Transcript Slide 1

Medication Use in the Older Patient
Anthony J. Caprio, MD
Kevin Biese, MD, MAT
Ellen Roberts, PhD, MPH
Jan Busby-Whitehead, MD
Picture of pills
The University of North Carolina at Chapel Hill
With Support from The Donald W. Reynolds Foundation and
The John A. Hartford Foundation
© The University of North Carolina at Chapel Hill, Center for Aging and Health.
All Rights Reserved.
Objectives
1) Identify risk factors for Adverse Drug Events
(ADEs) in older adults
2) Identify the physiologic changes associated with
normal aging that influence pharmacokinetics
and pharmacodynamics
3) Recognize ADEs when an older adult presents
with a new clinical condition or complaint
4) Avoid potentially harmful medications for older
adults
5) Utilize strategies for shortening medication lists
and carefully introducing new medications
2
Mrs. Anderson
• 87yo female from nursing home; fell last night with
complaint of left hip and back pain
• Unable to recall events, agitated; says “yes,” when
asked if she is in pain. Seems very confused
• Reportedly able to ambulate short distance with walker
at baseline, needs assistance with dressing, bathing,
toileting. Able to feed herself
• Note from nursing home about rectal bleeding 2 days
ago
• Electronic medical record indicates that she was in the
ED last month for a heavily bleeding laceration after a
fall and supratherapeutic INR of 5.6 (while on
antibiotics for a urinary tract infection)
3
Past Medical History
1)
Dementia (MMSE 20/30)
12) Osteoarthritis, especially
hips and knees
2)
Parkinson’s disease
3)
13) Macular degeneration
CVA with residual L-sided
weakness
14) Type 2 DM
4)
Osteoporosis
15) Peripheral neuropathy
5)
Urinary incontinence
16) Chronic renal insufficiency
6)
Recurrent UTIs
17) Anemia
7)
Hypertension
18) Hypothyroidism
8)
CAD s/p stent 2 years ago
19) COPD on oxygen
9)
CHF (EF 30%)
20) Diverticulosis
10) Atrial Fibrilation
11) Hyperlipidemia
4
Medications
Picture of pills
1)
Donepezil (Aricept) 5mg po Daily
18)
Docusate sodium 100mg po BID
2)
Carbidopa/Levodopa 10/100 po TID
19)
PEG powder (Miralax) 17g po Daily
3)
Aspirin 325mg po Daily
20)
4)
Warfarin (Coumadin) 5mg po qHS
Tiotropium (Spiriva) 18mcg inhaled
Daily
5)
Tolterodine (Detrol) 2mg po BID
21)
Montelukast (Singulair) 10mg po Daily
6)
Atorvastatin (Lipitor) 40mg po qHS
22)
Fluticasone/Salmeterol (Advair) 100/50
inhaled BID
7)
Insulin (long-acting and sliding scale)
23)
8)
Gabapentin (Neurontin) 300mg po TID
Albuterol/Atrovent nebulizers prn
wheezing
9)
Iron sulfate 325mg po TID
24)
Multivitamin one po Daily
10)
Trazodone 50mg po qHS
25)
Vitamin E 400 IU po Daily
11)
Levothyroxine 50mcg po Daily
26)
Calcium Carbonate 500mg po TID
12)
Furosemide (Lasix) 60mg po BID
27)
Vitamin D 800 units po Daily
13)
Potassium Chloride 20meq po Daily
28)
Nitrofurantoin (Macrodantin) 100mg po
qHS
14)
Metoprolol 100mg po BID
15)
Lisinopril 20mg po Daily
16)
Amlodipine 10mg po Daily
17)
Acetaminophen 1000mg po TID
5
Challenges of Prescribing
for Older Adults
Multiple medical conditions
Multiple medications
Multiple prescribers
Different metabolisms and responses
Adherence and cost
Supplements, herbals, and over-the-counter
drugs
Lancet. 1995;346(8966):32–36.
6
Lots of Medications
and Little Evidence
• 2/3 of older adults are on regular medications
• Adults age >65 account for 1/3 of all
prescriptions, but only represent 15% of the
US population
• Older adults are frequently not included in
clinical trials, which makes it difficult to
predict drug metabolism or drug effects
Health Care Financ Rev. 1990;11:1-41.
7
Dangers of Multiple Medications:
“Polypharmacy”
• Adverse effects (side effects)
• Drug-drug interactions
• Duplication of drug therapy
• Poor adherence
» Cost
» Decreased quality of life
8
Adverse Drug Events (ADEs)
• Adverse symptoms
• Adverse clinical outcomes
»
»
»
»
»
Doctor visits or hospitalizations
Falls
Functional decline
Changes in cognition (delirium)
Death
• Poor adherence, poor quality of life
• Increased cost
9
Most Common Medications
Causing ADEs
•
•
•
•
•
•
•
•
Antibiotics
Analgesics
Anticoagulants
Antihistamines
Anticonvulsants
Antipsychotics
Cardiovascular meds
Diabetic meds
JAMA 2006; 296:1858–1866
JAGS 2004;52:1349–1354
NEJM 2003;348:1556–64
10
Prevalence of ADEs
•
•
•
•
35% of community-dwelling older adults
5-28% of inpatient geriatric admissions
2/3 of nursing home patients (over 4 years)
In the emergency department:
» 2.0 per 1000 for adults under 65
» 4.9 per 1000 for aged 65 years or older
» 6.8 per 1000 for aged 85 years or older
JAGS 1997;45:945-948
JAGS 1996;44:194-197
Am Pharm Assoc 2002;42:847-857
JAMA 2006; 296:1858–1866
11
Potential Risk Factors for
Adverse Drug Events (ADE)
>6 chronic disease
>12 doses/day
≥ 9 medications
Low BMI (<22kg/m2)
Age >85 years
Creatinine clearance < 50 mL/min
History of prior ADE
12
Consult Pharm 1997;12:1103–11.
Is Mrs. Anderson at Risk for an ADE?








6 chronic disease
>12 doses/day
≥ 9 medications
Low BMI (<22kg/m2) likely
Age >85 years
Creatinine clearance < 50 mL/min possibly
History of prior ADE
Nursing home resident
13
Why is Mrs. Anderson at Risk?
• Multiple drugs (high “exposure” )
» Risk of ADE is proportional to number of drugs
» Increased probability of drug-drug interactions
• Physiologic changes (increased susceptibility)
» Associated with disease states
» Associated with NORMAL AGING
14
Physiologic Changes with
Normal Aging
• Less water
• More fat
Picture of Jack LaLanne
• Less muscle mass
• Slowed hepatic metabolism
• Decreased renal excretion
• Decreased responsiveness and
sensitivity of the baroreceptor
reflex
15
Absorption
• Not affected by the normal aging process
• Can be altered by drug interactions
» Antacids
» Iron
• Can be effected by disease
» Lack of intrinsic factor (B12 absorption)
» Delayed gastric emptying
16
Distribution
• Less water = ↓ volume of distribution
Higher concentration of water soluble drugs
• More fat = ↑ volume of distribution
Prolonged action of fat-soluble drugs
(increased half-life)
• Lower serum proteins (like albumin) increases
the concentration of unbound (free or active)
form of drugs
17
Metabolism
• Slowed Phase I, cytochrome P450, reactions
» Oxidation, reduction, dealkylation
» Warfarin and phenytoin levels may be higher
because of altered metabolism
• Phase II reactions are essentially unchanged
» Conjugation, acetylation, methylation
• Drug-drug interactions
» Increased risk with increased number of drugs
18
Excretion
• Hepatic
• Renal
» Renal clearance may be reduced
» Serum creatinine may not be an accurate
reflection of renal clearance in elderly
patients.
(decreased lean body mass)
• Active drug metabolites may accumulate
» Prolonged therapeutic action
» Adverse effects
19
Physiologic Changes
Associated with Disease States
• Cardiac disease
» Impaired cardiac output (decreased
absorption, metabolism, clearance)
» Greater susceptibility to cardiac adverse
effects
• Kidney and liver disease
» Decreased drug clearance and altered
metabolism
• Neurological diseases
» Diminished neurotransmitter levels
» Greater susceptibility to neurological
effects
20
Why Did Mrs. Anderson Fall?
• Functional status
» Uses walker at baseline
» Dependent in other ADLs (like bathing)
• Sensory impairments
» Macular degeneration
» Peripheral neuropathy
• Neurological diseases
» Dementia
» Parkinson’s Disease
• Co-morbid diseases
» Cardiovascular (syncope)
» Diabetes mellitus (hypoglycemia)
» Anemia (hypotension)
21
Orthostatic Hypotension, Falls,
and Hip Fractures
• Baroreceptor sensitivity decreases with age
• Trazodone
» New medication according to nursing home med record
» Associated with orthostatic hypotension
• Diuretic use can cause volume depletion and orthostatic
hypotension
• Falls and hip fractures are associated with significant
morbidity and mortality in older adults
22
Why is Mrs. Anderson
Confused?
• Head injury?
» Contusion on forehead
» Recent history of supratherapeutic INR
• Dementia
» Moderate dementia by history
» What is her baseline?
• Delirium
» Infection (history of UTIs)
» Drugs (Adverse Drug Event)
» Hospital (change in environment)
23
Delirium
• More than confusion
» Acute onset, fluctuating course
» Inattention
» Disorganized thinking or altered level of
consciousness
• Associated with low levels of acetylcholine
» Low levels in patients with dementia at
baseline
» Risk with use of anticholinergic medications
24
Anticholinergic Medications
• Drug classes
• Antihistamines
• Tricyclic antidepressants
• Antispasmodics and muscle
relaxants
Diagram of the parasympatheic nervous system.
• Adverse effects
•
•
•
•
Dry Mouth
Urinary retention
Constipation
Delirium
25
Pharmacologic Tug-of-War
•
Tolterodine (Detrol)
» Potent anticholinergic
» Relaxes detrusor muscle to treat urge incontinence
(detrusor hyperactivity; “overactive bladder”)
» Can worsen delirium, constipation
•
Donepezil (Aricept)
»
»
»
»
•
Acetylcholinesterase Inhibitor
Higher levels of acetylcholine may help improve cognition
Can cause detrusor hyperactivity and diarrhea
Could cause symptomatic bradycardia and syncope (also
on β-blocker)
Incontinence and falls
» Dementia is a risk factor for both incontinence and falls
» Incontinence may be an ADE related to Donepezil
» Diuretic use can worsen incontinence and cause orthostatic
hypotension
26
Principle 1: “Think Drugs”
Before Making a New Diagnosis
• Consider adverse drug effect as etiology of
new signs/symptoms
• Consider discontinuing or dose-reducing
medications
• Avoid prescribing a new medication to treat an
adverse drug effect (“Prescribing Cascade”)
• Remember that over-the-counter drugs,
supplements, and herbals can be the culprit
27
28
Slide courtesy of Anthony Caprio, MD
Common Conditions Could
Really Be Adverse Drug Effects
Constipation 
Calcium Channel Blockers; Iron
Incontinence 
α-blockers
Memory loss 
Antihistamines
Syncope
Tricyclics, α-blockers
Falls 
Benzodiazepines
Weight loss 
Fluoxetine (Prozac)
29
Mrs. Anderson: Acute Management
• Pain
» Morphine 2mg iv x 2 doses for pain
» More comfortable after the 2nd dose
• Nausea and vomiting
» Complains of “sick stomach”
» Vomits repeatedly
• Agitation
» Increasingly agitated, trying to climb out of bed
» Shouting “Veronica” repeatedly
30
What Do You Prescribe?
•Pain
•Nausea
•Agitation
31
Beers Criteria
• A consensus-based list of potentially
inappropriate medications for older adults
• The Beers criteria were published 1991 and
revised in 1997, 2002, and 2012
• Statistical association with adverse drug
events has been documented
• Does not account for the complexity of the
entire medication regimen
J Am Geriatrics Society, 2012
Online link to this article is: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf
Pharmacotherapy 2005;25(6):831–838
32
Beers Criteria: Potentially Inappropriate
Medications for Older Adults
• Table 2: Organ System or Therapeutic
Category or Drug
» Describes concern for prescribing certain drugs or classes
of drugs for older adults
» Rationale, recommendation, quality of evidence, and
strength of recommendation
•
Table 3: Due to Drug-Disease or DrugSyndrome Interactions
» Describes drugs or classes of drugs that can cause or
worsen a particular disease or syndrome
» Rationale, recommendation, quality of evidence, and
strength of recommendation
J Am Geriatrics Society, 2012
Tables available online at: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf
33
Pain Medications
• Caution with non-steroidal anti-inflammatory
drugs (NSAIDS)
» Indomethacin has significant CNS side effects
» Ketorolac (Toradol) can cause serious GI and renal
effects
• Meperidine (Demerol) has low oral efficacy,
active metabolites and CNS effects
• Morphine metabolites are renally cleared
Beers criteria: J Am Geriatrics Society, 2012
Tables available online at: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf
34
Anti-Emetics
• Antihistamines: promethazine (Phenergan)
» Anticholinergic, may worsen delirium
(↓acetylcholine)
» Beers Criteria medication
• Dopamine antagonists: metoclopramide (Reglan)
» May worsen Parkinsonism (↓dopamine)
» Beers Criteria medication
• Serotonin (5-HT3) antagonists: odansetron
(Zofran)
» Expensive, but likely safest for this patient
Beers criteria: J Am Geriatrics Society, 2012
Tables available online at: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf
35
Managing Agitated Delirium
• Treat pain
» Although opioids may cause confusion,
untreated pain may precipitate and perpetuate
delirium
• Assess for other sources of discomfort
» Hunger, thirst, cold
» Urinary retention, fecal impaction;
• Sensory
» Eye glasses and hearing aids
» Try to minimize sensory “overload”
» Reorientation
36
Antipsychotic Medications
• “Black Box” warning: increased risk stroke, death
• Typical (ie. haloperidol)
»
»
»
»
Potent antidopaminergic effects
Can severely worsen Parkinsonism
Beers Criteria medication
Intravenous haloperidol associated with arrhythmias
• Atypical (ie. risperidone, quetiapine, olanzepine)
» Olanzepine may be best choice in setting of
prolonged QTc
» Quetiapine safest for Parkinson’s Disease but may
not be as useful for acute management
37
Benzodiazepines
for Agitated Delirium
• Avoid if possible
» Appropriate if being used to treat alcohol
withdrawal
» If necessary, use lowest dose possible
» Beers Criteria medication
• May cause a paradoxical reaction in older adults
» Increased agitation and anxiety
» May lead to prescribing cascade (ie. antipsychotic)
• Avoid long-acting benzodiazepines
» Prolonged half-life in older adults (days)
» Sedation, aspiration, delirium
» Increased risk of falls and fractures
Beers criteria: J Am Geriatrics Society, 2012
Tables available online at: http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf
38
Conclusion: Mrs. Anderson
• Medicated with morphine for pain
• One dose of odansetron (Zofran) for nausea
• Evaluated by orthopedics and plan for
operative repair for pain control and since
patient ambulatory at baseline
• Fecal disimpaction
• Her family brings her eye glasses and
hearing aids to the hospital
Beers criteria: J Am Geriatrics Society, 2012
39
Clinical Case: Mr. Johnson
Mr. Johnson is 83 years old. He complains of a
“runny nose” during meals on a daily basis. He
asks if there is a medication to stop his runny
nose. Although inconvenient at mealtime, he is
not bothered by this symptom at other times
during the day.
Question: Does he need a prescription?
40
Vasomotor Rhinitis
• Likely diagnosis is vasomotor rhinitis
• May respond to ipratropium (Atrovent) nasal
spray.
• Disposable facial tissues are available
without a prescription and have few side
effects
• “Sedating” antihistamines can have
significant anticholinergic effects.
41
Am Fam Physician 2005;72:1057-62.
Principle 2: “Less is More”
(Keep the Medication List Short)
•
•
•
•
•
Question the need for new medications
Stop medications, whenever possible
Prioritize treatments
Weigh risks and benefits
But, avoid undertreating older patients
» Pain
» Systolic hypertension (stroke, renal failure,
heart disease)
» Anticoagulation and atrial fibrillation (stroke
prevention)
Drugs Aging 2003; 20: 23-57.
Lancet 2000; 355: 865–872.
Ann Intern Med 1999;131:492-501.
J Gen Intern Med 2005; 20:116–122.
42
Clinical Case: Mr. Jones
Mr. Jones is 82 years old with a history of
herpes zoster (shingles) 6 months ago. He
continues to experience severe daily pain in the
same dermatomal distribution as the original
rash.
• Question: What is the diagnosis?
• Question: What is the treatment?
43
Post-Herpetic Neuralgia
• Opioid medications
• Capsaicin
» OTC alternative
» Topical (better than systemic)
» May be poorly tolerated due to local effects
• Tricyclic antidepressants
» Effective, but have anticholinergic properties.
Amitriptyline > nortriptyline > desipramine
» Amitriptyline is a Beers Criteria medication
• Gabapentin (Neurontin)
» Clinical trials: 1800–3600mg/day divided doses.
» Dose-reduce with renal insufficiency.
Neurology 2002;59(7):1015–21.
Pain 1988;33(3):333–40.
Neurology 1998;51(4):1166–71.
JAMA 1998;280(21):1837–42.
44
Principle 3:
“Start Low and Go Slow…”
• Start one medication at a time
• Start with a low dose and increase gradually
• Monitor for response and adverse effects
• Once daily is usually best
• Assess adherence with regimen
45
“…But, Go All The Way!”
• Be conservative, but don’t miss the target!
• What is your goal? Are you achieving it?
• If you are not at goal, can the dose be
increased or are you limited by side effects?
• Are you observing a clinical benefit at lower
doses?
• Consider stopping if you can’t “go all the way”
and the benefits at lower doses are not clear.
46
Physiologic Changes
Associated with Normal Aging
• Absorption usually does not change
•
↑ concentrations of water soluble and free
(unbound) drugs
• Longer half-life for lipophilic drugs
• Slower phase I metabolism
• Impaired excretion
• Decreased responsiveness of the
baroreceptors
47
Prescribing for Older Adults
1) “Think drugs” before making a new
diagnosis
2) “Less is more” (keep the med list short)
3) Use caution with Beers Criteria medications
4) “Start low and go slow”…when starting a
new drug….“but go all the way.”
48
Acknowledgments and Disclaimers
This project was supported by funds from The Donald
W. Reynolds Foundation, the American Geriatrics
Society/The John A. Hartford Foundation Geriatrics for
Specialists Grant. This information or content and
conclusions are those of the author and should not be
construed as the official position or policy of, nor
should any endorsements be inferred by The Donald
W. Reynolds Foundation and/or The John A. Hartford
Foundation.
The UNC Center for Aging and Health, the UNC
Division of Geriatric Medicine, and the UNC
Department of Emergency Medicine also provided
support for this activity. This work was compiled and
edited through the efforts of Carol Julian.
49
© The University of North Carolina at Chapel
Hill, Center for Aging and Health. All
Rights Reserved.
50