drug therapy considerations for the older adult julia bareham, msc, bsp [email protected]
TRANSCRIPT
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
analgesicsDiscuss 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
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
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!!
MelatoninMinimally effective, but reasonable option in terms of safety1 to 3mg (max 5mg) 2-3 hours before bedtimeAge, neurodegenerative disorders (Alzheimer’s), T2DM, can ↓ melatonin secretions
Benefits: improve short-term sleep outcomes Estimate: ↓ sleep onset latency by 10 to 20 minutesEstimate: ↑ 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
dependence50% 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 short-
acting
Recommended starting dose has been to 3.75 mg The lowest effective dose for each pt should be usedThe 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/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
TrazodoneSedative 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
MirtazapineRole in major depression with associated insomniaUseful 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: drivingAnecdotally: ≤ 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 long-term 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. Allergies2. Risk for infections with resistant organisms
Recent antibiotics (<3 – 6 months)Recent hospitalizationTravel outside Canada/US within last 6 months
1. Allergies2. Risk for infections with resistant organisms3. Local antibiogram4. Renal function
Prevalence of CKD30% age 65 or older living in community50% 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. Allergies2. Risk for infections with resistant organisms3. Local antibiogram4. Renal function5. Drug-Drug/Drug-Disease Interactions
Clinically significant hyperkalemia
SMX/TMP, trimethoprim alonewatch for high dosesolder age renal insufficiency combination with other drugs that cause ↑ K+ (e.g. ACEI)
Often occurs within 4 to 5 days of starting therapymonitor 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. Allergies2. Risk for infections with resistant organisms3. Local antibiogram4. Renal function5. Drug-Drug/Drug-Disease Interactions6. Adverse effects7. Comparative costs8. 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
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 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
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!!!
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 ptBoth parties share informationClinician: offers options & describes their risks & benefitsPt: 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 1;366(9):780-1.
Do something? Do nothing?
Statin everyday for primary prevention?
Genetic & cancer screening tests?
pt’s awareness & understanding of treatment options & possible outcomes
Online, paper, videosCan 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.
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-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
Factors to consider when deciding if a medicine can be stopped include:
The wishes of the ptClinical indication & benefitPriority of medications to be discontinuedAppropriatenessDuration of useAdherenceThe prescribing cascade
82 year old femaleType II Diabetes (diagnosed 3 years ago)Glycemic targetsA1c 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 expectancyFunctional dependencyExtensive CAD at high-risk of CV eventsMultiple co-morbiditiesHistory of recurrent, severe hypoglycemiaHypoglycemia unawarenessAvailable 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 adultsChronological age often given greater weight than
physiological ageSubstantial 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 therapyPolypharmacy may result in ↑ DIs & ↑ pill burdenMusculoskeletal 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.
