Parkinson's Disease Flashcards
What are the 8 visible symptoms of someone with Parkinson’s?
"Cogwheel" rigitidy Postural Problems pill-rolling tremor (at rest) Bradykinesia Small handwriting Poor balance Stooped posture Shuffling gait
What are the 3 non-motor features of Parkinson’s disease?
Depression
Autonomic dysfunction (drooling, constipation)
Cognitive impairments
Most PD SYMPTOMS are caused by death of which neurons?
What percent loss is required before symptoms are present?
Nigrostriatal Dopamine neurons
Clinical symptoms are visible at 70%-80% loss
What kills nigrostriatal DA neurons when testing parkinsonism in rats?
6-OHDA
Dopamine (Enables/Disables) sensorimotor integration in the striatum
Enables
The Schallert lab series of experiments proves that DA depleted rats display forelimb akinesia due to (Sensory/Motor) disruption
Motor
What is MPTP? What does it cause? How?
Side product of Opiate analogues that can cause Parkinsonism by killing DA cells in the brain (crosses BBB)
MPTP kills (Mice/Rats) but not (Rats/Mice)
Kills mice but not rats
What drug protects DA cells from MPTP in mice?
Deprenyl
Where is MPTP converted to the toxic MPP+ and what enzyme does the conversion?
In Astrocytes, MAO B converts MPTP to MPP+
What are the two steps involved in MPTP toxicity? How can they blocked to protect against MPTP?
MPTP -MAO-> MPP+ -DAT-> MPP+ (in DA cell)
1) give Pargyline (MAO inhibitor)
2) give Nomifensine (DAT blocker)
What step is faster, MAO-catalyzed conversion of MPTP to MPP+ or DAT-mediated transport of MPP+ into the DA cell?
MAO step is MUCH faster than DAT step
True/False? DA cell damage occurs within 15 minutes, therefore treatment must be given immediately
True
Why does MPTP only kill Nigrostriatal DA cells (as opposed to the many other types of DA cells)?
Fucked if I know
How is Paraquat related to MPTP?
It is an analogue of the toxic MPP+, however it does not cross BBB (bisquaternary)
How does Rotenone kill DA cells?
Binds to complex I of ETC throughout brain
How is Alpha-synuclein related to Parkinson’s disease?
When misfolded, accumulates in DA (among other) neurons and forms “Lewy bodies”
PD in most patients is considered to be a “synucleinopathy”
True/False? Giving DA is enough to treat Parkinsonism
False
What is the first line drug for PD to enhance DA transmission in the brain/
L-DOPA (precursor to DA)
What are the effects of L-DOPA?
Increases DA release Decreases DA Reuptake Decreases MAO Stimulates Postsynaptic DA receptors Increases DA cell firing rate
Rank L-DOPA, DA agonists and MAO-B inhibitors in terms of rescue of Motor control for PD
L-DOPA > DA Agonist > MAO-B inhibitor
Rank L-DOPA, DA agonists and MAO-B inhibitors in terms of motor complication side effects
L-DOPA > DA Agonist ~ MAO-B
What is the problem with L-DOPA when given orally by itself? What is typically given to prevent this?
It is broken down before it gets into the brain
Given with AAADC or DDC (DOPA decarboxylase) inhibitor
Absorption of L-DOPA from the GIT is (Inhibited/Enhanced) by high-protein meals
Inhibits
Name a single AAAD inhibitor
Carbidopa
Where is L-DOPA converted to DA?
In DA cells
AND
In non-DA cells containing AAAD
What is bromocriptine?
A directly-acting DA receptor agonist
What are the theoretical advantages of bromocriptine over L-DOPA?
Work better than L-DOPA in complete absence of DA
Less DA release so fewer oxyradicals
Longer-half-life than L-DOPA
What are the clinical experiences of bromocriptine?
Less effective than L-DOPA
Useful in early PD to delay L-DOPA treatment
Useful adjunct used with L-DOPA
Adverse Effecs
PD drugs such as DA agonists and MAO-B postpone the need for L-DOPA. Which does a better job?
DA agonists - 5 years
MAO-B inhibitors - 1 year
What is the single good thing about smoking cigarettes?
It protects you from parkinson’s (somehow)
One theory is that something in smoke inhibits MAO B
