EXAM #3: NEURODEGENERATIVE DISORDERS Flashcards Preview

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Flashcards in EXAM #3: NEURODEGENERATIVE DISORDERS Deck (42):
1

What are the main characteristics of Neurodegnerative Disorders?

1) Loss of neurons
2) Due to BOTH genetic and environmental factors
3) Pathology= aggregation of misfolded proteins

2

What specific region is associated with neuronal loss in AD?

Hippocampus

3

What specific region is associated with neuronal loss in PD?

Basal Ganglia

4

What specific region is associated with neuronal loss in ALS

Cortical and spinal motor neurons

5

What protein accumulates in AD?

1) Beta-amyloid plaques
2) Neurofibrillary tangles

(Intracellular)

6

What protein accumulates in PD?

Alpha-synuclein

7

What protein accumulates in Huntington's Disease?

Huntington Protein

8

What protein accumulates in Prion Disease?

Extracellular prion amyloid plaques

9

Who first diagnosed Alzheimer's Disease?

Alois Alzheimer

10

Who was the first patient diagnosed with AD?

Frau August Deter

11

What is the most prevalent form of gradually progressive dementia?

AD

12

What are the cognitive symptoms of AD?

1) Loss of short-term memory
2) Aphasia
3) Apraxia
4) Agnosia
5) Disorientation

13

What is apraxia?

Inability to carry out motor activity despite intact motor system

14

What is agnosia?

Inability to recognize objects, persons, sounds, shapes, or smells

15

What are the noncognitive symptoms of AD?

1) Depression
2) Psychotic symptoms

16

What typically causes death in AD?

Complications of immobility i.e. pneumonia or PE

17

What is the Cholinergic Hypothesis of AD?

Memory deficits are due to a degeneration of subcortical cholinergic neurons

18

Describe the pathology of AD.

1) Amyloid Precursor Protein is cleaved to Beta-Amyloid
2) There is an imbalance between Beta-Amyloid production and clearance
3) Beta-Amyloid is toxic to neurons

19

What is the connection between Beta-Amyloid, AD, and Down's Syndrome?

APP gene (which is cleaved to Beta-Amyloid) is located on chromosome 21

20

What genes are mutated in early onset AD?

1) APP
2) Presenilin 1 and 2

21

What is the function of Presenilin?

Cleavage of APP

22

What genetic variation is late onset AD associated with?

Epsiolon 4 allele of ApoE

23

What is the role of ApoE in AD?

ApoE clears Beta-Amyloid

24

What is the function of Episolon 4 ApoE in AD?

This form of ApoE does not clear Beta-Amyloid as well as other isoforms and increases the development of AD

25

What is the Tau Hypothesis of AD?

- Tau normally supports microtubules and the neuronal cytoskeleton
- HYPERphosphorylation of Tau causes aggregates i.e. neurofibrillary tangles to form

26

What are the outcomes of neuofibrillary tangles in AD?

1) Microtubular disintegration and instability
2) Collapse of neuronal transport
3) Altered NT release and synaptic function
4) Cell death

27

What class of drug is the first line treatment for cognitive symptoms of AD?

Cholinesterase inhibitors

28

What is the mechanism of action of the Cholinesterase Inhibitors?

Block AChE and Butyrylcholinesterase mediated breakdown of ACh to choline and acetate

29

List the drugs that are used as Cholinesterase Inhibitors in the first line treatment of AD.

1) Tacrine
2) Donepezil
3) Rivastigmine
4) Galantamine

30

Why is Tacrine no longer used today for the treatment of AD?`

Hepatotoxicity

****Note that is also had a very short half-life and needed to be taken 4x per day*****

31

What is the mechanism of action of Donepezil?

AChE inhibition

32

What is unique about Donepezil compared to the other AChEs used to treat AD?

Long half life (70 hrs) that allows for ONCE A DAY dosing

33

Which of the first line agents for AD blocks BOTH AChE and Butyrylcholinesterase?

Rivastigmine

34

How often does Rivastigmine need to be dosed?

Twice per day

35

What AChE can be given as a transdermal patch? What are the clinical implcations?

Rivastigmine--less GI adverse effects

36

What are the typical side effects of AChEs used to treated AD?

1) Nausea
2) Vomiting
3) Diarrhea

37

What are the side effects of AChE overdose?

SLUDGE
- Salivation
- Lacrimation
- Urination
- Defecation
- GI cramps
- Emesis

38

What is the MOA of Memantine?

Non-competitive NMDA antagonist

39

What is the role of Memantine in AD?

Neuroprotection by reducing glutamate excitotoxicity

40

What class of drugs are primarily used to treat the psychotic symptoms of AD?

Atypical antipsychotics

41

What drugs should be used to treat depression in AD?

SSRIs

42

What drugs should NOT be used to treat depression in AD?

TCAs--alpha-1 effects cause orthostatic hypotension (fall risk)

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