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Two major microscopic changes seen in Alzheimer's; their pathogenisis
beta-amyloid plaques (forms aggregates and interferes with cell signaling->cell death); tau tangles (disrupts microtubule formation)
What are the lvls of beta-amyloid and tau tangles seen in altzhimer's patients.
decreasing beta amyloid and increasing tau
imaging technique that tracks beta amyloid levels in the brain
Pittsburg imaging compound-B (PIB-PET)
Four genetic alterations in early onset alzhemier's
amyloid precuror protein (APP) trippled in trisomy 21; presenilin 1 and 2; apolipoprotein E4.
Risk factors for develping dementia
obesity; HTN; high cholesterol
Potential treatments for Altzhimer's
Inhibit enzymes that produce amyloid beta; amyoid beta aggregator blockers; vaccines/Ab the clear beta amyloid; inhibit tau production; inhibid tau aggregation; neuroprotective drugs (NGF)
Four FDA approved drugs for treating Alzheimer's
"Donepezil; Rivastigmine; Galantamine; and Memantine. ""Don and Riva Galantly Mimed"""
reversible cholinesterase inhibitors (3)
Donepezil; Rivastigmine; Galantamine
Side effects of donepezil; galantamine; rivastigmine
N/D/anorexia; headache; insomnia
Contraindications of donepezil; galantamine; rivastigmine
cardiac conduction abnormalities; ulcers; seizures; asthma/COPD
Rivastigmine also inhibits _____ in addition to acetylcholineseterase; significance?
butyrylcholinesterase; prevents gilal cell degredation of acetylcholine
NMDA receptor antagonist what is it and what severity of alzheimer's does it treat?
Memantine--mild to severe.
MOA of memantine
"Block ""open"" NMDA receptors-> prevent Bet amyloid from constantly opening NMDA receptors. "
Other uses for memantine other than Alzheimer's
Huntington; AIDS dementia; vascular dementia
Side effects of memantine
Diziness; constipation; confusion; headache; HTN
Contraindications of memantine
Renal impairment; CVD ; seizures
DI of memantine
increase urinary pH reduce elimination; don't use with other NMDA antagonists