Pharmacology of drugs used in treatment of Parkinson’s disease medications Flashcards
What are the two major neuropathologic findings in Parkinson’s disease?
Loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc).
Presence of Lewy bodies (abnormal protein aggregates inside neurons).
tremor, rigidity, bradykinesia
Flow chart for parkinson neuropathology
Parkinson’s Disease Neuropathology
├── Substantia Nigra Pars Compacta (SNpc) Degeneration
│ ├── Dopaminergic Neuron Loss
│ ├→ Reduced Striatal Dopamine
│ └→ Motor Symptoms (Tremor, Rigidity, Bradykinesia)
└── Lewy Bodies
├── Alpha-Synuclein Aggregates
├→ Neuronal Dysfunction
└→ Non-Motor Symptoms (Cognitive Decline, Autonomic Dysfunction)
What is the significance of dopaminergic neuron loss in the SNpc?
The SNpc supplies dopamine to the striatum. Neuron loss disrupts motor control, leading to Parkinson’s disease symptoms
What are Lewy bodies?
Abnormal intracellular aggregates of alpha-synuclein protein that disrupt neuronal function and contribute to neurodegeneration
Where does the most prominent loss of dopamine neurons occur in Parkinson’s disease?
In the ventral lateral substantia nigra, a subregion of the substantia nigra pars compacta (SNpc).
Why is the ventral lateral substantia nigra particularly vulnerable in Parkinson’s disease?
This subregion contains dense dopaminergic projections to the striatum, critical for motor control. Degeneration here disrupts basal ganglia function.
How much dopaminergic neuron loss occurs before motor symptoms appear in Parkinson’s disease?
60-80% of dopaminergic neurons are lost before motor signs (e.g., tremor, bradykinesia) emerge.
Neurodegeneration in Ventral Lateral SNpc
Key Feature: Loss of dopaminergic neurons.
Timing: Begins years before symptom onset.
Threshold for Symptoms: Motor signs emerge after 60-80% neuron loss.
What is the primary pathological feature of parkinsonian dementia?
Extra-nigral Lewy bodies, often accompanied by senile plaques.
abnormal clumps of protein that build up in the brain
What does “extra-nigral” mean in the context of Lewy bodies?
Lewy bodies located outside the substantia nigra, such as in the cortex or nucleus basalis of Meynert (nbM).
Where were Lewy bodies first identified, and by whom?
In neurons of the nucleus basalis of Meynert (nbM) by Friedrich Lewy.
What is the function of the Nucleus Basalis of Meynert
It provides cholinergic innervation to the cerebral cortex, crucial for cognitive functions.
How does cholinergic loss compare between parkinsonian dementia and Alzheimer’s disease?
Neuroimaging shows cholinergic loss in parkinsonian dementia is similar to or more severe than in Alzheimer’s.
Where are muscarinic receptors primarily localized in the context of movement regulation?
Striatal neurons (part of the basal ganglia involved in motor control).
What is the clinical relevance of blocking muscarinic receptors in Parkinson’s disease?
Anticholinergic drugs reduce tremors by counteracting excessive cholinergic activity caused by dopamine deficiency.
Why might acetylcholine overactivity worsen Parkinson’s symptoms?
Muscarinic receptors inhibit dopamine release, exacerbating the existing dopamine deficit in Parkinson’s.
