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37 Cards in this Set
- Front
- Back
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Which neurons are lost in Alzheimer's?
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Hippocampal and cortical neurons
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What are some Non-AD causes of dementia in the elderly?
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Metabolic
Infectious Cardiovascular CNS Drug Rxns Miscellaneous Other Neurodegenerative Disorders |
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What kinds of metabolic disorders can cause dementia?
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Dehydration
Hyper/hypo-natremia Hyper/hypo-glycemia acidosis/alkalosis Hyper/Hypo-thyroid |
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Infectious causes of Dementia?
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Pneumonia
Meningitis UTI Abscess |
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Miscellaneous causes of dementia?
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Fecal Impaction
Sensory Deprivation/Overload Hyper/Hypo-thermia Thiamine Def Alcoholism |
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General Pathology of AD
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General Cerebral Atrophy-->pronounced sulci. Begins in temporal CTX and hippocampus
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Cellular Pathology of AD
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1. Extracellular beta-Amyloid Plaques around and within vessel walls and in brain parenchyma
2. Intracellular Neurofibrillary Tangles of hyperphosphorylated Tau in cell bodies and in neuronal processes (neuropil threads) |
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Neurochemical Issues involved in AD?
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BIG decrease in Acetylcholine
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Where does this acetylcholine loss originate?
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The atrophy and degeneration of subcortical cholinergic neurons, particularly in the basal forebrain (meynert).
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Most cases of AD are sporadic, but what are the genetic issues in Familial AD?
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Autosomal Dominant mutations involving either APP amyloid precursor or Presenilin (also screws with amyloid)
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what is one mutation that is a RISK FACTOR for AD?
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apoE mutation--> earlier onset
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What enzymes are involved in APP metabolism? why is this important?
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Alpha, Beta, and Gamma secretases.
Gamma secretase cleaves APP into longer fragments prone to aggregation (bad). Drugs can help push the metabolism to Alpha which -->shorter, non-toxic fragments. |
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How do drugs shift the metabolism of APP?
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They can activate teh PKC/PLA2 pathway via muscarinic receptors
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What are the main drugs used to treat AD?
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Tacrine
Donepezil Rivastigmine Galantamine Memantine |
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TACRINE
mechanism? |
Acetylcholinesterase Inhibitor
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TACRINE
SE's? |
hepatotoxicity
LIVER FXN MUST BE MONITORED WEEKLY |
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TACRINE
current use? |
not used much at all
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DONEPEZIL
Mech |
Acetylcholinesterase Inhibitor
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DONEPEZIL
SE's |
Not Hepatotoxic, so no weekly monitoring
Can create cholinergic overstimulation-->GI cramps, diarrhea, gastric acid secretion, N&V, depression |
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RIVASTIGMINE
mech |
Acetylcholinesterase inhibitor
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GALANTAMINE
mech |
Acetylcholinesterase Inhibitor
AND Activates central nicotinic acetylcholine receptors |
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MEMANTINE
mech |
Low to Moderate affinity NMDA Receptor Antagonist
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Why is memantine's mechanism important?
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Overexcitation of NMDA receptors by glutamate is thought to cause excitotoxicity --> cell dysfxn and cell death
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MEMANTINE
SE's? |
dizziness
HA constipation confusion |
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Typical Prescription given to an AD patient?
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Memantine + Donepezil (or another cholinesterase inhibitor)
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Which stages of AD are these drugs targeted for?
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The Cholinesterase inhibitors are best used for mild to moderately severe AD
Memantine is best for Moderate to Severe AD |
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What are some other drugs that can be used for AD?
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Estrogen
Selegiline NSAIDs Antioxidant Vitamins Alzheimer's Vaccine Statins |
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Why might these other drugs be useful?
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They're based on the suggested Inflammatory and Oxidative free radical theories of AD
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Usefulness of Estrogen?
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Estrogen Replacement in menopausal women significantly delays the time of onset of AD
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How might NSAIDs help?
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they MAY interfere with brain's inflammatory response to the disease process
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What is in the AD vaccine and how might it help?
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It consists of an immunogenic fragment of amyloid peptide that hopefully will block the deposition of plaques in the brain.
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What are Statins normally used for?
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To reduce Cholesterol Levels
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Why then might they be used for AD?
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There has been shown a relationship between cardiovascular risk factors and an increased risk of AD
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What is one new, possibly sweet AD drug?
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DIMEBON
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What is Dimebon's mechanism?
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It has multiple mechanisms that aren't completely well understood:
1. Blocking the neurotoxic beta-amyloid proteins 2. Inhibits L-type Ca channels-->modulated AMPA and NMDA receptors 3. Neuroprotective via protection of mitochondria |
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Other possible use of Dimebon?
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it has been shown (along with memantine) to increase cognitive abilities in young people
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What is the key to AD Rx efficacy?
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EARLY DIAGNOSIS
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