1. Geriatric Polypharmacy: A Pill for Every ill
Amelie Hollier, DNP, FNP-BC, FAANP
President, APEA

2. Geriatric Patients US Life Expectancy Women: 80 years Men: 75 years
Natl Vital Stat Rep. 2010;58:1-136

3. Geriatric Patients 2011 The “Baby Boomers” turned 65 years old in 2011
Elderly population increases by 30% each year from now until 2050!!!

4. Geriatric Patients
20% of people aged > 65 years take at least 10 medications
Termed: the “P” word
Patterns of medication use in the United States, A report from the Slone Survey. AnnualRpt/ SloneSurveyWebReport2006.pdf. Accessed February 1, 2013.

5. Geriatric Patients
As the number of medications increases, so does the risk of adverse drug events (ADEs)
ADEs: weight loss, falls, changes in cognition, loss of independence, hospitalization

6. It is MORE difficult to prescribe medications in Elderly Patients
Inter-individual variability
Polypharmacy
Concomitant diseases
Physiological changes associated with aging (renal, hepatic dysfunction)
Multiple Prescribers!

7. A Reasonable Approach: Always answers these 3 Questions before Prescribing
First: What is the Diagnosis?
Second: What drug?
Third: What dose?

8. What Diagnosis? What Disease?
First Question?
What Diagnosis? What Disease?

9. Unrecognized ADEs
In older adults, drug induced symptoms are commonly mistaken for a new disease or worsening of an existing disease
Some drug induced symptoms are indistinguishable from common older adult illnesses

10. Diagnosis in the Elderly
New onset of disease in an elderly patient usually affects an organ that has been weakened by a different disease process
Ex: Elderly adult develops anemia
Harrison’s Principles of Internal Medicine

11. Example 1: Mr. Smith
80 year old male who is mostly independent; he has a number of chronic diseases that are stable. He has developed iron deficiency anemia over the last 3 months from a “slow bleeding” polyp in large intestine.

12. How does an older adult with anemia present?
In older adults we see:
Shortness of breath
Chest pain (angina)
Fatigue (“I’m getting older”)

13. Example 2: Mrs. Jones
80 year old female who is very independent; she has several chronic diseases that are stable with medications. She has developed hypothyroidism over the last 4 months.

14. Diagnosis in Elderly
Elderly Adults have “atypical presentation” of diseases
Disease
Elderly Presentation
Non-Elderly Presentation
Anemia
SOB, Angina, Fatigue
Fatigue
Hypothyroidism
Cardiac conduction defects, cognitive changes, looks depressed
Menstrual changes, constipation, changes in hair and skin
UTI
Confusion, anorexia
Burning, frequency, urgency

15. Diagnosis in the Elderly
New onset of disease in an elderly patient usually affects an organ that has been weakened by a different disease process
Harrison’s Principles of Internal Medicine

16. What Diagnosis? What Disease?
First Question?
What Diagnosis? What Disease?

17. What Drug? (or do we even need a drug?)
Second Question?
What Drug? (or do we even need a drug?)

18. Example: Pain in Older Adults
Nonpharmacologic Management
Ice
Heat
Massage
Relaxation
Biofeedback
PT interventions: exercise, splints, braces

19. Second Question?
What Drug?

20. Beers Criteria
Most widely used criteria (since 1991) to assess inappropriate drug prescribing in elderly
AGS Updated 2012 Beers Criteria for Potentially Inappropriate Medication (PIMS) Use in Older Adults

21. Beers Criteria
Goal is to improve care of older adults by reducing exposure to PIMs

22. Inappropriate Medications
Anti-cholinergic Side Effects
Memory impairment, confusion, hallucinations, dry mouth, blurred vision, urinary retention, constipation, tachycardia, acute angle glaucoma

23. “An Ode to an Anticholinergic Med”
Oh this drug, it makes me pink, Sometimes, I can’t think or even blink. I can’t see, I can’t pee I can’t spit I can’t (**it) (“defecate”)

24. Mrs. Thomas
80 year old female who is completely independent; she has a several chronic diseases that are stable with medications. She complains of difficulty sleeping when her arthritic knee aches. She takes an OTC medication with diphenhydramine for sleep.

25. Is this harmful if she uses this only three times weekly?
Mrs. Thomas
Is this harmful if she uses this only three times weekly?

26. Potentially Inappropriate Medications AVOID
Antihistamines (First Generations)
Brompheniramine (Bromfed)
Carbinoxamine (Chlor-Trimeton)
Diphenhydramine (Benadryl)
Hydroxyzine (Atarax, Vistaril)
Promethazine (Phenergan)
Others
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

27. Anti-Histamines What’s the Problem with these?
They are highly anti-cholinergic
Clearance reduced with advanced age
Tolerance develops when used as hypnotic
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

28. High Risk Medications
Diphenhydramine: impaired cognition, urinary retention (next day sedation, impaired driving)

29. Good Rule: “Avoid First Generation Anti-histamines”
Suppose Mrs. Thomas had an acute allergic reaction after eating boiled crawfish in South Louisiana?

30. Anti-Histamines Cetirizine ++ Loratadine + Fexofenadine Levocetirizine
2nd Gen Anti-Histamine
Sedative Effect
Cetirizine ++
Loratadine +
Fexofenadine
Levocetirizine
Desloratadine

31. Good Rule of Thumb
Choose an agent from a different generation; or the least potent in the medication class
“Hay Fever”: Consider a topical nasal anti-histamine {Asteline (Azelastine)}

32. Good Rule of Thumb Consider a different class of medication
What about a topical nasal steroid?

33. Mrs. Jones is 75 years old. She is diagnosed with a UTI
Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 50 mL/min.
Which anti-infective should be avoided in her because of inadequate drug concentration in the urine?
Sulfa drug
Ciprofloxacin
Amoxicillin
Nitrofurantoin
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

34. Mrs. Jones is 75 years old. She is diagnosed with a UTI
Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 50 mL/min.
Beers Criteria recommends nitrofurantion avoidance:
CrCl < 60 mL/min
For long-term suppression
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

35. What about drugs that need dose adjustment due to renal insufficiency?

36. Excretion Age related changes in kidney function
Decreases in renal mass
Decreases in renal blood flow (1-2% decline/year after age 40)

37. Measure of Kidney Function
Creatinine production is related to muscle mass
Creatinine production decreases with advancing age & loss of muscle mass. This produces decreased serum Cr levels
So…..Normal serum Cr, but impaired renal function

38. What Affects Creatinine Levels?
What you look like
What you eat
Who you are

39. What affects serum Cr? Muscle Mass
More
Less
More muscle mass, more serum creatinine
Less muscle mass, less serum creatinine

40. What affects serum Cr? Diet
Meat Eater
Vegetarian Diet
Creatinine Increases
but may be temporary
Creatinine Decreases

41. What affects serum Cr? Age and Gender
Creatinine decreases as you age (due to less muscle mass)
Creatinine greater in males due to greater muscle mass

42. How does obesity affect serum creatinine?
Increases Cr
Decreases Cr
Has no effect
Copyright 1998 Advanced Practice Education Associates

43. So…. many Factors Affect Creatinine Levels
A better measure of kidney function is CrCl (mL/min)
Most accurate CrCl is collected over a 24 hour period, but it’s a major drag to collect!!
GFR (Glomerular filtration rate = mL/min) can be used to estimate CrCl (Not Perfect, but it’s pretty good!)

44. GFR is usually estimated by Labs: eGFR
eGFR Normal Range > 60mL/min/1.73m2
About 38% of individuals aged 70 years or older without HTN or DM, had GFRs of < 60mL/min/1.73m2
Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Am J Kidney Dis. 2003;41(1):1.

45. Excretion Decrease in GFR (50% decline between 50 and 90 years)
Decrease in Creatinine Clearance

46. Mrs. Jones is 75 years old. She is diagnosed with a UTI
Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is < 50 mL/min.
Which anti-infective should be avoided in her because of inadequate drug concentration in the urine?
Sulfa drug (none as long as CrCl > 30 mL/min)
Ciprofloxacin (none as long as CrCl > 30 mL/min)
Amoxicillin (none as long as CrCl > 30 mL/min)
Nitrofurantoin (AVOID!)

47. Known Decreased Renal Clearance in Elderly
Acetaminophen
Anti-arrhythmics
Anti-convulsants
Anti-depressants
Anti-psychotics
Benzos, beta blockers, theophylline
Warfarin
Many, many others!

48. Excretion
Many drugs with dosage adjustments: allopurinol, many antibiotics, digoxin, lithium, gabapentin, H2 blockers, anti-arrhythmics

49. Good Rule of Thumb Be familiar with the medications you prescribe!
Remember: Some drugs require renal dosing and hepatic dosing

50. What patient is most likely to present with benign prostatic hyperplasia?
20 year old
40 year old
60 year old
80 year old
Copyright 1998 Advanced Practice Education Associates

51. Benign Prostatic Hyperplasia
What medication class do we prescribe to improve urinary flow?
What’s the most common side effect?

52. Non-selective Alpha Blocker
Beers Criteria Recommends “Avoid” alpha blockers for routine treatment of hypertension
OK to use alpha blockers for BPH with education and precautions
Non-selective Alpha Blocker
Medications
Doxazosin
Cardura
Prazosin
Minipress
Terazosin
Hytrin
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

53. Alpha Blockers for treatment of BPH or Urinary outflow problems
Uro-specific Alpha Blockers
Comments
*Uroxatral
Alfuzosin (needs renal and hepatic dose adjustments)
*Flomax (generic)
Tamsulosin (no renal or hepatic precautions); sulfa allergy precaution
*Rapaflo
Silodosin (needs renal and hepatic dose adjustments)
*Possible intraoperative floppy iris syndrome (IFIS) during cataract surgery

54. Good Rule of Thumb
Choose an agent that is most specific in the medication class for the problem you are treating.

55. “Mrs. Dash” Is this a Problem?
73 year old female who has osteoarthritis in both knees. She is still mobile but complains of daily pain in her knees. She is not a surgical candidate at this time. She self-medicates with ibuprofen and she reports good pain control using 400 mg ibuprofen 2-3 times daily.
Is this a Problem?

56. Beers Criteria “Avoid”: NSAIDs
Non-COX selective NSAIDs, oral
Aspirin > 325 mg daily
Ibuprofen
Diclofenac, Etodolac
Meloxicam
Naproxen
Ketorolac, Indomethacin (most adverse GI effects)
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

57. Gastrointestinal Risk
Treated 3-6 months: 1% risk of Upper GI ulcers, bleeding or perforation
Treated 1 year: 2-4%

58. Proton Pump Inhibitors
Very effective at preventing ulcers
Once daily
Usually better tolerated than misoprostol; slightly less effective
Hooper L, Brown TJ, Elliott R, et al. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ 2004; 329:948.

59. PPI OTC and Rx Omeprazole and Na bicarb (Zegerid)
Na bicarb = baking soda
Allows omeprazole to be absorbed a little bit faster
Each cap contains 300 mg Na
Avoid in HTN, HF, or other patients in whom Na should be restricted

60. PPI plus clopidogrel
Absolutely not omeprazole (inh 2C19 activity)! Reduces conversion of clopidogrelantiplatelet activity
Do not use esomeprazole (Nexium)
Use dexlansoprazole, lansoprazole, pantoprazole, or HD famotidine

61. Increases pH PPI Use Alters the absorption of many drugs
Calcium, Fe, Vitamin B12

62. PPI Harms
Fracture Risk in patients > 50 years, high doses, or use > 1 year
25% increase in all fractures
47% increase in spinal fractures
FDA requires fracture risk info added to labeling in OTC and Rx PPIs

63. PPI Harms
Fracture Risk in patients > 50 years, high doses, or use > 1 year
WHY???

64. PPI Harms Possible decreased calcium absorption caused by PPIs
Inconclusive relationship between PPIs and bone density

65. PPI Harms
Infection
Pneumonia/C. difficile: R/T gastric acid suppression may allow bacterial growth
Care in use with patients with COPD, asthma, increased age, immunosuppression

66. What about Vitamin B12 Deficient Patients on PPIs?
Consider using a different mucus membrane
Sublingual, intranasal

67. …Back to “Mrs. Dash” IF GI risks high: consider PPI IF CV risks high….
73 year old female who has osteoarthritis in both knees. She self-medicates with ibuprofen and she reports good pain control using 400 mg ibuprofen 2-3 times daily.
IF GI risks high: consider PPI
IF CV risks high….

68. AHA Recommends for Pain
CV disease or risk factors for ischemic heart disease
Acetaminophen
Aspirin
Tramadol
Opioids
Nonacetylated salicylates (Diflunisal)
NSAIDs with low COX-2 selectivity
NSAIDs with some COX-2 selectivity
COX-2 selective agents

69. Beers: Aspirin for Primary Prevention of cardiac events
Lack of evidence of benefit versus risk in individuals aged > 80 years
FYI: Strength of recommendation is “weak”
Quality of Evidence is Low

70. Beers: “Avoid” Drug-Disease or Drug Syndrome Interactions
Heart Failure
Syncope
Dementia and Cognitive Impairment
Falls and Fractures
Insomnia
Constipation

71. Beers Criteria “Avoid”: Heart Failure
Digoxin > mg daily
Higher doses associated with no additional benefit and may increase toxicity
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

72. Age Related Change in Pharmacokinetics
As aging occurs, there is a DECREASE in total body water (10-15%)

73. Distribution So, smaller distribution of water soluble drugs
Decrease in total body water (10-15%)
So, smaller distribution of water soluble drugs

74. Increased Drug Concentration!
Serum levels increase due to decreased volume of distribution Examples: Digoxin

75. Mrs. Boudreaux
78 year old female who is very active and enjoys playing cards with her friends one evening per week. During the card game she has dinner and a couple of glasses of wine. She states that this has been her habit for several years but now she becomes dizzy before finishing her second glass of wine. She has had no change in weight, medications (or wine).

76. What is going on with Mrs. Boudreaux?
The wine glasses are getting bigger.
She just can’t hold her liquor anymore.
This is an age related change with EtOH metabolism.
Copyright 1998 Advanced Practice Education Associates

77. Distribution Decrease in total body water (10-15%)
So, smaller distribution of water soluble (EtOH) drugs

78. 1. Increased EtOH Concentration!
Serum levels increase due to decreased volume of distribution Examples: EtOH (Mrs. Boudreaux’ wine)

79. 2. Changes in EtOH Metabolism
Liver mass decreases
Hepatic blood flow decreases
First pass metabolism decreases

80. 3. Decreased Production of CYP 450 enzymes
Can decrease up to 30% in elderly!

81. What is going on with Mrs. Boudreaux?
The wine glasses are getting bigger.
She just can’t hold her liquor anymore.
This is an age related change with EtOH metabolism.
Copyright 1998 Advanced Practice Education Associates

82. Beers: “Avoid” Drug-Disease or Drug Syndrome Interactions
Heart Failure
Syncope
Dementia and Cognitive Impairment
Falls and Fractures
Insomnia
Constipation

83. Sleep Complaints in Older Adults
50% of older adults complain of at least one sleep complaint
Impairs functional ability
Increases risk of accidents and falls
1/3 of elderly patients in North America receive a benzo hypnotic for insomnia (or non-benzo)

84. Beers Criteria “Avoid”: Benzos Hypnotics
Benzodiazepines:
Avoid for insomnia, agitation, or delirium
Avoid in dementia (worsens symptoms)
Increased sensitivity to these and slower metabolism
Increased risk of falls, cognitive impairment
A short acting agent can behave like an intermediate or long acting agent
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

85. Benzodiazepines Agent Brand Duration Alprazolam Xanax
Short/intermediate
Lorazepam
Ativan
Short/Intermediate
Oxazepam
Serax
Clonazepam
Klonopin
Long
Diazepam
Valium
Flurazepam
Dalman

86. But if you just have to use one for anxiety…
Generally speaking, consider 1/3 to ½ adult dose for elderly, titrate
Lorazepam (Ativan): Pharmacokinetics are not significantly affected by age
Avoid doses over 3 mg
Ottawa (ON): Canadian Pharmacists Association; c2011. Benzodiazepine monograph [October 2009]. (Accessed February 8, 2013).
Potentially harmful drugs in the elderly: Beers list and more. Pharmacist's Letter/Prescriber's Letter 2007;23(9):

87. Sleep Changes in Older Adults
Take longer to fall asleep
Have less total nighttime sleep
Increased nighttime wakefulness
Daytime sleepiness
Awaken early

88. Sleep Changes in Older Adults
Common Causes
Arthritic pain
Depression
Shortness of breath (HF, COPD, angina)
Parkinson’s (nightmares, night terrors, levodopa)
Medications: SSRIs, SNRIs, theophylline, cimetidine, phenytoin, steroids, bronchodilators
Dementia: nighttime wandering

89. First Steps Non-Pharmacologic
Avoidance of nicotine, alcohol, and caffeine
Increasing daytime exercise and light exposure
Limit or eliminate daytime napping
Reduce light and noise
Comfortable room temperature
Meals > 2-3 hours before bedtime

90. Beers Criteria “Avoid”: Non-benzo Hypnotics (aka: Z-drugs)
Benzodiazepine Receptor Agonists:
Less rebound insomnia, tolerance, and dependence than benzos
Eszopiclone (Lunesta), Zolpidem (Ambien), Zaleplon (Sonata)
Elderly patients have same side effects as with benzos (delirium, falls, fractures)
2012 Beers Criteria Update Expert Panel
J AM Geriatr Soc. 2012;60(4):

91. Sleep Changes in Older Adults
Pharmacologic
Melatonin
No serious adverse events
Interacts with warfarin, ASA, clopidogrel, ticlopidine, antidiabetic agents (decreased glucose tolerance and insulin sensitivity)

92. High Risk Medications
Insulin and SUs: Aggressive glycemic control often yields more harm than good

93. Endocrine
Target A1C
A1C: goal is <7% in most patients (but not all elderly!)
>7% for some patients with many co-morbids or too abbreviated a lifespan to benefit from intensive therapy
Copyright 1998 Advanced Practice Education Associates

94. What do these drugs all have in common?
Macrolides, quinolones, telithromycin, sulfonamides
Amitriptyline, citalopram, paroxetine, sertraline, venlafaxine, fluoxetine
Albuterol, levalbuterol, salmeterol
Phenylephrine, pseudoephedrine
Cocaine

95. QT Prolongation Long QT Syndrome (LQTS)
Increased risk of ventricular tachycardia

96. Torsades de Pointes Polymorphic V-tach
Many drugs are culprits, but often it is combo of drugs

97. What increases the risk?
Low potassium, magnesium
Bradycardia
Anything that prolongs myocardial repolarization

98. What DRUGS increase the risk?
Quinolones
Risk is additive with other drugs or conditions that increase risk

99. WHO is at risk? Elderly Psychiatric patients
Patients with eating disorders (electrolyte imbalances)

100. Osteoporosis

101. Bisphosphonates Osteoporosis Efficacy wanes with time
What’s optimal duration?
New labeling from FDA (no consensus what it should say!)

102. Bisphosphonates FLEX Trial
Compared bisphos with stopping after 5 years of continuous use
Alendronate > 5 years did not provide much additional protection against fractures
Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment. The Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006;296:

103. What dose?
Most drug studies do not include geriatric patients in clinical trials

104. Underprescribing “Unintended underutilization”
Example: Patient with MI: BB, ACE, ASA, statin plus other meds
Don’t underprescribe to improve compliance

105. Consider ADEs for ANY NEW symptom in an elderly patient!!!
Take Home Points!
Consider ADEs for ANY NEW symptom in an elderly patient!!!

106. Follow the Beers list to keep elders from unintended harm! And PIMs!
Take Home Points!
Follow the Beers list to keep elders from unintended harm! And PIMs!

107. Final Take Home Points!
Do we really need a drug? Can a safer drug be used instead?

108. Questions???
Amelie Hollier, DNP, FNP-BC, FAANP Advanced Practice Education Associates