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Pharm blk4- AD

Alzheimer's Dz

What are the physical (2), genetic (2), and environmental (3) RF for AD Physical: 1.small head circumference, 2.low IQ, Genetic: 1.gene like: presenilin, beta-app, down’s, 2.Apoe4, Envirnomental: 1.head injury, 2.not smoking (smoking reduce risk), 3.young/old mother
How is AD dxed (3) 1.memory problem, 2.other cognitive problem (memory not enough), 3.exclude other things
What area of the brain is greatly atrophied in AD (other than hippo) Frontal
What are the two main patho features of AD 1.amyloid plaques, 2.neurofibrillary tangles
what are the 5 we need to know for AD (which one is not used anymore AntiAChE: 1.Tacrine, 2.Donepizil, 3.Rivastigmine, 4.Galantamine, NMDA antagonist: 5.Memantine
What are 8 tx under investigation for AD (+names, MOA) 1.antioxidants 2.vaccines (anti-memapsin - cleaves amyloid) 3.anti-inflam 4NT agents, 5.Lipid lowering (atorvastatin - reduce ApoE4), 6.anti-diabetic: resiglitazone (PPARgama agonist, regulates APP degradation 7.anti-epileptic drugs 8.Nootropics (like Ach
The cholinergic hypothesis states that: (2 location, 1 receptor) Cholinergic system in the brain (1. Nucleus basalis of meynert, 2. septo-hippocampal area) are damaged or that there are decrease receptors for them: those would be NICOTINIC receptors
Why are AChE inhib used to increase ACh in the brain (2) 1.choline doesn’t work and make you smell bad, 2.ACh agonist are not specific enough (we want to target nicotinic receptors only)
What was the 1st AChE inhib Tacrine
Why wasn’t tacrine also approved for severe AD/dementia If there is no nucleus basalis left at all, there is no ACh being made and there is no point in blocking AChE
What is the main AE of tacrine Hepatotoxic (transaminase level should be checked every other week)
How come tacrine is so commonly overdosed (what is the lethal dose) (describe) (antidote) 12 x 40 x 4 times per day is max, but ppl with AD forget that they took their meds. They go into ACh stimulation: vomiting, diarrhea, tremor. Antidote: IV atropine
What is the 2nd gen AChE What are the advantages over tacrine
What is galantamine trying to mimic, how (+note) Smoking (which upregulates nicotinic receptors), however it seems to protect more than it promote new receptors
What is the only AChE that can be taken once a day Donepezil, - Tacrine is x4 – Galantamine, Rivastigmine is x2
How long do the benefit from AChE last (4) Donepezil is more than 2 years, Gal & Riv is more than 1 year, Tacrine is unknown
The excitotoxic hypothesis is about: (a compound) Glutamate
Glutamate has 2 role in the brain: (one can go wrong) 1.it is the primary excitatory NT in the brain, 2.it is neurotoxic and allows the brain to prune circuits (this can go array: during brain injury and degenerative diseases like AD)
what are the 3 receptors for glutamate (which one is important for AD
What is the drug that targets NMDA (possible MOA) Memantine is a NMDA antagonist that recude neuronal loss
While targeting all NMDA receptors memantine manages to be selective, how Preferential binding to active/open channels
Discuss pharmaco, and AE of memantine 1.high bioavailability, 2.little protein bound, 3.little AE
Describe the pros/evidence in favor (4) and against (4) the Amyloid hypothesis: PROS: 1.Presenillins 1,2, 2.APP on chr 21 (Down’s), 3.Apoe4, 4.mutation in tau (chr 17) leads to frontotemporal dementia not AD, CONS: 1.plaques are not located where disease is, 2.amount of plaques not always related to severity, 3.animal models can have
What was blamed for the meningoencephalitis in vaccines Adjuvant used in inoculation
Does the AD vaccine work on animals Yes
what is a possible novel vaccine Against memapsin-2/beta-secretase, the enzyme that cleaves Amyloid to A-beta Amyloid
Describe the pros and cons of the Tau hypothesis: PROS: 1.correlates with area, 2.correlates with cognition better than plaques, CONS: mutation in tau causes other dementias not AD
discuss estrogen level and AD women have less risk for AD before menopause, if women are on HRT they maintain this lower risk (unless they start the HRT long after menopause in which case it makes it worst)
Created by: mcafej02