Transcript Delirium Part 2: Evaluation & Management

Curriculum for the Hospitalized Aging Medical Patient
CHAMP
Drugs and Aging
Paula M. Podrazik, MD
University of Chicago
Case of Mrs. T…..
• 85 y/o with h/o DM, CHF, lumbar spinal stenosis admitted with increasing
confusion and falls. Lives alone, daughter involved. Daughter notes patient h/o
anxiety but c/o insomnia and phoning her continuously throughout the night for the
past 3 nights.
• Brought to U of C ER by daughter after a witnessed fall. New patient to the U of C
system. Admitted at 3AM to telemetry.
• On exam, alternately agitated and somnolent, oriented to person only.
VS: T99, P54, RR20, BP110/50 lying supine wt. 100lbs. 5’1”
Cor: RRR, +S3
Lungs: dry crackles in bases
Abd: soft, nontender, nondistended, firm stool felt throughout colon
• ER data:CT head neg., dirty urine, CXR with  cor, KUB FOS, BUN 48/CR 2.7, glc=
74, K+ hemolyzed at 6.3 F/U pending,INR=3.0, EKG SB-rate 58, no peaked t waves.
Given dose IV antibiotics in ER.
Case of Mrs. T…..
Meds:
Lisinopril 40mg q daily
Glipizide ER 20mg BID
Lasix 40 mg q daily
KCL 20 meq q daily
Paxil 20 mg q daily
Amiodarone 200mg q daily
Digoxin 0.25 mg q daily
Coumadin 5mg q daily
T#3 prn
Ativan 1mg prn
Unsom (OTC) prn sleep
Lomotil (OTC) prn
Senna and colace prn
Questions Raised….
• Why is this patient on so many meds?
• Could some of these meds be causing her
decline?
• What is involved in medication
management in the aging population?
• Why is medication management so
difficult in this population?
• Are there principles help guide
medication management?
Drugs and Aging: Topics for Review
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Information Gap
Aging Pharmacology
Polypharmacy
Drugs to Avoid
Adverse Drug Reactions
Cost
Compliance
Medication Review
Drugs and Aging
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Information Gap
Aging Pharmacology
Polypharmacy
Drugs to Avoid
Adverse Drug Reactions
Cost
Compliance
Medication Review
Older patients under-represented in drug trials
• Statins: 47 RCTs
– Only 1/3 reported proportion of patients
>65 years
– Median % of patients >65 in US trials was
21.1%
• Acute Coronary Syndromes
– Of patients hospitalized for ACS in 1995,
37% were >75 years
– Only 9% of patients in ACS trials 1991 to
2000 were >75 years
Bartlett, et al. Heart 2003; 89: 327-328.
Adverse Drug Events, Research and Aging
• Elderly excluded from investigational trials
• small sample sizes Phase III trials
• exclusion criteria=vulnerable elder
•“in vivo” no look at drugs in combo
• Under-reporting of drug safety problems
Schmucker DL, et al:J Clin Pharmacol 1999;39:1103-8
Avorn J: Br Med J 1997;315:1033-1034
Drugs and Aging
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Information Gap
Aging Pharmacology
Adverse Drug Reactions
Drugs to Avoid
Polypharmacy
Cost
Compliance
Medication Review
Aging Pharmacology:
Objectives
• Definitions
• Pharmacokinetics
– Aging & drug absorption
– Aging drug distribution
– Aging & Drug Clearance
• Renal Metabolism
• Hepatic Biotransformation
• Pharmacodynamics
Drug Absorption with Normal Aging
•  in gastric pH, motility, absorptive surface
•  gastric emptying time
• May see slower absorption,  time to effect
Bottom line: No clinically sign. age-related
change in drug absorption with normal aging.
Drug Distribution with Aging
•  body fat to age 60-70  antipsychotics, TCAs
•  in lean body mass and fat after 70  digoxin
conc.
•  protein-binding can effect Vd warfain +
amiodarone, phenytoin, ketaconazole
Bottom Line: Drug dosing is a dynamic process
with aging.
Hepatic Biotransformation and Aging
• Age- related decline
– Reduction in liver blood flow
• High-clearance drugs affected: propanolol,
labetolol, esmolol, lidocaine
– Reduction in hepatic oxidation: CYP450
• No age-related changes
– Hepatic acetylation
– Hepatic conjugation
Cytochrome P450 Systems
• CYP3A
– Metabolizes >60% of prescribed drugs including:
Calcium channel blockers, certain beta-blockers, most
“statins”, warfarin, amiodarone
• CYP2D6
– Metabolizes: metoprolol, propranolol, tramadol,
codeine,oxycodone,TCAs, SSRIs
Cytochrome P450 Inhibitors
• CYP3A Inhibitors
– Amiodarone, cimetadine, cyclosporin,
erythromycin, itra-/ketoconazole,grapefruit
juice
• CYP2D6 Inhibitors
– Cimetidine, SSRIs, quinidine
Renal Clearance and Aging
• ~ age 40, renal func. declines 1% per year
• Normal serum Cr  normal GFR
• Estimate using Cockcroft-Gault equation
Creatinine clearance =
(140-age) * Wt (kg) (  0.85 in women)
72 * serum Cr
• Modified MDRD
GFR estimate=
186x(Cr)-1.154x (Age)-0.203x (0.742, if female) x (1.21, if African
American)
Aging Pharmacodynamics
With aging:
• Beta-adrenergic responsiveness 
• Anticholinergic drugs   CNS effects
• Baroreceptor reflex blunted
Medication use based on aging
pharmacology principles
• Start low, go slow, dose to effect
• Adjust for decrease in renal clearance
• ID drugs w/narrow toxic/therapeutic
index
• ID drugs that effect CPY450 system e.g.,
inhibitors/inducers
• Adjust for anticholinergic properties of
drugs
• Remember the blunted barorecepter reflex
Drugs and Aging
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Information Gap
Aging Pharmacology
Polypharmacy
Adverse Drug Reactions
Drugs to Avoid
Cost
Compliance
Medication Review
Case of Mrs. K…..
75 y o F with CAD, HTN, OP, LBP
Walks 1 mile 3x per week & Tai Chi 2x per week & water aerobics class
1x per week
Med list:
asa 81 q day
lisinopril 20 q day
atenolol 25 q day
hctz 25 q day
lipitor (atorvastatin) 10 q day
fosamax (alendronate) 70 mg q week
MVI q day
tums 3 q day
vicodin (hydrocodone/acetaminophen) prn
What is the prevalence of drug use in the
elderly?
• Ambulatory adults > 65 surveyed
– 12% take > 10 meds
– 50% take 5 or > meds
Kaufman DW, et al The Slone survey. JAMA 2002;287:337..
2040 projections  > 65 = 20% of population &
consume 50% prescribed meds
Will polypharmacy continue to escalate?
Factors that influence prescribing in the
elderly
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More chronic conditions w/advancing age
Newer Rx for diseases (e.g., Alzheimer’s)
Wider indications for CV drugs
Lower thresholds @ which diseases Rx’d (e.g.,
hypercholesterolemia)
– Increased use of primary/secondary
prevention
Drug Interactions  with 5 or > drugs
Hazzard, Principles of Geriatric Medicine and Gerontology
Polypharmacy definitions?
• > 5 medications used
• Concurrent use of multiple prescriptions
& over-the-counter meds
• Definitions w/measure of
"appropriateness"
– Use of one med to treat adverse effects of
another
– Medical regimen includes > one unnecessary
med
– Use of more meds than clinically indicated
Polypharmacy & Adverse Drug Reactions
Rochon PA, Gurwitz JH BMJ 1997;315:1097
What is the risk of polypharmacy?
• Risk of drug-drug interactions increases
with increasing # of meds
• Up to 73% of ADRs involved unnecessary
meds
• 10-17% of hospital admissions due to
ADEs
Bergendal L, et al. Pharm World Sci. 1995;17:152.
Lindley CM. et al. Age Ageing. 1992;21:294.
Beard K. Drugs Ageing. 1992;2:356.
Drugs and Aging
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Information Gap
Aging Pharmacology
Polypharmacy
Drugs to Avoid
Adverse Drug Reactions
Cost
Compliance
Medication Review
Explicit Criteria --Beers
• List of medications to avoid in elderly
nursing home patients
• Developed by consensus panel in 1991
• Updated in 1997 and 2002
Beers, et al. Arch Intern Med 1991; 151: 1825-1832.
Beers MH. Arch Intern Med 1997; 157(14): 1531-1536.
Fick DM, et al. Arch Int Med 2003; 163: 2716-24.
Drugs to Avoid in the Elderly
Drug Classes/Drugs
• antihistamines
• antispasmodics
• certain CV meds
– methyldopa, (AldometTM), reserpine
– disopyramide (NorpaceTM)
– dipyridamole (PersantineTM)
• certain psychotropics
– amitriptyline( ElavilTM), doxepin (SinequanTM)
– meprobamate(MiltownTM), diazepam,
flurazepam (DalmaneTM), barbs
Beers MH Arch Intern Med 1997;157:1531-1536
Drugs to Avoid in the Elderly
Drug Classes/Drugs
• certain analgesics
– propoxyphene (DarvonTM)
– merperidine (DemerolTM)
– pentazocine (TalwinTM)
• chlorpropamide (DiabenaseTM)
• trimethobenzamide (TiganTM)
• certain anti-inflammatory agents
– indomethacin (IndocinTM),ketorolac (ToradolTM),
piroxicam(FeldeneTM)
Beers MH Arch Intern Med 1997;157:1531-1536
Interactions to Beware
Drug-Disease Interactions to Avoid
 dementia, falls + benzodiazepines
 BPH, constipation + antihistamines,
antispasmodics, TCAs
 CRF, CHF, PUD + NSAIDS
 DM + steroids
 asthma, COPD, PVD, HB + beta blockers
Beers MH Arch Intern Med 1997;157:1531-1536
Limitations of Explicit Criteria
• Clinical relevance
– Many medications outdated or not used
– Requires update by consensus panel
• Validity of data
– Criteria developed from nursing home data
– Applied in many unvalidated settings
• Room for clinical judgement?
Buetow SA, et al. Soc Sci Med 1997; 45(2): 261-271.
Drugs and Aging
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Information Gap
Aging Pharmacology
Polypharmacy
Drugs to Avoid
Adverse Drug Reactions
Cost
Compliance
Medication Review
ADR/ADE--defined
• Adverse Drug Reaction (ADR)
any undesirable or noxious drug effect at
standard drug treatment doses
WHO;1996 Technical Report Series No. 425
• Adverse Drug Event (ADE)
ADRs + errors in drug administration
ADRs
Side-effects
Drug-drug interaction
Amplified drug effects
ADRs
Drug-disease interaction
Drug-nutrient interaction
*not therapeutic failures
*not ADWEs
ADR Risk Factors
Carbonin P, et al JAGS 1991;39:1093-1099
ADR Risk Factors
# of drugs
# medical problems
high risk drugs
? aging pharm
Adverse
Drug
Reaction
? prior ADRs
? fragmented care
ADEs and Hospitalization
Recent inhospital studies look at ADEs
How big a problem?
• 4th-6th leading cause of hospital death (serious
ADRs 6.2%, fatal ADRs 0.32%)
• Increased length of stay
• Increased cost
Lazarou J, et al JAMA 1998; 280(20):1741-44
Classen D, et al JAMA 1997; 277(4): 301-6
Drugs and Aging
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Information Gap
Aging Pharmacology
Adverse Drug Reactions
Drugs to Avoid
Polypharmacy
Cost
Compliance
Medication Review
Drugs and Aging:
Cost
• Important to ask: “How do you pay for your
medications?”
• Federal poverty level: $10,400 for individual,
$14,000 for couple
• Potential sources of aid: Medicare Part D,
Medicaid, Circuit Breaker, Illinois Care Rx, Rx
buying club, manufacturer-sponsored
programs
Drugs and Aging
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Information Gap
Aging Pharmacology
Adverse Drug Reactions
Drugs to Avoid
Polypharmacy
Cost
Compliance
Medication Review
Compliance
• Compliance Adherence Concordance
• Non-adherence 25 to 59% in the elderly
• Factors associated with non-adherence
– Physical impairment
– Psychosocial risks
– Medication related factors
• Higher risk of re-hospitalization
• Risk of noncompliance after discharge
Ryan AA. Int’l J Nursing Studies 1999; 36: 153-62.
Van Eijken M, et al. Drugs & Aging 2003; 20: 229-40.
Drugs and Aging
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Information Gap
Aging Pharmacology
Adverse Drug Reactions
Drugs to Avoid
Polypharmacy
Cost
Compliance
Medication Review
Strategies for improving quality of
medication use in the elderly
• Medication Review
– Implicit criteria vs. explicit criteria
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Enlisting the pharmacist
Use of the CPOE
Enlisting the patient
Simplifying administration
– Polypill
– Single daily dosing
– Pill organizers
Medication Review
• Explicit criteria
– Drugs/classes of drugs w/high risk/ low
benefit
– U.S. example: Beers drugs-to-avoid criteria
• Requires updating
• Validity of data in other settings?
• ? Room for clinical judgment/ "patient-centered"
care
• Implicit criteria
– IDs individual elements of prescribing as
inappropriate e.g., MAI
– Time consuming, pharmacist driven
Fick DM, et al. Arch Int Med. 2003;163:2716.
Hanlon JT, et al. J Clin Epidemiol 1992;45:1045.
Samsa GP, et al. J Clin Epidemiol 1994;47:891.
The Medication Appropriateness Index
Hanlon JT, et al J Clin Epidemiology 1992;45:1045.
Balancing the polypharmacy tension
with a view to improving quality
Every drug listed ……
• has clinical indication
• is actually being taken
• has a risk/benefit analysis that is
recognized/understood/accepted
• is at the lowest effective dose
• is evaluated for cost
Key to med review in the elderly
is the clinical context
• Takes into account unique patient needs guided
by goals of care
– patient preferences
– estimated remaining life expectancy (RLE)
– best medical evidence including time until benefit
• Need a “captain of the ship” for med review
– Need to prioritize meds for patients with multiple
conditions
– Address new symptoms by including med review as
part of the process
Holmes HM, et al. Arch Intern Med 2006; 166:605.
Enlist the pharmacist
• Use in the clinical care team
• Examples
– Coumadin clinics
– Multidisciplinary interventions
• ICU
• COPD
• CHF
Holland R, et al. Homer trial BMJ 2005;330:293.
Lenaghan E, et al. Age & Ageing 2007;36:292.
Chiquette E, et al. Arch Intern Med 1998;158:1641.
Leape LL, et al. JAMA 1999;282:267.
Strom BL, et al JAMA 2002;288:1642.
Rich MW, et al N Engl J Med 1995;333:1190.
Use of Computerized Physician Order Entry (CPOE)
Leapfrog CPOE Evaluation Test Clinical Decision Support Categories
* Therapeutic Duplication
*Single & Cumulative Dose Limits
*Allergies & Cross Allergies
*Contraindicated Route of Administration
*Drug-Drug & Drug-Disease Interactions
* Contraindications/Dose Limits Based on Patient Diagnosis
*Contraindications/ Dose Limits Based in Patient Age or Weight
*Contraindications/Dose Limits Based on Laboratory Studies
*Contraindications/Dose Limits Based on Radiology Studies
*Corollary
*Cost of Care
* Nuisance
Bates DW, et al JAMA 1998;1311-16.
Classen DC, et al J Am Med Infromat Assoc 2006 14:48.
Case of Mrs. T…..
• 85 y/o with h/o DM, CHF, lumbar spinal stenosis admitted with increasing
confusion and falls. Lives alone, daughter involved. Daughter notes patient h/o
anxiety but c/o insomnia and phoning her continuously throughout the night for the
past 3 nights.
• Brought to U of C ER by daughter after a witnessed fall. New patient to the U of C
system. Admitted at 3AM to telemetry.
• On exam, alternately agitated and somnolent, oriented to person only.
VS: T99, P54, RR20, BP110/50 lying supine wt. 100lbs. 5’1”
Cor: RRR, +S3
Lungs: dry crackles in bases
Abd: soft, nontender, nondistended, firm stool felt throughout colon
• ER data:CT head neg., dirty urine, CXR with  cor, KUB FOS, BUN 48/CR 2.7, glc=
74, K+ hemolyzed at 6.3 F/U pending,INR=3.0, EKG SB-rate 58, no peaked t waves.
Given dose IV antibiotics in ER.
Case of Mrs. T…..hospital day #5
Lisinopril 40mg q daily
Glipizide ER 20mg BID
Lasix 40 mg q daily
KCL 20 meq q daily
Paxil 20 mg q daily
Amiodarone 200mg q daily
Digoxin 0.25 mg q daily
Coumadin 5mg q hs
T#3 prn
Ativan 1mg prn
Unsom (OTC) prn sleep
Lomotil (OTC) prn
Senna and colace prn
Lisinopril 20mg q daily
Glipizide ER 20 mg daily
Lasix 40 mg q daily
Amiodarone 200mg q daily
Digoxin 0.125 mg q M,W,Fri
Coumadin 3mg q hs
Tylenol 1000mg TID
Cipro 250 mg BID
Medication use based on aging
pharmacology principles
• Start low, go slow, dose to effect
• Adjust for decrease in renal clearance
• ID drugs w/narrow toxic/therapeutic
index
• ID drugs that effect CPY450 system e.g.,
inhibitors/inducers
• Adjust for anticholinergic properties of
drugs
• Remember the blunted barorecepter reflex
Med Review: Intersecting Safeties
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PCP plays key role in med review (prioritize & individualize)
New symptom consider a medication in the D/Dx
Meds on list guided by goals of care
Review meds on list for
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Indication
Dose
Interactions—drug/drug & drug/disease
Duplications
Adherence
Cost
• Enlist the pharmacist
• Enlist a CPOE system
• Review for medication underuse
Into the future……
• Increase knowledge base on drugs in the
elderly
– Clinical trials vs. post marketing surveillance
• Broaden testing/implementation of
technologies e.g., CPOE
• Multidisciplinary monitoring
• Support continued affordable drug
coverage
Special Thanks
• CHAMP core faculty
• Holly Holmes, MD
• Visit our website
@http://champ.bsd.uchicago.edu
CHAMP: Drugs and Aging
Bibliography
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CHAMP: Drugs and Aging
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CHAMP: Drugs and Aging
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CHAMP: Drugs and Aging
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Illinois Department of Public Aid website, ©2004.