Geropharmacology

1
Geropharmacology

• Everything that you wanted to know about drugs
  and the elderly, but were afraid to ask
• Jim Webster MS, MD
• Supported by a grant from the Retirement Research
  Foundation

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Therapeutic Response
Therapeutic Window
Toxic Response
3
The Precipice
Physiologic Reserves Available
Physiologic Reserves Already In Use
Increasing Age
4
The Message for Today

• Start low
• Go slow (but get to therapeutic levels)
• Sometimes say no (how about other non-drug
  treatments?)

5
What Geriatricians Do (that makes a difference)

• Counsel families about dying
• Stop drugs !
• --- because although the elderly are 14 of the
  population they use 40 of the prescriptions,
  and
• They are especially likely to suffer adverse drug
  events (ADEs)

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Pharmacokinetics 101

• Absorption
• Distribution
• Metabolism
• Clearance

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Absorption

• From a practical standpoint this is not usually a
  problem in the elderly
• Caveat Tube feedings may reduce absorption if
  continuous

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Distribution

• In the elderly this is significantly altered as a
• result of age related changes in --
• Low serum albumen -- results in changing the free
  vs. bound proportion of drugs
• Increased fat -- increases the half life of
  lipophylic drugs (e.g. valium, anesthetics)
• Decreased body water -- the most important
  change, lower Vd. in polar drugs
• Decreased muscle mass

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Clearance via Kidney-Reduced

• Lower GFR (decreased size, tubular secretion,
  renal blood flow)
• Serum creatinine is not a reliable measure and
  Cockcroft-Gault is an estimate Renal (fx) shows
  big individual variations in the elderly
• (140-age) x body wt. (kg.)
  
  
• Cr cl. 72 x Serum Cr.
• (x 0.85 for Women)

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Drug Metabolism is Very Liver Dependent

• Reduced liver (fx) due to decreased liver size,
  blood flow, and dsz. (e.g. CHF)
• Phase I - first pass oxidative/reduction
  activities are reduced (e.g. propranolol)
• Phase II - drugs are preferred (oxazepam)
• In general, biotransforming enzymes are reduced
  in the elderly

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Pharmacodynamics

• Alterations are complex and poorly studied
• Generally the elderly are more sensitive to drug
  effects (e.g. the blood/brain barrier and
  anticholinergics and benzodiazapines)
• But, Beta-adrenergic effects are reduced
• Homeostasis is more effected by drugs (e.g.
  postural BP, extrapyramidal system,
  thermoregulation, cognition)

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Adverse Drug Events (ADEs) in the Elderly are

• Common in both in-patients and out-patient
  environments ( ? 35 !)
• A frequent cause of hospitalization
• Costly
• Under-diagnosed
• Mostly preventable, and are due to errors in
  prescribing (40) or monitoring and supervision
  (50)

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Medications Causing Preventable Averse Drug
Events (PADEs) in Ambulatory Settings

• Diuretics 22
• Other CV Drugs 25
• Hypoglycemics 11
• Anticoagulents 10
• Analgesics 15
• Sedative Hypnotics 17
• Gurwitz

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PADE Errors

• Excess Dosing 24
• Wrong Drug 27
• Known Interaction 13
• Inadequate Pt. Educ. 18
• Pt. Adherence 21
• Inadequate Monitoring 36
• Gurwitz

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ADE Risk Factors

• Six drugs or gt 12 doses a day
• Female
• Low BMI
• High of comorbidities (Charleson Index Score)
• gt 85 years old
• Low Cr. Cl.

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High Risk Drugs for Elderly

• Warfarin
• Digoxin gt 0.125/day
• Meperidine
• Ticlodipine
• Antihistimines (especially Diphenhydramine-Benadry
  l!)
• Imdomethicin
• Chlorpropamide
• NSAIDS
• Propoxyphene (Darvon)

• Review the indications, dose, and monitoring of
• Corticosteroids
• Anticholinergics
• Amnioderone
• Anticoagulents
• Benzodiazapines (especially the long acting ones)

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In Prescribing for Elderly Ask

• Are there non-drug Rxs? (e.g. for sleep,
  anxiety, PT for Msk. Sxs)
• Could these sxs. be due to a drug effect?
• What is the end point?
• Can this patient afford this medication?
• Can they open the pill container?
• Will they understand how and when to take it?

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Writing Prescriptions

• Use the Computer whenever possible
• Sit down and print
• Watch decimal points (mcg. 0.5, 1)
• What is this for?
• When is it taken?
• Watch spaces (Inderal40)
• No as directed directions
• Stamp out abbreviations

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Verbal orders

• Spell Drugs out
• Use Pilot numbers one five not 15 mgs
• Speak clearly and slowly
• Clearly specify concentrations
• Have the receiver (R.N. or RPh.) read back the
  order

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Adherence in the Elderly

• Is better in the functional older patient than in
  most patients (They like and trust us!)
• Non-adherence may be up to 50 in some older
  populations, frequently those who need
  medications the most
• Consider the patients financial, cognitive and
  functional status, and their health beliefs

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Strategy I - Simplify It

• Once a day dosing
• Large fonts on the labels
• Pill boxes, calendars and drug diaries
• Decrease the numbers of meds.

22
Strategy II - Clarify Administration

• Put the indication on the label or diary
• Specify the exact times of administration
• Give written instructions and information,
  encourage package inserts
• Involve others such as family, home health

23
Strategy III - Systems Approaches

• Have a (computerized?) medication list on every
  chart
• A brown bag inventory by staff each visit
• Patient to use one pharmacy (?print out)
• Computerized prompts for blood levels

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In Summary For Elderly Patients

• Start low
• Go slow (But get to therapeutic levels)
• Sometimes say no
• Thats all folks ! Thank you