Lecture 12 - Parkinson's Disease Flashcards
(46 cards)
At what age do symptoms of Parkinson’s disease generally appear?
Around age 60
What are the symptoms of Parkinson’s disease?
- Rhythmic tremor - often occurs at first in one hand, resembles “pill rolling”
- Leaning forward or backward when upright
- Muscle rigidity - pushing on an arm causes it to move in jerky increments instead of smoothly
- Difficulty rising from a sitting position
- Speech*
What are marker’s of Parkinson’s disease?
- Muscle rigidity
- Slow movements
- Loss of spontaneous movements
- Resting tremor, first in one hand
Which motor pathways control voluntary movement?
- Upper motoneurons
- Lower motoneurons
- Corticospinal pathways
- Pyramidal tracts
Which motor pathways control involuntary movement?
- Extrapyramidal system
- Basal ganglia
- Reticular system
- Vestibular system
What is the neuropathophysiology of Parkinson’s disease?
- Loss of neurons in substantia nigra causing loss of dopamine innervation of striatum
- Balance btwn acetylcholine and dopamine is lost causing abnormal signalling and impaired mobility
At what stage of neuron loss do symptoms of Parkinson’s disease generally appear?
When about 70% of nigrostriatal neurons are lost
What normally inhibits and excites GABA neurons?
- Inhibited by dopamine
- Stimulated by acetylcholine
Which symptoms of Parkinson’s disease are controllable by drug therapy?
- Bradykinesia (slow initiation of movement)
- Tremor at rest
- Muscle rigidity
- Abnormal posture
- Early treatment for “neuronal sparing”
What are the pharmacological targets of drugs for Parkinson’s disease?
- Increase dopamine signalling in corpus striatum and substantia nigra
- Decrease cholinergic activity
- Decrease peripheral dopamine effects at D1/D2 dopamine receptors
- Decrease peripheral L-DOPA metabolism
What is the function of COMT w/ respect to dopamine synthesis in substantia nigra?
Catalyzes L-DOPA -> 3-OMD
What is the function of DDC (dopa decarboxylase) w/ respect to dopamine synthesis in substantia nigra?
Catalyzes L-DOPA -> dopamine
What is the function of TH (tyrosine hydroxylase) w/ respect to dopamine synthesis in substantia nigra?
Catalyzes tyrosine -> L-DOPA
What does the D1 subfamily of dopamine receptors do?
Increases cAMP
What does the D2 subfamily of dopamine receptors do?
Decreases cAMP
What are first line drugs to treat the early stage of Parkinson’s disease?
- MAO-B inhibitors (rasagiline, selegiline)
- Levodopa (levodopa/carbidopa or levodopa/benserazide)
Does L-Dopa cross the BBB?
Yes, but only 1% enters the brain, causing side effects in the periphery
Where is L-Dopa metabolized?
Intestine, blood, and peripheral tissues
What are the therapeutic effects of L-Dopa?
- Reduces rigidity and bradykinesia
- Improves motor function and speech
- Return of facial expression
What is the first choice drug for improving motor dysfunction from Parkinson’s disease?
L-Dopa
What is the most common side effect of L-Dopa that causes people to discontinue use of the drug?
Dyskinesias (abnormal involuntary movements)
What are some side effects of L-Dopa besides dyskinesias?
- Nausea, vomiting
- Hypotension and cardiac arrhythmias
- Wearing off
- “On-off” effect
- Insomnia, confusion
- Psychosis, hallucinations
What does carbidopa do?
- Inhibits dopa decarboxylase (DDC) or aromatic L-amino acid decarboxylase (AADC)
- Prevents breakdown of L-Dopa in periphery and allows more to cross BBB
What are common adjunct therapies w/ L-Dopa?
- L-Dopa and carbidopa = Sinemet
- L-Dopa and benserazide = Prolopa
