alzheimer's disease Flashcards
compare and contrast multi-infarct (vascular) versus alzheimer’s type demetia
multi infarct: abrupt onset, step-wise deterioration, PMHx includes HTN/ASCVD, focal neural exam (specific part of brain)
Alzheimer’s: gradual onset, slow/progressive deterioration, non-cardiac disease, non-focal neural exam
what are reversible causes of cognitive impairment
drugs
depression
metabolic (changes in glucose, hyponatremia, hypercalcemia)
what drug classes are associated with cognitive impairment in the elderly
anticholinergics
anticonvulsants
antihistamines
antiparkinson
analgesics
cardiovascular
gastrointestinal
psychotropics
which anticholinergics have the highest risk
amitriptyline
atropine
benztropine
carisoprodol
dicyclomine
diphenhydramine
hydroxyzine
meclizine
oxybutynin
difference between dementia and delirium
dementia: decline in cognitive function over time, memory loss
delirium: short period of time (hours to days), acute change in level of consciousness, decline in cognition
risk factors for alzheimer disease
old age >65
female (2x more than male)
positive family history (apolipoprotein E4 allele)
in alzheimer disease, ________ neutrons are destroyed
acetylcholine-synthesizing
4 major alterations in AD
extracellular B-amyloid plaques (inflamm)
intracellular neurofibrillary tangles (tau protein)
degeneration of cholinergic neurons
cortical atrophy
what is the difference between activities of daily living (ADLs) and independent activities of daily living (IADLs)
ADLs: bathing, dressing, toileting, feeding, transferring, walking
IADLs: shopping, financial management, cooking, housework, telephone, driving
t/f the goal of pharmacologic treatment is to cure
false; goal is to improve QOL both of the patient and the family, improve mood/behavior
what are the two drug classes used for treatment of cognitive symptoms in AD
cholinesterase inhibitors
NMDA antagonist
which drugs are the cholinesterase inhibitors
tacrine (no longer)
donepezil
rivastigmine
galantamine
why is tacrine no longer marketed
hepatotoxicity
mechanism of cholinesterase inhibitors
inhibits acetylcholinesterase, preventing the hydrolysis of acetylcholine so thus increasing acetylcholine in the synaptic cleft
what are the drug interactions with cholinesterase inhibitors
anticholinergics
beta blockers
st john’s wort
side effects with donepezil
insomnia (dosing time)
nausea/diarrhea (dose related)
why is donepezil most commonly used/preferred
once daily dosing
less side effects
dosing of donepezil
starts at 5 mg once daily given at bedtime without regard to meals
can increase to 10 mg after 4-6 weeks
rivastigmine side effects
CNS: dizziness, headache
GI: n/v, diarrhea, anorexia, abdominal pain
patch can cause extrapyramidal symptoms like tremor
dosing considerations with rivastigmine
more complex titration than donepezil
BID dosing (disadvantage)
PO administered with meals
Transdermal patch replaced q24 hours
galantamine side effects
nausea vomiting diarrhea
dosing considerations for galantamine
complex titration
dose adjust in renal/hepatic impairment
take with food
which drug is a NMDA antagonist
memantine
mechanism of memantine
blocks the effects of too much glutamate by binding to where Magnesium binds on the NMDA receptor
side effects of memantine
dizziness, headache, somnolence, constipation, diarrhea, vomiting
drug interactions with memantine
trimethoprim
increases concentrations of memantine, increasing risk of myoclonus, delirium
when is mementine used for AD
moderate to severe
or add on therapy with donepezil
dosing considerations for memantine
without regard to meals
complicated titration; adjusted in severe renal impairment
what is the combination product available for moderate to severe AD
memantine + donepezil (namzaric)
considerations for the combination memantine + donepezil product
drug interactions with anticholinergics, beta blockers, trimethoprim
give in evening without regard to meals
should be stabilized on donepezil 10 mg/day prior to starting
what happens upon discontinuation of cholinesterase inhibitors
abrupt decline of cognition
what are the disease modifying therapies for AD
anti-amyloid antibodies
aducanumab (removed from the market)
lecanemab
what are side effects with the anti-amyloid antibodies
ARIA: amyloid related imaging abnormalities- potentially serious ADE that includes edema of the brain tissue and bleeding of the brain
why might the anti-amyloid antibodies be a controversial treatment
patients are not a candidate for anticoagulation or antithrombotics when on therapy: because ARIA can cause hemorrhage in the brain. if patient has a stroke on it, can’t get thrombolytics. if they get Afib, can’t go on anticoagulation.
considerations for lecanemab
prior to treatment, must confirm presence of amyloid beta pathology
medicare will cover for those in NIH studies
when might pharmacotherapy be indicated for behavioral problems
hallucinations, delusions, agitation, aggression
which drug classes might be used for behavioral symptoms
atypical antipsychotics
antidepressants (SSRIs)
which atypical antipsychotics might be preferred
olanzapine, ziprasidone
mat be the least anticholinergic
considerations when using atypical antipsychotics for behavioral symptoms in AD
SHORT TERM use
FDA warning for increased mortality in elderly patients with dementia
may prolong QT interval, metabolic effects
which SSRIs may be used
citalopram, sertraline
recommended over TDAs (safety), venlafaxine, mirtazapine, bupropion not well studied
should antiepileptics like carbamazepine or valproate be used for mood stabilizing properties?
steer clear; no real evidence
should benzos be used?
NO!!! do not recommend. limited value. causes worsening gait, potential paradoxical reaction, physical dependence. reserve for acute very stressful episodes
