Neurodegenerative disorders Flashcards Preview

Year 2 Pharmacology > Neurodegenerative disorders > Flashcards

Flashcards in Neurodegenerative disorders Deck (31):
1

what characterizes the deficits in Alzheimer's disease?

loss of hippocampal and cortical neurons resulting in impaired memory formation and cognitive deficits

2

what characterizes the deficits in parkinson's disease and huntington's disease?

loss of dopaminergic neurons in basal ganglia leading to altered movement control

3

what characterizes the deficits in amyotrophic lateral sclerosis?

degeneration of cortical and spinal motor neurons resulting in muscular weakness

4

what are the protein accumulations associated with AD?

extracellular beta amyloid and intracytoplasmic neurofibrillary tangles

5

what are the protein accumulations associated with ALS and parkinsons?

intracytoplasmic aggregates

PD - alpha synuclein

6

what are the protein accumulations associated with huntingtons?

intranuclear inclusions of huntingtin protein

7

what are the cognitive symptoms associated with AD?

loss of short term memory
aphasia
apraxia (inability to carry out motor activities)
agnosia
disorientation

8

what are the noncognitive symptoms associated with AD?

depression, psychotic

9

what is the cholinergic hypothesis of AD?

deficiency in Ach due to degeneration of subcortical cholinergic neurons (memory formation areas - hippocampus)

PRIMARY PATHOGENESIS HYPOTHESIS

10

what is the amyloid hypothesis of AD?

extracellular accumulations of beta amyloid peptides (BA) are toxic to neurons

11

does deposition of BA plaques correlate with neuronal loss?

no

12

early onset AD is associated with mutations in what genes? what is the result?

APP, PSEN1, PSEN2

overproduction of AB

13

what is the role of PSEN1 and PSEN2?

encode for membrane proteins involved in cleaving APP

14

what is the role of APP?

encodes amyloid B precursor peptides

15

what is the tau hypothesis in AD?

hyperphosphorylation of tau forms aggregates and neurofibrillary tangles

16

what is the result of tau hyperphosphorylation?

microtubular disintegration and instability
collapse of neuronal transport system
altered NT release and synaptic function
cell death

17

what is the first line therapy for symptomatic treatment of cognitive impairments in mild to moderate AD? does it modify the progression?

cholinesterase inhibitors

no

18

what is the MOA of the cholinesterase inhibitors?

reduce breakdown of endogenously released Ach, resulting in greater activation of postsynaptic Ach receptors

19

what are the cholinesterase inhibitor agents for AD?

tacrine
donepezil
rivastigmine
galantamine

20

donepezil inhibits primarily what enzyme?

AchE

21

what is the MOA of rivastigmine?

inhibits AchE and BchE

22

which AD agent appears selective for hippocampus and prefrontal cortex?

rivastigmine

23

what is the route for rivastigmine?

transdermal pouch

24

what are the cholinergic side effects of cholinesterase inhibitors?

SLUDGE

salivation
lacrimation
urinary incontinence
diarrhea
GI cramps
emesis

25

what is the main side effect associated with donepezil?

bradycardia

26

what is the glutamate antagonist agent for AD?

memantine

27

what is the MOA of memantine?

non-competitive antagonist of the NMDA glutamate receptor with long half life

provides neuroprotection by reducing intracellular calcium influx and glutamate induced neurotoxicity

28

which hormone is used as replacement therapy in women with AD?

estrogen

29

what is the main treatment options for the psychotic symptoms associated with AD?

atypical antipsychotics

risperidone, olanzapine, quetiapine

30

what is the main treatment options for the depression symptoms associated with AD?

SSRIs

sertraline, citalopram

31

which drugs should be avoided in treating the depression associated with AD? why?

TCAs

side effects - anticholinergic affects, orthostatic hypotension

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