Alzheimers Flashcards
Alzheimer Disease
progressive memory loss, impaired thinking
neuropsychiatric symptoms (hallucinations, delusions)
Sixth leading cause of death
Pathologic findings in AD
cerebral atrophy
neuron degeneration
neuritic plagues
neurofibrillary tangles
what can drugs do for AD
little to relieve symptoms or prevent neuronal loss
no significant delay in AD progression
what causes AD
its idiopathic
neural degeneration
- starts in hippocampus (memory)
- later in cerebral cortex
reduced cholinergic transmission
- Advanced: ACH 90% below normal
Beta- Amyloid and Neuritic Plagues
Form outside neurons
- hallmark of AD
Neurofibrillary tangles and Tau
tangles form INSIDE disrupted microtubules / Tau spreads
Drugs approved for AD
3 cholinesterase inhibitors
1) Donepezil
2) Galantamine
3) Rivastigmine
Cholinesterase Inhibitors mechanism
prevent breakdown of ACh by Acheylcholinesterase (AChE)
Results in enhanced transmission by cholinergic neurons that have not yet been destroyed
Therapeutic Use for Cholinesterase Inhibitors
- mild to moderate symptoms
- only benefits 1/12 patients
-benefits short lived
what Cholinesterase Inhibitor is approved for severe symptoms
Donepezil (doon-epa-zill)
Adverse Effects of Cholinesterase Inhibitors
Gi
CNS
Lungs
Increased ACh in periphery
- GI effects
-CNS: dizziness, headache
-Lungs: bronchoconstriction
Drug interactions with Cholinesterase Inhibitors
drugs that block cholinergic receptors should be avoided
Dosing Cholinesterase Inhibitors
highest doses= greatest benefits but most intense adverse effects
Individual Cholinesterase Inhibitors
Rivastigmine (ri-vuh-stig-meen)
Galantamine (gull-ant-a-meen)
Rivastigmine )ri-vuh-stig-meen) properties
Approved for AD and Parkinsons, demential
IRREVERSIBLE inhibition of AChE
PO dosing
Rivastigmine Adverse Effects
Anorexia, bradycardia, fall-related fractures
Symptoms of increased ACh in patients with peptic ulcer disease, urinary obstruction and lung disease
Rivastigmine Drug Interactions
NO significant drug interactions
- does not interact with liver metabolizing enzymes
Galantamine (gull-at-a-meen) Properties
REVERSIBLE inhibitor for mild to moderate AD
Prepared by extract of daffodil bulbs
Benefits short lived :(
Galantamine adverse effects
GI tract
Anorexia
Weight loss
Bradycardia–> from too much ACH in periphery
Bronchoconstriction
N-Methyl-D-Asparate Receptor Antagonist (NMDA) drug
Memantine (prototype)
normal physiology NMDA receptor
Resting state
- Mg occupies NDMA receptor = blocks calcium uptake
Activated State
- Glutatmate bind to NMDA = Mg displaced
- Calcium enters
Returns to Resting
= a “signal” in learning and memory process
Pathophysiology NMDA receptor
Improper glutamate binding
- PERSISTENT activated state
- slow excessive influx Ca2+
= impaired learning, memory and eventually neuronal death
Memantine mechanism of action
Binds to NMDA receptor
- block Ca2+ entry when extracellular glutamate is low
= STOPS CA2+ INFLUX
= ALLOWS post synaptic Ca2+ levels to normalize
- once appropriate glutamate released, memantine is displace
- glutamate diffuses away
–> MEMANTINE AGAIN BLOCKS CHANNEL
Therapeutic Use Memantine
Modest benefits for moderate to severe AD
- sometimes symptoms improve
