OBJECTIVES

1. Prescribing Medications for the ElderlyAPN Pharmacology Update ConferenceMarch 28, 2014Patricia M. Curtin, MD, FACP, CMD Section Chief, Geriatric Medicine Member, Pharmacy and Therapeutics CommitteeClinical Assistant Professor, Jefferson Medical College

2. OBJECTIVES Know and understand: The pathophysiology of aging related to processing medications in older adults Strategies for prescribing medications in older adults in order to avoid adverse drug events Medications that should be avoided in older adults and why

3. TOPICS COVERED Challenges in geriatric pharmacotherapy Key issues in geriatric pharmacology Principles of prescribing for older patients Risk factors for adverse drug events for older patients/mitigate AGS 2012 Updated Beers Criteria for Potentially Inappropriate Medication (PIM) Use AGS “Choosing Wisely” Campaign: What physicians/patients should question (related to medications) Hot off the press: JNC 8, ADA, FDA, CCHS Wish Lists

4. CCHS Pharmacy ADR reports Medication Safety Committee Wish List AGS Beers Criteria (article, pocket card-$1) ABIM Choosing Wisely Campaign—AGS List Geriatric Dosage Handbook (Semla) CCHS Formulary (Lexicomp)-Geriatric Considerations CCHS Nurse-Pharmacist Referral (Powerchart) WISH Website (References>Staff references>WISH) Epocrates www.epocrates.com iGeri app (iPhone, iPad)-($2.99) Sources and Resources

5. WHY GERIATRIC PHARMACOTHERAPY IS IMPORTANT • Now, people age 65+ are 13% of US population, buy 33% of prescription drugs • By 2040, will be 25% of population, will buy 50% of prescription drugs • Geriatrics Review Syllabus 8th Edition, 2013, Chapter 11, Pharmacotherapy, Semla, PharmD

6. WHY GERIATRIC PHARMACOTHERAPY IS CHALLENGING More drugs are available each year FDA and off-label indications are expanding Formularies change frequently; substitutions made Drugs change from prescription to OTC-easier access “Nutraceuticals” (herbal preparations, nutritional supplements) Multiple Providers and Prescribers - 20% of Medicare beneficiaries have 5 or more chronic conditions and 50% receive 5 or more medications - Guideline based therapy Data on medication efficacy and dosing come from clinical trials: Older adults are excluded from many randomized controlled trials Studies that include older adults often are not representative Exclude multiple chronic illnesses We don’t know what we don’t know

7. Increased Body fat Decreased lean body mass Decreased total body water Decreased serum albumin (protein) Decreased hepatic cell mass Decreased liver blood flow Decreased metabolism Decreased renal mass Decreased renal blood flow What we do know: Age Related Changes in Physiology

8. PHARMACOKINETICS Absorption Distribution Metabolism Elimination

9. FACTORS THAT AFFECTDRUG ABSORPTION Absorption (bioavailability) is not changed much by aging Route of administration What is taken with the drug (meds/tube feeds) Gastric pH may increase or decrease absorption of some drugs GI motility and enzymes Peak serum concentrations may be lower OR higher-variable Co-morbid illnesses GRS 8; Pharmacotherapy

10. EFFECTS OF AGING ONVOLUME OF DISTRIBUTION (VD) Age-associated changes in body composition can alter drug distribution (where a drug penetrates and time to do so)  body water  lower VD for hydrophilic (likes water) drugs  lean body mass  lower VD for drugs that bind to muscle (digoxin- lean body mass, increase concentrations of dig)  plasma protein (albumin)  higher percentage of drug that is unbound (active) (phenytoin)  fat stores  higher VD for lipophilic (likes fat) drugs (benzos, phenytoin, valproic acid, lidocaine) GRS 8; Pharmacotherapy

11. AGING AND METABOLISM The liver is the most common site of drug metabolism Aging decreases liver blood flow, size and mass Metabolic clearance of a drug by the liver may be reduced GRS 8; Pharmacotherapy

12. KEY CONCEPTS ABOUTDRUG ELIMINATION Half-life: Time for serum concentration of drug to decline by 50% Clearance: Volume of serum from which the drug is removed per unit of time (eg, L/hour or mL/minute) GRS 8; Pharmacotherapy

13. KIDNEY FUNCTION IS CRITICAL FOR DRUG ELIMINATION Most drugs exit the body via the kidney Reduced elimination  drug accumulation and toxicity Aging and common geriatric disorders can impair kidney function GRS 8; Pharmacotherapy

14. THE EFFECTS OF AGING ON THE KIDNEY  kidney size  renal blood flow  number of functioning nephrons  renal tubular secretion Result: Lower glomerular filtration rate (GFR) GRS 8; Pharmacotherapy

15. SERUM CREATININE DOES NOT REFLECT CREATININE CLEARANCE  lean body mass  lower creatinine production and  glomerular filtration rate (GFR) Result: In older people, serum creatinine may stay in normal range, masking change in creatinine clearance (CrCl) Normal Creatinine Clearance: >60ml/min (age dependent) GRS 8; Pharmacotherapy

16. TWO WAYS TO DETERMINE CREATININE CLEARANCE Measure Requires 24-hour urine collection Time-consuming Estimate Usually done with the Cockroft-Gault equation* (*one of the most important equations to know) (140 – age)(Ideal weight in kg) x (0.85 if female)=ml/min 72 X Creatinine (mg/dL)

17. Which of these meds need to be renally dosed for reduced Creatinine clearance? Ultram (Tramadol) Zantac (Ranitidine) Neurontin (Gabapentin) Claritin (Loratadine) Levaquin (Levofloxacin) Tenormin (Atenolol) Zyloprim (Allopurinol) Bactrim (Trimethoprim-Sulfa)

18. PHARMACODYNAMICS Definition: Physiologic effects of the drug May change with aging, for example: Benzodiazepines may cause more sedation and poorer psychomotor performance in older adults (likely cause: reduced clearance of the drug and resultant higher plasma levels) Older patients may experience longer pain relief with morphine

19. SUCCESSFUL PHARMACOTHERAPY Uses the correct drug Prescribes the correct dosage Targets the correct condition Is appropriate for the patient Failure in any one of these can result in adverse drug events (ADEs) (75% of ADEs are dose related)

20. Start low, Go slow, but Go and Avoid starting 2 drugs at same time (if possible) GeriatricPharmacotherapy Principle:

21. Adverse Drug Effects (ADEs) ADEs occur in 35% of community-dwelling older adults • Incidence of ADEs in hospitals: 26/1000 beds (2.6%) • ADEs are responsible for 5% to 28% of acute geriatric hospital admissions

22. MEDICATIONS MOSTCOMMONLY INVOLVED IN ADEs Cardiovascular drugs, diuretics, NSAIDs, hypoglycemics, antipsychotics, and anticoagulants Medications with a narrow margin of safety (synthroid, phenytoin, lithium, valproic acid, aminoglycosides, anticoagulants, digoxin, hypoglycemic agents, etc) CCHS….same, except add opioids/benzodiazepines Geriatrics Review Syllabus, Pharmacotherapy, Semla et al Adverse Drug Events After Hospital Discharge in Older Adults: Types, Severity, and Involvement of Beers Criteria Medications J Am Geriatr Soc. 2013; 61: 1894-1899

23. RISK FACTORS FOR ADEs Age 85 or older Female Low body weight or low BMI Estimated CrCl < 50 mL/min 5-9 or more medications 12 or more doses of drugs/day 6 or more concurrent chronic conditions Prior adverse drug event

24. ADE PRESCRIBING CASCADE Drug 1 Adverse drug effect— misinterpreted as a new medical condition - Drug 2 Adverse drug effect— misinterpreted as a new medical condition

26. OPTIMIZING PRESCRIBING Achieve balance between over and under prescribing of beneficial therapies >20% of ambulatory older adults receive at least one potentially inappropriate medication Nearly 4% of office visits and 10% of hospital admissions result in prescription of medications classified as never or rarely appropriate

27. AGS UPDATED 2012 BEERS CRITERIA FOR POTENTIALLY INAPPROPRIATE MEDICATION USE IN OLDER ADULTS

28. Mark H Beers, MD 1954-2009 MD, Univ of Vermont First med student to do a geriatrics elective at Harvard‘s new Division on Aging Geriatric Fellowship, Harvard Faculty, UCLA/RAND Co-editor, Merck Manual of Geriatrics Editor in Chief, Merck Manuals “A ballet-dancing opera critic who hiked the Alps and took up rowing after diabetes cost him his legs”

29. BEERS CRITERIA Originally developed in 1991, 1997, 2003 and updated in 2012 by the American Geriatrics Society (by 11 member panel) Intend to improve drug selection and reduce exposure to potentially inappropriate medications (PIM) in older adults Recommendations are evidence-based and in 3 categories: Drugs to avoid Drugs to avoid in patients with specific diseases or syndromes Drugs to use with caution Available at AGS web site: www.americangeriatrics.org American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2012;60:616–631.

30. BEERS CRITERIA Potentially inappropriate medications include medications that: Have limited effectiveness in older adults Are associated with poor outcomes Delirium GI bleeding Falls Have safer alternatives available American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2012;60:616–631.

31. Table 1: Designations of Quality and Strength of Evidence: ACP Guideline Grading System, GRADE Quality of Evidence High Consistent results from well-designed, well-conducted studies that directly assess effects on health outcomes (2 consistent, higher-quality RCTs or multiple, consistent observational studies with no significant methodological flaws showing large effects) Moderate Sufficient to determine effects on health outcomes, but the number, quality, size, or consistency of included studies, generalizability , indirect nature of the evidence on health outcomes (1 higher-quality trial with > 100 participants; 2 higher-quality trials with some inconsistency, or 2 consistent, lower-quality trials; or multiple, consistent observational studies with no significant methodological flaws showing at least moderate effects) limits the strength of the evidence Low Insufficient to assess effects on health outcomes because of limited number or power of studies, large and unexplained inconsistency between higher-quality studies; important flaws in study design or conduct, gaps in the chain of evidence Or lack of information on important health outcomes

32. Table 1: Designations of Quality and Strength of Evidence: ACP Guideline Grading System, GRADE Strength of Recommendation Strong Benefits clearly > risks and burden OR risks and burden clearly > benefits Weak Benefits finely balanced with risks and burden Insufficient Insufficient evidence to determine net benefits or risks

33. What can Prescribers and other interdisciplinary team members do? Collaborate with other team members/disciplines using AGS POCKETCARDS

34. Tables (*pocket card limited to first 3 tables) Table 2 – PIMs (organ system/therapeutic category) Table 3 – PIMs due to Drug – Disease/Syndrome Interaction Table 4 – Medications to be used with caution Table 5 – Medications moved or modified Table 6 – Medications removed Table 7 – Medications added Table 8 – Antipsychotics Table 9 – Drugs with strong anticholinergic properties (Tables 2,3,4 in article=Tables 1,2,3 in pocket card)

35. Table 9: Drugs with strong “anticholinergic” properties?What’s the problem? May reduce acetylcholine levels in patients who already have reduced levels: those who are elderly, have dementia and/or delirium Increased risk of anticholinergic side effects=confusion/delirium, constipation, urine retention, orthostasis, paradoxical excitement, tachycardia, visual disturbances, dry mouth

36. Over 600 drugs with Anticholinergic Activity Furosemide (Lasix) Triamterene/HCTZ Digoxin Dipyridamole (Persantine) Theophylline anhydrous Warfarin (Coumadin) Prednisolone Nifedipine (Procardia) Isosorbide Dinitrate Codeine Diphenhydramine Olanzapine Paroxetine Promethazine Tune, L.E. , Egell, S. Dementia. Geriatric Cognitive Disorders 1999. Courtesy of Susan Scanland, MSN, APRN, GNP AGS Beers Criteria, 2012 Captopril Imipramine/Desipramine Amitriptyline (Elavil) Cimetidine (Tagamet) Ranitidine (Zantac) Tobra/clinda/gentamycin Ampicillin Hydralazine Diazepam (Valium) Oxybutynin(Ditropan)

37. Table 2 (Table 1 in pocket guide): Drugs to Avoid

38. DIGOXIN Digoxin itself or Digoxin toxicity can cause: Confusion nausea loss of appetite lethargy bradycardia heart block

39. DIGOXIN 0.125 mg. dose effective; rarely use 0.25 mg Half-life is 30-40 hours; up to 70 hrs in elderly May be able to dose 2-3x/week Therapeutic “range”-.7-2.0. Patients don’t need to always be “in the range”. Lower levels may be better (.5-.8) (DIG trial, elderly CHF patients)

40. Table 2: Drugs to Avoid

41. What Benzodiazepines should we use in elderly? NONE - but if necessary (pre-med, COPD, etc): Ativan (Lorazepam)-(0.25mg. - 0.5 mg. q 8 hr. PRN (po/IM/IV) (half-life 10-16 hrs); (maximum daily dose 2 mg) Peaks at 1 hr. OR Serax (Oxazepam) 10 mg. q 8-12 hr. po prn (half-life 5-20 hrs); (max dose 30mg/d) For Sleep—refer to CCHS Sleep Protocol, WISH Website Sedatives/Hypnotics

43. Disease/Syndrome Drug Recommend/Rationale/QOE/SR Heart Failure NSAIDS Avoid, Moderate, Strong CCBS (fluid retention) Delirium All TCAs, Antichol Avoid, Moderate, Strong Benzos, hypnotics (adverse CNS effects) H2 Antagonists Dementia Antichol, Benzos Avoid, High, Strong H2Antagonists (adverse CNS effects) Zolpidem, Antipsychotics (increased risk of CVA/mortality) Falls Anticonvulsants, Avoid, High, Strong Antipsychotics, (ataxia, impaired psychomotor fcn, Benzos, Hypnotics syncope) TCAs, SSRIs Table 3: PIMs to Avoid due to Drug-Disease or Drug-Syndrome Interactions

44. Take homes: AGS 2012 Beers Criteria Don’t let the perfect be the enemy of the good Beers PIMs are only part of appropriate prescribing Target initiatives to high prevalence/high severity meds (based on local data, where possible) Stopping meds should be done with same consideration as starting Not meant to supersede clinical judgment or individual patient values or needs

45. AGS Beers Criteria Website • Criteria • Full Article • Editorial • Perspective • Beers Criteria Pocket Card • Beers Criteria App • Public Education Resources for Patients & Caregivers • AGS Beers Criteria Summary • 10 Medications Older Adults Should Avoid • Avoiding Overmedication and Harmful Drug Reactions • What to Do and What to Ask Your Healthcare Provider if a Medication You Take is Listed in the Beers Criteria • My Medication Diary - Printable Download • Eldercare at Home: Using Medicines Safely - Illustrated PowerPoint Presentation Available at: Americangeriatrics.org

46. 1. Don’t recommend percutaneous feeding tubes in patients with advanced dementia; instead offer oral assisted feeding Don’t useantipsychotics as first choice to treat behavioral and psychological symptoms of dementia Avoid using medicationsto achieve Hgb A1C <7.5% in most adults age 65 and older: moderate control is better Don’t use benzodiazepinesor other sedative-hypnotics in older adults as first choice for insomnia, agitation, delirium Don’t use antimicrobialsto treat bacteriuria in older patients unless specific urinary tract symptoms are present www.choosingwisely.org/doctor-patient-lists/american-geriatrics-society ABIM: CHOOSING WISELY CAMPAIGNAGS: Top Ten Things Physicians and Patients Should QuestionMedications (2013)

47. Don’t prescribe cholinesterase inhibitors for dementia without periodic assessment for perceived cognitive benefits and adverse GI effects Don’t recommend screening for breast or colorectal cancer, nor prostate cancer (w PSA test) without considering life expectancy and the risks of testing, overdiagnosis and over treatment Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, provide feeding assistance and clarify patient goals and expectations. Don’t prescribe a medication without conducting a drug regimen review. Avoid physical restraints to manage behavioral symptoms of hospitalized older adults with delirium ABIM: CHOOSING WISELY CAMPAIGNAGS: Top Ten Things Physicians and Patients Should QuestionMedications (2014)

48. Hold parameters for antihypertensives Add STOP dates to Antibiotic orders Appropriate use of PPIs (pantoprazole, etc) Add senna/docusate when starting opioids Avoid antipsychotic use for acute delirium Try to avoid concomitant use-opioids/benzos Anticoagulants-new, bridging, reversals CCHS Pharmacists’ “Choosing Wisely” WISH LIST

49. Reconcile and validate list/how pt takes meds Provide an indication for each medication Calculate Creatinine Clearance on every pt. DO NOT start dementia medications as an inpatient (donepezil, memantine, etc)-no benefit in hospital, risk of ADEs Watch acetaminophen dosing 3000-4000mg Consider new JNC8 goal of >60yo, BP<150/90 Speaker’s “Choosing Wisely” Wish List

50. CASE (1 of 4) A 77-year-old man comes to the office because he has had increased difficulty with urination, including straining to void and occasional urinary incontinence. History includes benign prostatic hyperplasia, depression, seasonal allergies, type 2 diabetes mellitus, and peripheral neuropathy. Medications include tamsulosin 0.4 mg at bedtime, metformin 1,000 mg q12h, fluticasone inhaler 2 sprays in each nostril daily, diphenhydramine 25 mg q12h as needed, and aspirin 81 mg/day.