1. 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

2. Learning Objectives
State morbidity and mortality statistics associated with 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

3. 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

4. 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”

5. 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

6. 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

7. 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

8. 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: )
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.

9. 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

10. 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

11. 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
Lean-to-fat ratio altered – digoxin (Lanoxin*)
Decreased total body water - lithium
Protein concentration changes – warfarin (Coumadin*)

12. 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
Diazepam (Valium*), chlordiazepoxide (Librium*), alprazolam (Xanax*), flurazepam (Dalmane*)
Phase II (conjugation) metabolic pathways do not appear to diminish with age
Lorazepam (Ativan*), oxazepam (Serax*), triazolam (Halcion*), temazepam (Restoril*)

13. Pharmacokinetic Changes of Aging
Elimination (clearance)
Majority of people over the age of 50 lose 10% of renal function per decade
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

14. Pharmacodynamic Changes of Aging
Alterations in receptor affinity
Alterations in receptor number
Enhanced or diminished post-receptor response

15. Pharmacodynamic Changes of Aging
Central nervous system sensitivity
Enhanced receptor response
Reduced CNS dopamine
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
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

16. Common Drugs With Anticholinergic Effects
Antihistamines
Antipsychotics
Antidepressants
Antispasmodics
Chlorpheniramine
Hydroxyzine
Diphenhydramine
Chlorpromazine
Haloperidol
Thioridazine
Clozapine
Amitriptyline
Nortriptyline
Imipramine
Doxepin
Protriptyline
Belladonna alkaloids
Dicyclomine
Hyoscyamine
Oxybutynin
Propantheline
Tolterodine
Antiemetics
Antiulcerants
Antiparkinsonians
Antidiarrheals
Miscellaneous
Dimenhydrinate
Meclizine
Prochlorperazine
Trimetho-benzamide
Cimetidine
Ranitidine
Amantadine
Benztropine
Diphenoxylate/ atropine
Clonidine
Codeine

17. Anticholinergic Activity (atropine equivalents
Serum Anticholinergic Activity Ranked by Frequency of Prescription Use in Elderly
Medication
Anticholinergic Activity (atropine equivalents
Furosemide
Digoxin
HCTZ/Triamterene
Theophylline
Warfarin
Prednisone
Nifedipine
Isosorbide dinitrate
Codeine
Cimetidine
Captopril
Ranitidine
0.22
0.25
0.08
0.44
0.12
0.55
0.15
0.11
0.86
0.02

18. 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

19. Medication Classes Requiring Special Consideration in the Elderly

20. 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

21. 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

22. Antiarrhythmics/Digitalis Glycosides
Principles:
Increased cardiosensitivity and altered kinetics
Pay attention to ECG effect to assess toxicity

23. 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®)

24. 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

25. 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®)

26. 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

27. 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

28. Antiulcer Therapy Preferred Avoid Proton Pump Inhibitors
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*)

29. Hypoglycemic Agents Principles Avoid
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

30. OTCs/Herbals Principles Be aware of increased sensitivity
Monitor for drug-drug interactions carefully
Seven of the top ten selling herbal supplements interact with warfarin (increasing bleeding risk)

31. 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, 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)

33. Question?