Parkinson's Flashcards
Epidemiology for Parkinson’s
1 million ppl in the U.S
2:1 males
Usually occurs between 50 and 80 years of age (mean 55)
Etiology of Parkinson’s Disease
*most idiopathic
no clear triggers
some genetic aspect
Patho/Phys of Parkinson’s
progressive depletion of dopaminergic neurons in the substantia nigra (SN) of the basal ganglia
70-80% of dopamine lost by the time a patient presents with symptoms
What are Lewy Bodies
spherical, abnormal aggregates of protein) are found in the remaining DA cells in the SN
4 Clinical Characteristics Associated with Parkinson’s
Bradykinesia and akinesia: slowness of movement
Tremor: unilateral, at rest; described as “pill-rolling”
Rigidity: resistance to passive movement of the joints; “cog wheeling” or ratchet motion
Postural Instability
How do you diagnose Parkinson’s?
Bradykinesia and at least one of the following:
Limb muscle rigidity (often with cogwheel quality)
Resting tremor
Postural instability
If one of the above is present: possible diagnosis
If at least 2 are present: probable diagnosis
If at least 2 are present and positive response to antiparkinsonian pharmacotherapy: definitive diagnosis
Symptoms of idiopathic PD usually appear how? (2)
unilaterally and progress asymmetrically
3 Ddx for Parkinson’s?
Drug-Induced Parkinsonism antipsychotics
Parkinsonism-Plus Syndromes lots of different things that its degenerative neurologic d/o
Idiopathic Parkinsonism
Acute Dopaminergic Challenge
Carbidopa/levodopa or apomorphine used
Onset of motor effects observed within 30 minutes
5 Stages of Parkinson’s?
Stage 1: unilateral involvement only and no/minimal functional impairment
Stage 2: bilateral involvement but no impairment of balance
Stage 3: postural imbalance and some restricted activities; disability considered mild to moderate
Stage 4: patients severely disabled
Stage 5: patients confined to a wheelchair
What are 5 clinical predictors for progression of Parkinson’s?
Older age at onset
Rigidity or hypokinesia as presenting symptom
Male gender
Presence of comorbidities
Stroke
Auditory defects
Visual impairments
Decreased response to dopamine
What are 5 goals of pharmacotherapy for Parkinson’s?
Preserve motor function for as long as possible
Improvement of nonmotor features
Minimize adverse effects
Manage long-term complications of disease progression
Maintain best quality of life
6 medications used in Parkinson’s Disease?
MAO-B inhibitors
Amantadine
Anticholinergic symptom relief
Stimulation of endogenous D2 dopamine receptors (dopamine agonists, DAs)
(Carbidopa/levodopa)
(catechol-O-methyltransferase [COMT] inhibitor
Initiation of Pharmacotherapy depends on what? (2)
Begin treatment with MOA-B inhibitor or DA if patient is younger with functional impairment
Begin treatment with LD if patient is older, has cognitive impairment, or has moderate to severe functional impairment
MAO-B INHIBITORS – SELEGILINE (ELDEPRYL®) (5)
Irreversible MAO-B inhibitor
**not usually used due to Metabolized into a neurotoxic amphetamine derivative
Provides mild relief of symptoms vs. placebo
Allows for lower dose of LD when used in adjunct therapy
Can delay need for starting LD by 9 months
MAO-B INHIBITORS – RASAGILINE (AZILECT®) (4)
Second-generation irreversible selective inhibitor of MAO-B
Indicated as monotherapy in early PD (1 mg daily) or as adjunct to LD in advanced disease
Greater potency and may be neuroprotective (is not metabolized into potentially neurotoxic amphetamine-based metabolites)
Added to LD, improves motor fluctuations, reduces “off time”
MAO-B INHIBITORS – RASAGILINE (AZILECT®) Side effects(3)
headache, dizziness, nausea
AMANTADINE (SYMMETREL®) (5)
Antiviral agent with mild therapeutic effect in PD
MOA in PD unclear
Initiated in early stages when mild symptoms occur
Improvements in bradykinesia, rigidity, and tremor
Tachyphylaxis develops within 4-8 weeks***
Anticholinergic Agents (3)
When used, do not discontinue abruptly due to potential withdrawal reactions
Avoid in pts with cognitive deficits
used in early stages of parkinsons
DOPAMINE AGONISTS – DAS (3)
DAs can delay need for LD therapy for 4-5 years in 80% of patients
Patients less likely to develop dyskinesias and motor fluctuations when LD used as adjunct to DA therapy
**titrate by starting low and going slow!
DOPAMINE AGONISTS – DAS ERGOT DERIVATIVES (3)
Rarely used in PD
Bromocriptine (Parlodel®)
Moderate affinity for D2 and D3 dopamine receptors
Pergolide (Permax®)
Removed from the market March 2007; associated with cardiac valve fibrosis
DOPAMINE AGONISTS – DAS NON-ERGOT DERIVATIVES 4 medications used=
used regularly!
Pramipexole (Mirapex®)
Ropinirole (Requip®)
Rotigotine (Neupro®)
Apomorphine (Apokyn®)
6 side effects for Non Ergot derivatives for dopamine agonists
Nausea Confusion Orthostasis Postural instability Dizziness/light-headedness Hallucinations Rare: Risk for daytime somnolence and “sleep attacks” Hypersexuality Pathological behaviors
DA – PRAMIPEXOLE (MIRAPEX®) (2)
Dosing adjustments are required for renally impaired patients
ER and IR used
DA – ROPINIROLE (REQUIP®)
Titrate cautiously in patients with hepatic impairment
Monitor LFTs
IR and ER
DOPAMINE AGONISTS – DASROTIGOTINE (NEUPRO®)
transdermal patch
Indicated for early-stage idiopathic PD and advanced stages
Side effects: application site reactions, nausea and vomiting, somnolence, dizziness, hallucinations, abnormal dreaming
DOPAMINE AGONISTS – DAS APOMORPHINE (APOKYN®) (2)
FDA approved for intermittent treatment of hypomobility in patients with advanced stages of PD
Not recommended as 1st line therapy
Rescue of “delayed on”/ “no on” or “freezing episodes”
DOPAMINE AGONISTS – DAS APOMORPHINE (APOKYN®)
Side effects and use for prophylaxis
Due to significant N/V, must use prophylaxis with an antiemetic
Start trimethobenzamide 3 days before apomorphine and continue for first 2 months of treatment (300 mg po TID)
Do not use with serotonin antagonists such as ondansetron – the combination may result in severe hypotension
Side effects: Nausea, vomiting, somnolence, dizziness, yawning
DOPAMINE AGONISTS – DAS APOMORPHINE (APOKYN®) Disadvantages
Onset of therapeutic effect rapid
Peak plasma levels within 60 minutes
Administer a 2 mg test dose
Dosed 3-5 times/day, prn
Disadvantages
No oral dosing formulation (subcutaneous injection)
Patients may require someone else to inject once hypomobility had occurred
LEVODOPA – LD
LD is an immediate precursor to dopamine
Improves motor symptoms from progressive loss of dopaminergic neuronal function
Cornerstone of treatment for PD
Nearly all patients will require supplementation with LD
In the periphery LD is rapidly metabolized to dopamine by L-amino acid decarboxylase
Dopamine cannot cross the BBB
LD alone causes significant nausea and vomiting at high doses required to achieve adequate concentrations within the substantia nigra
Carbidopa/Levodopa side effects
Nausea Vomiting Orthostasis Confusion Postural hypotension Vivid dreams Wearing-off fluctuations Dyskinesias
Carbidopa (CD) is what?
is a peripheral decarboxylase inhibitor
Used in combination with LD to increase LD’s bioavailability across the BBB
Carbidopa does not cross the BBB
80% less LD dose required to achieve same effect
2 types of Carbidopa/Levodopa?
immediate release
controlled release
Controlled release Carbidopa/ Levodopa should be taken with what?
Should be taken with food to slow movement through the GI tract
Immediate release Carbidopa/ Levodopa should be avoided with what?
Avoid high-protein meals
Take 30 minutes before or 60 minutes after meals due to competition with other amino acids for gastrointestinal absorption
What are 5 concerns with Carbidopa/ Levodopa?
End of dose wearing off
Peak-dose dyskinesia
“Delayed on” or “no on”
Freezing or start hesitation
Off period dystonias
End of Dose Wearing Off is what?
Patients experience a wearing off effect and experience an increase in PD symptoms prior to the time of the next dose
End of Dose Wearing off should be treated how?
Decrease dosing interval of LD (increase frequency)
Add MAO-B inhibitor, COMT inhibitor, or Dopamine agonist
Peak Dose Dyskinesias is what?
May be thought of as excessive movement secondary to excessive striatal dopamine stimulation
Peak Dose Dyskinesia should be treated how?
*Smaller and more frequent doses of CD/LD
Add amantadine
“Delayed on” and “no on” is what?
May be due to delayed gastric emptying or decreased absorption in the duodenum.
“Delayed on” and “no on” should be treated how?
Give on an empty stomach before meals
Use ODT formulation
Avoid CD/LD CR use
Add apomorphine
Freezing, start hesitation is what?
Sudden, episodic inhibition of lower-extremity motor function
Freezing, start hesitation should be treated how?
Increase CD/LD dose
Add Dopamine agonist or MAO-B inhibitor
Utilize physical therapy and assistive walking devices or sensory cues
Off period Dystonia is what?
Sustained muscle contraction may occur; most common in distal lower extremity. Often occur in the early morning hours, prior to the first dose of L-dopa.
Off period Dystonia should be treated how?
Add SR CD/LD
Add ropinirole CR at bedtime
Initiate Baclofen
Initiate Botulinum toxin
Myoclonus is what?
Occurs during sleep; repetitive jerking of limbs may occur
Myoclonus should be treated how?
Decrease nighttime LD dose
Initiate clonazepam
COMT Inhibitors (3)
Has to be used in combo therapy
Can decrease “wearing-off”
Increases “on time” by 1-3 hours
COMT INHIBITORS – ENTACAPONE (COMTAN®) (3)
No reports of hepatotoxicity
8 doses a day
Brownish-orange urinary discoloration may occur
COMT INHIBITORS – TOLCAPONE (TASMAR®)
Longer t1/2 than entacapone
TID
Use limited due to potential for serious liver dysfunction (strict monitoring of LFTs)
Brownish-orange urinary discoloration may occur
2 Other Therapies that are thought to be helpful?
Antioxidants
Vitamin E (alpha-tocopherol) 2,000 International units/day
Theorized to prevent neuronal damage
Doses >400 International units/day linked to ’d risk of cardiovascular adverse effects
Vitamin C (ascorbic acid) Theorized to potentiate antioxidant activity of vitamin E
