alzheimer's disease

Question 1

compare and contrast multi-infarct (vascular) versus alzheimer’s type demetia

Answer 1

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

Question 2

what are reversible causes of cognitive impairment

Answer 2

drugs
depression
metabolic (changes in glucose, hyponatremia, hypercalcemia)

Question 3

what drug classes are associated with cognitive impairment in the elderly

Answer 3

anticholinergics
anticonvulsants
antihistamines
antiparkinson
analgesics
cardiovascular
gastrointestinal
psychotropics

Question 4

which anticholinergics have the highest risk

Answer 4

amitriptyline
atropine
benztropine
carisoprodol
dicyclomine
diphenhydramine
hydroxyzine
meclizine
oxybutynin

Question 5

difference between dementia and delirium

Answer 5

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

Question 6

risk factors for alzheimer disease

Answer 6

old age >65
female (2x more than male)
positive family history (apolipoprotein E4 allele)

Question 7

in alzheimer disease, ________ neutrons are destroyed

Answer 7

acetylcholine-synthesizing

Question 8

4 major alterations in AD

Answer 8

extracellular B-amyloid plaques (inflamm)
intracellular neurofibrillary tangles (tau protein)
degeneration of cholinergic neurons
cortical atrophy

Question 9

what is the difference between activities of daily living (ADLs) and independent activities of daily living (IADLs)

Answer 9

ADLs: bathing, dressing, toileting, feeding, transferring, walking
IADLs: shopping, financial management, cooking, housework, telephone, driving

Question 10

t/f the goal of pharmacologic treatment is to cure

Answer 10

false; goal is to improve QOL both of the patient and the family, improve mood/behavior

Question 11

what are the two drug classes used for treatment of cognitive symptoms in AD

Answer 11

cholinesterase inhibitors
NMDA antagonist

Question 12

which drugs are the cholinesterase inhibitors

Answer 12

tacrine (no longer)
donepezil
rivastigmine
galantamine

Question 13

why is tacrine no longer marketed

Answer 13

hepatotoxicity

Question 14

mechanism of cholinesterase inhibitors

Answer 14

inhibits acetylcholinesterase, preventing the hydrolysis of acetylcholine so thus increasing acetylcholine in the synaptic cleft

Question 15

what are the drug interactions with cholinesterase inhibitors

Answer 15

anticholinergics
beta blockers
st john’s wort

Question 16

side effects with donepezil

Answer 16

insomnia (dosing time)
nausea/diarrhea (dose related)

Question 17

why is donepezil most commonly used/preferred

Answer 17

once daily dosing
less side effects

Question 18

dosing of donepezil

Answer 18

starts at 5 mg once daily given at bedtime without regard to meals
can increase to 10 mg after 4-6 weeks

Question 19

rivastigmine side effects

Answer 19

CNS: dizziness, headache
GI: n/v, diarrhea, anorexia, abdominal pain
patch can cause extrapyramidal symptoms like tremor

Question 20

dosing considerations with rivastigmine

Answer 20

more complex titration than donepezil
BID dosing (disadvantage)
PO administered with meals
Transdermal patch replaced q24 hours

Question 21

galantamine side effects

Answer 21

nausea vomiting diarrhea

Question 22

dosing considerations for galantamine

Answer 22

complex titration
dose adjust in renal/hepatic impairment
take with food

Question 23

which drug is a NMDA antagonist

Answer 23

memantine

Question 24

mechanism of memantine

Answer 24

blocks the effects of too much glutamate by binding to where Magnesium binds on the NMDA receptor

Question 25

side effects of memantine

Answer 25

dizziness, headache, somnolence, constipation, diarrhea, vomiting

Question 26

drug interactions with memantine

Answer 26

trimethoprim increases concentrations of memantine, increasing risk of myoclonus, delirium

Question 27

when is mementine used for AD

Answer 27

moderate to severe or add on therapy with donepezil

Question 28

dosing considerations for memantine

Answer 28

without regard to meals complicated titration; adjusted in severe renal impairment

Question 29

what is the combination product available for moderate to severe AD

Answer 29

memantine + donepezil (namzaric)

Question 30

considerations for the combination memantine + donepezil product

Answer 30

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

Question 31

what happens upon discontinuation of cholinesterase inhibitors

Answer 31

abrupt decline of cognition

Question 32

what are the disease modifying therapies for AD

Answer 32

anti-amyloid antibodies aducanumab (removed from the market) lecanemab

Question 33

what are side effects with the anti-amyloid antibodies

Answer 33

ARIA: amyloid related imaging abnormalities- potentially serious ADE that includes edema of the brain tissue and bleeding of the brain

Question 34

why might the anti-amyloid antibodies be a controversial treatment

Answer 34

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.

Question 35

considerations for lecanemab

Answer 35

prior to treatment, must confirm presence of amyloid beta pathology medicare will cover for those in NIH studies

Question 36

when might pharmacotherapy be indicated for behavioral problems

Answer 36

hallucinations, delusions, agitation, aggression

Question 37

which drug classes might be used for behavioral symptoms

Answer 37

atypical antipsychotics antidepressants (SSRIs)

Question 38

which atypical antipsychotics might be preferred

Answer 38

olanzapine, ziprasidone mat be the least anticholinergic

Question 39

considerations when using atypical antipsychotics for behavioral symptoms in AD

Answer 39

SHORT TERM use FDA warning for increased mortality in elderly patients with dementia may prolong QT interval, metabolic effects

Question 40

which SSRIs may be used

Answer 40

citalopram, sertraline recommended over TDAs (safety), venlafaxine, mirtazapine, bupropion not well studied

Question 41

should antiepileptics like carbamazepine or valproate be used for mood stabilizing properties?

Answer 41

steer clear; no real evidence

Question 42

should benzos be used?

Answer 42

NO!!! do not recommend. limited value. causes worsening gait, potential paradoxical reaction, physical dependence. reserve for acute very stressful episodes