Marilyn N. Bulloch, PharmD , BCPS Assistant Clinical Professor Harrison School of Pharmacy

1. Avoiding Hobson’s choice in older patients: Managing multi-morbidity and multiple medications in geriatrics Marilyn N. Bulloch, PharmD, BCPS Assistant Clinical Professor Harrison School of Pharmacy Auburn University

2. The Hobson’s Choice in Geriatric Pharmacotherapy

3. Objectives • Discuss the impact of the aging population on healthcare utilization. • Understand age-related pharmacokinetic and pharmacodynamics changes that may affect pharmacotherapy in older adults • Describe complications of chronic medication therapy in the aging patient. • Identify strategies to optimize benefit and minimize harm with chronic medication therapy in older adults.

4. Our Patients Are Aging Available: http://www.aoa.gov/Aging_Statistics/future_growth/future_growth.aspx#age (Accessed April 2013)

5. Patients Are Living Older Longer Available: http://www.aoa.gov/Aging_Statistics/future_growth/future_growth.aspx#age (Accessed April 2013)

6. Chronic Conditions in Older Adults Available: http://www.aoa.gov/Aging_Statistics/future_growth/future_growth.aspx#age (Accessed April 2013)

7. Multi-morbidity • Co-occurrence of: • Index disease • Preexisting age-related health condition or diseases • Impact • Affect disease progression • Decrease quality of life • Increase risk and severity of disability • Increase risk of mortality Shi et al. Eur J ClinPharmacol2008;64:183-199

8. Patients with Multi-morbidity Adapted from Figure 1. Fried et al. NCHS Data Brief 2012;100:1 Adapted from Figure 2. Fried et al. NCHS Data Brief 2012;100:2

9. Multiple Medications in Older Adults

10. Evidence-Based Geriatric Medicine • Studies involving geriatrics • 3% randomized, controlled studies • 1% meta-analyses • Make up 2-9% study subjects • In 2000 • 3.45% of controlled trials • 1.2% of meta-analysis Le Couteur et al. AusFamPhys2004;33:777-781

11. Applying EBM to Older Adults Does your patient resemble the studied population? How many older adults with multi-morbidity were included? What are the intended outcomes – are these applicable to older patients? Are there clinically important variation in baseline factors that affect intended outcome? Are the risks of the intervention known in older adults with multi-morbidity? What is known about the comparator intervention in older adults? What is the time until benefit or harm? Adapted from Table 1. J Am GeriatrSoc2012;60:1957-68

12. Age-Related Physiologic Changes DrugAdministration Adapted from Figure 1. Huang A. 28th Annual Scientific Meeting of the Canadian Geriatric Society 2008;11(10):7

13. Absorption Changes Hubbard et al. Eur J ClinPharmacol2013;69:319-326 McLean et al. Pharmacol Rev 2004;56:163-184 Corsonello et al. Cur Med Chem2010;17:571-584 ↓ saliva production ↓ gastric acid secretion ↓ gastrointestinal blood flow Delayed gastric emptying Intestinal atrophy Changes in body fat and lean muscle Pulmonary changes Skin changes Conjunctiva changes

14. Distribution Changes Hubbard et al. Eur J ClinPharmacol2013;69:319-326 Sitar. Expert Rev ClinPharmacol2012;5:397-402 McLean et al. Pharmacol Rev 2004;56:163-184 Corsonello et al. Cur Med Chem2010;17:571-584 ↑ body fat ↓ lean muscle ↓ total body water ↓ albumin ↑ CNS penetration

15. Metabolism Changes • ↓ hepatic blood flow • ↓ liver volume • ↓ plasma esterase quantity & activity • Associated more with health status than age • Phase I pathways more impacted than Phase II McLean et al. Pharmacol Rev 2004;56:163-184

16. Elimination Changes ↓ glomeruli causes ↓kidney mass ↓ GFR in 2/3 of patients ↑ drug elimination half-life McLean et al. Pharmacol Rev 2004;56:163-184

17. Pharmacokinetic Questions • How readily absorbed is the medication? • What is the onset and duration of desired therapeutic action? • What is the patient’s body composition? • Is the medication excreted unchanged? • What is the major route of elimination? • Does the medication have an metabolite? • Is the metabolite active or toxic? • How is the metabolite eliminated? Adapted from Table 2. Lamy. J Am GerSoc1982;11;s11-s19

18. Pharmacodynamic Changes • Receptor down regulation • Change in receptor sensitivity • Increased • Decreased • Impaired homeostatic mechanisms and/or physiologic reserves

19. Complications of Geriatric Medication Use

20. Polypharmacy Quantity Quality More medications than is clinically indicated No indication Lack efficacy Duplications Requires more thorough review of medications • ≥ X Medications • Limiting - assumes > X is incorrect DeSovo et al. Prim Care Clin Office Pract2012;39:345-362

21. Reasons for Polypharmacy • Age • Ethnicity • Rural residence • Education level • Insurance • Multiple healthcare providers • Poor health status • Provider visits • Chronic diseases • Anemia • Angina • Asthma • Depression • Diabetes • Diverticulosis • Gout • Hypertension • Osteoarthritis DeSovo et al. Prim Care Clin Office Pract2012;39:345-362

22. Avoidable Costs of Polypharmacy

23. Adverse Drug Reactions Boparai MK et al. Mt Sinai J Med 2011;78:613-626 Gurwitz et al. JAMA 2003;289:1107-1116 Steinman et al. J Gerontol A BiolSci Med Sci2011;66:444-451 • Unwanted and/or harmful effects that can occur at standard doses • Gurwitz et al • 50.1 ADRs per 1000 person years • 13.8 preventable ADRs per 1000 person years • VA GEM Study • 33% of patients experienced an ADR within 12 months of hospital discharge • 38% considered preventable

24. Risks for ADRs • Prior ADR • Polypharmacy • Dementia/cognitive impairment • Multi-morbidity • Frailty • CrCl < 50 mL/min • Female • Fragmented care • Altered stimuli-induced adaptation capacity • Recent hospital admission • Age ≥ 85 years • Low body weight • ≥ 1 oz alcohol intake/ day • Vision or hearing impairment • Compliance • Regimen complexity DeSovo et al. Prim Care Clin Office Pract2012;39:345-362 Boparai MK et al. Mt Sinai J Med2011;78:613-626

25. Medications Causing ADRs Gurwitz JH, et al. JAMA 2003;289;107-116

26. Types of ADRs Occurring Figure 1. Percent patients suffering selected injuries commonly studied among patients who experienced adverse drug events: Reducing and Preventing Adverse Drug Events To Decrease Hospital Costs. March 2001. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/research/findings/factsheets/errors-safety/aderia/figure1.html (Accessed April 24, 2013)

27. ADR Consequences Le Couteur et al. AusFamPhys2004;33:777-781 Budnitz et al. N Eng J Med 2011;365”2002-2012 Boparai MK et al. Mt Sinai J Med 2011;78:613-626 • Health care utilization • 10% of emergency room visits • 10-17% of hospitalizations • $1.33 to manage medication-related morbidity and mortality for each $1 spent on older adults in nursing homes • Can be fatal • Symptoms should be considered ADRs until proven otherwise.

28. Drug Interactions McDonnell, et al. Ann Pharmacother2002;36:1331-1336 Qato et al. JAMA 2008;300:2867-2878 Reimche et al. ClinPharmacol2011;51:1043-1050 Lindblad et al. ClinTherapeu2006;28:1133-1143 • Many types • 15-46% patients have ≥ 1 interaction • 1 in 25 community patients at risk for severe interaction • Over 26% cause ADRs that require hospitalization • 25% serious or life-threatening • Approximately 20% occur in the hospital • Potential for drug-drug interaction in over 6% of medication orders

29. Drug Interactions • Age • 60-74 years – 24% • ≥ 80 years – 36% • Risk increases with # medications • ≥ 2 medications – 13% • > 6 medications – 82% • ≥ 8 medications – almost 100% Boparai MK et al. Mt Sinai J Med 2011;78:613-626 Stegemann et al. Age Research Rev 2010;9:284-298

30. Minimizing ADRs and Interactions • Know allergies – including reactions • Evaluate cognitive function • Have a drug information source • Use safest/most effective medication • Match medications to indications • Use fewest medications possible • Use simple dosing • Do not start 2 medications at the same time • Screen for DDIs routinely • Dose for renal & hepatic function • Recognize a symptom as an ADR • Give prophylaxis for known side effects when able • Stop medications without benefit • Stop PRN medications not used in past month • Medication lists • Involve caregivers Adapted from: BoparaiMK et al. Mt Sinai J Med2011;78:613-626

31. Non-Adherence Adherence in patients with chronic conditions only 50-60% Responsible for up to 70.4% of medication-related ER visits May account for 39-69% of drug-related hospitalizations each year Costs $100 billion/year Coleman et al. J Manag Care Pharm 2012;18:527-539 Orwig et al. Gerontologist 2006;46:66

32. Cost of Non-Adherence

33. Types of Non-adherence • Forgetfulness • Confusion over dosage schedule • Intentional underuse • Primary non-adherence • Non-persistence • Nonconforming non-adherence • Intentional overuse Coleman et al. J Manag Care Pharm 2012;18:527-539

34. Risk Factors for Non-Adherence • Communication • Regimen complexity • Patient-provider relationship • Transition of care • Health literacy • Mental health disorders • Cognition • Smoking • Asymptomatic chronic diseases • Age • Physical impairment • Lack of social support • Minority demographic • Patient beliefs • Sensory changes • Product use • Dysphagia

35. Dosing Influence on Adherence Coleman et al. J Manag Care Pharm 2012;18:527-539

36. Overcoming Adherence Barriers Steinman et al. JAMA 2010;304:1592-1601

37. Evaluating Medication Management ability

38. Drug Regimen Unassisted Grading Scale (DRUGS) Adapted from Edelberg et al. J Am GeriatrSoc1999;47:592-596

39. MedTake Test Adapted from Appendix I. Raehl et al. Pharmacotherapy 2002;22:1239-1248

40. MedTake Test Adapted from Appendix I. Raehl et al. Pharmacotherapy 2002;22:1239-1248

41. Medication Regimen Complexity Index • Checklist style tool to evaluate regimen • Only for prescribed medications • Medication Regimen Complexity = Total (A) + Total (B) + Total (C) • Open index • # medications and directions vary by patient George et al. Ann Pharmacother2004;38:1369-1376

42. MRCI Section A: Dosage Forms Adapted from Appendix II. George et al. Ann Pharmacother2004;38:1374-1375

43. MRCI Section B: Dose Frequency Adapted from Appendix II. George et al. Ann Pharmacother2004;38:1374-1375

44. MRCI Section C: Directions Adapted from Appendix II. George et al. Ann Pharmacother2004;38:1374-1375

45. Medication Management Instrument for Deficiencies in the Elderly Adapted from Orwig et al. Gerontologist 2006;46:661-668

46. Medication Management Instrument for Deficiencies in the Elderly Adapted from Orwig et al. Gerontologist 2006;46:661-668

47. Hopkins Medications Schedule Appendix. Carlson et al. J Gerontol A BiolSci Med Sci2005;60;223

48. Auxiliary Labels & the importance of verbal counseling