Parkinson's Disease (General) Flashcards
How do neurodegenerative diseases develop
A protein misfolds from mutational external factors
Misfolded proteins aggregate forming insoluble aggregates
Forms deposits –> Neurotoxicity
Amyloid / Amyloidosis
Proteins Aggregate
How are misfolded proteins repaired
Molecular Chaperones
What Protein Misfolds in Parkinson’s
alpha-synuclein
What Amyloid Deposit forms in Parkinson’s
Lewy Bodies
What is Parkinson’s Disease
Degenerative disease of basal ganglia
(Substantia Nigra and Corpus Striatum)
- Suppresses Voluntary Movement
- Tremors at Rest
- Muscle Rigidity
As PD progresses what symptoms can develop
Disorder of movement, can also develop cognitive decline
What drugs cause Parkinson?
Antipsychotics
How does Parkinson’s Develop
Alpha-Synuclein proteins misfold and aggregate into intracellular Lewy Bodies
–> Causes loss of dopaminergic neurons in substantia nigra and corpus striatum
What kinds of signals does Parkinson effect
Damages Neurons that control Dopaminergic, 5-HT, NA, and Cholinergic
–> Leads to overactivation of GABAergic signalling to thalamus
–> Reduces excitatory signalling to motor cortex that is supposed to initiate movement
Levodopa (L-DOPA)
Acts as a dopamine precursor and enters brain
Replaces deficient neurotransmitter
Carbidopa
Given in combination Levodopa
–> Prevents L-DOPA being converted into dopamine in the periphery
Peripheral DOPA Decarboxylase Inhibitors that does not cross BBB
Entacapone
Given in combination Levodopa
–> Slows metabolism of L-DOPA
Catechol-O-methyl transferase Inhibitor
(COMT)
Levodopa Unwanted Effects
Involuntary Movements
Effects are On and OFF (With Off effects causing sudden worsening of bradykinesia & rigidity)
Hypotension
Psychological Effects
Pramipexole Mechanism of Action
Dopamine Receptor Agonist
Controls Parkinson’s by activation of dopamine receptors in the neuronal circuitry responsible for motor control
Pramipexole Unwanted Effects (D2)
Pramipexole is selective for D2 receptors and thus, causes less nausea and vomiting
Pramipexole Unwanted Effects
Nausea and Vomiting
Somnolence (Sleepiness)
Hallucinations
Compulsive Behaviours
Selegiline Mechanism of Action
Monoamine Oxidase B Inhibitor
(MAO-B Inhibitor)
Protects dopamine from extraneuronal degradation
–> Selective for MAO-B
–> Lacks periphery side effects
MAO-A (Mostly Found In)
Found in brain and outside of CNS
MAO-B (Mostly Found In)
Mostly found in the brain
Thus, MAO-B Inhibitors lack unwanted peripheral effects
Amantadine
Increases Dopamine Release
Inhibits Amine Uptake
Acts on Dopamine Receptors
Orphenadrine Mechanism of Action
Muscarinic Receptor Antagonist
Inhibits M4 (mAchR) on dopaminergic nerve terminals
- M4 usually inhibits the release of dopamine
- Inhibiting M4 leads to enhancement of dopamine release
Orphenadrine is used to treat?
Parkinsonian Symptoms caused by antipsychotics
–> Antipsychotics are usually dopamine receptor antagonists
