Neuro 2 Parkinsons Flashcards
What is Parkinsons?
degeneration of substantial nigra in the cerebellum
Why does it occur?
loss of dopamine producing neurons
What may worsen symptoms?
Mismatch between Ach and DA
Classic triad of disease?
- Bradykinesia
- Rigidity
- Tremor
What is the phenomenon?
“on-off”, periods of dyskinesia (on, hyper movement) and alternating hypokinesia (off, no movement) so disease is difficult to manage
6 Therapeutic Maneuvers
- Replenish dopamine supply
- Agonize dopaminergic stimulation
- Inhibit dopamine metabolism
- Release dopamine for stores
- Inhibit dopamine reuptake
- Reduce cholinergic over-play
What may antipsychotics do?
antidopaminergics, may precipitate “drug-induced parkinsonism”
What is Levodopa?
naturally occurring amino acid precursor (l dopa) of dopamine
Why not use dopamine? (2)
rapidly metabolized in the gut, blood, and liver.
DA will NOT cross BBB
What 2 things metabolizes dopamine?
COMT & MAO
Does IV dopamine work centrally?
NO- poor lipophilicity
L-dopa is rapidly absorbed where? What converts it to dopamine?
Gut, transported across BBB within CNS, converted to DA via Central Dopa Decarboxylase
What is a cofactor in the peripheral conversion of L-dopa to DA?
Vitamin B6 (pyridoxine)
What is the therapeutic limitation?
As mono therapy, most of l-dopa metabolized by peripheral dopadecarboxylase
How can you prevent this limitation?
co-administor with decarboxylase inhibitors
Do you want decarboxylase inhibitor to cross BBB?
NO, you want l-dopa to be metabolized once it gets through BBB
Decarboxylase inhibitor drug interactions? what happens?
Non-selective MAO, can lead to HTN urgency / emergency
Also antipsychotics
Bromocriptine is what? Used how?
D2 agonist (dopamine receptor)
Dosed in combination with L-dopa
How is Bromocriptine administered
PO- rapidly absorbed so dosed multiple times/day
Bromocriptine A/E?
N/V (low doses)
Hallucinations, confusion (high dose)
What is another use of Bromocriptine? Who may use this? What is the drug called?
Hyperprolactinemia- dopamine hates prolactin
Galactorhhea, pituitary adenoma
Cabergoline (NOT for Parkinsons)
What is Rotigotine? Indicated for what? Administered how?
Dopamine agonist for Parkinson’s and Restless Leg Syndrome
QD transdermal patch
A/E of Rotigotine? (2)
- Psychosis
- Acute compulsive behavior
Entacapone works how?
COMT inhibitor (enzyme that metabolizes DA)
Prolongs the activity of l-dopa
