Geriatric Pharmacotherapy 1: Changes Associated …...Geriatric Pharmacotherapy 1: Changes Associated with Aging Anna Barbato, PharmD, CGP PHPP 518 (IT‐IV) April 19, 2011 Learning

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)


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




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



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




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



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


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


• 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


• Which medications may be inappropriateWhich medications may be inappropriate according to Beers criteria?


• 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 [( ) ( )]/( ) /


• 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 ( )/( ) /


• 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.

Documents

Geriatric Pharmacotherapy 1: Changes Associated …...Geriatric Pharmacotherapy 1: Changes Associated with Aging Anna Barbato, PharmD, CGP PHPP 518 (IT‐IV) April 19, 2011 Learning