Alzheimers Disease Flashcards
What is the obvious sign of AD?
reduced functional capacity along with mild cognitive impairment
What is the specific genotype that causes a 2-10 fold risk of AD?
APOE4
What are the 3 causes of AD?
- beta-amyloid misfolding
- Tau misfolding
- low amount of cortical neurons due to misfolding
What is the AD pathophysiology?
increase amount of Amyloid plaques due to misfolds
What neurotransmitter is decreased in AD?
Ach
What is the cholinergic hypothesis?
a deficiency of Ach is critical for the genesis of the AD symptoms
What are the two therapeutic strategies in AD?
- Acetycholinesterase Inhibitors
- N-methyl-D-aspartate glutamate receptor antagonists
How do acetylcholinesterase Inhibitors work?
prevent Ach from being broken down and increasing it in the synaptic cleft; therefore increasing its chances of binding the receptor
What are the three Acetylcholinesterase Inhibitors?
- Donzepil (Aricept)
- Rivastigmine
- Galantamine
What are the main side effects of Acetylcholinesterase Inhibitors?
- nausea
- vomiting
- diarrhea
What is unique about Donzepil (Aricept)?
used to treat mild-severe AD
What is unique about Rivastigmine?
utilizes esterases not CYP for metabolism
What is unique about Galantamine?
- competitive inhibitor
- allosterically modulates nicotinic receptors which improves cholinergic neurotransmission
How does Memantine (Namenda) work?
- NMDA-receptor antagonist; prevents CA and other ions; while also lowering the amount of glutamate lowering excitation
What is unique about Memantine?
reduces the rate of clinical deterioration in moderate-severe AD
used as an adjunct therapy
What is unique about Memantine/Donepezil (Namzaric)?
does a good job with cognitive symptoms, but not with Non-cognitive symptoms
How do monoclonal antibodies work?
attach to protein and target it for removal
What is unique about Lecanemab?
recognizes protofibrils and prevents amyloid-beta deposition (attacks before the plaque preventing it from growing into a serious plaque
What is unique about Aducanumab?
targets and removes beta-amyloid that accumulate into plaques
When are monoclonal antibodies used in treatment for alzheimers disease?
early symptoms
What is Huntington’s Disease?
gradual onset of motor incoordination and cognitive decline
How is Huntington’s Disease presented?
- corea (brief jerk like symptoms)
- personality changes
What is the pathology of Huntington’s Disease?
expansion of CAG near the huntingtin protein
What neurotransmissions are decreased in Huntington’s Disease?
- GABA
- Ach
this leads to an imbalance with dopamine
What are the treatment options for Huntington’s Disease?
VMAT2 inhibitors; take up dopamine lowering the amount of dopamine fixing the imbalance
What is unique about Tetrabenzine (Xenazine)
- reversible inhibitor (VMAT2) which will cause chorea
What is unique about ALS?
- fast acting
- affects the spinal cord and cortical neurons
What neurotransmitter is important in ALS?
glutamate
What is unique about Riluzole (Rilutek)?
only drug shown to have any effect on survival
reduces glutamate-induced excitotoxicity
- non-competitive block of NMDA receptor mediated responses
