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Medication Management
Considerations for the Older Patient
Mark A. Stratton, Pharm.D., BCPS, CGP, FASHP
Professor of Pharmacy and Langsam Endowed Chair in Geriatric Pharmacy
College of Pharmacy, University of Oklahoma
Learning Objectives
 State morbidity and mortality statistics associated with
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medication related problems in the older patient
List factors responsible for “America’s Other Drug
Problem”
Describe changes that predispose older patients to
increased morbidity and mortality from medication
therapy
Compare and contrast potentially inappropriate
medications in the elderly with safer alternatives
Discuss management considerations to minimize DRPs
Did You Know…
 One-third of hospital admissions by patients over 65 are
linked to drug related problems (DRPs)
 Either due to an adverse drug reaction (ADR) or to the effects
of poor adherence
 51% of all deaths and 39% of hospitalization due to ADRs
occur in the elderly
 50,000-75,000 older people die each year due to a drug
related problem…making this the fourth to sixth leading
cause of death in the geriatric population
 Half of these deaths are considered to be preventable
Did You Know…

Estimated cost of inappropriate medications and their
consequences in older people approaches $200
billion/year

$32.8 billion associated with DRPs resulting in LTC
admissions

Now referred to as “America’s Other Drug Problem”
Contributors to “America’s Other Drug Problem”
 Polypharmacy (Rx and OTC)
 Consequences of drug-drug interactions
 Adherence issues
 Pharmacokinetic changes of aging
 Pharmacodynamic changes of aging
 Effects of co-morbidity on kinetics and dynamics
Polypharmacy
 Over 30% of prescription medications are taken by
those over the age of 65 (13% of population)
 An estimated 40 to 50% of OTC medications are
consumed by older people
 Unknown percentage of herbal/alternative medications
are consumed by the elderly
 Over 80% of older people take at least one medication
per day
 Community living elders take 3 to 4 different
medications per day
 Nursing home living elders take 7 to 9 different
medications per day
Polypharmacy
 An estimated 25% of all prescribed medications for
older people are potentially inappropriately selected or
dosed (Beer’s List)
 Pre-Part D data from Oklahoma revealed that 42% of
Medicaid recipients and 34% of state retirees were on a
potentially inappropriate medication
 An estimated 30% of all medications for older people
are considered unnecessary
Inappropriate Medications
 Beer’s List – a list of approximately 90 medications and
doses considered to be potentially inappropriate for the
elderly in that the risk exceeds the benefit and there exist a
safer alternative (Fick, DM et al. Arch Int Med
2003;169:1326-1332)
 Use of medications on this list is associated with decreased
quality of life and increased risk of hospitalizations
 Insulin, warfarin and digoxin account for one-third of ER
visits due to ADRs in the elderly. This points out that
although a medication might be justified we are not
appropriately monitoring these for side-effects such as
blood glucose, INRs and serum levels or ECGs.
Drug-Drug Interactions
 Increased likelihood of clinically significant drug-drug
interactions with increased number of medications used
 Increased morbidity and mortality associated with drug-
drug interactions in the elderly due to decreased
physiologic reserve
Adherence Issues
 Prior to the start of Medicare Part D on January 1, 2006
one-third of older people failed to take medications as
prescribed due to cost issues
 Today, while Medicare Part D has resulted in increased
utilization of medications by the elderly, 10 to 15% still
have accessibility issues due to cost.
 “Doughnut Hole” effect
 Low income subsidy qualification issues
Pharmacokinetic Changes of Aging
 Absorption
 Though numerous structural and physiological age-related changes
in the GI tract exist, they are of minimal clinical significance in the
absence of gastrointestinal pathology
 Decreased first-pass after oral administration – morphine,
isosorbide dinitrate (Isordil*)
 Heart failure can affect the absorption of some medications
including furosemide (Lasix*)
 Effects of aging on percutaneous, subcutaneous and intramuscular
absorption is largely unknown but in states of poor perfusion expect
delayed or incomplete absorption
 Distribution (volume of distribution)
 Body Composition Changes
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Lean-to-fat ratio altered – digoxin (Lanoxin*)
Decreased total body water - lithium
Protein concentration changes – warfarin (Coumadin*)
Pharmacokinetic Changes of Aging
 Metabolism (clearance)
 Liver size, blood flow decline with age altering the
metabolism of drugs with high-flow dependent
metabolism such as propranolol (Inderal*) and
verapamil (Calan*)
 Some but not all Phase I metabolic pathways performed
by the CYP system (oxidation, reduction, hydrolysis)
diminish with age
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Diazepam (Valium*), chlordiazepoxide (Librium*),
alprazolam (Xanax*), flurazepam (Dalmane*)
 Phase II (conjugation) metabolic pathways do not
appear to diminish with age
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Lorazepam (Ativan*), oxazepam (Serax*), triazolam
(Halcion*), temazepam (Restoril*)
Pharmacokinetic Changes of Aging
 Elimination (clearance)
 Majority of people over the age of 50 lose 10% of renal
function per decade
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Digoxin, aminoglycosides, vancomycin, pencillins,
cephalosporins, salicylate metabolites, quinolones, etc.
Reliability of the Cockroft-Gault equation for estimating CrCl
 Underestimates true CrCl in older people of normal weight
 Overestimates true CrCl in older people who are under weight
MDRD equation (Modification of Diet in Renal Disease) – not
validated in older people
Pharmacodynamic Changes of Aging
 Alterations in receptor affinity
 Alterations in receptor number
 Enhanced or diminished post-receptor response
Pharmacodynamic Changes of Aging
 Central nervous system sensitivity
 Enhanced receptor response
 Reduced CNS dopamine
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Increased EPS symptoms
 Reduced serotonin receptor function
 Enhanced sensitivity to antidepressants
 Altered GABA-benzodiazepine receptor function
 Increased sensitivity to benzodiazepine, alcohol, barbiturate
 Reduced CNS acetylcholine
 Enhanced anti-cholinergic side effects
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Sedation, confusion, psychosis, delirium
Urinary retention, constipation
Use of drugs with anticholinergic effects are associated with a decline in
various measures of cognitive function, especially in the very old or those
with pre-existent dementia
Common Drugs With Anticholinergic Effects
Antihistamines
Chlorpheniramine
Hydroxyzine
Diphenhydramine
Antiemetics
Dimenhydrinate
Meclizine
Prochlorperazine
Trimethobenzamide
Antipsychotics
Chlorpromazine
Haloperidol
Thioridazine
Clozapine
Antiulcerants
Cimetidine
Ranitidine
Antidepressants
Amitriptyline
Nortriptyline
Imipramine
Doxepin
Protriptyline
Antispasmodics
Belladonna alkaloids
Dicyclomine
Hyoscyamine
Oxybutynin
Propantheline
Tolterodine
Antiparkinsonians
Antidiarrheals Miscellaneous
Amantadine
Benztropine
Diphenoxylate/
atropine
Clonidine
Codeine
Serum Anticholinergic Activity Ranked by
Frequency of Prescription Use in Elderly
Medication
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Furosemide
Digoxin
HCTZ/Triamterene
Theophylline
Warfarin
Prednisone
Nifedipine
Isosorbide dinitrate
Codeine
Cimetidine
Captopril
Ranitidine
Anticholinergic Activity
(atropine equivalents
0.22
0.25
0.08
0.44
0.12
0.55
0.22
0.15
0.11
0.86
0.02
0.22
Pharmacodynamic Changes of Aging
 Alterations in Na, K-ATPase and Ca++ channels leads
to enhanced toxicity of digoxin and antiarrhythmics
 Changes in homeostatic control mechanisms
(baroreceptors) making orthostatic changes in blood
pressure more likely from antihypertensive.
 Diminished beta receptor sensitivity leads to need for
increased beta agonist or antagonist for desired effect
 Impaired glucose counter-regulation predisposes
elders to hypoglycemia from antidiabetic agents
Medication Classes Requiring
Special Consideration
in the Elderly
Antihypertensives/Diuretics
 Principles:
 Increased likelihood of electrolyte disturbances
 Start low (HCTZ 12.5 mg)
 Cornerstone for hypertension management
 Define goals especially in the very old
Other Antihypertensives
 Principle:
 Select agents which act peripherally and are not highly
lipophilic
 Avoid agents which act centrally or are highly lipophilic
 Preferred:
 ACE inhibitors, ARBs, CC blockers, atenolol
 Avoid:
 Methyldopa, clonidine, propranolol
 Short-acting nifedepine
Antiarrhythmics/Digitalis Glycosides
 Principles:
 Increased cardiosensitivity and altered kinetics
 Pay attention to ECG effect to assess toxicity
Antianxiety/Sedative Agents
 Principles:
Select agents which are short-acting, without active metabolites
Evaluate need for therapy frequently
Use lowest possible dose for the shortest possible time
Avoid agents which are long-acting with active metabolites
 Preferred
 Oxazepam (Serax®), lorazepam (Ativan®), triazolam (Halcion*),
temazepam (Restoril*)
 Zolpidem (Ambien®), Zaleplon (Sonata®), Eszopiclone
(Lunesta®) – use one-half the adult dose in geriatric patients
 Ramelteon (Rozerem®) – melatonin agonist
 Avoid
 Diazepam (Valium®), chlordiazepoxide (Librium®), flurazepam
(Dalmane®), alprazolam (Xanax®)
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Antipsychotic Agents
 Principles
 Use least sedating agents with minimal anticholinergic side effects
and minimal orthostatic changes in blood pressure. Be aware of black
box warning – increased risk of sudden death and CVA in patient with
dementia
 Consider GDR (Gradual Dose Reduction) in long term care residents
as required by CMS guidelines
 Preferred
 Atypical antipsychotics
 Risperidone (Risperdal®) – first choice amongst atypicals based on
cost, effectiveness and side-effect profiles
 Olanzapine (Zyprexa®)
 Ziprasidone (Geodon®)
 Quetiapine (Seroquel®)
 Aripiprazole (Abilify®)
 Avoid
 Older antipsychotics – haloperidol, thioridazine
Antidepressants
 Principles
 Use least sedating agents with minimal cardiotoxicity, minimal
anticholinergic side effects and minimal orthostatic changes in
blood pressure
 Treat to remission, “start low – go slow – but go”
 Preferred
 SSRIs: Sertraline (Zoloft®), paroxetine (Paxil®), citalopram
(Celexa®), escitalopram (Lexapro®)
 Mixed: Bupropion (Wellbutrin®), Venlafaxine (Effexor®),
Duloxetine (Cymbalta®)
 Tricyclic Antidepressant: Secondary amines –
nortriptyline (Aventyl®), desipramine (Norpramin®)
 Tetracyclics – mirtazapine (Remeron®)
 Avoid
 Select tertiary amine tricyclic antidepressants – amitriptyline
(Elavil®), imipramine (Tofranil®)
Anticoagulants
 Principles
 Be aware of increased sensitivity to warfarin, especially
in patients with decreased protein.
 Be aware of increased risk of bleeding.
 Re-evaluate need for therapy frequently.
 Start low - go slow.
 Increased mortality with tinzaparin in people over 70
with renal insufficiency
Analgesics
 Principle
 Be aware of increased GI risk associated with NSAIDS.
Supplement with PPI to prevent GI bleeding if long term use is
indicated
 COX-2 Inhibitors: celecoxib (Celebrex®)
 Be aware of salt and water retaining properties in patients with
hypertension or CHF and other potential CV effects.
 Due to these risk the 2009 AGS guidelines recommend use of
NSAIDs with extreme caution. Use acetaminophen and mild
opioids may be more appropriate.
 Be aware of increased sensitivity to narcotic analgesics.
 Be aware of additive CNS depressant effect of narcotics with other
agents.
 Avoid
 Ketoralac, propoxyphene, meperidine or pentazocine
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Antiulcer Therapy
 Preferred
 Proton Pump Inhibitors
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May have concern regarding Calcium homeostasis increasing
risk of osteoporosis (and fractures), and Vitamin B12
deficiency anemia
 Use H-2 antagonist carefully, use one-half the usual
adult dose
 Avoid
 Cimetidine (Tagamet*)
Hypoglycemic Agents
 Principles
 Be aware of altered kinetics and sensitivity
 Be aware of altered glucose counter-regulatory response
to hypoglycemia. Be aware of altered presentations of
hypoglycemic symptoms
 Initiate therapy at one-half the usual adult dose
 Avoid
 First generation sulfonylureas (chlorpropamide) and
second generation sulfonylurea - glyburide
 Possible increased mortality in the elderly on
rosiglitazone compared to pioglitazone
OTCs/Herbals
 Principles
 Be aware of increased sensitivity
 Monitor for drug-drug interactions carefully
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Seven of the top ten selling herbal supplements interact with
warfarin (increasing bleeding risk)
Management Considerations
 Minimize number of medications, attempt gradual dose reduction
 Maximize non-pharmacologic alternatives
 Titrate therapy to the individual patient
 Improve monitoring of narrow therapeutic index drugs (warfarin,
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insulin, digoxin, etc.)
Educate the patient and caregiver
Review all medications annually
Improve communications skills (practitioner and consumer)
Use a single pharmacy for all medication needs, learn how to utilize
your pharmacist to help manage medications and cost
Improve interdisciplinary communication and cooperation
Use extra caution during transitions between care facilities and
providers (reconciliation)
Question?