Pharmacological Treatment of Dementia Flashcards
The goal of dementia treatment is to…
Improve quality of life for individual and caregivers, maintain optimal function, and provide maximum comfort
The three cholinersterase inhibitors include…
Donepezil
Galantamine
Rivastigmine
MOA of cholinesterase inhibitors is to…
Prevent the breakdown of acetylcholine - main neurotransmitter involved in learning + memory
Efficacy of cholinesterase inhibitors…
Modest benefit - may show small improvements in measures of cognition, and may slow progression by months
Time to benefit for cholinesterase inhibitors is…
3-6 months, but long-term benefit is not clear
Common AE’s with cholinesterase inhibitors include…
Cholinergic Fx
N/V/D, loss of appetite
Insomnia
Urinary urgency/frequency +/- incontinence
Opposite of anticholinergic
Less common AE’s with cholinesterase inhibitors include…
Weight loss
Agitation, behaviour disturbances
Bradycardia, Syncope
Bronchoconstriction
GI bleed
Nightmares
AE’s with cholinesterase inhibitors are ____, but can become tolerable with…
Dose-related; slow titration, taking with food, trying anti-emetic
CI’s with cholinesterase inhibtors include…
Uncontrolled/severe asthma, or severe COPD (can cause bronchoconstriction)
Cardiac conduction abnormalities, bradycardia (HR < 55 bpm)
Precautions with cholinesterase inhibitors include…
Peptic ulcer disease or uncontrolled GERD
Urinary incontinence
Seizure history
Concurrent anticholinergics
The NMDA antagonist that can be used is…
Memantine
MOA of NMDA antagonist is…
Blocking glutamate at NMDA receptor (thought that persistent activation of NMDA may contribute to symptoms)
Efficacy of NMDA antagonists is…
Modest - some evidence of benefit on cognitive testing, minimal clinical benefit in most cases
AE’s of NMDA antagonists include….
Dizziness, headache, insomnia
Nausea, constipation
Hypertension
Restlessness, akathisia
NMDA antagonists are cautioned for…
CV disease
Seizures
NMDA antagonist differs from cholinesterase inhibitors where the issue is primarily…
Lack of efficacy, rather than tolerability
Risk vs. benefit with the dementia medications considers…
Small potential improvement with high risk of AE’s, especially with cholinesterase inhibitors
Consider that a small AE can drastically decrease QoL; is it worth a few months of slowed progression?
Examples where risk is greater than benefit for dementia medications includes…
Adverse effects impeding QoL
Frail + multiple co-morbidities
Problematic urinary incontinence
Pt. experiencing significant weight loss/anorexia
Pt. has significant aggression/agitation
Severe dementia
Adherence concern
Financial restriction
Examples where benefit is greater than risk for dementia medications includes…
Early-onset dementia in a relatively healthy individual (few co-morbidities, no CI)
Early on in disease progression
Few AE’s once started
No concerns about adherence or management of AE’s
General consesus of when to discontinue dementia treatment with cholinesterase inhibitors + NMDA antagonist, is…
Loss of ability to perform ADL’s independently (dementia progressed to stage where there would be no meaningful benefit remaining)
Any situation where risk > benefit
When discontinuing NMDA antagonist or cholinesterase inhibitor, we should…
Taper carefully over 2-4 weeks
Monitor for worsening of cognitive symptoms or BPSD
Taper to prevent anticholinergic rebound with cholinesterase
Currently, for prevention of dementia…
There is no evidence of pharmacological help to prevent cognitive decline or dementia
Mostly non-pharm (CV risk reduction), education/social engagement, exercise, diet
New monoclonal antibodies are disease modifying for alzheimer’s, where they…
Reduce beta-amyloid plaques in the brain
So far, efficacy of monoclonal antibodies shows that…
Clinical significance is unclear - may slow progression of amyloid pathology
ONLY indicated for Alzheimer’s
Significant AE’s, administration challenges
Before starting pharmacotherapy for BPSD, we should consider…
Treating any medical/medication causes or contributors (similar to delirium)
Explore and minimize psychological + environmental triggers
Pharmacotherapy should only be initiatied for BPSD if…
Behaviour is causing harm/significant distress to individual, caregiver, and others
AND
Is persistent or recurrent
Assessing for and treating medical causes of BPSD may involve…
Taper/stop any medications that may be contributing to cognitive decline (think of delirium)
Look for + manage any underlying medical issues - infection, endocrine, electrolytes, urinary retention, pain
Offer food/drink for hunger/thirst
Manage constipation proactively
If we are using drugs for managing BPSD, we should re-evaluate drug regimen every…
3 months
Ways that we can help manage psychological triggers of BPSD include…
Avoid social isolation
Allow individual to make decisions - simple, clear choices, simple instructions
Warm, kind, mannerisms
Do not argue
Ways that we can help manage environmental triggers include…
Encourage use of glasses, hearing aids
Provide regular, structured routine in familiar environment
Avoid overstimulation
Engaging activities + social opportunities
Bright light exposure in the day, dark at evening
Antidepressants may be given for BPSD if…
It is found that depression or anxiety is the root trigger of behaviour - once daily
Try and find ones that might help with co-morbid conditions (duloxetine for neuropathic pain, mirtazapine for sleep)
These AD’s should be avoided…
TCA’s, paroxetine - anticholinergics
Fluoxetine - more DI’s, long half-life
We should avoid benzodiazepines for anxiety/sedation because…
Worsen cognitive impairment
Increase fall risk
Worsen disinhibition
Occasionally may be used following stressful event or preventatively before dental work
AP’s should only be given if…
Behaviour is causing harm and/or has not responded to non-pharmacological methods
These AP’s are preferred due to…
Atypical - decreased risk of EPS
A black box warning of AP’s with dementia is ____ - therefore, we should…
Increased risk of mortality - try to taper and stop q3months
With AP usage, we need to watch for…
Weight gain, orthostatic hypotension
Anticholinergic effects, sedation, falls, EPS
Tardive dyskinesia, urinary retention
TITRATE SLOW
NEEDS to be monitored
Olanzapine should be…
Avoided - very anticholinergic and sedating
For acute delirium, we could give…
Haloperidol PRN
NOT for parkinson’s due to EPS
Stimulants for BPSD is…
Unfavorable - AE’s usually outweigh any potential benefit (increased BP, decreased appetite, dizziness, insomnia, agitation)
External activity + environmental stimulation is more effective
OCCASIONALLY used to treat apathy, loss of motivation
Sedatives may potentially be considered for BPSD when…
Behaviour is thought to be directly correlated with lack of sleep OR behaviours are during the night - but consider risks of dependence, tolerance, increased delirium + falls
Analgesics for BPSD are…
Warranted when pain is thought to be the cause of behaviour - trial of acetaminophen is often overlooked
QoL !!
