CPTP 3.19 - Neurodegenerative Disorders

Question 1

In alzheimers disease in terms of macro-characteristics - which areas of the brain enlarge and which shrink?

Answer 1

Ventricular enlargement
Hippocampal atrophy
Entorinhal atrophy
Temporal cortex atrophy

Question 2

In alzheimers disease in terms of micro-characteristics - describe what happens?

Answer 2

Deposition of A-beta amyloid plaques and Tau neurofibrillary tangles
Neuronal loss

Question 3

What neurochemical changes occur with dementia?

Answer 3

Corticle cholinergic loss

Loss of 5HT and Nor epi

Question 4

Name the two actylcholinergic pathways within the brain?

Answer 4

Nucleus basillis to cortex (learning and memory)

Pedunculopontine nucleus to thalamus (sleep/wake)

Question 5

Describe cholinergic neurotransmission?

Answer 5

Choline take up into neurone and converted to Ach (via choline acytyl transferase) and then stored into vesicles by VAchT
Released into synaptic cleft via synaptobrevin (vesicle membrane)/snap25/syntaxin

Question 6

Upon which receptors does Ach act on?

Answer 6

Muscarinic

Nicotinic

Question 7

How are the actions of Ach terminated?

Answer 7

Actylcholinesterase

Question 8

Name an anti-cholinesterase inhibitor that may be used to treat Alzhimer’s disease and state its side-effects?

Answer 8

Donepzil

Bradycardia, G.I complaints, sleep disturbance

Question 9

Describe B-amyloid pathology?

Answer 9

B-amyloid synthesised by amyloid precursor protein (APP) found on the membrane - cleaved by nasty Beta and gamma secretase enzymes) into AlphaBeta plaques

Question 10

Describe the movement disorders associated with Parkinson’s disease?

Answer 10

Bradykinesia
Rigidity
Tremor
Abnormal posture

Question 11

Describe the pathology underlying Parkinson’s disease?

Answer 11

Abnormal Dopa sythesis and transmission -
Degeneration of the nigrostriatal Dopa pathway
Therefore there is an IMBALANCE of Dopa/Ach in the striatum and this causes motor dysfunction

Question 12

Describe in basic terms the mechanisms of treatment underlying Parkison’s disease treatment?

Answer 12

Either Increase Dopa OR decrease Ach to restore the balance within the striatum

Question 13

Describe dopaminergic neurotransmission?

Answer 13

Tyrosine enters the pre-synaptic neurone and is converted into L-Dopa (via tyrosine hydroxylase) and then L-Dopa is converted into Dopamine (via Dopa decarboxylase)
(In Nor epi neurones this Dopamine is converted further into Nor-epi (via Beta hydroxylase))

Question 14

In clinical practise why can’t L-Dopa be used by itself as a prodrug?

Answer 14

Although its metabolised into Dopa by dopa decarboxylase in the periphery and CNS - L-Dopa is metabolised into Nor epi by B-hydroxylase
This causes sympathetic side-effects

Question 15

Name a decarboxylase inhibitor that may be used to treat Parkinson’s disease and state some side-effects?

Answer 15

Co-careldopa

During peak doses = dyskinesia

Question 16

Name a DA receptor agonist that may be used to treat Parkinson’s disease?

Answer 16

Bromocriptine - partial D1/full D2

Question 17

Name a MOA-B inhibitor that may be used to treat Parkinson’s disease?

Answer 17

Selegiline