Parkinsons Disesae Flashcards
What’s the role of substantia nigra that dies or becomes impair in PD?
Dopamine (that’s why there’s a dopamine shortage in PD)
Primary s/sx of PD?
TRAP
Tremor - seen during rest, usually worsened by anxiety
Rigidity - arms, legs, trunk and face (mask-like face)
Akinesia/bradykinesia - lack of movement or slow initiation of
movement
Postural instability - poor balance, which may lead to freq falls
Other signs of PD?
Small, cramped handwriting (micrographia)
Shuffling walk
Stiff facial expression, reduced eye blinking
Muffled speech, drooling, dysphagia
Depression, anxiety (psychosis in advanced dx)
Constipation, incontinence
What’s frustrating and challenging about PD complications?
Eventually, even with high doses of the 2 most effective classes of drugs (Carbidopa/Levodopa and dopamine agonists) the “off” periods will increase
What has the highest efficacy for tx in PD pts with depression?
Tricyclic antidepressants-preferably secondary amines (desipramine and nortriptyline)
SSRIs or SNRIs commonly used but some concern they may contribute to tremor or increased serotonin syndrome risk in patients taking other serotonergic drugs
Whats preferred antipsychotic in PD pts (psychosis can present with advanced dx)?
Quetiapine (low risk of movement disorders, but will require monitoring due to metabolic complications, including blood glucose & cholesterol)
clozapine has low risk of worsening movement but high risk for agranulocytosis, seizures and other serious complications
List drugs that may worsen PD (drug-induced PD)?
Phenothiazines (Prochlorperazine, etc)-used for psychosis, nausea & agitation
FGAs-butyrophenones (esp, haloperidol-used for psychosis and behavior disorders) or droperidol used for nausea
SGAs Risperidone (Risperdal) at higher doses and paliperidone
Metoclopramide (Reglan) - dopamine blocking agent that is really cleared and can accumulate in elderly patients
Which agent is most commonly used and most effective and is sometimes better tolerated for initial tx in elderly?
Carbidopa-Levodopa (Sinemet)
What could be used for initial tremor in younger pts?
centrally acting anticholinergic-Beers criteria recommends to avoid these in elderly
Amantadine-useful for dyskinesia
MOA of Carbidopa/Levodopa?
Carbidopa Inhibits dopa decarboxylase, preventing peripheral metabolism of levodopa
(Levodopa is a precursor of dopamine-dopamine prodrug that’s converted to dopamine in the brain)
Brand name of Carbidopa/Levodopa
Sinemet
Sinemet CR
Rytary ER capsule
Duopa (enteral J-tube suspension)
T/F? Sinemet can be cut into half?
True-the CR tab can be cut in half at thescore line
BUT don’t crush or chew
ER (Rytary)-take whole or sprinkle on applesauce
How much Carbidopa is required to inhibit peripheral conversion (dopa decarboxylase) and to reduce nausea?
70-100mg of Carbidopa
SEs of Sinemet (Carbidopa/Levodopa)?
Nausea
Dizziness
Orthostasis
Dyskinesia (abnormal movement)
Brown, black or dark urine, saliva or sweat and discolor clothing
Sinemet (Carbidopa/Levodopa) and unusual sexual urges?
Sinemet (Carbidopa/Levodopa) may cause unusual sexual urges, priapism
Effect of Long-term use of Sinemet (Carbidopa/Levodopa)?
Response may fluctuate after long-term use and lead to dyskinesias
What does Sinemet (Carbidopa/Levodopa) need to be separated from?
Iron
May be protein
MOA of COMT-INHIBITOR?
Inhibit enzyme COMT to prevent peripheral and central conversion of levodopa
Role of COMT-inhibitor in therapy?
Used only with levodopa to increase levodopa duration of action- take 200mg PO with each dose of carbidopa/levodopa-max 1600mg/d
COMT-inhibitor agents?
Entacapone (Comtan)
Entacapone+Carbidopa/Levodopa (Stalevo)
Brand name of Entacapone? (COMT-inhibitor agent)
Comtan
Brand name of Levodopa/Carbidopa + Entacapone? (Sinemet + COMT-inhibitor agent)
Stalevo
List dopamine (DA) agonists agents
Pramipexole (Mirapex, Mirapex ER)
Ropinirole (Requip, Requip XL)
Rotigotine (Neupro)
Brand name of Pramipexole (DA-agonist)?
Mirapex
Mirapex ER
Brand name of Ropinirole (DA-agonist)?
Requip
Requip XL
SEs of Pramipexole (Mirapex, Mirapex ER) & Ropinirole (Requip, Requip XL) - DA agonists?
NODD-H
Nausea
Orthostasis
Drowsiness, including sudden daytime sleep attacks
Dizziness
Hallucinations
Dyskinesias
SEs of Rotigotine (Neupro) - DA agonists?
Peripheral edema
Drowsiness
HA
Fatigue
Orthostasis
Sleep disturbances (trouble irritating/ maintaining sleep)
Hallucinations
Application site (skin) rxns
Hyperhidrosis
How should Rotigotine (Neupro) be applied?
Same time each day (don’t apply to same site for at least 14 days)
Don’t apply heat source over patch
Remove patch in MRI
Avoid if sensitive to sulfites
Role of DA-agonist injection (Apomorphine - Apokyn) in therapy?
For advanced dx: a “rescue” movement agent for “off” periods
SEs of Apomorphine (Apokyn) - DA-agonist injection?
Severe nausea and vomiting
Hypotension
MOA of Amantadine?
Blocks DA reuptake into presynaptic neurons, increases DA release from presynaptic fibers
Role of Amantadine in PD?
Used for mild dx
Or
For Dyskinesias in advanced dx
SEs of Amantadine?
Dizziness
Toxic delirium/psychosis (with renal impairment, reduce dose)
Cutaneous rxn called livedo reticularis (reddish skin mottling - d/c drug)
Role of selective MAO-B inhibitors?
Primarily used as carbidopa/levodopa adjunct. rasagaline (Azilect has an indication for mono therapy)
Note: may need to reduce levodopa dose when beginning therapy with selective MAO-B inh
Selective MAO-B inhibitors agents used in PD?
Selegiline (Eldepryl, Zelapar ODT, Emsem patch—patch is only used for depression NOT PD)
Rasagiline (Azilect)
Safinamide (Xadago)
Dose of Selegiline (selective MAO-B inhibitors in PD)?
5 mg BID with breakfast & lunch-second dose midday-activating
selegiline is activating-don’t take Eldepryl or Zelapar at bedtime-
Dose of Zelapar (selective MAO-B inhibitors in PD)?
1.25-5 mg daily
selegiline ODT
Dose of Rasagiline (selective MAO-B inhibitors in PD)?
0.5-1 mg daily
Azilect
When is Selegiline beneficial in PD?
Only when used with Levodopa
selefiline & safinamidea re adjust only…rasagaline can be adjunct or mon
SEs of selective MAO-B inhibitors?
Tyramine interactions: Low risk, but possible, HTN crises can occur
Drug interactions with selective MAO-B inhibitors?
Contraindicated with other MAOi (including linezolid), opioids, SNRIs, TCAs
Meperidine (Demerol) - can be fatal
Tramadol
Methadone
Propoxyphene
Dextromethropan
St. John’s wort
Mirtazapine
Cyclobenzaprine
List centrally acting anticholinergics used in PD?
Benztropine (Cogentin)
Trihexyphenidyl
Role of centrally-acting anticholinergics in therapy?
Used primarily for tremor in younger patients
BEERS criteria says avoid use in elderly
What’s the correct titration schedule for ropinirole or pramipexole?
Wait about 1 wk b4 increasing dose
Advantage of using Carbidopa with Levodopa?
Decrease nause
Common SE of Ropinirole use?
Somnolence
Which PD med req dose reduction in renal impairment?
Pramipexole
Amantadine
Howz Pramipexole (Miraplex) dosed?
Start at 0.125mg TID
Titrate weekly to 0.5-1.5mg TID
Howz Pramipexole (Miraplex ER) dosed?
Start at 0.375mg daily, can increase approx 5-7 d to max dose of 4.5mg/d
Howz Ropinirole (Requip) dosed?
Start at 0.25mg TID
Titrate weekly to 1-4mg TID
Howz Ropinirole (Requip XL) dosed?
Start 2mg daily
Can increase approx 1-2 wks dose of 24mg/d
What’s Parkinson’s Dx (PD)?
Brain disorder that occurs when neurons in a part of the brain called the substantia nigra die or become impaired
