Pharmacotherapy

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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/edu
  cation/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
• gt 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 lt 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 ElderlyA 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 allstay
  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 cant 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

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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

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Dose Administered
Absorption
Distribution
Kidneys/ Liver
Circulation
Tissue
Elimination
Dynamics Kinetics
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
Disease-related
Drug-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 Old
(140-80) 72
(140 - 40) 72
cr cl
cr cl
72 (1.0)
72 (1.0)
cr cl 100 ml/min
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 lowgo 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 lowgo 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.

48
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.

49
Drug Induced Mobility Impairment

• 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.

50
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.

51
Drug Induced Mental Status Changes

• Cognitive impairment
• Dementia, memory loss
• Methyldopa
• Propranolol
• Hydrochorothiazide
• Reserpine
• Neuroleptics

• Opiate narcotics
• Cimetidine
• Amantadine
• Benzodiazepines
• 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.
52
Drug Induced Mental Status Changes
Behavioral toxicity insomnia, nightmares,
sedation, agitation, irritability, restlessness
leading to delirium, psychosis, hallucinations

• Anticholinergics
• Cimetidine
• Ranitidine
• Digoxin
• Bromocriptine
• Amantadine

• Baclofen
• Levodopa
• Opiate narcotics
• Sympathomimetics
• 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.
53
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.

54
Prevalence of Non-adherence

• Common problem for all ages
• Prevalence of non-adherence ranges 40-70
• Intentional non-adherence more common in seniors

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I seem to be feeling better Maybe Ill 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
Treatment-related factors
Prescriber / patient interactions
Behavioral / Attitudinal
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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