Exam 4 - Parkinson's/Movement Disorders Flashcards
Define tremor, chorea, ballismus, athetosis, and dystonia?
- Tremor: Rhythmic movement around a joint; tremor at rest is a hallmark of Parkinsonism.
- Chorea: Muscle jerks in various areas
- Ballismus: Violent abnormal movements.
- Athetosis: Slow, writhing, twisting movements.
- Dystonia: abnormal posture
What is the relationship between the basal gangila, thalamus, and motor cortex?
Motor cortex- sends information the the muscles for movement and to the basal ganglia cells, which relay information to the thalamus.
Thalamus- sends signals to the motor cortex to slow down or enhance movement, fine tuning them.
Basal ganglia - regulates activity of the thalamus, primarily by the substantia nigra (SN). The SN releases dopamine which inhibts and excites information to the thalamus.
What is the pathology of movement related disorders?
The substantia nigra dopaminergic neurons are degraded, leading to decreased dopamine levels.
Dopamine is inhibits muscle movements.
What are the common signs of Parkinson’s disease?
TRAP
T- tremor
R - rigidity
A - akinesia; loss or impairment in power of voluntary movement
P - posture and balace instability
What are the risk factors for Parkinson’s?
- Age > 60
- Heriditary
- Men > women
- Teaching, healthcare, or farming as an occupation
- Exposure to pesticides
What is the function of synuclein?
Describe the conditions where abnormal synuclein is found?
Found in the substatia nigra that is normally diffuse within the cell. In Parkinson’s, synuclein is misfoldied and aggregated together called Lewy bodies.
Lewy Bodies are found in Parkinsons, and Alzheimers.
What are non-pharmacologic treatments for Parkinsons?
Physical Therapy and exercise
What is the MOA of Levodopa?
Why is it given with carbidopa?
- Levodopa is a prodrug that is converted to dopamine in the body, but only 1-3% cross into the brain
- Carbidopa increases crossing of the BBB to 10% by preventing breakdown by DOPA decarboxylase and COMT in the periphery
What are the adverse effects of levodopa and their treatments?
- Anorexia
- Dyskinesias
- Tachycardia, a fib (low incidence)
- N/V - improved with carbidopa
- Depression, anxiety, hallucinations, delusions (high incidence)
-Made worse by carbidopa
-Can be treated with Pimavanserin (Nuplazid), an antipsychotic that is an inverse agonist of the 5-HT2a receptor in the visual cortex.
What is the metabolism pathway of Levodopa?
Broken down by COMT and MOA-B, converted to dopamine by DOPA decarboxylase.
What drugs work on the dopamine metabolism pathway and their MOA?
- Pramipexole – agonizes dopamine receptors to increase the release of dopamine
- Tolcapone – COMT inhibitor, preventing breakdown of dopamine
- Selegeline – Selective MAO-B inhibitor preventing the breakdown of dopamine
- Carbidopa - Inhibits dopamine breakdown in periphery by blocking DDC and COMT
What is the MOA of apomorphine?
Derivative of morphine that is a dopamine agonist
What is the “On-Off” Phenomenon?
Periods of increased mobility, followed by marked akinesia; associated with long term Levodopa use
What is essential tremor and its treatment?
B1 receptor dysfunction; treatment is beta blockers
What is benign hereditary chorea and its treatment?
Chorea movements, does not progress or cause dementia; treatment is tetrabenazine, a dopamine receptor blocker
What is Gower’s sign?
When a child with Duchenne’s is asked to stand up from a downward dog position, instead of standing straight up, they will push their upper body up with their hands on the knees.
What is the pathogenesis of Huntington’s disease?
Treatments?
- GABA is reduced in the basal ganglia
- Tetrabenazine - dopamine receptor antagonist
- Dopamine receptor blockers (Haloperidol)
- Genetic counseling, speech and physical therapy
