Neurodegenerative Disorders Flashcards
What are neurodegenerative disorders characterized as?
the progression and the irreversible loss of neurons in specific regions
What is selective vulnerability?
the idea that there are specific neurons in the brain that cause specific neurodegenerative disorders
Where are the neurons that are affected in PD?
neurons in the substantia nigra
Where are the neurons that are affected in AD?
neurons in the hippocampus and the neocortex
Where are the neurons that are affected in HD?
neurons in the neostriatum
Where are the neurons that are affected in ALS?
spinal cord and cortical neurons
What are the two common cellular mechanisms in neurodegenerative disorders?
- misfolded proteins
- excitotoxicity
What is excitotoxicity?
excessive amount of glutamate that causes cell death
What is Parkinson’s Disease?
neurodegenerative disorder that has an increase in lew body structures (misfolded alpha-synuclein) in the substantia nigra that causes the loss of coordination and problems with movement
What are the symptoms of PD?
“TRAP” T-tremors, R-Rigidity, A-Akinesia, P-postural instability
What is the etiology of PD?
loss of dopamine, which leads to less inhibition of Ach , which causes abnormal signaling which causes an imbalance of impaired mobility
What is the goal of PD therapeutic strategy?
to increase the amount of dopamine and relief of symptoms, but it does not reverse PD
What are the classes of drugs to treat PD?
- Dopamine precursors
- Inhibitors of GI and peripheral L-dopa metabolism
- Dopamine receptor agonists
- NMDA-receptor antagonists
- Antimuscarinic agents
- Multimodal agents
How do dopamine precursors work?
give L-dopa to increase the amount of dopamine in the CNS because it can cross the blood brain barrier and metabolizes into dopamine
How do Levodopa metabolism inhibitors work?
the goal is to get dopamine out of the periphery which causes side effects and there are multiple ways to do this
How does carbidopa work?
DOPA decarboxylase inhibitor, stops L-dopa from being metabolized in the periphery; increases the concentration of L-dopa and a better chance to reach the CNS
How does Levodopa/Carvidopa work?
usually given in combination so L-dopa reaches the CNS and Carvidopa inhibits the enzyme that metabolizes L-dopa causing a dopamine concentration in the periphery
What is unique about Pimavanserin (Nuplazid)?
helps with patients that have a combination of hallucinations and delusions associated with PD
What is the MOA of Pimavanserin?
inverse agonist and antagonist for seritonin receptors which is good because it does not affect Dopamine concentration
What is the purpose of COMT Inhibitors?
inhibits the metabolism of L-Dopa by COMT to 3-O methyl dopa
What is the goal of COMT inhibitors?
increases L-dopa chances of reaching the CNS to then get metabolized to dopamine lowering the amount of side effects; decreasing the “wearing-off” symptoms
What is unique about Entacapone?
- short duration of action out of the COMT inhibitors
- periphery effects only (does not cross the BBB)
What is unique about Tolcapone?
- long duration of action out of the COMT inhibitors
- periphery effects and CNS effects (can cross the BBB)
- has a harsh adverse effects of fulminating hepatic necrosis
What is the goal of selective MAO Type B Inhibitors?
- decrease the metabolism of dopamine leading to the longevity of dopamine in the CNS
