Alzheimer’s disease Flashcards
risk factors for Alzheimer’s
Age is major risk factor
Genetic mutations → early onset AD
symptoms of Alzheimer’s
Memory loss, disorientation/ confusion, language problems, personality changes, poor judgement
name 3 theories for Alzheimer’s
Beta-amyloid (Aβ)
Tau aggregation
Inflammation
where is amyloid pre cursor protein normally found
neuornal membrane
describe the Beta-amyloid (Aβ) hypothesis
β-secretase incorrectly process APP→ β-amyloid plaques
what do tau proeins do and where are they found
Soluble protein present in axons
Important for assembly & stability of microtubules
describe the Tau aggregation hypothesis
Hyperphosphorylated tau → neuronal instability/toxicity
+ microtubule instability
what property of hyperphosphorylated tau makes it have this effect
Hyperphosphorylated tau is insoluble
self-aggregates to form neurofibrillary tangles
describe the inflammation hypothesis
inflammation leads to increase activity of microglial cells
dereaese levels of neuroprotective proteins
Increase phagocytosis + inflammatory mediators
name to drug types used to treat Alzheimer’s
Anticholinesterases
NMDA receptor blocker
how do Anticholinesterases work
Block cholinesterases → can’t break
down ACh → ACh in cleft for longer →
prolonged effects
what severity of Alzheimer’s are anticholinesterases used for
moderate Alzheimer’s
symptoms relief
give 3 examples of antcholinesterases
Donepezil
rivastigmine
galantamine
describe the pharmocology of Donepezil
reversible cholinesterase inhibitor
long duration of action
long plasma half life
describe the pharmocology of Rivastigmine
psuedo-reversible AChE and BChE
half life = 8 hours
how has Rivastigmine been reforumalted to lengthen its action
reformulated as transdermal patch
describe the pharmocology of Galantamine
reversible cholinesterase inhibitor
has additional nAChR
agonist properties
(neuronal nictotic agonist)
8 hour half life
how do NMDA receptor blockers work
Can’t stimulate dopaminergic
neurones in VTG to release
dopamine into NA
what happens to neuronal transmission during neuronal degeneration
less GABA activity more Glutamate activity
viscous cycle more degeneration = more NMDA activity
what normally activates NMDA rc
glutamate
what severity of Alzheimer’s is NMDA rc blocker used for
Moderate- severe
alzheimer’s symptom relief
(late stage)
give an example of an NMDA rc blocker
Memantine
describe the pharmacology of memantine
Use-dependent non-competitive NMDA receptor atagonist with low channel affinity
Long plasma half-life
