1. Drugs for Parkinson's Flashcards
What are the 11 anti-Parkinson’s drugs?
Levodopa (w/ carbidopa) Entacapone Tolcapone Bromocriptine Selegiline (deprenyl) Rasagiline Benztropine Trihexyphenidyl Pramipexole Ropinirole Rotigotine
What are the extrapyramidal tracts?
Where they found, target
Mainly found in reticular formation of the pons and medulla
Target neurons in the spinal cord involved in reflexes, locomotion, complex movements, and postural control
Slide 4
What modulates the extrapyramidal tracts?
Extrapyramidal tracts are modulated by various parts of the central nervous system
This includes the nigrostriatal pathway, basal ganglia, cerebellum, vestibular nuclei, etc
These are all part of the extrapyramidal system- modulate motor activity without directly innervating motor neurons
Slide 4
What is the extra-pyramidal motor system (EPS)?
Directs the stimulation and inhibition of antagonistic muscle groups allowing smooth and coordinated movement
EPS output reflects a balance between dopamine-mediated inhibition and acetylcholine-mediated excitation of GABA output neurons
Slide 5
What happens in the extra-pyramidal motor system during Parkinson’s?
How can it be fixed?
Dopamine inhibition becomes deficient due to the death of substantia nigra (SN) neurons (or presence of dopamine antagonists)
Acetylcholine excitation is unchecked and GABA output becomes excessive
The dopamine/acetylcholine balance can be restored by augmenting dopamine inhibition or by reducing acetylcholine excitation (try and get balance back to normal)
Slide 6-7
What is Parkinson’s disease?
Symptoms?
Neurodegenerative disorder of the CNS in the elderly >65 years old
Symptoms: Akinesia- can’t initiate movement Bradykinesia- slow movement, shuffle Muscle rigidity- stiff limbs, trunk Tremor at rest- pill rolling (shaky) Mask-like faces- expressionless Cogwheel locomotion Dementia and mood depression
Slide 8
What does Parkinson’s disease kill off?
Parkinson’s causes death of dopamine cell bodies in the substantia nigra
Loss of dopamine nerve terminals in the neostriatum comes first before you lose cell bodies (don’t notice it)
When about 80% of the original number of dopamine neurons in the substantia nigra have died, symptoms appear
What are Lewy bodies?
What are they made of?
Lewy bodies are abnormal aggregates of protein that develop inside nerve cells in Parkinson’s patients
They are made of α-synuclein
What are the 3 main categories of Parkinson’s treatment?
Dopamine replacement therapy- levodopa, carbidopa, entacapone, selegiline
Dopamine receptors agonists- bromocriptine, pramipexole
Anti-cholinergic therapy- benztropine, trihexyphenidyl
Anti-oxidant therapy- oxidative stress can cause death of dopamine neurons in substantia nigra but not proof anti oxidants work
What is dopamine replacement therapy?
Dopamine can’t cross the blood brain barrier
Levodopa (l-dopa) can cross it and is taken up by surviving dopamine neurons
Restores dopamine/ACh balance and normal output of the extrapyramidal motor system
L dopa is precursor to dopamine and gets converted to dopamine in the brain
Slides 12-17
What do dopamine receptor agonists do?
Reverse the symptoms of Parkinson’s disease when added to l-dopa plus carbidopa or benserazide
What is anti-cholinergic therapy?
The imbalance of dopamine/ACh can be restored by muscarinic ACh antagonists such as benztropine or trihexyphenidyl
How can adding more levodopa be bad in some Parkinson’s cases?
Adding l dopa to inflamed substantia nigra is like adding fuel to fire for more deaths of dopamine neurons
Study paper summary then read case study slide 21
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