lecture 45 Flashcards
campbell - pharmacotherapy of dementia/alzheimer's disease
what is associated with a mild neurocognitive disorder?
evidence of modest cognitive decline from a pervious level of performance in one or more cognitive domains
does NOT interfere
what is associated with a major neurocognitive disorder?
evidence of significant cognitive decline from a previous level of performance in one or more domains
cognitive deficits interfere with independence
what are the neurocognitive domains?
complex attention, executive function, learning and memory, language, social cognition, and perceptual/motor
basic for diagnostic criteria
what are drugs with ACB score of 2?
amantadine (symmetrel)
belladonna
carbamazepine (tegretol)
cyclobenzaprine (flexeril)
cyproheptadine (periactin)
loxapine (loxitane)
meperidine (demerol)
methotrimeprazine (levoprome)
molindone (moban)
oxcarbazepine (trileptal)
pimozide (orap)
what is the ACB?
anticholinergic cognitive burden list (ACB)
higher score means increase risk of cognitive impairment and an increase risk in death
what are the classes that mostly fall on the ACB?
skeletal muscle relaxants
tricyclic antidepresants
bladder antispasmodics
antihistamines
OTC allergy/cough cold, rx anti-emetics
what antihistamines (including OTC allergy/cough cold and rx anti-emetics) are ACB 3?
brompheniramine (dimetapp_
carbinoxamine (histex, carbihist)
chlorpheniramine (chlor-trimeton)
clemastine (tavist)
dimehydrinate (dramaine)
diphenhydramine (benadryl)
hydroxyzine (atarax, vistaril)
meclizine (antivert)
promethazine (phenergan)
scolopamine (transderm-scop)
what skeletal muscle relaxants are ACB 3?
methocarbamol (robaxin)
orphenadrine (norflex)
what TCAs are ACB 3?
amitriptyline (elavil)
amoxapine (asendin)
clomipramine (anafranil)
desipramine (norpramin)
doxepin (sinequan, silenor)
impiramine (tofranil)
nortriptyline (pamelor)
trimipramine (surmontil)
what bladder antispasmodics are ACB 3?
hyoscyamine (anaspaz, levsin)
darifenacin (enablex)
dicyclomine (bentyl)
flavoxate (urispas)
oxybutynin (ditropna)
propantheline (pro-banthine)
trifluoperazine (stelazine)
what are other drugs that don’t fit into the most frequent category, but are still ACB 3?
atropine (sal-tropine)
benztropine (cogentin)
chlorpromazine (torazine)
clozapine (clozaril)
olanzapine (zyprexa)
paroxetine (paxil)
perphenazine (trilafon)
quetiapine (seroquel)
thioridazone (mellaril)
trihexyphenidyl (artane)
what are the courses that different types of dementia make?
vascular - stepwise
alzheimers - diagonal line progressive
lewy body - up and down (sometimes better, but progressively gets worse with less high)
what are the different types of dementia?
alzheimer’s
vascular
lewy body
if a person with AD is experiencing mild to moderate symptoms, what are the characteristics during this time period?
cognitive symptoms
diagnosis
between 0-4 years
if a person with AD is experiencing moderate to severe symptoms, what are the characteristics during this time period?
loss of functional independence
behavior problems
nursing home placement
between 4-8
what is life expectancy for a person with AD?
9 years from diagnosis
what is the only treatment goal of dementia?
slow the symptoms of cognitive decline and preserve functioning for as long as possible
what is the potential new treatment goal of dementia?
remove pathology
but impact on long-term progression and disease course needs to continued to be studied
what are the two drug classes for dementia tx?
cholintesterase inhibitors (donepezil, rivastigimine, galantamine)
NMDA receptor antagonist (memantine, donepezil/memantine)
when should cholinesterase inhibitors be used?
first-line tx with no preference as to agent
all approved for mild-moderate tx, but donepezil is approved also for severe
why is donepezil (aricpet) using first line?
ease of dose titration
once daily dosing
approved for up to severe dementia
what are the characteristics of NMDA receptor antagonists?
does not slow or prevent neurodegeneration
approved in moderate to severe dementia only
not useful in mild cognitive impairments
marginal benefits usually realized in AD
what is the dosing of donepezil (aricept)?
initiate 5mg QHS
increase to 10mg QHS after 4-6 weeks
what are the SE of donepezil (aricpet)?
GI bleeding (caution if using with NSAID)
NVD
bradycardia
syncope
insomnia
weight loss
p450 CYP2D6 and 3A3/4 substrate
what is the dosing of galantamine (razadyne)?
IR - 4mg BID for 4 weeks with breakfast and diner
doses over 16 mg/day are not recommended for moderate renal/hepatic impairment
what are the SE of galantamine (razadyne)?
GI bleeding, weight loss –> warnings
NVD
bradycarida
syncope
insomnia
P450 CYP2D6 and 3A4 substrate
what is the dosing of rivastigimine (exelon)?
1.5 mg BID
take with meals to minimize GI effects
what are the SE of rivastigimine (exelon)?
toxicity due to not removing previous patch every day, significant NVD
esophageal rupture in one case (reason for need to restart lower dose if therapy interrupted)
no P450 interactions
what is the dosing of memantine (namenda)?
IR tablets only available as generic
dos adjustment required in severe renal impairment (so CrCl between 5-29) –> initiate 5mg QD x1w then if tolerate target 5mg BID`
what are the SE of memantine (namenda)?
use with caution in pts with seizure disorders
hallucinations, insomnia, confusion
use with cuation with carbonic anhydrase inhibitors and sodium bicarbonate (clearance of memantine is reduced by 80% if urine is alkalinzed)
no P450 interactions
what is the dosing of memantine/donepezil (namzaric)?
if already on donepezil 10mg –> 7/10 QD and increase by 7mg increments as tolerated to target 28/10 QD
if already on memantine 10mg BID or ER 28 mg QD –> swithc to 28/10 with evening meal QD
what are the warnings of memantine/donepezil (namzaric)?
warning for vagotonic effects like bradycardia and heart block
increased risk of GI ulceration
NVD
bladder outflow obstructions
what is the initial treatment for dementia and when should it be changed?
start with a cholinesterase inhibitor
if decline noted despite treatment at maximum tolerate dose, add an NMDA receptor antagonist in combo if pt is in in moderate-severe stage
what are key concepts to note with oral AD agents?
target dose is highest tolerated
AE are possible and likely –> early recognition may aid benefit/risks discussion
sudden start/stops should be avoided
withdrawal therapy consider with progressed symptoms
management of behavior symptoms
what cholinesterase inhibitor is most likely to cause AE in younger pts?
rivastigamine (N –> V –> Dizziness –> D –> Anorexia)
then galantamine then donepezil
nausea most common
what cholinesterase inhibitor is most likely to cause AE in geriatric pts?
galantamine (dizziness –> D –> N –> Anorexia –> V)
donepezil (D –> N/Dizziness –> Anorexia –> V)
rivastigamine (D –> N/Anorexia –> Dizziness –> V)
diarrhea most common
how do cholinesterase inhibitors effect the different systems?
donepezil (neuro > musc/skel > GI > urinary > CV)
rivastigmine (GI > musc/skel > neuro > urinary = CV)
galantamine (musc/skel > neuro > GI > urinary > CV)
what is special about aducanumab and lecanemab?
investigational use drugs only
requires presence of amyloid beta pathology prior to initiating treatment
aducanumab – covered by CMS only if enrolled in a clinical trial
what are the SE of aducanumab and lecanemab?
same with ARIA –> up to 40%; requires MRI of brain within one year of starting treatment
aducanumab –> is also before 7th and 12th dose
lecanemab –> is also before 5th, 7th, and 14th dose
what are non-PCOL interventions?
cognitive stimulation
maintain a consistent, structured environment
reminders and orientation cues
keep things simple (reduce choices, avoid complex task)
monitor for sudden changes (like delirium)
what are agitation interventions?
recognize triggers
intervene early/recognize behavior
add in outdoor activities
introduce distraction techniques
maintain calmness (avoid arguing/trying to reason/conforntation)
minimize audio and visual stressors
when should antipsychotics be used in dementia?
when psychosis or severe behavioral problems (psychomotor agitation, combativeness) are present
NOT for repetitive behaviors
what are the atypical antipsychotics used in behavioral disturbances? and what is their BBW?
brexipirazoole (only FDA-approved agent)
quetiapine
risperidone
BBW - increased risk of death/stroke in older adults with dementia
when should antidepressants be used in dementia?
sometimes useful (controversial) in depression as a co-morbidity
what antidepressants can be used in depression associated with dementia?
SSRIs usually first line (except paroxetine)
consider also mirtazapine, venlafaxine, or bupropion
what are sleep disturbance interventions?
consistent bedtime
minimize napping
restrict alcohol/caffeine intake
avoid changes in daily routine
avoid television
what is vascular dementia?
cognitive decline usually a result of a vascular insult (like stroke)
what are the drug interventions of vascular dementia?
treat vascular condition (like HTN)
use a cholinesterase inhibitor (especially useful if its a mix between vascular and AD)
what is lewy body dementia?
fluctuating cognition with variations in attention and alertness
visual hallucinations are common
what are the drug interventions of lewy body dementia?
cholinesterase inhibitors and memantine may be helpful
VERY sensitive to SE of antipsychotics –> if use, do low dose quetiapine
