Parkinsons, Huntington, ALS Flashcards
What is the biggest risk factor in development of Parkinson’s diease?
- Age
- 1st degree relative
- M > W
What are the most common clinical findings for Parkinson’s Disease?
- Resting Tremor - pill rolling / Chin Tremor <– unique
- Increases resistance to passive movement - Rigidity
- Slow movements / Decreased arm swing - bradykinesia
- Dragging of one leg or foot – imbalanced gait
- Masked facial expression
What are nonmotor early signs of Parkinson’s Disease?
- REM Sleep Behavior disorder
- Loss of Smell
What is a characteristic finding in histology for Parkinson’s Disease?
- Loss of Substandia Nigra
- Lewy Bodies w/ Alpha Synuclein inside
What are common gene mutations found in Parkinson’s disease?
- Parkin Gene – younger onset typicallly
- Alpha-Synuclein mutation – accumulates in Lewy Bodies
What is the confirmatory test for Parkinson’s Disease?
- Responds to L-Dopa (or Dopa-angonists)
What disorder also is found to have Lewy Bodies and loss of substania nigra, but different clinical presentation?
Lewy Body Dementia
How are Parkinson’s and Lewy Body Dementia different?
- Lewy Body Dementia has earlier onset of dementia compared to Parkinson’s usually within a year or two from onset of Parkinsonian symptoms / fluctuating cognition. Parkinson’s patient’s don’t develop dementia until many years into the disease.
What is typically the first line therapy for parkinson’s diease?
Dopamine Receptor Agonists - restore function of the indirect pathway to release inhibition of thalamas
- Pramipexole
- Ropinerole
If a patient is being given Pramipexole and Ropinerole, what do they do?
D2 Agonists – induces striatum to release GABA to Globus Palladus Externa – allowing release of inhibition of thalamas by subthalamic nucleus
What drug is used for Parkinson’s Disease when the typical treatments have failed, or for immediate therapy of an attack?
Apomorphine – D4 Agonist
What are the most common side effects of Dopamine Agonists?
- sudden sleep attacks
- CNS toxicity with confusion / disorientation / too much movement
What patient population would typically get L-DOPA over Dopamine Agonists?
- Older patients with Parkinson’s
What is an advantage of Dopamine Agonists over L-DOPA?
- longer half lives
- effectiveness does not decline over time
- less oxidative damage from dopamine degradation
What is the common drug administered with L-Dopa?
- Carbidopa - peripheral inhibitor of L-AAAD and does not cross the blood brain barrier
How does co-administering Carbidopa help with L-Dopa?
– increases half life in order of the dopamine to get into the CNS and fill up the vesicles
What is the difference between Carbidopa and Entacapone?
Carbidopa – blocks peripheral L-AAAD
Entacapone – blocks peripheral COMT
How are Tolcapone and Entacapone different?
Both inhibit COMT
Tolcapone – inhibits both peripheral and CNS COMT
- limits peripheral side effects of dopamine and increases half life
- Hepatotoxicity – must monitor
Entacapone – only inhibits peripheral COMT to help with side effects mostly
What must be monitored when a patient is on Apomorphine?
- can develop a Prolonged QT
How can MAO Inhibitors help with Parkinson’s disease?
- increases dopamine half-life in the body
- decreases oxidative stressers from the breakdown
- Can be used with L-Dopa in progressed disease
What is a complication with using MAO inhibitors?
- Tyramine builds up from random foods, which is usually broken down in the liver by MAO
- Tyramine acts like NE causing sympathetic symptoms
- Serotonin Syndrome – hyperthermia, agitation
What do Selegiline and Rasagiline do?
- MAO Inhibitors
- irreversible
- can be used at first diagnosis of Parkinson’s
What can be used for Parkinson’s, if the patient has Glaucoma or Psychosis (contraindication for dopamine therapy)?
Anticholinergic Drugs (3rd line therapy)
- Trihexyphenidyl
- Benztropine
What effects do Trihexyphenidyl and Benztropine have on Parkinson’s?
- Since cholinergic neurons induce release of GABA to the globus palladus externa – preventing subthalamic inhibition
- if you inhibit cholinergics, then can reduce subthalamic activation (on inhibiting thalamas)
How can Amantadine help with Parkinson’s disease?
- increases dopamine release from synapse
- mild anti-cholinergic
- blocks NMDA receptors
When is Amantadine most commonly used?>
Given with L-Dopa when its effectiveness is wearing down and Amantadine can help the effects of it, but also diminishes over time as well
If a patient has progressive chorea with several family members who have had similar symptoms, but ended up committing suicide, what might be the condition?
Huntington’s Disease
- autodominant
- chorea - too much movement
- develop dementia over time and depression
What is most characteristic genetic finding with Huntington’s Disease?
- Huntingtin Gene mutation
What is the finding of “Anticipation” within families with Huntinington’s diease consistent with?
Number of CAG repeats within the gene
– the most the repeats the earlier onset of the disease
How does Huntington’s disease affect the basal ganglia?
- Loss of Cholinergic Neurons in the Striatum -
Thus, unable to inhibit the Globus Palladus Externa from constantly inhibiting the subthalamic nucleus (not allowing it to stop thalamus activation) - Unregulated Movement!
What is the therapeutic solution to Huntington’s Disease?
Treat the Symptoms
- Antidepressant – Fluoxetine
- Tetrabenzine – inhibits VMAT from filling vessicles, so can help with the overactive basal ganglia
If a patient notices that he has progressive weakness in his upper extremities, new onset difficulties with his vision and swallowing. What might be the most concerning diagnosis?
Amyotrophic Lateral Sclerosis
What is the best treatment option for ALS?
- Riluzole – can prolong life by a few months
- inhibits NMDA channels
What are common symptoms associated with ALS?
- LMN degradation – muscle atrophy, fasiculations
- UMN degradation – loss of reflexes
- CNS degradation – cranial nerves
What are typical genetic and histologic findings with ALS?
Familial - Superoxide Dismutase Mutation
- Accumulation of TDP-43
- Atrophy of anterior spinal roots
- degradation of multiple tracts in the spinal cord
