Safe Medication Use in the Older Adultin the Older Adult

Holly Divine, PharmD, CGP, CDEAssociate ProfessorAssociate ProfessorUniversity of KentuckyCollege of PharmacyDepartment of Pharmacy Practice & Science

Obj tiObjectives

Know the principles of medication use in the Know the principles of medication use in the elderlyId tif t ti ll i i t di ti Identify potentially inappropriate medications for older adultsA i t l ib di ti f ld Appropriately prescribe medication for older adults

I t d tiIntroduction Elderly comprise 13% of population Elderly comprise 13% of population Use over 30% of all prescription medications 90% of age > 65 take at least one medication 90% of age > 65 take at least one medication Use 5.8 Rx drugs concurrently with 3.2 OTC drugs Cost of medications: >$25 5 billion/year Cost of medications: >$25.5 billion/year

Beers MH, Baran RW, Frenia K. Drugs and the Elderly, Part 1: The Problems Facing Managed Care. The American Journal of Managed Care 2000; 6(12):1313-1320.

What are some concerns with d i ld d lt ?med use in older adults?

Changes in aging Drugs affect older adults differently Drugs affect older adults differently

Compliance/Adherence Overuse Underuse Underuse

Polypharmacy Unclear medication regimeng All practitioners should do a thorough medication history at

EVERY visit! Inappropriate diagnoses/ignoring ADRspp p g g g Attributing adverse effects to normal “aging” or a new

illness Underreporting of symptoms Atypical symptomsyp y p

Treatment of sx vs. treatment of disease

C li /AdhCompliance/Adherence Reasons for noncompliance Reasons for noncompliance Lack of understanding Barriers to communications Complex regimen Differing doses

I i t h d li Inconvenient scheduling Lack of perceived need Adverse events Adverse events Cost Social isolation

C li /AdhCompliance/Adherence

Discrepancies between medical record and Discrepancies between medical record and actual medication use 76% had discrepancies 76% had discrepancies 51% taking medications not recorded in chart 29% not taking a recorded medication 29% not taking a recorded medication 20% taking different dosage than recorded

Bedell SE, et al. Arch Intern Med 2000;160:2129-34

P l hPolypharmacy More chronic medical conditions = more More chronic medical conditions = more

medications Patient and prescriber’s need to “do something”

even for common ailments with no cure Doctor shopping-often for the same problem Do not reveal all information at each visit Do not reveal all information at each visit

Meds prescribed to treat side effects of other meds! “Save” or borrow medications; self-medicate;

Ph ki tiPharmacokinetics Pharmacokinetics Pharmacokinetics How the body affects the drug

Management of the drug by the bodyg g y y Absorption, distribution, metabolism, excretion

NOTE: These changes are not universal. We all diff tl U l id liage differently. Use as general guidelines.

Pharmacokinetic ChangesAb tiAbsorption Changes Changes Decreased surface area and blood flow to GI Decreased GI motility Increased pH

Result Essentially unchanged Essentially unchanged

May have slightly decreased absorption-little effect Drugs affected: ketoconazole, iron supplements

(th th t i idi i t)(those that require an acidic environment)

Pharmacokinetic ChangesDi t ib tiDistribution

Protein binding Decreased albumin with age

Binds acidic drugs Binds acidic drugs Institutionalized, malnourished, and sick elderly Results: need lower dose of acidic protein bound drugsI d id l t i & li t i Increased α1-acid glycoprotein & lipoproteins Increases with inflammation, stress, injury-binds basic

drugsA th iti i tit ti li d Arthritis, institutionalized

Results: need higher dose of basic protein bound drugs

Pharmacokinetic ChangesDi t ib tiDistribution

C Common DrugsCommon Drugs Affected by Albumin

Common Drugs Affected by α1-Acid Glycoprotein/Lipo-

DigoxinTheophylline

y p pproteins

Propranololp yPhenytoin Warfarin

PropranololQuinidineLidocaine

DiazepamLidocaine

Pharmacokinetic ChangesDi t ib tiDistribution Volume of Distribution Volume of Distribution Less total body water Age 20 to 80, decrease 15% Results: need a lower dose for hydrophilic drugs Results: need a lower dose for hydrophilic drugs Lower Vd can result in increased serum concentration

Higher fat content Men from 18% to 36%; Women from 33% to 45% Men from 18% to 36%; Women from 33% to 45% Results: need a lower dose for lipophilic drugs Do not use or use cautiously, especially CNS drugs

Lower lean muscle mass (decreased muscle) Lower lean muscle mass (decreased muscle) Digoxin binds to muscle; therefore, conc increases as

a result of increased Vd = dig toxicity at doses lower than expectedthan expected

Pharmacokinetic ChangesDi t ib tiDistribution

Hydrophilic Drugs Lipophilic DrugsHydrophilic Drugs Lipophilic Drugs

Lithium PhenothiazinesAminoglycosidesEthanol

PhenytoinDiazepamBarbituratesPropranolol

Pharmacokinetic ChangesM t b liMetabolism Reduced hepatic blood flow Reduced hepatic blood flow Some drugs’ rate of metabolism is dependent upon rate of

hepatic blood flow Decrease hepatic flow Reduced amount of drug that is

extracted by the liver for metabolism during first pass Increased bioavailability of that drug y g

Drugs affected: calcium channel blockers, beta blockers, narcotics, nitrates, tricyclic antidepressants, hydralazine, labetalollabetalol

Sloan, RW. Principles of Drug Therapy in Geriatric Patients. Am Fam Phys 1992; 45: 2709-2718.

Pharmacokinetic ChangesM t b liMetabolism

Reduced hepatic mass and number of Reduced hepatic mass and number of functioning hepatocytes

Phase I and II metabolism performed by cyt P- Phase I and II metabolism performed by cyt P450 system Decline in Phase I (oxidative) metabolism in elderly Phase II unaffected by aging Major drugs affected: diazepam, alprazolam,

chlordiazepoxide amitriptylinechlordiazepoxide, amitriptyline Benaodiazepine Pearl: Use L.O.T.

Lorazepam, oxazepam, temazepam

Pharmacokinetic ChangesE ti /Eli i tiExcretion/Elimination Renal function generally decreases with age Renal function generally decreases with age CrCl decreases ~ 10%/decade after age 40 in 2/3

persons Pearl: Is serum creatinine a good indicator of renal

function in the elderly? NO! NO! Scr is a product of muscle breakdown

Decreased muscle mass in agedreduced production of Scrcould produce normal Scr in person with reducedScrcould produce normal Scr in person with reduced renal function

CrCl is better indicator of renal function

Pharmacokinetic ChangesE ti /Eli i tiExcretion/Elimination

Common Renally-eliminated Drugs

Allopurinol AminoglycosidesRanitidine, famotadine,

nizatidineCiprofloxacin

Most ACE inhibitors (except fosinopril)DigoxinCiprofloxacin

MeperidineMagnesium

DigoxinLithium

DiureticsMetformin

Potentially Inappropriate M di ti B C it iMedications: Beers Criteria Beers MH Ouslander JS Rollingher J et al Beers MH, Ouslander JS, Rollingher J, et al.

Explicit criteria for determining potentially inappropriate medication use in nursing home

id t A h I t M d 1991 151 1825 32residents. Arch Intern Med 1991; 151:1825-32. Beers MH. Explicit criteria for determining

potentially inappropriate medication use by the p y pp p yelderly. Arch Intern Med 1997;157:1531-1536.

Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriateBeers criteria for potentially inappropriate medication use in older adults. Arch Intern Med2003; 163:2716-24.

Potentially Inappropriate M di ti B C it iMedications: Beers Criteria Medications or classes that should generally be Medications or classes that should generally be

avoided in persons 65 years or older because they are either ineffective or they pose unnecessarily y p yhigh risks for older persons and a safer alternative is available

48 di ti l t id 48 medications or classes to avoid Medications that should not be used in older

persons known to have specific medical conditionspersons known to have specific medical conditions 20 diseases or conditions and medications to avoid

Potentially Inappropriate M di ti B C it iMedications: Beers Criteria Propoxyphene • Chlordiazepoxide Propoxyphene Indomethacin

M l R l t

Chlordiazepoxide, diazepam

• Long acting Muscle Relaxants Amitriptyline, doxepin

M idi

g gbenzodiazepines

• GI antispasmodics Meperidine Flurazepam

• Diphenhydramine• Ticlopidine

B bit t t Anticholinergics & antihistamines

• Barbiturates, except for seizures

Source: Fick DM, et al. Arch Intern Med 2003; 163:2716-24.

Beers MH. Explicit Criteria for Determining Potentially Inappropriate Medication Use by the Elderly. Arch Int Med. 1997;157:1531-1536.

Potentially Inappropriate Medications Considering Dx:Medications Considering Dx: Beers Criteria COPD: beta-blockers sedative/hypnotics COPD: beta blockers, sedative/hypnotics Ulcers: NSAIDs Seizures: metoclopramide, some antipsychotics Bladder outflow obstruction: anticholinergics &

antihistamines Arrhythmias: tricyclic antidepressantsy y p Insomnia: decongestants, theophylline, SSRIs Hypertension: pseudoephedrine

C iti i i t ti h li i Cognitive impairment: anticholinergics Chronic constipation: calcium channel blockers,

anticholinergics, TCAg

Source: Fick DM, et al. Arch Intern Med 2003; 163:2716-24.Beers MH. Explicit Criteria for Determining Potentially Inappropriate Medication Use by the Elderly. Arch Int Med. 1997;157:1531-1536.

Potentially Inappropriate M di ti Zh C it iMedications: Zhan Criteria

Zhan C Sangl J Bierman AS et al Zhan C, Sangl J, Bierman AS, et al. Potentially inappropriate medication use in the community-dwelling elderly: findings fromthe community-dwelling elderly: findings from the 1996 medical expenditure panel survey. JAMA 2001;286:2823-2829JAMA 2001;286:2823 2829.

Potentially Inappropriate M di ti Zh C it iMedications: Zhan Criteria

Reevaluated Beers criteria with expert panel Reevaluated Beers criteria with expert panel to evaluate in community-dwelling elderlyAl id 11 di ti Always avoid: 11 medications Barbiturates, flurazepam, meperidine, etc.R l i t 8 di ti Rarely appropriate: 8 medications Diazepam, propoxyphene, cyclobenzaprine, etc.

Some indications: 14 medications Amitriptyline, diphenhydramine, doxepin, etc.

H ll d i ?How well are we doing? 765 423 patients 65 and older in a PBM were 765,423 patients 65 and older in a PBM were

reviewed 21% of patients had 1 or more prescriptions filled for

drugs of concern 51% of those claims were for drugs with the

potential for severe adverse effectspotential for severe adverse effects 23% of claims were for amitriptyline and doxepin

15% of patients filled prescriptions for 2 drugs of concern 4% filled for 3 or more within the same year

Arch Intern Med. 2004;164:1621-1625. “Inappropriate Prescribing for Elderly Americans in a Large Outpatient Population”

H ll d i ?How well are we doing?Setting >1 ReferenceSetting >1

InappropriateReference

Nursing facility 40.3% Beers, 1992Nursing facility 40.3% Beers, 1992

Community 28.7% Willcox, 1994

Homebound 39 7% Golden 1999Homebound 39.7% Golden, 1999

Community 25.0% Zhan, 2001

ALF 16.0% Sloane, 2002

Residential Care 22.0% Gray, 2003

Community 21.2% Curtis, 2004

Outcomes of Inappropriate P ibiPrescribing

In nursing home residents: In nursing home residents: 30% higher risk of hospitalization

21% higher risk of death 21% higher risk of death Sample 3372 residents with >3 consecutive

months of staymonths of stay

Lau DT, et al. Arch Intern Med 2005;165:68-74.

Outcomes of Inappropriate P ibiPrescribing

1117 medical records reviewed in 15 nursing 1117 medical records reviewed in 15 nursing homes with high risk of polypharmacyAd t h it li ti ED i it Adverse outcomes: hospitalization, ED visit, or death

Any inappropriate prescription increased Any inappropriate prescription increased likelihood of an adverse outcome

One of the first studies to prove that inappropriate One of the first studies to prove that inappropriate medications (as defined by Beers) is associated with adverse outcomes

Perri III M, et al. Ann Pharmacother 2005;39:March.

Ad D R tiAdverse Drug Reactions Unintended unwanted harmful or unexpected Unintended, unwanted, harmful, or unexpected

effect of a drug 28% of hospitalizations in the elderly attributed to

ADRs (17%) and non-adherence (11%) 10-35% of elderly outpatients experience ADRs May occur in as many as 44% of hospitalized elderly May occur in as many as 44% of hospitalized elderly ADR risk doubles when drug use increases from 1

to 4 drugs; increases 14-fold in elders who use 7 g ;drugs

Beers MH, Baran RW, Frenia K. Drugs and the Elderly, Part 1: The Problems Facing Managed Care. The A i J l f M d C 2000 6(12) 1313 1320American Journal of Managed Care 2000; 6(12):1313-1320.

Col N, et al. Arch Intern Med 1990; 150:841-5.

Hanlon JT, et al. JAGS 1997; 45:945-8.

Chrischilles EA, et al. Ann Intern Med 1992; 117:634-40.

C f ADRCauses of ADRs

Improper drug or dosage selection Improper drug or dosage selection Non-adherence to drug regimen Altered pharmacokinetics Multiple medications Multiple providers

ADR Ri k F tADR Risk Factors Advanced age (>85) Dementia Advanced age (>85) Female Lower SES

Dementia Hepatic or renal

insufficiency (CrCl<50 Lower SES Lives alone Lower body weight

insufficiency (CrCl 50 ml/min)

Multiple prescribers Lower body weight Hx prior drug reactions Regular use of alcohol

Long duration of use Polypharmacy

Regular use of alcohol Prior ADR Recent hospitalization

Multiple chronic diseases

Recent hospitalization

Hajjar ER, et al. Am J Geriatr Pharmacother 2003;1:82-9.

ADR P lADR Pearl

Any symptom in an older adult should beAny symptom in an older adult should be considered a drug side effect until proven

otherwise!otherwise!

• Fall • Depression• Fall• GI distress

Depression• Anxiety

C f i• Incontinence• Constipation

• Confusion• Insomnia

C ADR i Eld lCommon ADRs in Elderly Falls Falls Sedative/hypnotics, anticonvulsants,

antihypertensives, antipsychotics, antineoplastics, yp , p y , p ,hypoglycemics

GI Distress Aspirin, NSAIDs, iron, theophylline, lipid-lowering

agents, antibiotics Incontinence Incontinence Caffeine, diuretics, theophylline, alcohol,

sedative/hypnoticsyp

C ADR i th Eld lCommon ADRs in the Elderly

Constipation Verapamil/diltiazem, antipsychotics, antidepressants,

ti di ti t id (Al/C ) ti h li inarcotics, diuretics, antacids (Al/Ca), anticholinergics Confusion Any CNS agent, anti-Parkinson’s agents, digoxin, y g , g , g ,

metoclopramide, beta-blockers Depression Beta blockers (propranolol) sedative/hypnotics Beta-blockers (propranolol), sedative/hypnotics,

hormones, NSAIDs, digoxin, metoclopramide Anxiety/insomnia Caffeine, theophylline, SSRIs, decongestants, steroids

P ibi C dPrescribing CascadeMedications prescribed to treat side effects of otherMedications prescribed to treat side effects of other

medications!!!

“As older patients move through time, often from physician to physician, they are at increasing risk of accumulating layer upon layer of drug therapy, as a reef accumulates layer upon layer of coral.” Jerry

Avorn M DAvorn, M.D.

Gurwitz JH. Arch Intern Med 2004;164:1957-9.

D I t tiDrug Interactions Drug-Drug-too many to list! Drug-Drug-too many to list! Common disease states associated with high risk of drug

interactions: autoimmune, cardiovascular, gastrointestinal, infection psychiatric d/o respiratory seizure d/oinfection, psychiatric d/o, respiratory, seizure d/o

2 medications = 13% risk 5 medications = 38% risk >7 medications = 82% risk Preventable drug interactions account for about 1/3 of

ADRs

http://www.scoup.net/M3Project/topten/

Goldberg RM, et al. Am J Emerg Med 1996;14:447-50.

P l f S f M di ti UPearls for Safe Medication Use

Every drug must have clearly defined Every drug must have clearly defined indicationP ti t d ti Patient education

Records containing complete medication i i l di OTC d h b lreview, including OTCs and herbals

Therapeutic endpoints and ADRs must be it dmonitored

Provide annual drug regimen review

S ll C St d 1Small Case Study 1

MH is a 77 year old female residing in a NH MH is a 77-year-old female residing in a NH. Weight=112 lbs. Scr=1.0M di ti itidi 150 bid t l l Medications: ranitidine 150 mg bid, atenolol50 mg qam, diazepam 5 mg qhs, acetaminophen 1g q6h prn pain MOM 15 mlacetaminophen 1g q6h prn pain, MOM 15 ml qid prn

S ll C St d 1 KSmall Case Study 1-Key

CrCl = 37 2 ml/min CrCl = 37.2 ml/min Monitor MOM use

Ranitidine: dec dose to once daily Ranitidine: dec. dose to once daily Diazepam

N t d d h t LOT (if d d) Not recommended; change to LOT (if needed) Pearl: Why do you think she’s taking

di ? Sl ? H tb l t d?diazepam? Sleep? Heartburn-related?

S ll C St d 2Small Case Study 2 CK is a 82-year-old male entering your primary care CK is a 82-year-old male entering your primary care

clinic for an initial visit to establish care. Your interview reveals the following:

C Tylenol PM qhs, diazepam 2.5 mg qhs, Combivent 2-4 puffs 4 times daily, doxazosin 4 mg qhs

Dx: COPD, insomnia, BPH, hypertension What meds would you deem potentially

inappropriate and why?

S ll C St d 2 KSmall Case Study 2-Key

Tylenol PM has diphenhydramine not Tylenol PM has diphenhydramine-not appropriate for elderly or in BPHDi t i t f ld l i Diazepam-not appropriate for elderly or in COPD

S ll C St d 3Small Case Study 3

PT is an 81 year old female She enters the PT is an 81-year-old female. She enters the clinic pharmacy today after a visit to her primary care provider. She requests some OTC productsproducts. Med profile: Triamterene/HCTZ 75/50 mg qd;

metoprolol 50 mg bid; glyburide 10 mg bid; insulin 70/30 25 U bid; celecoxib 200 mg qd; propoxyphene-N-70/30 25 U bid; celecoxib 200 mg qd; propoxyphene N100 mg qid

OTC list: hard candies, glucose tablets, calcium, Depends, glucosamine, APAP

What questions should be asked? What are some potential problems?

S ll C St d 3 KSmall Case Study 3-Key MAJOR FALL RISK! MAJOR FALL RISK! Potential hypoglycemia, hypotension, and confusion

(propoxyphene)T ki C l i h OP Taking Calcium, so may have OP

Propoxyphene not recommended in elderly Using Depends + diuretic?? Using Depends + diuretic?? May be having increased pain. . . Did she already

have a fall???