1. Drug therapy considerations for the older adult
Julia Bareham, MSc, BSP
julia@rxfiles.ca

2. For older adults…
Discuss the risks & benefits presented by tx options
to improve sleep complaints
Understand the risks & benefits of the various
antibiotic tx options for UTIs
Explore the various tx & scheduling options for
analgesics
Discuss shared-decision making, QoL issues, T2B &
the role of 1° prevention in CV risk reduction

4. Difficulty falling asleep, staying asleep, waking up
too early, or sleep that is non-restorative
Sleep difficulty, lasting ≥ 1 month (for 3 nights/week),
occurs despite adequate opportunity for sleep
Insomnia is clinically relevant if associated with
significant distress or daytime impairment (fatigue,
mood, cognitive, social/work dysfunction, etc…)

5. Manage any underlying cause of insomnia or
associated comorbidities
Address any medication/substance use that may
be worsening sleep

7. Encourage & facilitate as many non-drug measures as
possible
Non-pharmacological methods are essential for long-
term success (~75% of those treated will benefit)
Avoid the assumption that patients expect a sedative
prescription & are unwilling to modify sleep-related
behaviours.
• Sleep hygiene
• Light therapy
• Stimulus control
• Sleep restriction
• Relaxation techniques
• CBT

11. Try to reserve for situations where poor
quality sleep is negatively impacting daytime
functioning

13. Use the lowest effective dose, short-term (ideally ≤
2 weeks)
Re-evaluate chronic sedative use for efficacy &
potential harm
Taper & discontinue gradually if previously used
long-term

14. Trytophan
Might ↓ sleep latency & improve mood in healthy people
with insomnia compared to placebo
 insufficient reliable evidence!!
Melatonin
Minimally effective, but reasonable option in terms of safety
1 to 3mg (max 5mg) 2-3 hours before bedtime
Age, neurodegenerative disorders (Alzheimer’s), T2DM, can
↓ melatonin secretions

16. Benefits: improve short-term sleep outcomes
Estimate: ↓ sleep onset latency by 10 to 20 minutes
Estimate: ↑ total sleep time by ~30 minutes

17. Harms – a costly trade-off with the benefits:
Rebound insomnia when stopped abruptly may be a
trigger for chronic use
Development of tolerance, dependence & withdrawal
reactions: continuing long-term may serve only to
prevent withdrawal symptoms as effectiveness is
progressively reduced
~10-30% of chronic benzodiazepine users develop physical
dependence
50% suffer withdrawal symptoms
↑ risk with drugs of shorter duration of action, older patients,
daily long-term use, higher doses, alcoholism, etc.

18. Harms – a costly trade-off with the benefits:
Hangover effects (varies between agents, strongly dependent
on dose & duration of effect)
Other serious adverse effects: fall risk, fractures & memory or
performance impairment. Whether zopiclone or zolpidem is
any safer than benzos is uncertain
If using a benzo for elderly, short to intermediate-acting agents
(e.g. lorazepam, temazepam) are preferred
 AVOID those with a very long half-life as well as those that are very short-
acting

19. Recommended starting dose has been ↓ to 3.75 mg
The lowest effective dose for each pt should be used
The prescribed dose should not exceed 5 mg in
elderly pts, in pts with hepatic or renal impairment or
those currently treated with potent CYP3A4
inhibitors. Dose adjustment may be required with
concomitant use with other CNS-depressant drugs.
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2

20. Reserve for when other treatments fail or when
insomnia is associated with a co-morbid condition (e.g.
depression, pain) or in patients with a history of
substance abuse
Unknown whether sleep improves in elderly with 1°
insomnia
There is no single antidepressant or class of
antidepressants that is most effective for insomnia in
those with depression

21. Trazodone
Sedative dose lower than those used to treat depression
Lacks anticholinergic effects but is associated with CV
adverse effects (e.g. orthostatic hypotension), next-day
sedation (longer half-life in the elderly), & priapism (rare)
Start low & go slow
 e.g. initial dose: 25-50mg
Usual sedative dose: 50-100mg
 Lower than antidepressant dose which ranges from 150-600mg in
divided doses
Half-life ~6.4 hrs in younger adults & 11.6 hrs in elderly

22. Mirtazapine
Role in major depression with associated insomnia
Useful alternative or co-prescription for patients with
insomnia induced by other antidepressants (e.g. bupropion, some
SSRIs)
Associated with increased appetite & weight gain
Long half-life may cause daytime sedation caution: driving
Anecdotally: ≤ 15mg may be more sedating than higher doses
because of increased affinity for anticholinergic receptors at
the lower dose
Doxepin SILENOR 3,6mg
New ultra-low dose of old TCA indicated for insomnia

23. Tolerance to sedative effects occurs after day 3 to 4 of
continuous use
Avoid especially if glaucoma, asthma, & urinary
retention
It is unknown if these agents improve sleep quality in
older adults; poor evidence of efficacy & lacking long-
term safety data

24. A number of sleep studies have found that atypical antipsychotics,
as a class, can improve aspects of sleep in normal controls & those
with psychiatric disorders. However, quetiapine’s sleep effects in
older adults, especially with dementia, are relatively unstudied.
The PK alterations due to aging may contribute to ↑ AEs; use lowest
dose
 Extended-release agents may not be an optimal choice due to slowed motility
of GIT & altered pharmacokinetic parameters
Many drug interactions are possible
 May ↑ levels/effects of: alcohol, anticholinergics, CNS depressants,
methylphenidate, QTc-prolonging agents, quinine.
 May ↓ levels/effects of: amphetamines, anti-parkinson’s agents (dopamine
agonist)
AEs include: ↑ risk of stroke, QT-prolongation, diabetes & death

26. Ensure the individual has symptomatic versus
asymptomatic bacteriuria by looking for
symptoms!

27. http://www.rxfiles.ca/rxfiles/uploads/documents/ltc/HCPs/UTI/Sask%20Health%20UTI%20Guidelines.pdf

31. 1. Allergies
2. Risk for infections with resistant organisms
Recent antibiotics (<3 – 6 months)
Recent hospitalization
Travel outside Canada/US within last 6 months

32. 1. Allergies
2. Risk for infections with resistant organisms
3. Local antibiogram
4. Renal function
Prevalence of CKD
30% age 65 or older living in community
50% amongst nursing home residents.
Of the 1st
& 2nd
line antimicrobial agents for treatment of
UTI, only one agent does not require consideration for
kidney function
Assess renal function to guide drug selection & dosing!

33. 1. Allergies
2. Risk for infections with resistant organisms
3. Local antibiogram
4. Renal function
5. Drug-Drug/Drug-Disease Interactions

34. Clinically significant  hyperkalemia
SMX/TMP, trimethoprim alone
watch for high doses
older age
renal insufficiency
combination with other drugs that cause ↑ K+ (e.g. ACEI)
Often occurs within 4 to 5 days of starting therapy
monitor or select an alternative antibiotic when possible
Canadian Pharmacist’s Letter. Sept 2010; Vol 26.

35. Clinically significant  serious bleeding
(hospitalization)
WARFARIN interacts with many abx’s used to treat
UTIs:
HIGH—RISK of interaction:
Cipro / levofloxacin, TMP--SMX
LOW—RISK of interaction:
cephalexin, amoxicillin
VERY LOW—RISK of interaction:
nitrofurantoin, trimethoprim, fosfomycin
The American Journal of Medicine (2014), doi:10.1016/j.amjmed.2014.01.044.

36. Remember: any antibiotic can ↑ INR (by reducing GI
flora)
Empiric dosing changes not recommended
Monitor INR on day 3-5, again if needed, and as
needed for any warfarin dose adjustments made

37. 1. Allergies
2. Risk for infections with resistant organisms
3. Local antibiogram
4. Renal function
5. Drug-Drug/Drug-Disease Interactions
6. Adverse effects
7. Comparative costs
8. Duration of therapy
Community-based adults
LTC uncomplicated
LTC complicated

39. If pain is chronic non-cancer, consider both pain &
function!
Elimination of pain is often not realistic, & if pursued,
may come at a cost of functional impairment & adverse
events (e.g. confusion/fall risk)
 Pain reduction: ↓ 30-50%
 Improved Function
Self Report of Pain: important due to subjective
nature of pain

40.  ↓ mobility & functional status
 sleep disturbance
 may contribute to depression, anxiety, agitation
 may interfere with personal relationships
 overall lower quality of life / needless suffering
“Pain is inevitable; suffering is optional.” – M. Kathleen Casey

41.  Multiple age-related changes to the body can greatly
affect how medications work in the elderly
 Expect ↑ drug levels / prolonged drug levels leading to
greater risk of side effects
 Decreases in kidney function
 Changes in the way the liver metabolises drugs
 Body composition changes (e.g. fat stores)
Elderly often require ½ -1/3 of the usual adult dose

42.  Analgesic but NOT for inflammation
 Useful for musculoskeletal type pain (OA, LBP, etc.)
 Well tolerated @ recommended doses
 Short- & long-acting formulations available
 e.g. Tylenol Arthritis, 2 phase release  1st
layer of caplet provides
quick relief, 2nd
layer slowly provides medicine over time – option for
night/early morning pain
 Can be found in combination
 e.g. Tylenol #3: acetaminophen & codeine; Caffeine; Cough & cold
 Always be mindful of total daily dose from all sources

43.  Maximum daily dose ≤ 4g/day. For chronic dosing
consider limiting to ≤3.25g/day.
 Monitor: Liver function tests if used long-term OR with
high alcohol consumption

44.  Potential for side effects needs to be seriously
considered with benefits vs. risks weighed
 Heart – worsen heart failure, ↑ events (heart attacks)
 Kidney – acute renal failure
 Gastrointestinal – upset stomach, ulcers, bleeds
 CNS – e.g. indomethacin (gout) – dizziness, vertigo, confusion
 Monitor: new onset of breathing difficulty, swollen
ankles – fluid retention, signs of bleeding
 Topicals

45.  GI effects: constipation, bowel obstruction, nausea
 Bowel regimen is essential (e.g. laxatives)
 CNS: sedation, cognitive dysfunction, confusion
 Most likely to occur upon starting & with dose changes
 ↑ risk of falls / fractures
 Normal responses to continued exposure of opioids:
 Tolerance: results in ↓ of one or more of the drug’s effects over time.
 Will likely not develop to constipation; tolerance in a few days to
sedative/cognitive/nauseous effects; tolerance can happen to the pain
relieving effect requiring a dosage ↑
 Dependence: (physical) withdrawal effects
START LOW & GO SLOW!!!

46.  Addiction to pain medicine in older adults is RARE
(particularly if no history of substance abuse) when that medicine is
used as prescribed for relief of acute or chronic
conditions.
 Pain medications can be misused in any population, but
treatment of significant pain is appropriate and not a
misuse.
 Be mindful of the fear of addiction, the language you use
to describe opioids & be confident in providing
reassurance to your patients

50. Respect for the pt’s values, preferences, & expressed
needs
Clear, high-quality information & education for the
patient and family
Involves at minimum a clinician & the pt
Both parties share information
Clinician: offers options & describes their risks & benefits
Pt: expresses his/her preferences & values
“What matters to you?” as well as “What is the
matter?”
Barry MJ, Edgman-Levitan S. Shared decision making--pinnacle of patient-centered care. N Engl J Med. 2012 Mar

51. Do something? Do nothing?
Statin everyday for
primary prevention?
Genetic & cancer
screening tests?

52. ↑ pt’s awareness & understanding of treatment options &
possible outcomes
Online, paper, videos
Can efficiently help patients absorb relevant clinical evidence
& aid them in developing & communicating informed
preferences
Result of using these tools (Cochrane review):
 ↑ knowledge
 More accurate risk perceptions
 ↑ # of decisions consistent with pt’s values
 ↓ level of internal decisional conflict for pts
 Fewer pts remaining passive or undecided
Barry MJ, Edgman-Levitan S. Shared decision making--pinnacle of patient-centered care. N Engl J Med. 2012 Mar
1;366(9):780-1.

53. http://shareddecisions.mayoclinic.org
Succinct, easy to use tools that provide
graphic displays of the benefits &
harms of different options organised
around concerns that are important to
patients

56. ↓ polypharmacy
↓ risk of adverse events
↓ risk of drug interactions
↓ pill burden
↓ medication costs
In some circumstances, the only way to know
whether or not to stop a medicine is to actually
stop it & see what happens
Alexander GC, Sayla MA, Holmes HM, Sachs GA. Prioritizing and stopping prescription medicines. CMAJ
2006;174(8):1083-4.

57. Medicines can be grouped as:
1. Those that keep the pt well and improve day-to-
day QOL
2. Those that are used for the prevention of illness
in the future
A practical guide to stopping medicines in older people. Best Practice Journal 2012;27

58. Factors to consider when deciding if a
medicine can be stopped include:
The wishes of the pt
Clinical indication & benefit
Priority of medications to be discontinued
Appropriateness
Duration of use
Adherence
The prescribing cascade

60. 82 year old female
Type II Diabetes (diagnosed 3 years ago)
Glycemic targets
A1c 6.5%?
A1c 7.0%?
A1c 8.5%?

61. ↓ cardiovascular events
(MI, stroke, CV death, HF)
↓ all-cause mortality
↓ hospitalizations
↓ new / worsening nephropathy
↓ retinopathy
↓ neuropathy
↓ foot care complications

62. UKPDS-34 (metformin vs standard tx in obese
T2DM)
↓ all-cause mortality NNT=14/10.7 years
↓ stroke NNT=48/10.7 years
 A1C achieved was 7.4% vs 8%
~10 years
ADVANCE (mostly gliclazide ± metformin)
↓ microvascular events NNT=67/5 years
 A1C: 6.5 vs7.3
~5 years

64. .
*Priority = Hypoglycemia prevention

65. When individualizing targets, consider:
Limited life expectancy
Functional dependency
Extensive CAD at high-risk of CV events
Multiple co-morbidities
History of recurrent, severe hypoglycemia
Hypoglycemia unawareness
Available support & resources

67. What to do when it comes to statins
& older adults??
This is an area of some controversy….
 RCT studies only include up to age ≤82
 Risk vs benefit of lowering cholesterol in the very old is
not well established. Is lower always better?
 Risk of myopathy with: ↑ age & ↓ renal function
 If treating, does the pt tolerate the statin well enough to
maintain an active lifestyle (relative to previous degree of
activity tolerated)?
 some patients may "stop walking" if too much myalgia

68. Cardiovascular Disease
Older adults have ↑ risk of CV disease. However,
epidemiological studies suggest that the relative risk
for CHD associated with high cholesterol ↓ with age.
In old age, there is an inverse relationship between
high cholesterol & the risk of stroke & there are
conflicting data on the relationship between high
cholesterol & non-CV mortality.
Kronmal RA, Cain KC, Ye Z, Omenn GS. Total serum cholesterol levels and mortality risk as a function of age. A report based
on the Framingham data. Arch Intern Med 1993;153:1065-73.
Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, et al. Blood cholesterol and vascular mortality by age,
sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet
2007;370:1829-39.

69. Shorter life expectancy than younger adults
Chronological age often given greater weight than
physiological age
Substantial variation in physiological age between
individuals attributable to frailty, comorbid
disease, & cognitive decline
Risk factors for ASCVD do not predict outcomes as
well as they do for younger individuals

70. Competing causes of mortality mask the potential
benefits of some therapies
Frailty may exacerbate adverse effects of therapy
Polypharmacy may result in ↑ DIs & ↑ pill burden
Musculoskeletal function, pain, & cognition AEs of
therapies (not restricted to statins) are more severe
in older individuals because these factors predispose
to reduced physical activity, sarcopenia, & falls.

71. Are there other risk factors?
 Smoking
 Hypertension
 Diabetes
 Shared-informed decision-making
 Risks versus benefits

73. 1° Prevention
Statins lower risk of CV events in moderate to high risk
pts without a prior CV event
 Absolute benefits are modest relative to 2° prevention
 Mortality: NNT = NS over ~5yrs
 CV Events: NNT = 91 over ~3.3yrs ASCOT
Those with lower CV risk have less absolute benefit
from a statin which must be weighed against the
uncertainties regarding potential benefits versus
harms over longer durations
 Statins have not been well studied in very elderly patients (>age 82)
 Consider ↑ potential for AEs, patient values, etc.

74. julia@rxfiles.ca