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Drug therapy considerations for the older adult
Julia Bareham, MSc, BSP
[email protected]
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
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…)
Manage any underlying cause of insomnia or
associated comorbidities
Address any medication/substance use that may
be worsening sleep
Encourage & facilitate as many non-drug measures as
possible
• Sleep hygiene
• Light therapy
• Stimulus control
• Sleep restriction
• Relaxation techniques
• CBT
Non-pharmacological methods are essential for longterm success (~75% of those treated will benefit)
 Avoid the assumption that patients expect a sedative
prescription & are unwilling to modify sleep-related
behaviours.
Try to reserve for situations where poor
quality sleep is negatively impacting daytime
functioning
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
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
Benefits: improve short-term sleep outcomes
 Estimate: ↓ sleep onset latency by 10 to 20 minutes
 Estimate: ↑ total sleep time by ~30 minutes
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.
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 shortacting
New Warning!
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-rappelavis/hc-sc/2014/42253a-eng.php
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
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
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
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 longterm safety data
 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
Ensure the individual has symptomatic versus
asymptomatic bacteriuria by looking for
symptoms!
http://www.rxfiles.ca/rxfiles/uploads/documents/ltc/HCPs/UTI/Sask%20Health%20UTI%20Guidelines.pdf
1. Allergies
2. Risk for infections with resistant organisms
 Recent antibiotics (<3 – 6 months)
 Recent hospitalization
 Travel outside Canada/US within last 6 months
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!
1. Allergies
2. Risk for infections with resistant organisms
3. Local antibiogram
4. Renal function
5. Drug-Drug/Drug-Disease Interactions
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.
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.
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
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
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
 ↓ 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
 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
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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
 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
 Potential for side effects needs to be seriously
considered with benefits vs. risks weighed
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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
START LOW & GO SLOW!!!
 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
 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
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
Statin everyday for
primary prevention?
Do something?
Genetic & cancer
screening tests?
Do nothing?
  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):
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 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.
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
 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.
Medicines can be grouped as:
1. Those that keep the pt well and improve day-today 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
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
82 year old female
Type II Diabetes (diagnosed 3 years ago)
Glycemic targets
A1c 6.5%?
A1c 7.0%?
A1c 8.5%?
↓ cardiovascular events
 (MI, stroke, CV death, HF)
↓ all-cause mortality
↓ hospitalizations
↓ new / worsening nephropathy
↓ retinopathy
↓ neuropathy
↓ foot care complications
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
.
*Priority = Hypoglycemia prevention
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
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
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.
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
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.
Are there other risk factors?
 Smoking
 Hypertension
 Diabetes
 Shared-informed decision-making
 Risks versus benefits
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.
[email protected]