Neurology: Parkinson Disease Flashcards
What 5 chromosomes and which 3 genes are involved in hereditary forms of Parkinson Disease?
Chromo: 1,2,4,6,12
Genes:
alpha-synuclein & parkin - both involved in a proteosome pathway
DJ-1 gene is involved in antioxidant pathways
How many neurons in the Substantia nigra die before Parkinsonian symptoms start to arise?
80-90%
What are two environmental toxins associated with PD?
- MPTP
2. Fertilizers/Pesticides
Describe the INTRINSIC mechanism leading to PD.
- DA metabolism by MAO-B forms free radicals
- Free radicals cause lipid peroxidation of cell membranes
- Membrane dysfunction leads to nigral damage and PD
Describe the EXTRINSIC mechanism leading to PD.
- Some toxin (ex. MPTP) is metabolized by MAO-B (forms MPP+)
- The toxin (MPP+) causes mitochondrial dysfunction
- Dysfunctional mitochondria causes nigral damage and PD.
What are 5 risk factors associated with oxidative damage that are especially damaging to brain tissue?
- Brain is mostly lipids which are affected by radicals easily
- Brain uses 20% of body’s O2 demand so oxygen is abundant
- Brain doesn’t have much oxidative protection
- Brain is postmitotic (non-dividing)
- Brain has lots of iron which acts as a catalyst in free radical generation
How is the PD tremor and rigidity described?
Resting and pill rolling tremor
Cogwheel rigidity
What is the Myerson Sign?
Glabellar Sign
- physician taps between the eyes of a patient and the patient keeps blinking
- indicates PD
Which classes of drugs are most common to induce Parkinsonian like symptoms?
Antipsychotics and antiemetic drugs
What is the best way to diagnose PD?
H&P
-there are no definitive tests for it, the only confirmatory diagnosis is brain biopsy during autopsy.
How does selegiline treat PD?
MAO-B inhibitor: prevents DA metabolism
What types of drugs should be avoided if a patient is taking selegiline and why?
Any drugs that increase the amount of 5HT in the synapse
-TCAs, meperidine, SSRI’s
Can lead to serotonin syndrome
How does rasagiline treat PD?
MAO-B inhibitor taken 1x/day
Has anti-apoptotic effects to preserve mitochondria in substantia nigra cells
How do benztropine, trihexyphenidyl and biperiden treat PD?
Anti-cholinergics
- treat rigidity and tremors
- does not treat the Bradykinesia
- not used in elderly
Which drug should be given to elderly patients that cannot tolerate the Anti-cholinergic medications and how does it work?
Amantadine: weak dopaminergic effects
How do bromocriptine, ropinirole, pramipexole, rotigotine, and cabergoline function?
DA agonists used in early stages of PD.
May be more effective in parkinsonian-like diseases.
Do NOT require intact substantia nigra to function.
How do tolcapone and entacapone treat PD?
They are catechol-o-methyl transferase (COMT) inhibitors that prevent the metabolism of DA.
Often used in conjuction with L-dopa and carbidopa.
(entacapone has less liver toxicity)
How does Sinemet Treat PD?
Combo of L-dopa (dopamine analog) and carbidopa (inhibits dopa decarboxylase). The combination allow L-dopa to make it to the CNS without metabolism so that it can be used by the brain.
How much carbidopa is required in order to inhibit dopa decarboxylase?
70mg
What can happen in a PD patient when too much L-dopa is given?
The main effect is dyskinesia. This refers to the dance-like movements or chorea seen in PD patients after a new dose. Usually resolves as the L-dopa is metabolized and cleared by the system.
What type of meal can inhibit the uptake of L-dopa from the GI tract?
High protein meals, the L-dopa competes for the same transporters as Amino Acids from the diet.
How do surgical procedures generally treat PD?
They treat the movment symptoms.
- pallidotomy, thalamotomy
- pacemaker in subthalamic nucleus
What is Progressive Supranuclear Palsy (PSP)?
Neurodegenerative disease with Parkinsonian symptoms: bradykinesia, rigidity, pseudobulbar signs, dementia, and Babinski. Very hyperreflexive.
Much more aggressive, death occurs in 10 years.
What is one general characteristic that differentiates PD from PSP on physical exam?
Due to posturing:
PD patients tend to fall forwards late in the disease
PSP patients tend to fall backwards late in the disease
