Parkinson's Disease Flashcards
True or False: Parkinson’s Disease is characterized as a syndrome of motor and non-motor symptoms
True
What does diagnosis of PD rely on?
Signs/symptoms and ruling out other causes
-no lab testing available for diagnosis
What are the risk factors of PD?
- Age (60 or older)
- heredity (close relative)
- Sex (M>F)
- Toxin exposure
Describe the Dopamine imbalance in PD
Progressive loss of Dopamine in nigrostriatal tracts of brain; acetylcholine increased–> imbalance
Clinical presentation (symptoms) can be separated into what 3 categories?
- Motor symptoms
- autonomic symptoms
- cognitive and psychiatric symptoms
What are the motor symptoms of PD?
- abnormal gait, posture, impaired fine movements (buttoning shirt), masked facies, micrograph
- dysphagia, drooling, less blinking
What are the autonomic symptoms of PD?
- Orthostatic hypotension
- impaired GI motility and constipation
- bladder dysfunction and sexual dysfunction
What are the cognitive and psychiatric symptoms of PD?
- Cognitive decline
- hallucinations
- anxiety, depression, sleep disorders
- behavioral symptoms and agitation
What are the cardinal features of PD?
Resting tremor (pill rolling), rigidity, bradykinesia
What resources are used to diagnose a patient with PD?
- medical history and physical exam
- Neurologic Exam (cardinal features): one cardinal feature (possible), at least two (probable), at least two and positive response to levodopa (Definite)
- Neuroimaging to rule out other causes
What drug classes may be used in the treatment of PD?
- carbidopa/levodopa
- dopamine agonists
- anticholinergics
- MAO-B inhibitors
- COMT inhibitors
Which drug class is best for treatment of tremors? What if the patient is over the age of 65 with CC of tremors?
- anticholinergics
- use carbidopa/levodopa because anticholinergics increase fall risk
Which dopamine agonists are used in the treatment of PD?
Bromocriptine, Rotigotine, Ropinirole, Pramipexole, apomorphine
What are the benefits/downsides of Dopamine agonist use?
- Not as effective as levodopa
- fewer motor complications than levodopa
- longer half-life than levodopa (less daily dosing needed)
- non-ergot derivatives (pramipexole and ropinirole) preferred over ergot derivatives (bromocriptine) b/c of cardiac fibrosis and valve disease
Which dopamine agonist has renal dosing? What is its dosage form?
pramipexole (mirapex); IR or ER tablet
how is apomorphine administered
subcutaneous injection for intermittent freezing episodes
Ropinirole dosage form
IR tablet, XL tablet
Rotigotine Dosage form
transdermal patch; rotate app sites daily
Bromocriptine dosage form
Tablet or capsule; give with food; give within 2 hours of waking in the morning
What are the benefits and drawbacks of Levodopa for PD?
- most clinically effective therapy for PD symptoms
- 1st line in elderly
- long term use–> dyskinesia and motor complications
- effective for all cardinal symptoms
Why is carbidopa administered with levodopa?
carbidopa reduces levodopa dose requirements and improves tolerability
What is the difference between IR and CR carbidopa/levodopa (sinemet)
CR formulation is 30% less bioavailable compared to IR; must increase dose by 10% and titrate if switching from IR to CR
What are the motor complications caused by Levodopa?
Freezing, on/off effect, wearing off, drug holiday
Levodopa: Freezing
immobility in the morning b/c of short half life of levodopa
-take am dose upon waking, intermittent apomorphine, add DA or MAO-B, physiotherapy, assistive walking device, and sensory cues
Levodopa: on/off effect
random mobility fluctuations
-add MAO-B, COMT inhibitor or DA
Levodopa: Wearing off
dose ends at latter part of dosing interval
-CR levodopa, shorten dosing interval, add MAO-B, DA, or COMT inhibitor
Levodopa: Drug holiday
brief period of drug withdrawal (at least one week) to improve response and minimize side effects of long term therapy
What are some reasons why Levodopa treatment may fail?
misdiagnosis, inadequate dosage, drug interactions
Why are COMT inhibitors used in PD?
inhibits metabolism of levodopa, only useful in combo with levodopa
-may cause brown-orange urine
What are the adverse effects of COMT inhibitors?
- Entacapone is preferred tx; may cause severe diarrhea
- tolcapone has BBW for fatal hepatotoxicity
Why are MAO-B inhibitor used in treatment of PD?
- blocks oxidative degradation of dopamine thru MAO-B inhibition
- can be used as initial therapy or adjunct with levodopa
- not as good as DA and levodopa for motor symptom control
what should be avoided when taking MAO-B inhibitors?
tyramine-containing foods
Why are Anticholinergics used in treatment of PD?
- blocks excitatory Ach, minimizing the effect of increase in cholinergic sensitivity
- corrects balance b/t Ach and dopamine
- best for tremors
- less effective than DA and levodopa/carbidopa for bradykinesia and rigidity
Why is amantadine used in treatment of PD?
- used as adjunct to levodopa
- treats dyskinesia
- not generally considered as appropriate monotherapy option
- may improve tremor, rigidity, and bradykinesia
- improvement in days
- renal adjustments needed
- tachyphylaxis
