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P2 Spring: PHRM 845 > Exam 3: Dementia/ Alzheimers > Flashcards

Exam 3: Dementia/ Alzheimers Flashcards

(60 cards)

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1
Q

what is the major cause of dementia?

A

AD

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2
Q

what is the ratio for female:male in AD?

A

2:1 female:male

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3
Q

what is the AD neuropathology? (what is it made of)

A

amyloid plaques and neurofibrillary tangles

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4
Q

what are amyloid plaques?

A
  • extracellular
  • consist of amyloid-b peptides
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5
Q

what are neurofibrillary tangles?

A
  • intracellular
  • consist of hyper-phosphorylated tau
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6
Q

what is the entorhinal cortex in charge of?

A

memory function and consolidation

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7
Q

what is the hippocampus in charge of?

A

memory formation and consolidation

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8
Q

what is the basal forebrain cholinergic system in charge of?

A

learning

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9
Q

what is the neocortex in charge of?

A

memory, learning, cognition

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10
Q

what is the nucleus basalis in charge of?

A

memory, attention, arousal, perception

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11
Q

what is a synapse loss and how does that deal with AD?

A

results in reduced levels of NTs; especially ACh. But also 5-HT, DA, NE

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12
Q

what is Trisomy 21 associated with and where is it located?

A

associated with AD like phenotype and the APP gene is located on chromosome 21

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13
Q

Mutations in the APP gene favor cleavage by ____ or ____. This results in the production of more ____ compared to ____.

A
  • b or y secretase
  • more AB42 than AB40
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14
Q

Mutations in the gene encoding PSEN1 or PSEN 2, which are components of ______, alter app cleavage by _____, resulting in production of more _____ compared to ____.

A
  • y secretase complex
  • y secretase
  • AB42 than AB40
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15
Q

What are the effects of AB aggregation on tau pathology?

A
  1. Kinase activation
  2. tau hyper-phosphorylation
  3. neurofibrillary tangles
  4. disruption of cytoskeleton, axonal trafficking
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16
Q

How does synaptic dysfunction occur within the neurofibrillary tangle?

A

In unhealthy areas where tangles have accumulated, the cytoskeletal tracks are disrupted and disorganized, resulting in defects in axonal transport

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17
Q

What causes neuroinflammation?

A

Activated microglia release pro-inflammatory cytokines (prostaglandins, interleukins, tumor necrosis factor a)

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18
Q

What causes oxidative stress?

A

Activated microglia also release reactive nitrogen species and reactive oxygen species

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19
Q

Individuals with one or two ____ alleles have an ____ risk of AD. Inheritance of ____ alleles have a ___ risk of AD.

A
  • ApoE4; increased
  • ApoE2; decreased
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20
Q

What structure is this?

A

Donepezil

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21
Q

What structure is this?

A

Rivastigmine

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22
Q

What structure is this?

A

Galantamine

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23
Q

What is donepezil?

A

specific, reversible inhibitor of acetylcholinesterase

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24
Q

what is rivastigmine?

A

inhibits acetylcholinesterase AND butyrylcholinesterase

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25
what is galantamine?
selective, reversible inhibitor of acetylcholinesterase AND enhance the action of ACh on nicotinic receptors
26
what is memantine?
NMDA antagonist that blocks glutamatergic neurotransmission via noncompetitive mechanisms, reduces excitotoxicity
27
what is Florbetapir?
radiolabeled agent that binds to amyloid beta and visualized for PET scanning
28
What is the MOA of donanemab?
- induces a decrease in AB levels in the brains of AD pts - shows slow cognitive decline; especially in early stage with low/med. tau patho
29
what are the major side effects of donanemab?
ARIA; brain swelling or microhemorrhages
30
Is there monitoring necessary for donanemab and if so what/why?
YES; MRI monitoring during Tx; especially for pts with two ApoE4 alleles
31
What affects are seen with lecanemab for decreasing levels of AB in the brain of AD pts?
similar results as donanemab; decrease
32
What is vascular dementia and why does it occur?
1. impaired judgement or executive function 2. results from brain injury associated with vascular disease or stroke
33
What is dementia with lewy bodies and what is a core feature?
1. combination of cognitive decline and parkisonism symptoms 2. visual hallucinations are a core feature 3. presence of lewy bodies in cortical
34
What is FTD? What is it known as?
1. disinhibited behavior 2. tau accumulations present (pick's bodies) 3. known as Picks' disease
35
What are the neurocognitive domains?
1. complex attention 2. learning & memory 3. perceptual/motor 4. executive function 5. language 6. social cognition
36
what is the DSM-5 for MILD neurocognitive disorders?
1. modest cognitive decline from a previous level of performance in one or more domains 2. does not interfere with independence
37
what is the DSM-5 for MAJOR neurocognitive disorders?
1. significant cognitive decline from a previous level of performance 2. interferes with independence
38
What are the most frequent anticholinergics leading to cognitive burden?
1. skeletal muscle relaxants 2. tricyclic antidepressants 3. bladder antispasmodics 4. antihistamines (otc allergy/cough/cold/ emetics)
39
What are the rating scales for dementia and AD?
MMSE, ADAS, MoCA, SLUMS
40
what are cholinesterase inhibitors approved for?
mild to moderate dementia - donepezil (severe dementia)
41
what are NMDA receptor antagonists used for?
mod-severe dementia
42
What is the dosing in Adults for Donepezil?
5mg qhs titrated to 10mg after 4-6 weeks
43
what are the side effects of donepezil?
- GI bleeding (caution if NSAIDs) - N/V/D - Bradycardia - syncope - insomnia - weight loss - P450 2D6 and 3A3/4 substrate
44
what is the adult dosing for galantamine?
- 4mg bid for 4 weeks with BF and Dinner and inc. in 8mg increments = 24 mg max - Doses >16 mg/d are not recommended for mod renal/hepatic impairment
45
What are the side effects for galantamine?
- GI bleeding - weight loss - N/V/D - bradycardia - syncope - insomnia - P450 1D6 and 3A4 sub
46
what is the dosing for rivastigmine? Counseling?
- 1.5 mg bid and titrate q2wks with max 6mg - take with meals to min. GI SEs
47
what are the adverse effects of rivastigmine?
- Toxicity if not removed previous patch (N/V/D; very significant) - Weight los and GI bleed - esophageal rupture (reason to dec. dose)
48
What is the dosing for memantine? (specifically for a dose adjustment)
- required in severe renal impairment <29ml/min - 5mg for one week then bid if tolerated max 14mg
49
what are the side effects for memantine?
1. use with caution in pts with seizure disorder 2. hallucinations 3. insomnia 4. confusion 5. clearance is reduced by 80% when used with carbonic anhydrase and sodium bicarb
50
what are the side effects for memantine/donepezil?
warnings for vagotonic effects like bradycardia and heart block; increased risk of gi ulceration; diarrhea; nausea; vomiting; bladder outflow obstructions
51
what is the dosing for memantine/donepezil?
ON donepezil 10mg = Namzaric 7/10 daily and increase by 7mg to target 28/10 qd ON memantine 10mg bid or ER 28 qd; Namzaric 28/10 qd with evening meal
52
what are the side effects for aducanumab?
ARIA: up to 40%; requires MRI of brain within one year of starting then before 7th and 12th doses
53
what form of memantine is only available as generic?
IR tablets
54
What are the side effects of lecanemab?
ARIA: up to 30% requires MRI of brain within one year starting and then before 5,7,14 doses
55
what is the eligibility requirements for the "mabs"?
requires presence of amyloid beta pathology prior to initiating treatment
56
what are the boxed warnings for antipsychotics for psychosis?
increased risk of death or stroke in older adults with dementia
57
what is recommended for vascular dementia?
cholinesterase inhibitors
58
what is helpful in lewy body deentia?
cholinesterase inhibitors and memantine may be helpful
59
What can you do regarding agitation interventions?
introduce distraction techniques and turn attention to something pleasant
60
what are the three types of mild NCDs or in general?
1. AD 2. Vascular dementia 3. Lewy body disease

P2 Spring: PHRM 845 (10 decks)

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