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The prevalence of PD increases with...?
In people with PD, there is a lack of _______ in the brain.
A lack of dopamine in the brain can cause:
- -relay of messages is disturbed
- -problem with control of movement
Causes of Parkinson's Disease?
- -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
- use of NSAIDs
- estrogen replacement in postmenopausal women
4 characteristics that a patient will present to diagnose with PD
- Tremor at rest
- Akinesia or Bradykinesia
- Postural instability
- ***diagnosis of PD requires identifying 2 of these 4 features***
- 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
- 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
- MAO-B inhibitors
- Dopamine agonists
- COMT inhibitors
Which is the single most effect agent in PD, but has greater incidence of motor fluctuations?
Which class may provide initial symptomatic treatment in order to confer mild benefit prior to the institution of dopaminergic therapy?
Which class have less motor complications, but more dose-related adverse effects?
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?
How often do dose adjustments need to be made in titrating carbidopa/levodopa?
every 2 to 3 days
Name adverse effects of carbidopa/levodopa
- choreiform movements (caused by excess dopamine)
- dyskinesias(dance-like movements)
- orthostatic hypotension
- psychotic episodes
- 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:
- postural hypotension
- 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)
- serotonin modulators
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)
Is it necessary to taper with dopamine agonists?
Dopamine agonists adverse effects
- vivid dreams
- dry mouth
- "sleep attacks"
- impulse control symptoms
Dopamine agonists drug interactions
- dopamine antagonists (phenothiazines, butyrophenones, thioxanthines)
- non-specific MAO inhibitors
MOA of COMT inhibitors:
reversible inhibitor of COMT, an enzyme responsible to breaking down levodopa in ther peripheral circulation
Name COMT inhibitiors
- entacapone (Comtan)
- carbidopa/levodopa/entacapone (Stavelo)
- tolcapone (Tasmar)
T/F: withdrawal may lead to worsening of PD symptoms?
True, tapering may not help
Common adverse effects of COMT inhibitors:
- nausea, diarrhea, dyskinesia, orthostatic hypotension
- tolcapone: excessing dreaming, hallucinations
What is the black box warning for tolcapone?
risk of potentially fatal, acute fulminant liver failure
MOA of amantadine (Symmetrel)
- blocks the reuptake of dopamine into presynaptic neurons or increases dopamine release from presnaptic fibers
- smoothing out the fluctuations in movement
adverse effects of amantadine
- ****experience a fall-off effectiveness after a few months****
Name some anticholinergics used in PD and their MOA
- benztropine (Congentin)
- trihexyphenidyl (Artane)
tend to diminish the characteristic tremor associated with PD
MOA of bromocriptine
directly stimulates dopamine receptors
name some treatment strategies for PD
- -early symptomatic therapy to preserve activity level
- -no evidence that early medical therapy accelerated disease progression
- -continuous dopaminergic stimulation may avoid long-term motor fluctuations
T/F: Patients with younger onset of PD symptoms are probably at increased risk of the development of motor fluctuations due to dopamine
Treatment strategies for motor fluctuations:
- more frequent, smaller doses of levodopa
- use of longer-acting levodopa
- addition of dopamine agonist
- COMT inhibitors
- MAO-B inhibitors
- use of amantadine
- deep brain stimulation
Tremor vs. dyskinesia: which has a rhythmic oscillation?
tremor vs. dyskinesia: which could indicate a medication dose increase is needed?
tremor vs. dyskinesia: which is jerky and not rhythmic?
tremor vs. dyskinesia: which could indicate a dose decrease is needed?
What are preferred treatments for tremor?
- may be used with or without levodopa
name some non-motor symptoms
- dry mouth
- weight loss
- sleep disorders
- emotional changes
- difficulty with swallowing/chewing
- speech changes
- muscle cramps/dystonias
Tx of depressoin from PD
- clozapine (Clozaril) highest level of evidence
- quetiapine (Seroquel)
Tx of dementia with PD
- Donepezil (Aricept)
- rivastigmine (Exelon)
Tx for constipation in PD
- increase fiber
- increase fluid intake
- polyethylene glucol
Tx of dry mouth with PD
- chewing gum, hard candy
- regular dental visits
- good oral hygeine
sleep disorders in PD
- restless sleep
- REM behavior disorder
- difficulty staying asleep at night
- nightmares and emotional dreams
- sdden sleep onset during the day
tx of ED in PD