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
• < 5% of US residents ≥ 65 live in long‐term care
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, polypharmacyElderly 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
gcartilaginous 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/calcificationsI d t i l ll tiff• Increased arterial wall stiffness
• Decreased baroreceptor reflex• Increased catecholamines, but desensitized beta‐adrenergic receptors
CNSCNS
• 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)
Norepinephrine
• Atrial natriureticpeptideDHEA (gradual)
• Renin
• Aldosterone
peptide
• Insulin
• Parathyroid hormoneAldosterone
• Erythropoetin
Parathyroid hormone
Pharmacokinetic ChangesPharmacokinetic Changes
• AbsorptionAbsorption
• Distribution
b li• Metabolism
• Excretion
AbsorptionAbsorption
• Most patients: Increased GI transit timeMost patients: Increased GI transit time delayed absorption (no change in AUC)
• Some patients: Decreased stomach acid• Some patients: Decreased stomach aciddecreased 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 yprotein larger free drug fraction (eg, phenytoin, warfarin)p y , )
MetabolismMetabolism
• Smaller liver decreased hepatic blood flowSmaller liver, decreased hepatic blood flowdecreased 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 < 0.8 mg/dL, but gno good evidence for rounding up
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 neurotransmittersSmaller reserve of brain neurotransmittersincreased 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 UseAnna 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 deadults.
• Recognize common medications that are gconsidered 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 medications etchistory, other medications, etc.
• Recommend strategies for optimizing medication use in older adultsuse in older adults.
Suboptimal Drug Use in the ElderlySuboptimal Drug Use in the Elderly
• Inappropriate medicationsInappropriate medications
• Insufficient monitoring
i dh• Patient nonadherance
• Overdosage
• Inadequate treatment
Inappropriate MedicationsInappropriate Medications
• Medications for which there is no indicationMedications for which there is no indication
• Allergies/history of intolerance
d d di i i• Drug‐drug or drug‐disease interactions
• Unnecessary duplication
• “Prescribing cascade”
• Beers criteriaBeers criteria
Mini‐Case: Inappropriate MedsMini Case: Inappropriate Meds
• AM is an 81‐year‐old • Meds:AM is an 81 year old woman who presents to the brown bag table at
– Fosamax 70 mg PO weekly
V l f i 75 POthe CoP health fair. – Venlafaxine 75 mg PO BID
– Promethazine 25 mg PO gTID PRN N/V
– Modafinil 100 mg PO qam
– OTC Calcium + D (500mg/400 units) PO ( g/ )BID
Beers CriteriaBeers Criteria
• AKA “Beers list”AKA Beers list
• Consensus guidelines for medication use in older adultsolder adults
• Originally developed 1991, last updated 2003
• 3 categories, with high or low severity ratings:– Generally inappropriate drug choices
– Excess dosages/frequencies
– Drug/disease interactionsg
Generally InappropriateGenerally Inappropriate
High severity rating Methyltestosterone Amiodarone
Amitriptyline Mineral oil
Nitrofurantoin Chlorpropamide
Disopyramide Orphenadrine
Pentazocine Doxepin
Indomethacin Trimethobenzamide
Ketorolac
Meperidine
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724. Holuby, RS. Medication Safety in Older Adults.
Generally InappropriateGenerally Inappropriate
High severity rating (continued)High severity rating (continued) Gastrointestinal antispasmodics (dicyclomine, hyoscyamine, propantheline, belladonna alkaloids, clidinium‐chlordiazepoxide)
Long‐acting benzodiazepines (chlordiazepoxide, diazepam, flurazepam quazepam halazepam clorazepate)flurazepam, quazepam, halazepam, clorazepate)
Muscle relaxants and antispasmodics (methocarbamol, carisoprodol, chlorzoxazone, metaxalone, cyclobenzaprine)
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724. Holuby, RS. Medication Safety in Older Adults.
Potentially Inappropriate in Certain Circumstances
High severityHigh severity Fluoxetine (used daily) Longer half‐life nonsteroidal anti‐inflammatory agents (long‐term use of full‐dosage naproxen, oxaprozin, piroxicam)
Short‐acting benzodiazepines (lorazepam 3 mg, oxazepamg p ( p g, p60 mg, alprazolam 2 mg, temazepam 15 mg, triazolam 0.25 mg)
Stimulant laxatives (long‐term use of bisacodyl cascara Stimulant laxatives (long‐term use of bisacodyl, cascara sagrada, castor oil except in presence of opiate analgesic use)
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724.
Potentially Inappropriate in Certain Circumstances
Low severityLow severity Digoxin (> 0.125 mg/day, except when treating atrial arrhythmias)
Ferrous sulfate (> 325 mg/day)
Reserpine (> 0.25 mg/day)
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724.
Potentially Inappropriate / din Certain Diseases/Conditions
Disease/Condition Drug Concern Severity Rating (High or Low)
Heart Failure Disopyramide and high sodium content d
Negative inotropic effect. Potential to promote fluid t ti d
High
drugs retention and exacerbation of heart failure
Hypertension Pseudoephedrine; May produce elevation of HighHypertension Pseudoephedrine;diet pills and amphetamines
May produce elevation of blood pressure secondary to sympathomimeticactivity
High
Gastric or duodenal ulcers
NSAIDs and aspirin (>325 mg); coxibsexcluded
May exacerbate existing ulcers or produce new ulcers
High
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724.
Potentially Inappropriate / din Certain Diseases/Conditions
Disease/Condition Drug Concern Severity Rating (High or Low)
Seizures/epilepsy Bupropion, clozapine, hl i
May lower seizure thresholds High
chlorpromazine, thioridazine and thiothixene
Blood clotting Aspirin NSAIDs May prolong clotting time and HighBlood clotting disorders or receiving anticoagulant therapy
Aspirin, NSAIDs, dipyridamole, ticlopidine andclopidogrel
May prolong clotting time and elevate INR values or inhibit platelet aggregation, resulting in increased potential for
High
bleeding
Arrhythmias Tricyclic antidepressants
Proarrhythmic effects and ability to produce QT interval changes
High
changes
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724.
Potentially Inappropriate / din Certain Diseases/Conditions
Disease/Condit Drug Concern Severity Rating ion (High or Low)
Bladder outflow b t ti
Anticholinergics, antihistamines, GI antispasmodics, muscle l t b t i IR
May decrease urinary flow, l di t
High
obstruction relaxants, oxybutynin IR, flavoxate, antidepressants, decongestants and tolterodine IR
leading to urinary retention
Stress Alpha‐blockers anticholinergics May produce HighStress incontinence
Alpha blockers, anticholinergics, tricyclic antidepressants and long‐acting benzodiazepines
May produce polyuria and worsening of incontinence
High
Insomnia Decongestants, theophylline, methylphenidate, MAOIs and amphetamines
CNS stimulant effects
High
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724.
Potentially Inappropriate / din Certain Diseases/Conditions
Disease/Condition Drug Concern Severity Rating (High or Low)
Parkinson’s disease Metoclopramide, antipsychotics and t i
Antidopaminergic/ cholinergic effects
High
tacrine
Cognitive impairment
Barbiturates, anticholinergics, antispasmodics
CNS‐altering effects High
antispasmodics, and amphetamines
Depression Long‐term benzodiazepine
Produce or exacerbate
Highp
use, methyldopaand reserpine
depression
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724.
Potentially Inappropriate / din Certain Diseases/Conditions
Disease/Condi Drug Concern Severity Rating tion (High or Low)
Anorexia/malnutrition
Amphetamines and fluoxetine
Appetite‐suppressing effects
High
Syncope or falls
Short‐ to intermediate‐acting benzodiazepine and tricyclic antidepressants
May produce ataxia, impaired psychomotor function, syncope and additional falls
High
additional falls
COPD Long‐acting benzodiazepines, non‐selective beta‐blockers
CNS adverse effects, may induce or exacerbate respiratory
High
p ydepression
Fick et al. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716‐2724.
Dose Calculations CaseDose Calculations Case
65‐year‐old African‐American male present65 year old African American male present to clinic for DM checkup. Pt reports not monitoring glucose at homep g g
• PMH: Type 2 DM x 16 years HTN x 2 years Hyperlipidemia x 5 years COPD x 8 yearsy Insomnia x 10 years GERD x 4 years (self‐treated with OTC)
With thanks to S. Holuby, PharmD
Dose Calculations Case (cont’d)Dose Calculations Case (cont d)
• Labs:Labs: BUN 27 mg/dl Scr 1.6 mg/dl
Ca2+ 9.3 mg/dl Phos 2.5 mg/dlLDL 152 /dl(1.3 mg/dl 1 yr prior)
K+ 5.2 mEq/L Glucose 54 mg/dl
LDL 152 mg/dl HDL 46 mg/dl TG 198 mg/dlGlucose 54 mg/dl
HgbA1c 6.4% Hgb 12.2 g/dl
g/ 24 hr urine: 2.1 L Urine creatinine 30 mg/dl
/ Hct 36.5% Urine albumin 680 mg/24 hr
Dose Calculations Case (cont’d)Dose Calculations Case (cont d)
• Meds:Meds: Cimetidine 200 mg po bid
Diazepam 10 mg po qhs prn sleepp g p q p p
Chlorpropamide 250 mg po daily
Metformin 1000 mg po bid
Albuterol/Ipratropium inh 2 puffs 4 times daily
Lisinopril 40 mg po bid
Propranolol LA 120 mg po daily
Pravastatin 20 mg qhs
Dose Calculations Case (cont’d)Dose Calculations Case (cont d)
• Which medications may be inappropriateWhich medications may be inappropriate according to Beers criteria?
Dose Calculations Case (cont’d)Dose Calculations Case (cont d)
• Calculate the pt’s ClC using:Calculate the pt s ClCr using:Cockroft‐Gault Cl = (140 – age) x weight (kg)/(S x 72) Clcr = (140 age) x weight (kg)/(Scr x 72)
Clcr = [(140 ‐ 65) x (68.4)]/(1.6 x 72) = 45 ml/mincr [( ) ( )]/( ) /
Dose Calculations Case (cont’d)Dose Calculations Case (cont d)
• Calculate the pt’s ClC using:Calculate the pt s ClCr using:24‐hour urine Cl = (U x V)/(S x 1440) ClCr = (UCr x V)/(SCr x 1440)
ClCr = (30 x 2100)/(1.6 x 1440 ) = 27 ml/minCr ( )/( ) /
Dose Calculations Case (cont’d)Dose Calculations Case (cont d)
• Which medications may need to be adjustedWhich medications may need to be adjusted, changed or stopped?
Insufficient MonitoringInsufficient Monitoring
• Associated with 45.4% of ADEs in ambulatory ycare
• >60% of these required hospitalization• Pharmacist’s Letter has a great chart on monitoring parameters for common drugs
• Insufficient safetymonitoring• Insufficient safetymonitoring – Preventable ADEs
• Insufficient efficacymonitoringy g– Unnecessary cost– Unnecessary risk of ADEsU d di l di i– Untreated medical condition
Fundamentals of Geriatric Pharmacotherapy: An Evidence‐Based Approach
OverdosageOverdosage
• Remember pharmacokinetic and e e be p a aco et c a dpharmacodynamic changes!
• Generally start at lowest dose and titrate slowlyy y• MONITOR.• Toxicity may take several half‐lives to appear, and y y pp ,half‐lives may be prolonged: symptoms may appear weeks or months after starting drug
• Changes in renal function, etc may make a stable dose suddenly too high
Mini‐CaseMini Case
• LM is an 86 y/o female admitted to the ED with s a 86 y/o e a e ad tted to t e tdelirium. Spouse reports she adheres to med regimen but does not self‐monitor BP or HR at hhome.
• PMH: A fib (new dx 1 month ago), HTN, CKD, OA, GERDGERD
• Meds: Digoxin 0.25 mg daily (added 1 month ago) metoprolol XL 25 mg daily warfarin 3 mgago), metoprolol XL 25 mg daily, warfarin 3 mg daily (added 1 month ago), APAP 650 mg TID, omeprazole 20 mg daily, MVI 1 dailyp g y, y
Fundamentals of Geriatric Pharmacotherapy: An Evidence‐Based Approach
Mini‐Case, ContinuedMini Case, Continued
• Allergies: NKDAe g es:• Wt 113 lbs, Ht 64”, BP 101/58, HR 52• PE: Elderly female with AMS, no signs of bruising,PE: Elderly female with AMS, no signs of bruising, bleeding, or other injury.
• Labs: Na 138, K 4.0, Cl 99, CO2 27, BUN 33, SCr, , , , ,1.2, glucose 109, INR 3.8, digoxin 2.4 ng/mL.
• Assessment and Plan?• What went wrong? How could this have been prevented?
Inadequate TreatmentInadequate Treatment
• Untreated medical problemUntreated medical problem
• Inadequately treated medical problem
ffi i d• Insufficient dose
Mini‐Case: Inadequate TreatmentMini Case: Inadequate Treatment
• JR is a 72‐year‐old male • Vitals: 124/70, 74, 18, ywho comes in to your ambulatory care clinic for routine follow up
/ , , ,98.2, 96% RA.
• NKDAfor routine follow‐up. He feels well today and is without complaints.
• Meds:– Lisinopril 20 mg PO dailyF id 10 PO
p• PMH: HTN, hyperlipidemia, CHF, t th iti
– Furosemide 10 mg PO daily
– Simvastatin 20 mg PO osteoarthritis.
• Recent labs: FLP at goal BMP wnl
daily– APAP ER 650 mg, 1‐2 tabs PO BID PRN paingoal, BMP wnl. p
Patient NonadherancePatient Nonadherance
• May be intentional or nonintentionalMay be intentional or nonintentional
• 5 most common reasons:F f id ff t– Fear of side effects.
– Disbelief in the medication's benefits.
– Difficulty in incorporating the regimen into a daily schedule.
F f b i d d t th di ti– Fear of becoming dependent on the medication.
– Cost of the medication.
Geriatric Pharmacotherapy: A Guide for the Helping Professional
Medication Appropriateness IndexMedication Appropriateness Index
1 Is there an indication for the medication?1. Is there an indication for the medication?
2. Is the medication effective for the condition?
3 h d ?3. Is the dosage correct?
4. Are the directions correct?
5. Are the directions practical?
6 Are there clinically significant drug‐drug6. Are there clinically significant drug drug interactions?
Medication Appropriateness IndexMedication Appropriateness Index
7. Are there clinically significant drug‐disease y g ginteractions?
8. Is there unnecessary duplication with other medication(s)?medication(s)?
9. Is the duration of therapy acceptable?10 Is the medication the least expensive alternative10. Is the medication the least expensive alternative
compared to others of equal utility?
What else needs to be asked in a drug regimen review?
Seven prescriptions for the H E L P I N G f i lH.E.L.P.I.N.G. professional
• H: Hear and see the elderly as whole persons, most of whom are bl t ti i t i d i i di th i t t t dable to participate in decisions regarding their treatment and medications.
• E: Earn the trust of the elderly through caring communication, cultural competence and being confident in what you recommendcultural competence, and being confident in what you recommend.
• L: Lead your professional colleagues into improving their collaborations with each other, which in turn may result in better treatment of the elderly.
• P: Protect the elderly from inappropriate medications, polypharmacy, and ADRs.
• I: Identify high‐risk elderly while improving their adherence to di i imedication regimens.
• N: Never forget the age‐related changes that affect drug dynamics of absorption, distribution, metabolism, and excretion.
• G Generate a complete drug history to document care follow up• G: Generate a complete drug history to document care, follow‐up, and the outcomes of any recommendation or intervention.