Parkinson's Flashcards
The presence of what 3 things are considered the hallmark motor features of idiopathic Parkinson disease (PD)?
Bradykinesia, along with tremor at rest, rigidity, and postural instability (instability of balance)
Parkinson’s is a disorder of the ________________ system
extrapyramidal
Epidemiology:
1) How many US cases?
2) Who is it found more in?
1) 1 million in US
2) Prevalence increases with age: 0.5% of population in 60s; 2.5% of population ≥ 80 years old
-Males > females
What is the true etiology of Parkinson’s?
Unknown + occurs spontaneously
What does the High levels of oxidative stress in dopaminergic neurons in substantia nigra in Parkinson’s cause? (2 things)
1) ↑ dopamine degradation = ↑hydroxyl and hydroperoxyl radicals
2) ↓ glutathione antioxidants
Etiology of Parkinson’s:
1) What are consistently associated with a lower risk?
2) What forms of parkinsonism are associated with mitochondrial dysfunction and oxidative stress?
1) Cigarette smoking and caffeine consumption
2) Pesticide exposure and genetic forms
Pathophys:
1) What degenerates?
2) What does the basal ganglia regulate?
3) Neuronal projections from the SNc to the striatum are referred to as the ________________ pathway
1) Dopaminergic neurons (axons + soma)
2) Voluntary movement
3) nigrostriatal
Pathophys:
1) D1 receptor activation results in ____________ of the striatal GABAergic neurons
2) D2 receptor activation results in ______________of striatal GABAergic neurons
1) stimulation
2) inhibition
In PD, reduced dopaminergic activation of D1 and D2 receptors and the sequential downstream effect on signaling pathways results in what?
A net inhibitory tone on the thalamus
COMT and MAOB in presynaptic neurons can both metabolize what?
Dopamine
1) Lewy bodies are aggregates composed of the protein ______________.
2) What stage of PD are they involved in?
3) What do they correlate with when not in the midbrain?
4) What do they do in the midbrain?
5) In advanced stages, Lewy pathology spreads to the ______, and this may correlate with cognitive and additional behavior changes
1) α-synuclein
2) Premotor stage
3) Changes in mood (e.g., anxiety, depression) and peripheral symptoms (e.g., constipation, impaired olfaction)
4) Leads to motor features emerging
5) cortex
1) What is the criteria for PD?
2) What are other Sx?
3) Any labs needed to Dx?
1) Patient has bradykinesia and one of the following: resting tremor, rigidity or postural instability
2) Hypomimia; Micrographia
3) No labs
Pharmacotoxicity is seen in PD with some drugs belonging to what 2 groups?
Antiemetics + antipsychotics
1) What 2 antiemetics demonstrate pharmacotoxicity with PD?
2) What is the MOA of one of them?
1) Metoclopramide, Prochlorperazine
2) Metoclopramide: dopamine antagonist; serotonin agonist
What antipsychotics demonstrate pharmacotoxicity with PD?
1) Chlorpromazine
2) Fluphenazine
3) Haloperidol
4) Olanzapine
5) Risperidone
6) Thioridazine
1st generation more so than 2nd generation
Describe the tremor seen in PD
-Tremor of an upper extremity occurring at rest (and occasionally an action or postural tremor) is often the sole presenting complaint
-Present most commonly in the hands
-Resting tremor often begins unilaterally and becomes bilateral with disease progression
-Only two-thirds of patients with PD have tremor on diagnosis, and some never develop this sign
1) What motor Sx can present as bradykinesia or akinesia?
2) What is one of the most disabling problems of the late stages that’s one of the least amenable to pharmacotherapy?
1) Hypokinesia
2) Postural instability
True or false: No treatments have been shown to effectively change the course of PD by slowing or halting its progression (disease modification)
True
Amantadine can cause hallucinations and ________________
livedo reticularis
What 4 drugs can all have dopamine excess side effects? (incl. confusion, drowsiness, edema, dizziness, nausea, orthostatic hypertension)
Ropinerole + Pramipexole, Rotigotine, MAO-B inhibitors
(all dopamine agonists)
Dopamine agonists:
1) Which do you need to rotate the patch application site for?
2) Which has the least SEs? What is its one SE?
3) What are the 2 side effects of Selegiline?
1) Rotigotine
2) Rasagiline; nausea
3) Agitation/ confusion + insomnia
What monotherapy provides greater symptomatic benefit for patients with mild-to-moderate impairment?
Dopamine agonist (start w. TID)
General Tx:
1) Ultimately, all patients will require the use of ______________ either as monotherapy or in combination with other agents.
2) With the development of motor fluctuations, patients should do what, or providers should consider what?
1) carbidopa/L-dopa
2) Administer carbidopa/L-dopa more freq., or add a COMT inhibitor, MAO-B inhibitor, or dopamine agonist to the carbidopa/L-dopa regimen
For management of carbidopa/L-dopa–induced peak-dose dyskinesias, what should be considered?
A reduction in L-dopa dose and/or addition of amantadine
What is the preferred surgical modality?
Deep-brain stimulation (DBS)
Increased _____________ activity is believed to contribute to the tremor of PD
cholinergic
Anticholinergics
1) List 2 that can be used
2) List the intolerable side effects (esp in elderly)
3) What is there a contraindication to?
1) Benztropine + Trihexyphenidyl
2) Blurred vision, confusion, constipation, dry mouth, memory difficulty, sleepiness, and urinary retention
3) Narrow angle glaucoma
Amantadine
1) Use Amantadine immediate-release 100 mg/day to 400 mg / day with creatinine clearances of what?
2) What should you do for creatinine clearances of 30-50 mL/min?
3) What abt if <15mL/min or hemodialysis?
4) When are extended-release products contraindicated?
1) > 50 mL/min
2) Amantadine immediate-release 100 mg/day
100 mg every other day for creatinine clearances of 15-29 mL/min
3) 200 mg every 7 days
4) CrCl < 15 mL / min
Amantadine:
1) When might you use it?
2) What are 2 SEs?
1) Dyskinesias induced by carbidopa/ldopa
2) Hallucinations + livedo reticularis
Carbidopa reduces the unwanted peripheral conversion of __________________ to _____________
L-dopa to dopamine
Carbidopa / levodopa (L-dopa)
1) The usual initial maintenance carbidopa/L-dopa regimen is what?
2) What can help minimize treatment-emergent side effects, such as drowsiness and nausea?
3) How’s it best taken?
4) What type of SEs can it cause?
1) 25/100 mg three times daily
2) Slow buildup of dose (e.g., increments of 100 mg L-dopa per week)
3) Empty stomach
4) Dopamine
List 4 common motor complications of carbidopa/ldopa
1) End-of-dose “wearing off” (motor fluctuation)
2) “Delayed on” or “no one” response
3) Start hesitation (“freezing”)
4) Peak-dose dyskinesia
Carbidopa/ldopa:
1) The terms “off” and “on” refer to what?
2) With advancing PD, the duration of action of a single carbidopa/L-dopa dose progressively shortens, and in some cases may produce benefits for as little as ___________.
3) What should be considered if this duration shortening occurs in order to lengthen it?
4) What can also be added to help w this wearing off?
1) Periods of poor movement (i.e., return of tremor, rigidity, or slowness) and good movement, respectively
2) 1 hour
3) Consider the addition of the COMT inhibitor entacapone or an MAO-B inhibitor.
4) Dopamine agonist
Carbidopa/ldopa: What can be used PRN for rapid relief of acute episodes?
Apomorphine or a L-dopa dry powder for inhalation
Carbidopa / levodopa (L-dopa) “Delayed on” or “no-on response”
1) What can help mitigate effects?
2) Why might you use a drug-free period (“drug holiday”)?
1) Chewing a tablet or crushing it and then drinking a full glass of water or using the ODT formulation on an empty stomach.
2) Decrease unpredictable off states (should be performed with medical supervision).
Carbidopa / levodopa (L-dopa)
Freezing is often is exacerbated by anxiety or when perceived obstacles (e.g., doorways, turnstiles) are encountered
Often is exacerbated by anxiety or when perceived obstacles (e.g., doorways, turnstiles) are encountered.
Carbidopa / levodopa (L-dopa): Dyskinesias
1) Another complication of L-dopa therapy is “on” period dyskinesias that are ______________________ movements involving.
2)
1) involuntary choreiform
2) Specific to L-dopa therapy
Carbidopa / levodopa (L-dopa):
1) What is it usually assoc. with?
2) What should be attempted when this occurs? What should you consider adding?
1) Peak striatal dopamine levels (peak-dose dyskinesia)
2) Lowering the dose of carbidopa/L-dopa
-Consider adding amantadine
Carbidopa / levodopa (L-dopa)
1) For early morning dystonia what should you do?
2) Persistent focal dystonias can also occur as what? What can help?
1) Include bedtime administration of a long-acting dopamine agonist, long-acting carbidopa/L-dopa, or baclofen
2) L-dopa peak dose effect
-Focal injections of botulinum toxin type A or B
Carbidopa / levodopa (L-dopa):
1) What is drugs is it contraindicated in?
2) What are 2 other drug interactions it has?
3) What food does it interact with?
1) Non-selective MAO inhibitors
2) Antipsychotics and metoclopramide
3) Iron and protein-rich meals ↓ absorption
1) What drug that was approved in 2024 is administered via pump that needs to be worn 24 hours a day (except for up to 1hr when in water)?
2) What does and does not affect this drug?
1) Foscarbidopa/foslevodopa (Vyalev)
2) Adj. dose based on activity; unaffected by food
Selegiline:
1) Undergoes ______________ hepatic metabolism, predominantly via cytochrome __________, ________, and ______ to end products of L-methamphetamine and L-amphetamine
2) How is the ODT formulation different?
1) first-pass; P450 (CYP450) 2B6 and 2C19
2) First-pass hepatic metabolism is bypassed as a consequence of transmucosal absorption of the drug; bioavailability is improved and formation of amphetamine metabolites is reduced
Selegiline SEs are minimal but can include what 2 things?
Agitation + insomnia
What MAO inhibitor is well tolerated with minimal gastrointestinal (GI) or neuropsychiatric side effects?
Rasagiline
Catechol-O-methyltransferase (COMT) inhibitors were developed to extend effects of ___________ and are indicated for managing “wearing off” and may increase “on” time by ____ to ______ hours
L-dopa; 1 to 2
Consider decreasing dose of carbidopa/levodopa by 10-30% when doing what?
Adding Catechol-O-methyltransferase (COMT) inhibitors
Catechol-O-methyltransferase (COMT) inhibitors: What are 2 of these? Which is not preferred and why?
1) Entacapone: first line
2) Tolcapone: not preferred; may cause severe hepatotoxicity
For younger patients, who are more likely to develop motor complications, what are preferred over carbidopa/L-dopa?
Dopamine agonists
List some adverse effects of dopamine agonists
Nausea, lower-extremity edema, and orthostatic hypotension
Dopamine agonist hallucinations and delusion should be managed using a systematic approach that starts with dose reduction or discontinuation of the dopamine agonist, and if needed, addition of what?
An atypical antipsychotic medication such as clozapine, pimavanserin (Nuplazid), or quetiapine
Rotigotine (transdermal patch)
1) What should you know about the patch application?
2) When should it be removed?
3) When should it be avoided?
1) Sites should be rotated to minimize skin irritation and rash; use Qday; do not use same site for at least 14 days
2) Prior to MRIs; aluminum in patch may cause skin burns
3) If sensitive or allergic to sulfites (not the same as a sulfa allergy)
With the changes in pharmacotherapy (e.g., drug addition, discontinuation, dose change) in PD, follow-up monitoring for efficacy and side effects should occur within _____ or _____ weeks and may occur via telephone
1 or 2
