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4 cardinal clinical features of Parkinson's
- postural instability
5 supportive features of Parkinson's
- stooped-flexed posture
- shuffling gait and festination
Non motor symptoms of Parkinson's
- disturbed sleep
- bowels demand stimulating medicines
- excessive sweating
- NOT SMELLING WELL
what is the pathology of Parkinson's
- 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)
- Olfactory dysfunction
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?
- rotigotine patch
Issues with dopamine agonists
- sudden onset sleep
- inpulse control disorders
2 major categories of drug therapy for Parkinson's
- dopaminergic agents
- anticholinergic agents
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
- cardiovascular effects
- 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
- Nonergot derivatives
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
- daytime somnolence
Adverse effects of pramipexole with levodopa
orthostatic hypotension and dyskinesias and increase in hallucinations
Two COMT inhibitors available
second/third line drug for PD
Nonmotor symptoms of PD
depression, dementia, psychosis ect.