Chitra Fernando, MD
March 18, 2008
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Definition
Statistics
Risk factors
Why older adults are more prone to ADE
Manifestations
Inappropriate medications for older adults
What can be done to minimize adverse drug
reactions
ADE is an Injury resulting from use of a drug
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Medication side effects
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Allergic reactions
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Medication interactions
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ADE - responsible for 5-28% acute geriatric
medical admissions.
80% of ADE are due to prescription
medications
The risk of an adverse reaction increases with
every new drug added to the treatment
regimen.
140,000 deaths per year due to ADE
95% ADE are predictable and 50% preventable
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Age > 85 y
Low body wt/BMI
> 6 concurrent chronic diagnosis
Cr clearance < 50 ml/min
> 9 meds
> 12 doses/day
Prior adverse drug reaction
Several prescribing Physicians
> 1 Pharmacy
More medical problems
` More medications/drug interactions
` Pharmacoeconomic issues
` Age associated changes in
pharmacokinetics and
pharmacodynamics
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Decreased lean body mass and body water
content - Increased concentration of water
soluble medications. Eg: Li, Digoxin
Increased body fat content – fat soluble
medications takes longer to clear. Eg:
Diazepam, Trazedon
Decreased serum albumin – increased
unbound fraction of med-Eg: Phenytoin,
Valproic acid, Cefriaxone, Warfarin
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Decreased metabolism (decreased liver mass
& blood supply)
Decreased clearance (decreased no of
functioning nephrons and decreased renal
blood flow )
Increased sensitivity. Eg: Narcotics, Benzo,
Psychotropic, Anticholinergics
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Increased falls
Confusion
Sedation
Decreased oral intake
Constipation/urinary retention
Failure to thrive
It is not uncommon for a physician to treat an
ADE with another medication.
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Inappropriate – greater potential to
harm than to benefit
Beers criteria – introduced in 1991 by
Beers et al
Original criteria was written for elderly
persons who were institutionalized and
updated in 1997 and 2003 to include
all persons over age 65.
Defined medications that should
not be prescribed to elderly
patients
&
` other medications for which
doses, frequencies, durations
should not be exceeded.
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Beers criteria is widely used as a
measure of health care quality and
safety
Center for Medicare & Medicaid
services incorporated Beers criteria
into Federal safety regulations for
long term care facilities in 1999.
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41 medications - Inappropriate
under any circumstances
7 medications – Inappropriate
when used over certain doses,
frequencies and durations
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Dry mouth, increased thirst,
urinary retention, constipation
Hypotension, Tachycardia, cardiac
arrhythmias, heart blocks
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Post op delirium, agitation,
hallucination, cognitive impairment,
increased risk of falls
Pupillary dilatation – worsening closed
angle glaucoma –may threaten vision
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TCA
Antihistamines-Diphenhydramine (Benadryl)
Hydroxyzine (vistaril, Atarax)
Antipharkinsonian drugs with atrophine like
activity.
Oxybutynin, Tolterodine
Hyoscyamine
Phenothiazine
Anticholinergic toxicity occurs more often when
two or more anticholinergic drugs are taken
together.
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High lipid solubility- slower elimination
Binds exclusively to plasma proteins-higher
plasma drug levels
Risk of 20,30 heart block - pre existing heart
disease.
Anticholinergic SE - Orthostatic hypotension,
falls and fractures
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Tertiary amines-amitriptyline,
impramine- more anti cho.SE
Secondary- nortriptyline and
desipramine –less anti cho. SE
Low dose- neuropathic pain
` SSRI is a better alternative for
depression
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To manage behaviors associated with
dementia-paranoia, agitation,
hallucinations & delusions
Not usefull in wandering, pacing, repetitive
vocalizations
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Anticholinergic effects, EP symptoms
(bradykinesia, stiffness, cogwheel rigidity, akinesia, akathisia)
– Lasts longer after d/c.
It is not uncommon to treat EP side effects
with anticholinergic antiparkinsonian meds –
results in excessive anticholinergic activity
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Atypical antiphychotic medications –
improved safety profile
Clozapine – agranulocytosis
Olanzapine , Risperidone, Quetiapine – Fever
extrapyramidal effects and TD
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Older-Diazepam, chlordiazepoxide,
flurazepam– highly lipid soluble
Newer-Lorazepam, oxazepam – low lipid
soluble – in low doses only for short term use
when indicated
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Older (diphenhydramine)- cross BBB
Hypnotic, cognitive slowing, delirium, falls –
more if pre-existing cognitive impairment
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Second generation antihistamines –
Fexofenadine, loratadine, cetrizine – safer, no
notable central effects
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10 – 20% of > 65 yr
15-35% of all peptic ulcer disease –
due to NSAIDs – 20,000 patients die
each year
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Many present with serious upper GI bleeding
– 60% individuals with mucosal erosions from
NSAIDs were asymptomatic – Naproxen, Piroxicam
Other SE include Renal impairement,
hyperkalemia, HTN, fluid retention, CHF,
Indomethacin – CNS toxicity
Alternatives – Acetaminophen, tramadol
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2004 - 2005 ADE requiring ER visits (177504)
3.6%
17.3%
13%
3.2%
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From Beers criteria
Warferin
Insulin
Digoxin
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ACEI ,Potassium sparing diuretics, potassium
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Benzo , antidepresent, antipsycotic
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Digoxin, Antiarrhythmics , verapamil
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Warfarin, NSAIDs, sulfa drugs, macrolides,
quinolones, phenyton
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When starting meds for chronic medical
conditions, start low and go slow
Try not to start two medications at the same
time
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New complaints, worsening of an existing
condition – R/O SE of medications
Discontinue any medication no longer
indicated
Consider non-pharmacological interventions
Avoid drug Interactions - Duplicating side
effects
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Consider medications with more than one
therapeutic effects
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Brown bag evaluation
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Maintain accurate records
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Educate patient and the care giver about the
new medications
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Simplify the profile
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Use only one pharmacy
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Consult pharmacists
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Saw palmetto
x Common use?
BPH
x Adverse Events?
Headache, nausea, GI distress, ED
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St. John’s wort
x Common uses?
Depression, anxiety
x Adverse Events?
Photosensitivity, hypomania
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Ginkgo
x Common uses?
Alzheimer’s disease, memory, intermittent
claudication, macular degeneration
x Adverse Events?
Bleeding, headache, nausea, GI upset,
diarrhea, anxiety
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Ginseng
x Common use?
Physical & mental performance enhancer
x Adverse Events?
Hypertension, tachycardia
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Garlic
x Common uses?
Hypertension, hypercholesterolemia,
platelet inhibitor
x Adverse Events?
Bleeding, GI upset, hypoglycemia
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Ginger
x Common uses?
Antiemetic, anti-inflammatory, dyspepsia
x Adverse Events?
Bleeding
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Kava kava
x Common uses?
Anxiety, sedative
x Adverse Events?
Sedation, hepatotoxicity
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Echinacea
x Common use?
Immune stimulant
x Adverse Events?
Hepatotoxicity
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Feverfew
x Common uses?
Anti-inflammatory, migraine prophylaxis
x Adverse Events?
Platelet inhibition, bleeding, GI upset
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Glucosamine
x Common uses?
Osteoarthritis, rheumatoid arthritis
x Adverse Events?
GI distress, anorexia, insomnia, painful &
itchy skin, peripheral edema, tachycardia