Neurodegenerative Disorders [7] Flashcards

1
Q

What is excitotoxicity

A

Release of glutamate
Causes neuronal death
Mediated through NMDA receptors
Calcium entry needed

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2
Q

Increased calcium causes

A

Arachidonic acid production
Free radicals
Damage to proteins and lipids in cells
Impaired mitochondrial function

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3
Q

What is the effect of glutamate

A

It kills cells if there is long exposure

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4
Q

Defence against glutamate neurotoxicity

A

Mitochondrial energy metabolism
ATP production
Maintains Na/K pump
Sustains membrane potential
Sustains Ca2+ uptake by ER

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5
Q

What is oxidative stress

A

Production of free radicals (°OH) - damage cellular components
From brain mitochondrial oxidative phosphorylation

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6
Q

2 defence mechanisms for oxidative stress

A

Enzymes - superoxide dismutase
Antioxidants - glutathione

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7
Q

Main symptoms of Parkinson’s disease

A

Tremor
Muscle rigidity
Hypokinesia

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8
Q

What causes PD

A

Degeneration of the substantia nigra which produces dopamine

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9
Q

Neurochemical changes in PD patients

A

<10% normal DA levels
Loss of cell bodies of dopaminergic neurones
5-HT and NA levels also low

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10
Q

How does levodopa differ from DA

A

Levo has an extra COOH side chain

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11
Q

What does Levodopa do

A

Stimulates D2 receptors

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12
Q

What is levodopa coadministered with

A

Decarboxylase inhibitor
Most levodopa is metabolised by decarboxylase before reaching the brain
This means you can give a smaller dose of levo for better safety profiling

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13
Q

Adverse effects of Levodopa

A

GI effects
Cardiac arrhythmias
Dyskinesia
On-off phenomenon

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14
Q

2 dopamine agonists used for PD

A

Bromocriptine - used for on-off phenomenon
Pergolide - stimulates D1 & D2 receptors

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15
Q

Example of a MAOI for PD

A

Selegiline - can be taken with levodopa
MAO- B inhibitor
Slows break down of DA
Enhances effects of levo

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16
Q

Why should you avoid combined administration of levo and an inhibitor of both forms of MAO

A

Can cause hypertensive crises

17
Q

Example of an acetylcholine blocking drugs

A

Benztropine
Anti Muscarinic action - improved tremor
Side effects include dry mouth and blurred vision

18
Q

What polymorphisms arise in familial forms of PD

A

In 2 genes
Alpha-synuclein & Parkin