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Phar 301 > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

1
Q

What are the 8 visible symptoms of someone with Parkinson’s?

A 
"Cogwheel" rigitidy
Postural Problems
pill-rolling tremor (at rest)
Bradykinesia
Small handwriting
Poor balance
Stooped posture
Shuffling gait
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2
Q

What are the 3 non-motor features of Parkinson’s disease?

A

Depression
Autonomic dysfunction (drooling, constipation)
Cognitive impairments

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3
Q

Most PD SYMPTOMS are caused by death of which neurons?

What percent loss is required before symptoms are present?

A

Nigrostriatal Dopamine neurons

Clinical symptoms are visible at 70%-80% loss

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4
Q

What kills nigrostriatal DA neurons when testing parkinsonism in rats?

A

6-OHDA

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5
Q

Dopamine (Enables/Disables) sensorimotor integration in the striatum

A

Enables

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6
Q

The Schallert lab series of experiments proves that DA depleted rats display forelimb akinesia due to (Sensory/Motor) disruption

A

Motor

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7
Q

What is MPTP? What does it cause? How?

A

Side product of Opiate analogues that can cause Parkinsonism by killing DA cells in the brain (crosses BBB)

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8
Q

MPTP kills (Mice/Rats) but not (Rats/Mice)

A

Kills mice but not rats

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9
Q

What drug protects DA cells from MPTP in mice?

A

Deprenyl

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10
Q

Where is MPTP converted to the toxic MPP+ and what enzyme does the conversion?

A

In Astrocytes, MAO B converts MPTP to MPP+

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11
Q

What are the two steps involved in MPTP toxicity? How can they blocked to protect against MPTP?

A

MPTP -MAO-> MPP+ -DAT-> MPP+ (in DA cell)

1) give Pargyline (MAO inhibitor)
2) give Nomifensine (DAT blocker)

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12
Q

What step is faster, MAO-catalyzed conversion of MPTP to MPP+ or DAT-mediated transport of MPP+ into the DA cell?

A

MAO step is MUCH faster than DAT step

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13
Q

True/False? DA cell damage occurs within 15 minutes, therefore treatment must be given immediately

A

True

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14
Q

Why does MPTP only kill Nigrostriatal DA cells (as opposed to the many other types of DA cells)?

A

Fucked if I know

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15
Q

How is Paraquat related to MPTP?

A

It is an analogue of the toxic MPP+, however it does not cross BBB (bisquaternary)

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16
Q

How does Rotenone kill DA cells?

A

Binds to complex I of ETC throughout brain

17
Q

How is Alpha-synuclein related to Parkinson’s disease?

A

When misfolded, accumulates in DA (among other) neurons and forms “Lewy bodies”

PD in most patients is considered to be a “synucleinopathy”

18
Q

True/False? Giving DA is enough to treat Parkinsonism

A

False

19
Q

What is the first line drug for PD to enhance DA transmission in the brain/

A

L-DOPA (precursor to DA)

20
Q

What are the effects of L-DOPA?

A 
Increases DA release
Decreases DA Reuptake
Decreases MAO
Stimulates Postsynaptic DA receptors
Increases DA cell firing rate
21
Q

Rank L-DOPA, DA agonists and MAO-B inhibitors in terms of rescue of Motor control for PD

A

L-DOPA > DA Agonist > MAO-B inhibitor

22
Q

Rank L-DOPA, DA agonists and MAO-B inhibitors in terms of motor complication side effects

A

L-DOPA > DA Agonist ~ MAO-B

23
Q

What is the problem with L-DOPA when given orally by itself? What is typically given to prevent this?

A

It is broken down before it gets into the brain

Given with AAADC or DDC (DOPA decarboxylase) inhibitor

24
Q

Absorption of L-DOPA from the GIT is (Inhibited/Enhanced) by high-protein meals

A

Inhibits

25
Q

Name a single AAAD inhibitor

A

Carbidopa

26
Q

Where is L-DOPA converted to DA?

A

In DA cells
AND
In non-DA cells containing AAAD

27
Q

What is bromocriptine?

A

A directly-acting DA receptor agonist

28
Q

What are the theoretical advantages of bromocriptine over L-DOPA?

A

Work better than L-DOPA in complete absence of DA
Less DA release so fewer oxyradicals
Longer-half-life than L-DOPA

29
Q

What are the clinical experiences of bromocriptine?

A

Less effective than L-DOPA
Useful in early PD to delay L-DOPA treatment
Useful adjunct used with L-DOPA
Adverse Effecs

30
Q

PD drugs such as DA agonists and MAO-B postpone the need for L-DOPA. Which does a better job?

A

DA agonists - 5 years

MAO-B inhibitors - 1 year

31
Q

What is the single good thing about smoking cigarettes?

A

It protects you from parkinson’s (somehow)

One theory is that something in smoke inhibits MAO B

Phar 301 (23 decks)

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