17 - Parkinson's disease and movement disorders Flashcards
What are the main symptoms of Parkinsons Disease
Tremor
Rigidity
Bradykinesia
Postural instability
What does death occur as a consequence of in Parkinsons Disease
Immobility
What is the cause of PD in the majority of causes
Unknown
What are some environmental factors of Parkinsons
Pesticides
Heavy metal poisoning
Viral infections
Drugs such as methamphetamine and Ritalin
What may provide protection for DA neuons
NSAIDs and caffeine
What is lost in PD
Dopamine neurones that project from the substantia nigra
When do symptoms become apparent
Reduction of dopamine levels by 80%
What controls the output of GABAergic neurones in the striatum
Acetylcholine
Dopamine
ACh causes GABA output to
Increase
DA causes GABA output to
Decrease
What occurs in PD to GABA output
Loss of DA neurones removes inhibitory effect on GABA output leading to increased GABA
What are some other aetiologies that may lead to the same symptoms
Toxins Medications (D2) Dementia puglistica Diffuse Lewy Body Disease Progressive Supranuclear palsy
What is the conversion pathway of dopamine
Tyrosine
Dopa
Dopamine
Can dopamine cross the BBB
No
Is normal dietary tyrosine sufficient to saturate tyrosine hydroxylase
Yes
What is the current treatment for PD
L-DOPA
How is the percent of L-DOPA crossing the BBB increased
Administration of carbidopa
What is the on-off effect of L-DOPA
L-DOPA effectively treats symptoms initially
By 5 years - 50% have severe symptoms
By 10 year s- 90%
What do PD symptoms oscillate between
Dyskinesia and akinesia
How can the drug regimen be fine tuned
More frequent doses at reduced concentrations
What is the main action of DA agonists
Direct stimulation of D2 receptors in striatum
What are two ergot derivative DA agonists
Bromocriptine
Pergolide
What are benefits of non-ergot derivatives
Less likely to induce dyskinesias
What are the main side effects of DA agonists
Postural hypotension
Hallucinations
Pulmonary fibrosis
How do MAOB inhibitors help
Reduce metabolism of levodopa and dopamine
Increased bioavailability of levodopa so less required
What is a a selective MAOBI
Selegeline
Why is non-selective MAOAI not advised
Possibility of ‘cheese or serotonin effect’
What are some muscarinic antagonists
Benztropine
Trihexyphenidy
Diphenhydramine
How do muscarinic antagonists aid PD
Reduce GABAergic output
Help with tremor and rigidity, not as effective as L-dopa
What is amantadine
Weak NMDA recepor antagonist
Amantadine MOA
Potentiates release of dopamine
Exact mechanism unclear
How does amantadine work on DA
Improved all symptoms of PD, without significant side-effects but effects modest and short-lived
What is the MOA of MPTP (4)
1) Crosses BBB
2) Converted to MPP+ by MAOB
3) MPP+ is taken up by DAT
4) inhibits oxidative phosphorylation and tyrosine hydroxylase
How does MPP+ help with modelling PD
Reproduces most of the symptoms and pathology of PD
