Transcript Draft 10-19-04 Pharmacotherapy & Older Adults Content for this project provided by: • The John A.

Draft 10-19-04
Pharmacotherapy
& Older Adults
Content for this project provided by:
• The John A. Hartford Foundation, Institute for Geriatric Nursing,
Online Gerontological Nursing Certification Review Course
http://www.nyu.edu/education/nursing/hartford.institute/course/
• Shelly L. Gray, Pharm.D., M.S., BCPS, Director, Geriatric
Pharmacy Program, Associate Professor, School of Pharmacy,
University of Washington
Support for this project provided to School of Nursing, University of
Washington by the John A. Hartford Foundation, Geriatric Nursing Education
Grant and Nursing School Geriatric Investment Program Grant.
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Pharmacotherapy
& Older Adults
Demographics
• Represent 12% of population
• Consumers of 25-30% of prescription drugs
• Consumers of 40% of OTC drugs
• Ambulatory older adults use 2 to 4 prescription drugs
regularly
• Long-term care residents use 2 -10 prescription drugs
regularly
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Pharmacotherapy
& Older Adults
Demographics
• > 60 yrs of age:
• 1/3 of drug-related hospitalizations
• 1/2 of drug-related deaths
• Misuse is 5th leading cause of death
• ~40% do not take meds as directed
(they take < prescribed amt)
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Pharmacotherapy
& Older Adults
Considerations
• Polypharmacy (& associated risks)
• Age and disease-related changes in
pharmacokinetics and pharmacodynamics
• Adverse drug reactions
• Compliance issues
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Drug Use in the Elderly
“A balancing act”
• Treat / manage /
prevent disease
• Avoid toxicity
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Polypharmacy
Use of more than one chemical
agent to effect a therapeutic
endpoint
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Polypharmacy
Why greater prevalence in older adults?
•  symptoms resulting from  prevalence of
disease
• Drugs prescribed to treat side effects of other
drugs
• Prescribers
• Drug advertising (…pills to cure all…stay young..)
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Polypharmacy
• Analgesics / antiarthritics
• Antacids and histamine2-receptor
antagonists
• Cardiovascular drugs
• Laxatives
• Nutritional supplements
• Psychotropics
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Polypharmacy
• Predisposition to taking medications
incorrectly (wrong dose, wrong time, wrong purpose)
•  probability of:
• Overlapping (“additive”) or antagonistic
pharmacologic effects
• Adverse drug reactions:
• drug-disease, drug-drug
• Patient non-compliance
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Adverse Drug Reactions
An undesired side effect or toxicity
caused by the administration of
drugs
• Onset may be sudden or take days
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Adverse Drug Reactions
May be undetected in older adults
because they can mimic the
characteristics of problems, disease,
or symptoms commonly present in
the elderly
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Case Study 1
SR, a 75 year old active female, visits
her MD with a 1 month history of sleep
complaints. She “just can’t fall asleep at
night” and would like something to help.
Her MD prescribes flurazepam
(Dalmane) 15 mg at bedtime as needed
(#30).
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ADRs Can Lead to
Hospitalization
1 week later, SR is rushed to the ER
after suffering a fall down a flight of
stairs. A fracture of the right femur is
seen on x-ray. While she tolerates the
surgery well, she has poor endurance
with therapeutic exercises and therefore
is sent to a local skilled nursing facility.
1yr later, she still requires use of a
walker.
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Adverse Drug Reactions
• Cognitive status
• Accidents and falls
• Renal Toxicity
• Hepatic Toxicity
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Detection of ADR in Elderly
• 80 yo female with:
–
–
–
–
diabetes mellitus
hypertension
CAD
knee osteoartritis
• Presents with
syncope
• BP sitting 165/80
standing 140/82
• Medications:
–
–
–
–
diltiazem 240 mg
HCTZ 25 mg am
glyburide 10 mg am
lorazepam 2 mg hs
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Prescribing Cascade
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Nursing Considerations
•  monitoring
• i.e., Coumadin™
• Attention to “additive effects,” such as with
anticholinergics, sedatives
• Dosing:  or extension of interval?
• Client education
• Assessment of compliance factors
Why are Elderly at Risk for
ADRs?
• Age-related changes in pharmacokinetics
• Age-related changes in pharmacodynamics
• baroreceptor response
• neurotransmitters
• Types of medication used
• High level of medication use
Kinetics
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Dose Administered
Absorption
Distribution
Kidneys/
Tissue
Circulation
Liver
Elimination
Dynamics
Drug at Effect Site
Efficacy
Adverse Events
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Pharmacokinetics
Age-related physiologic considerations
• Absorption
• Distribution
• Metabolism
• Excretion
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Altered Pharmacokinetics
Age-related
Drug-related
Disease-related
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Absorption
Age-related changes to GI tract
•  # of absorptive cells
•  gastric acidity ( gastric pH)
•  GI blood flow,  motility
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Absorption
• Generally, rate & extent of absorption are
not affected by age-related changes
• Some implications include:
•  dissolution of calcium carbonate
• Delayed onset of analgesic effect
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Absorption Issues in the
Elderly
• 75 yr old female with CHF, ulcer disease and
osteoporosis
• Medications:
– enalapril 10 mg q am
– lasix 40 mg q am
– KDUR 20 mEq q am
– omeprazole 20 mg q evening
– alendronate 10 mg q am
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Distribution
Age-related changes
•  % of fat
•  total body water
•  plasma protein concentration
(especially albumin)
•  lean muscle mass
•  blood flow to organs & tissues
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Distribution
• Fat soluble drugs have a larger volume
of distribution
• Highly protein-bound drugs have the
potential for greater (active) free
concentration until metabolic excretory
compensation occurs
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Distribution
Examples:
•  free concentration of Meperidine, phenytoin due
to  binding to RBCs
– Unable to trust total concentration if person has low
albumin
•  unbound fraction of propranolol
•  psychotropic distribution into fat - potential
accumulation
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Metabolism
Age-related changes
 liver mass & liver blood flow
+
concomitant diseases, nutritional status, genetics
=
Potential for  hepatic function
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Metabolism
Results of decreased metabolism:
•  concentrations of:
•
•
•
•
long-acting benzodiazepines
tricyclic antidepressants
ß-blockers
narcotic analgesics
•  potential for adverse events
• Lower doses may be therapeutic
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Metabolism
Extent of changes in drug metabolism?
• Not easily measured
• liver function tests not generally useful
• Assessment of pharmacologic or toxicologic
effects in a given client are necessary
• drug interactions are more likely the cause of 
metabolism than aging effects
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Elimination
•  renal function ( primarily  GFR )
• Drug interactions
• Presence of multiple diseases / acute &
chronic conditions
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Elimination
Renal function measurement
• Serum creatinine? Not reliable but still
important to assess
•  muscle mass +  muscle metabolism =
 creatinine production
• Creatinine clearance (ml/min) =
140 - age in yrs x weight in kg
72 x serum creatinine (% mg/100mL)
(for women, multiply result by .85)
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“Young”
cr cl =
(140 - 40) 72
72 (1.0)
cr cl = 100 ml/min
“Old”
cr cl =
(140-80) 72
72 (1.0)
cr cl = 60 ml/min
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Elimination
Watch for drugs requiring  dosing due to
 renal function
Examples:
• Allopurinol
•
•
•
•
Digoxin
Many cephalosporins
Ciprofloxacin
Histamine receptor antagonists (e.g., cimetidine, ranitidine,
famotidine)
• Venlafaxine
• Morphine
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Pharmacodynamics
• Change in sensitivity to some drugs
• Standard & lower concentrations show
altered drug response =  predictability
Considerations
• Start low…go slow!
• Dose-related toxicity
• Serious adverse effects
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Pharmacodynamics
• Effects may be  or  due to changes in:
• drug-receptor interaction
• Post-receptor events
• adaptive homeostatic responses
• organ pathology
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Pharmacodynamics
Examples:
• Morphine: Prolonged pain relief at lower
doses
• Benzodiazepines:  sedation & postural
instability
(extended effect r/t long ½ life)
• Warfarin:  sensitivity to anticoagulant effect
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Pharmacodynamics
Use caution with drugs that can have
serious adverse effects:
Examples:
• Morphine
• Warfarin
• ACE inhibitors
• Diazepam (especially parenteral route)
• Levodopa
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Pharmacodynamics
Watch for delayed signs of drug-related
toxicity for drugs with age-related 
effects
Examples:
• -blockers
• Tolbutamide
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NSAIDs & Older Adults
Use less toxic analgesics first
(e.g., acetaminophen)
• NSAID-induced GI bleeding
•  incidence - especially during first 3 months
• Risk factors: history of ulcer disease, NSAID dose
• Concurrent use of anticoagulants
•  incidence of upper GI bleeding
• NSAID-induced renal impairment
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Cardiovascular Drugs
Considerations
•  risk of orthostatic hypotension, especially with
volume depleting agents & vasodilators
• Digoxin - potential toxicity
(even with normal serum
concentrations and normal serum creatinine levels)
• If tolerated, diuretics are first choice for older
adults with high blood pressure
•  blockers: monotherapy, with diuretics, or not at
all?
• ACE inhibitors - renal protection – diabetes
– can cause  renal function
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Antiemetics
Considerations
• i.e., phenothiazine: may cause confusion,
orthostatic hypotension, blurred vision,
falls, dry mouth, and urinary retention
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Benzodiazapines
•  sensitivity to adverse effects
(especially after 75
yrs of age)
• excess sedation
• memory loss
• impaired physical function
•  frequency of falls, fractures
• Long-acting may have prolonged half lives
causing CNS toxicity
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Anticholinergics
• TCAs, antihistamines, anti-Parkinson drugs
•  sensitivity
• Adverse effects
•
•
•
•
•
urinary retention/constipation
dry mouth/dysphagia
mental status changes (delirium, memory impairment)
vision changes
orthostatic hypotension
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TCAs
• Sedating
– confusion, unstable gait
• Risk factors/adverse side effects:
– cholinergic effects, hypotension, tachycardia,
arrythmias
• Use with caution if glaucoma and cardiac
conduction disturbances
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Narcotics
•  sensitivity
• Start low…go slow!
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Drug Induced Incontinence*
Urinary retention
•anticholinergic agents & agents w/anticholinergic effects
•smooth muscle relaxants
•-agonists
Stress incontinence
• -antagonists
Urge incontinence
•polyuria: diuretics, lithium
•central inhibition: narcoleptics
Secondary incontinence
(related to over-sedation)
•benzodiazepines, sedative-hypnotics
*Owens NJ, Sillman RA, Fretwell, MD. (1989). The relationship between comprehensive functional assessment
and optimal pharmacotherapy in the older patient. DICP: the annals of pharmacotherapy, 23, 847-854.
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Drug Induced
Mobility Impairment*
Supporting structure
•Arthralgias, myopathies:
• corticosteroids, lithium
•Osteoporosis, osteomalacia:
• corticosteroids, phenytoin, heparin
Movement disorders
•EPS/tardive dyskinesia:
• neuroleptics, metoclopramide, amoxapine,
methyldopa
*Owens NJ, Sillman RA, Fretwell, MD. (1989). The relationship between comprehensive functional assessment and
optimal pharmacotherapy in the older patient. DICP: the annals of pharmacotherapy, 23, 847-854.
Drug Induced
Mobility Impairment*
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Balance
• Neuritis, neuropathies
• metronidazole, phenytoin
• Tinnitus, vertigo
• aspirin, aminoglycosides, furosemide, ethacrynic acid
• Hypotension
• -blockers, calcium channel blockers, neuroleptics,
antidepressants, diuretics, vasodilators, benzodiazepines,
levodopa, metoclopramide
• Psychomotor retardation
• neuroleptics, benzodiazepines, antihistamines, antidepressants
*Owens NJ, Sillman RA, Fretwell, MD. (1989). The relationship between comprehensive functional assessment
and optimal pharmacotherapy in the older patient. DICP: the annals of pharmacotherapy, 23, 847-854.
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Drug Induced
Mental Status Changes*
Metabolic alterations
Hyper- or hypoglycemia, electrolyte disturbances
• -blockers
• Corticosteroids
• Diuretics
• Sulfonylureas
*Owens NJ, Sillman RA, Fretwell, MD. (1989). The relationship between comprehensive functional
assessment and optimal pharmacotherapy in the older patient. DICP: the annals of pharmacotherapy, 23,
847-854.
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Drug Induced
Mental Status Changes*
Cognitive impairment
Dementia, memory loss
• Methyldopa
• Opiate narcotics
• Propranolol
• Cimetidine
• Hydrochorothiazide
• Amantadine
• Reserpine
• Benzodiazepines
• Neuroleptics
• Anticonvulsants
*Owens NJ, Sillman RA, Fretwell, MD. (1989). The relationship between comprehensive functional
assessment and optimal pharmacotherapy in the older patient. DICP: the annals of pharmacotherapy,
23, 847-854.
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Drug Induced
Mental Status Changes*
Behavioral toxicity
insomnia, nightmares, sedation, agitation, irritability,
restlessness leading to: delirium, psychosis,
hallucinations
• Anticholinergics
• Baclofen
• Cimetidine
• Levodopa
• Ranitidine
• Opiate narcotics
• Digoxin
• Sympathomimetics
• Bromocriptine
• Corticosteroids
• Amantadine
*Owens NJ, Sillman RA, Fretwell, MD. (1989). The relationship between comprehensive functional assessment and
optimal pharmacotherapy in the older patient. DICP: the annals of pharmacotherapy, 23, 847-854.
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Drug Induced
Mental Status Changes*
Depression
• Reserpine
• Methyldopa
• Beta-blockers
• Corticosteroids
*Owens NJ, Sillman RA, Fretwell, MD. (1989). The relationship between comprehensive functional
assessment and optimal pharmacotherapy in the older patient. DICP: the annals of pharmacotherapy, 23,
847-854.
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Prevalence of Non-adherence
• Common problem for all
ages
• Prevalence of nonadherence ranges 40-70%
• Intentional non-adherence
more common in seniors
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I seem to be feeling better
Maybe I’ll only take my blood
pressure medication once a day
instead of twice daily.
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Consequences of
Medication Non-adherence
• Increased morbidity
• Prescribing of additional drugs
• Increased health care utilization
• Increased mortality
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Potential Barriers to
Non-adherence
Physiological factors
Behavioral / Attitudinal
Treatment-related factors
Prescriber / patient
interactions
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Physiological / Health
Factors
• Vision
• Hearing
• Dexterity
• Cognition
• Depression
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Behavioral / Attitudinal
Factors
• Social isolation
• Health beliefs (perceptions!)
• severity of illness
• susceptibility to illness
• side effects and efficacy of treatment
• Financial status
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Treatment Factors
• Duration of treatment
• Number of medications
• Complexity
• Dosing frequency
• Types of medications (dosing forms)
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Assessment of Adherence
• Observation of home environment
• Ask client to gather all medications
• Open ended questions regarding each medication (time
consuming)
• what drugs are they taking? how are they taking?
• Direct questions:
• “do you ever forget to take your medicines?” “how many
times in the last week have you missed a dose?”
• “when you feel better do you stop taking your medicines”
• “sometimes if you feel worse do you stop taking your
medicines?”
• Pharmacy refill patterns