In people with PD, there is a lack of _______ in the brain.
Dopamine
A lack of dopamine in the brain can cause:
-relay of messages is disturbed
-problem with control of movement
Causes of Parkinson's Disease?
-idiopathic
-genetic
-environmental
-viruses
-oxidative stress
Describe the genetic cause of Parkinson's Disease
-mutation of alpha-synuclein gene
-some of the brain cells contained clumps of alpha-synuclein protein (Lewy bodies)
Name some risk factors of PD
a positive family hx
male gender (2:1 female)
head injury
exposure to pesticides
rural living
comsumptions of well water
Factors associated with a REDUCED incidence of PD
coffee drinking
smoking
use of NSAIDs
estrogen replacement in postmenopausal women
4 characteristics that a patient will present to diagnose with PD
Tremor at rest
Rigidity
Akinesia or Bradykinesia
Postural instability
***diagnosis of PD requires identifying 2 of these 4 features***
Define tremor:
most specific feature of PD
improves with intentional movement or sleep
usually the symptom that causes people to seek attention
involve the thumb and forefinger and appear as a "pill rolling" tremor
Define rigidity:
muscles remained constantly tensed and contracted, resistant to movement
becomes obvious when another person tries to move the patient's arm, which only moves in short, jerky movements, "cogwheel rigidity"
Define akinesia or bradykinesia:
slowing down of loss of spontaneous and automatic movement
cannon rapidly perform routine movement
simple activities may take hours (dressing, washing)
Define postural instability:
impaired balance
a stooped posture in which the head is bowed and the shoulders are dropped
diagnostic test for PD- pull on patient's back and try to make them fall
cane, walker, or wheelchair to prevent falls
physical therapy for gait training
Name the 5 drug classes that can be used to treat PD
levodopa
MAO-B inhibitors
Dopamine agonists
COMT inhibitors
Anticholinergics
Which is the single most effect agent in PD, but has greater incidence of motor fluctuations?
Levodopa
Which class may provide initial symptomatic treatment in order to confer mild benefit prior to the institution of dopaminergic therapy?
MAO-B inhibitors
Which class have less motor complications, but more dose-related adverse effects?
dopamine agonists
Why is levodopa generally given with carbidopa?
Carbidopa helps get more levodopa to the brain which prevens N/V because you have less dopamine floating around in the body.
T/F: All carbidopa/levodopa doses need to be titrated?
True
How often do dose adjustments need to be made in titrating carbidopa/levodopa?
every 2 to 3 days
Name adverse effects of carbidopa/levodopa
nausea
anorexia
vomitting
choreiform movements (caused by excess dopamine)
dyskinesias(dance-like movements)
orthostatic hypotension
psychotic episodes
depression
hallucinations
constipation
blepharospasm (contraction of eye lids, could mean dopamine toxicity)
Drug interactions with carbidopa/levodopa?
antihypertensive drugs (decreased bp)
iron salts (separate 2 hours)
MAOI's (serotonin syndrome, NMS)
metoclopramide (can cause parkinson-like symptoms)
do not take with high-protein foods (reduce absorption and effectiveness)
Name 2 MAO-B inhibitors:
selegiline (Eldepryl)
rasagiline (Azilect)
MOA of MAO-B inhibitors:
inhibit the enzyme MAO-b which breaks down dopamine in the brain. MAO-B inhibitors cause dopamine to accumulate in surviving nerve celss and reduce the symptoms of PD.
Adverse effects of MAO-B inhibitors:
nausea
postural hypotension
headache
dizziness
confustion, hallucinations
Adverse effects of selegiline:
do not take HS!! metabolized to an amphetamine-like compound cause insomnia
Adverse effects of rasagiline:
dyskinesias more common, should avoid caffeine, tyramine
MAO-B drug interactions:
CNS stimulants
analgesics (serotonin syndrome)
anesthetics
cyclobenzaprine
MAOIs
serotonin modulators
tca's
Name some dopamine agonists:
apomorphine injection (Apokyn)
pramipexole (Mirapex)
Ropinorole (Requip)
MOA of dopamine agonists:
stimulate dopamine receptors (mimic the effect of dopamine in the brain)
