loss of the pigmented dopaminergic cell in the substantial nigra pars compact and the formation of lewy bodies int he brainstem
lewy bodies are cytoplasmic inclusion bodies that contain alpha- synuclein
What percent of neurons are degenerated by the time of clinical Parkinson's?
Pre Parkinson's symptoms
rapid eye movement sleep behavior disorder (RBD)
What is RBD?
REM behavior disorder characterized by loss of normal muscle atonia during REM sleep resulting in violent limb and body movements and vocalizations allowing people to act out dreams (associated with hyposmia and poor color discrimination)
how long does it take for major Parkinson's symptoms to occur?
what is associated with long term use of levodopa?
what is the most efficacious drug to treat Parkinson's?
Levodopa is always administered with what?
what happens to the the therapeutic window of levodopa as the disease progresses?
what are the 3 dopamine agonists?
Issues with dopamine agonists
sudden onset sleep
inpulse control disorders
2 major categories of drug therapy for Parkinson's
what kind of drug is tylenol pm?
giving older people anticholinergic agents can cause delirium
what does dopamine agonists do?
either blocks the metabolism or acts like dopamine
What is the mechanism of action of levodopa?
promotes dopamine synthesis
What is the mechanism of action of of selegiline?
inhibits dopamine breakdown
What is the mechanism of action of COMT inhibitors?
enhance effects of levodopa by blocking its degradation
Effectiveness of levodopa over time
benefits diminish over time
considerations while taking levodopa
food delays absorption
neutral amino acids compete with levodopa for intestinal absorption and of transport across blood brain barrier
high protein foods will reduce therapeutic effects
adverse effects of levodopa
nausea and vomiting
may darken sweat and urine
can activate malignant melanoma
Advantages of carbidopa
No adverse effects
increases the available levadopa in CNS which allows for 75% decrease of levodopa dosage
what is the first line drug for parkinsons?
two types of dopamine agonists
derivatives of ergot
main nonergot dopamine agonists
How is pramipexole used?
used alone in early PD and with levodopa in advancing PD
How long does it take for pramipexole to see benefits?
Advese effects of pramipexole alone
Adverse effects of pramipexole with levodopa
orthostatic hypotension and dyskinesias and increase in hallucinations