Neurodegenerative Disorders Flashcards
1
Q
Neurodegenerative Diseases
A
- Progressive dysfunction and death of neurons
- Usually exclude disease of known vascular, toxic, metabolic, infective or autoimmunne origin
- Pathogenesis: genetic susceptibility, environment, and aging factors are important
- Abnormal protein accumulation in neurons is a typical feature
2
Q
Parkinson’s Disease
A
- Lewy Bodies
- Contain ubiquitan and synuclein
3
Q
Alzheimer’s Disease
A
- Neuritic plaques (outside neuron)
- Neurofibrillary tangles (inside neuron)
4
Q
Degeneration
A
- Often affects a specific system for a selective vulnerability
- Protein aggregates represent pathological hallmark lesions
- Could also originate from misfolded proteins and an inability to clear them (Ubiquitin => proteasome sytstem, autophagy)
5
Q
Idiopathic Parkinson Disease
A
-Most common
-Loss of substantia nigra dopamine neurons
Other causes: vascular disease, head trauma, tumors, and drug-induced parkinsonis
-Environmental agents: MPTP, illicit byproduct of a meperidine analogue
6
Q
Lewy Bodies
A
- Brains of Parkinson’s patients contain Lewy bodies
- Lewy bodies are a normal brain protein (alpha synuclein) that are misfolded and form aggregates
7
Q
Parkinson’s Mechanism of Dysfunction
A
- Glu antagonists or GABA agonists have little effect
- Imbalance in PD is a decrease in dopamine activity with an apparent increase in cholinergic activity
- Treatment: reverse the imbalance
8
Q
Ambroxol
A
- Reduces mucus production in respiratory tract
- Increases activity of lysosomal enzyme GBA
- May reduce build-up of excess lipids and proteins like alpha-nuclein
9
Q
Levodopa
A
- MoA: increase dopamine in remaining nigrostriatal neurons in caudate nucleus
- PD treatment
- Most of L-dopa is convered to DA in the periphery causing its peripheral toxicities
10
Q
Levodopa SE
A
- Orthostatic hypotension (increase NE)
- Cardiac stimulation (activitation of beta-adrenergic receptors)
- Vomiting: DA triggering CTZ
11
Q
Carbidopa
A
- Lodosyn
- Peripheral decarboxylase inhibitor that doesn’t cross BBB
- Decreased SE which allows for smaller doses of L-dopa
- Fixed combos, slow release, and a combination of IR/CR available
12
Q
L-Dopa Central Toxicities
A
- Dyskinesias: involuntary chorieform movements
- Behavioral: hallucinations, confusion, psychotic reactions (atypical antipsychotics may help)
- ON-OFF Syndrome: long term levodopa therapy SE
13
Q
ON-OFF Syndrome
A
- “Off Syndrome”: rapid loss of therapeutic effect between doses
- “On-Off Syndrome”: rapid fluctuations between the drug working and not working after a single levodopa dose
14
Q
Dopamine D2 Agonists
A
- Monotherapy or with L-dopa
- Ex: Pramipexole (Mirapex) and Rotigotine (Neupro Patch)
- MoA: Up-regulation of DA2 receptors in stiatum due to love levels of DA released, so better response to D2 agonists
15
Q
D2 Agonist SE
A
- Somnolence: falling asleep during daily living and higher hallucination risk
- N/V (trimethobenzamide for antiemetic therapy)
- Orthostatic hypotension
- Hallucinations
- Don’t stop suddently due to sudden DA withdrawal (anxiety, depression, fatigue)
- Lower risk of dyskinesias and on/off syndrome