Parkinsons, Huntington, ALS Flashcards
(35 cards)
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)
