Medication Management Considerations for the Older Patient

1. Mark A. Stratton, Pharm.D., BCPS, CGP, FASHP Professor of Pharmacy and Langsam Endowed Chair in Geriatric Pharmacy College of Pharmacy, University of Oklahoma Medication Management Considerations for the Older Patient

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;169:1326-1332) • 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.

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

17. Serum Anticholinergic Activity Ranked by Frequency of Prescription Use in Elderly

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 • 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 • 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?