Geriatric Pharmacotherapy 1: Changes Associated ... Geriatric Pharmacotherapy 1: Changes Associated

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  • Geriatric Pharmacotherapy 1:   Changes Associated with Aging

    Anna Barbato, PharmD, CGP

    PHPP 518 (IT‐IV)PHPP 518 (IT IV)

    April 19, 2011

  • Learning ObjectivesLearning Objectives

    • Recognize common physiologic changesRecognize common physiologic changes  associated with normal aging.

    • Describe barriers to evaluating health and• Describe barriers to evaluating health and  disease in elderly patients.

    D ib h ki i d• Describe common pharmacokinetic and  pharmacodynamic changes associated with 

    l inormal aging.

    • Estimate renal function in elderly patients.

  • EpidemiologyEpidemiology

    • Cutoffs vary but commonly ≥ 65 y/o (MedicareCutoffs vary, but commonly ≥ 65 y/o (Medicare  population)

    • First baby boomers turn 65 this yearFirst baby boomers turn 65 this year • Year 2000:  12.4% of US population ≥ 65  Y 2030 ti t d 20% f US ≥ 65• Year 2030:  estimated 20% of US ≥ 65 

    • Women outnumber men; gender gap increases  ith i iwith increasing age

  • EpidemiologyEpidemiology

    • Geriatric pts account for 49% of all hospitalGeriatric pts account for 49% of all hospital  days of care and 1/3 of US healthcare  spendingspending

    • Patients over 65 take twice as many  medications as those under 65medications as those under 65.

  • Barriers to EvaluationBarriers to Evaluation

    • Sensory deficits: vision hearingSensory deficits:  vision, hearing • Underreporting of symptoms:  “I’m just  getting old ”getting old.

    • Unusual manifestations:  Approx 50% of older  i h i lpts present with atypical symptoms or 

    complaints (eg, functional decline as only  l i )complaint)

  • Barriers to EvaluationBarriers to Evaluation

    • Difficulty recalling: more complicated PMHDifficulty recalling:  more complicated PMH,  drug regimens, etc

    • Fear: of illness hospitalization dying• Fear:  of illness, hospitalization, dying • Age‐related disorders and problems:   d i i /di f d idepression, pain/discomfort, dementia, etc  may hinder interview

  • Physiologic Changes in AgingPhysiologic Changes in Aging

    • GeneralGeneral • Cardiovascular C S• CNS

    • Renal and genitourinary • Endocrine

  • GeneralGeneral

    • Decreased functional reserve capacity (frailty)Decreased functional reserve capacity (frailty) – Small stressors may have disproportionately large  effectseffects

    • Multiple disorders, polypharmacy Elderly pts average 6 diagnosable disorders1– Elderly pts average 6 diagnosable disorders1

    – Treating a single problem in isolation may  exacerbate other problemsexacerbate other problems

    1.  Evaluation of the Elderly Patient.  In: Merck Manual for Healthcare Professionals.  2009.

  • Physiologic Changes with AgingPhysiologic Changes with Aging

    • ↓ Body water • Degeneration of y • ↓ Muscle mass • ↑ Body fat

    g cartilaginous tissues

    • ↓ Joint elasticity ↓ H i d• Loss of high‐frequency 

    hearing • ↓ Lens flexibility

    • ↓ Hepatic mass and  blood flow

    • ↓ Lung elasticity• ↓ Lens flexibility • ↑ Gastric pH • ↑ GI transit time

    ↓ Lung elasticity • ↓ FEV1 • ↓ Skeletal bone mass↑

    • ↓ T‐cell and B‐cell  function

    • Et cetera…

  • CardiovascularCardiovascular

    • Decrease in number of myocytesDecrease in number of myocytes • Increased ventricular stiffness • Decreased SA node pacemaker cells• Decreased SA node pacemaker cells • Valve dilations/calcifications I d t i l ll tiff• Increased arterial wall stiffness

    • Decreased baroreceptor reflex • Increased catecholamines, but desensitized  beta‐adrenergic receptors


    • Decreased brain mass and blood flowDecreased brain mass and blood flow • Intact crystallized cognitive ability

    d fl id i i bili• Decreased fluid cognitive ability • Decreased sleep efficiency, more frequent  awakenings, less time in stage 3/4  and REM  sleep

  • Renal/GenitourinaryRenal/Genitourinary

    • Decreased glomeruliDecreased glomeruli • Increased thickness of basement membrane Of h i i i• Often no change in serum creatinine

    • Impaired tubular function/Na+ reabsorption • Enlarged prostate in men • Urethral atrophy and decreased pelvic floorUrethral atrophy and decreased pelvic floor  strength in women

  • EndocrineEndocrine

    Decreased concentrations Increased concentrationsDecreased concentrations

    • Estradiol (rapid post‐ menopause)

    Increased concentrations

    • Epinephrine • Norepinephrinep )

    • Testosterone (gradual) • DHEA (gradual)


    • Atrial natriuretic peptideDHEA (gradual)

    • Renin • Aldosterone


    • Insulin • Parathyroid hormoneAldosterone

    • Erythropoetin Parathyroid hormone

  • Pharmacokinetic ChangesPharmacokinetic Changes

    • AbsorptionAbsorption • Distribution

    b li• Metabolism • Excretion

  • AbsorptionAbsorption

    • Most patients: Increased GI transit timeMost patients:  Increased GI transit time  delayed absorption (no change in AUC)

    • Some patients: Decreased stomach acid• Some patients:  Decreased stomach acid decreased acid‐dependent absorption  (examples: B Fe Ca2+)(examples: B12, Fe, Ca2+)

    • A few oddballs:  Ciprofloxacin and narcotic  l i h i d b ianalgesics have increased absorption; 

    indomethacin has decreased absorption.

  • DistributionDistribution

    • Decreased lean body mass total body waterDecreased lean body mass, total body water • Increased body fat

    d d f h d hili d (• Decreased Vd for hydrophilic drugs (eg,  aminoglycosides, ethanol)

    • Increased t1/2 for lipophilic drugs (eg, BZDs) • Some patients may have decreased serum p y protein larger free drug fraction (eg,  phenytoin, warfarin)p y , )

  • MetabolismMetabolism

    • Smaller liver decreased hepatic blood flowSmaller liver, decreased hepatic blood flow decreased first pass effect

    • Phase I metabolism may decline (inconsistent)• Phase I metabolism may decline (inconsistent) • No evidence for decrease in phase II reactions

  • ExcretionExcretion

    • BIG changes here!BIG changes here! • Average 1% drop in GFR per year of age > 20 D d l l bl d fl• Decreased renal mass, renal blood flow,  glomerular efficiency

    • Cockroft‐Gault vs MDRD • CG overestimates CrCl if SCr

  • Calculating Renal FunctionCalculating Renal Function

    • Per KDOQI estimates with 24‐hr urine collectionPer KDOQI, estimates with 24 hr urine collection  don’t increase reliability for most patients

    • Exceptions for significant variation in:Exceptions for significant variation in:   – dietary intake (vegetarian diet, creatine supplements)  – muscle mass (amputation malnutrition musclemuscle mass (amputation, malnutrition, muscle  wasting)

    • 24‐hour urine collection24 hour urine collection – ClCr =   (Ucr x V) UCr = urine creatinine

    (S x 1440) V = urine volume in 24 hrs(Scr x 1440)                  V   urine volume in 24 hrs

  • Pharmacodynamic ChangesPharmacodynamic Changes

    • Smaller reserve of brain neurotransmittersSmaller reserve of brain neurotransmitters increased difficulty compensating for changes

    • Increased susceptibility to most CNS active• Increased susceptibility to most CNS‐active  drugs, including BZDs, opioids

    I d i h li i i i i• Increased anticholinergic sensitivity • Increased susceptibility to drugs that prolong  QT interval

  • Bottom LineBottom Line

    • Geriatric pharmacotherapy is complexGeriatric pharmacotherapy is complex. • Medication changes may have unforeseen  consequencesconsequences.

    • Start low, go slow! • Monitor often. • Be aware of barriers to evaluation.  • Maintain high suspicion of ADEs and ask lots  of questionsof questions.

  • Copyright 2007 by the American Pharmacists Association

  • Geriatric Pharmacotherapy 2:   Detecting and Avoiding ProblematicDetecting and Avoiding Problematic 

    Drug Use Anna Barbato, PharmD, CGP

    PHPP 518 (IT‐IV)PHPP 518 (IT IV)

    April 19, 2011

  • Learning ObjectivesLearning Objectives

    • Describe types of suboptimal drug use in older esc be types o subopt a d ug use o de adults.

    • Recognize common medications that are g considered inappropriate in older adults  according to the Beers criteria.

    • Identify medications that may be inappropriate  for a specific patient because of past medical  history other me