skeletal muscle relaxants
skeletal muscle relaxants
antihistamines
diphenhydramine
hydroxyzine
diphenhydramine
hydroxyzine
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 hesitancy
High Risk For Cardiovascular Disease
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 estrogenmethyltestosterone
estropipate
↑ risk of stroke
High
Sodium
Drugs
Drug Interactions
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Drug interactions and polypharmacy
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Hospitalizations within one week of interactions
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Two drugs = DDI occurrence in ~ 13% of patients
Six drugs = DDI occurrence in ~ 80% of patients
Glyburide + cotrimoxazole= 35/909 patients
Digoxin + clarithromycin = 27/1051 patients
ACE inhibitors + diuretics = 43/523 patients
Concomitant alcohol use by 20% of elderly
Many patients report use of nutritional or herbal
supplements.
Watch Out For These Interactions
Watch Out For These Interactions
Drug Interactions With Herbals
gingko
ginseng
garlic
ginger
antithrombotic
X
X
X
X
ACEI/ARB
X
Ca++ blockers
X
X
-blockers
X
X
statins
X
X
amiodarone
X
digoxin
warfarin
X
St. John’s
wort
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
echinacea
X
X
X
X
X
X
ADEs: Drug Shortages and Recalls
Pre-diluted methotrexate was unavailable;
a vial of dry powder was reconstituted incorrectly
and the patient received less than the prescribed dose
Wrong dose of morphine administered after 4 mg/mL
prefilled syringes were replaced with 5 mg/mL vials
Cancellations of surgeries and procedures
Chemotherapy treatments delayed in a patient
with a high potential for remission while attempting
to find a source of the needed drug
Unintended intraoperative awareness occurred
when a patient was given too little propofol based
on weight in an attempt to conserve supplies
Shortage of IV sulfamethoxazole/ trimethoprim) led to
refractory cases of pneumocystis pneumonia from
alternative treatment with clindamycin and primaquine
Prevention of ADEs
Frequent medication review and reconciliation
Evaluation of indications, benefits, side effects
Review of preprinted orders or prescription pads
Ensure medication literacy
Pharmacologic “debridement”
Utilization of online drug evaluation tools
Routine pharmacist consultation
“We've put more effort into
helping folks reach old age
than into helping them enjoy it.”
~Frank A. Clark