Dementia Meds Flashcards
ssxs of dementia?
severe impairment in intellectual abilities (memory loss, areas of cognition including attention, language skills and problem solving)
how to dx dementia?
ssxs of cognitive dysfxn have to present for at least 6 mos
is dementia a normal consequence of aging?
NO
what needs to be addressed when a pt presents w/dementia/delirium?
neuro, vascular, endocrine, nutritional, infection, metabolism, trauma, toxicity
careful hx and PE as well as lab tests
supplementation w/what vitamin may be beneficial in preventing or diminishing dementia? how? potential risk?
Vit E
lowers free radical formation and ROS in the brain which may be neuroprotective
potential risk is that when given over 2000 IU of Vit E there is an increased risk for thrombosis
three OTC meds that were explored as alternatives to prevent dementia?
NSAIDS
estrogen
statins
labs to workup dementia? imaging?
labs: CBC, CMP (electrolytes, Ca2+, renal fxn, liver enzymes), thyroid tests, Vit B12, folic acid levels
imaging: CT, MRI, SPECT scan or PET scan
MC causes of dementia?
alzheimer’s dz
parkinson’s dz
dementia w/lewy bodies
dementia w/lewy bodies is characterized by what?
presence of lewy bodies which are clumps of alpha-synuclein and ubiquitin proteins in neurons
dx is usu only through post-mortem brain biopsies
DLB is more associated with what dz?
Parkinson’s over alzheimer’s
what do you lose in DLB, this leads to what? how does this differ from what happens in Alzheimer’s?
in DLB you lose cholinergic (Ach producing) neurons which is though to lead to the degradation of cognitive fxn (Alzheimer’s)
where as in Parkinson’s dz you lose dopaminergic neurons and this is thought to be the cause of the loss of motor control
does DLB appear slowly or quickly?
quick in onset usually
current approved meds for tx of Alzheimer’s?
AChE inhibitors, donepezil, galantamine, rivastigmine for mild to moderate AD
memantine (NMDA receptor partial antagonist) for moderate to severe AD
selectivity of doneprezil, rivastigmine and galantamine?
donepezil has higher selectivity for AChE
rivastigmine inhibits butyrylcholinesterase as well as AChE inhibitors
galantamine also effects nicotinic receptors as well as AChE inhibitors
SE of anticholinergic meds?
commonly cause memory impairment and confusion (thus why AChE inhibitors can be used to tx AD)
when treating AD and PD, tx themselves can cause what?
when treating the movement portion of PD, hallucinations and psychosis can worsen
while when treating the hallucinations and psychosis of AD it can worsen PD sxs
AChE inhibition leads to what?
results in increased ACh in synaptic cleft = brain has enhanced cholinergic transmission which can help to reduce the ssxs of Alzheimer’s dementia
approved uses of AChE inhibitors?
AD
DLB
myasthenia gravis
antidote to anti-cholinergic poisoning as can occur with organophosphate poisoning and nerve gas exposure
actions of AChE inhibitors on autonomic NS?
potent parasympathetic effects such as bradycardia, hypotension, increased urination, increased lacrimation, bronchoconstriction, GI tract hypermotility, N/V
what does SLUDGEM stand for? applicable to what?
Salivation Lacrimation Urination Defecation GI upset Emesis Miosis (pinpoint pupils) mnemonic to remember what acetylcholine causes
action of donepezil/aricept? main therapeutic use? off-label use? useful SEs? solubility? half life?
action: centrally acting reversible acetylcholinesterase inhibitor
main therapeutic use: AD (increases cortical ACh)
off-label: cognitive d/os including DLB and vascular dementia
useful SE: has been shown to improve sleep apnea in AD pts; possibly improves and increases vocabulary and expressive language of children with autism
easily crosses BBB, half life of ~70hrs so take once a day
SEs of donepezil/aricept?
most commonly experience bradycardia, N/D, anorexia, abd pn, vivid dreams
MOA of rivastigmine/exelon? approved for tx of what to do what? administration?
MOA: centrally acting reversible acetylcholinesterase inhibitor
approved to tx mild to moderate dementia dt AD/PD, has shown to provide meaningful symptomatic effects in these pts
can administer via orally or transdermal patch (scapulae, lower back, deltoids or pecs)
rivastigmine/exelon is particularly effective in treating what pt population? proposed MOA of this?
those w/a more aggressive course of the disease such as w/younger onset, poor nutritional status or those experiencing sxs such as delusions or hallucinations
proposed that these effects might be dt additional inhibition of butyrylcholinesterase which has been implicated in symptom progression
rivastigmine/exelon can potentially be used for what? SEs?
could potentially be used in those w/schizophrenia b/c of potential butyrylcholinesterase activity
SEs: N/V, dizziness, diarrhea, H/A, anorexia, abd pn (uncommonly decreased wt, insomnia, anxiety, asthenia, vertigo, fatigue)
use of galantamine/razadyne? indications?
indicated for AD and mild to moderate vascular dementia
can be used w/other cholinergics and anticholinergics such as Huperzine A; has been used as a “brain enhancer” to improve memory in brain-damaged adults
overdose of ACh-ase inhibiting drugs can cause what SEs? antidote?
N/V, salivation, sweating, bradycardia, hypotension, convulsions, circulatory collapse
antidote is atropine (acteylcholinesterase)
is there definitive proof that donepezil or similar agents alter AD course? what can you add to donepezil to enhance effects?
NO
but there is evidence suggesting that these drugs can delay the course of AD ssxs
can add memantine - has been shown to improve cognition, functioning and behavior
rivastigmine/exelon can potentially be used for what? SEs?
could potentially be used in those w/schizophrenia b/c of potential butyrylcholinesterase activity
SEs: N/V, dizziness, diarrhea, H/A, anorexia, abd pn (uncommonly decreased wt, insomnia, anxiety, asthenia, vertigo, fatigue)
MOA of memantine/namenda? other effects?
blocks NMDA glutamate receptors; antagonist of glutamatergic NMDA receptor sites
by binding to nMDA receptors it inhibits the prolonged influx of Ca2+ which appears to play an important role in neuronal excitotoxicity
other effects: non-competitive antagonist at 5HT3 receptor with a potency similar to that for the NMDA receptor; non-competitive antagonist at different neuronal nicotinic acetylcholine receptors similar to 5HT3 and NMDA sites; D2 receptor agonist
what happens to # of nicotinic receptors in pts w/AD?
of nicotinic receptors decreases in AD pts (thus why we can target them)
all the site memantine/namenda acts on?
non-competitive antagonist at 5H3 receptor
agonist at dopamine D2 receptor site
antagonist at nicotinic acetylcholine receptor sites
blocks NMDA glutamate receptors
abn functioning of what neurotransmission is hypothesized to also contribute to AD etiology? how does it work? drug ex?
glutamatergic neurotransmission
so targeting glutamatergic system, specifically NMDA receptors is a new approach to treating AD
memantine is the 1st drug which acts to block NMDA glutamate receptors
MOA of memantine/namenda? secondary effects?
blocks NMDA glutamate receptors; antagonist of glutamatergic NMDA receptor sites
by binding to nMDA receptors it inhibits the prolonged influx of Ca2+ which appears to play an important role in neuronal excitotoxicity
secondary effects: non-competitive antagonist at 5HT3 receptor with a potency similar to that for the NMDA receptor
what happens to # of nicotinic receptors in pts w/AD?
of nicotinic receptors decreases in AD pts (thus why we can target them)
all the site memantine/namenda acts on?
non-competitive antagonist at 5H3 receptor
agonist at dopamine D2 receptor site
antagonist at nicotinic acetylcholine receptor sites
blocks NMDA glutamate receptors
SEs of memantine/namenda? possible other indications for its use? (+) SEs of memantine/namenda?
confusion, dizziness, drowsiness, insomnia, H/A, agitation, hallucinations (less common = vomiting, anxiety, increased libido)
can possibly be used to reverse neurological impairment associated with MS
(+) SEs: positive effect on cognition, mood, behavior, ability to perform ADLs in moderate to severe AD
