Parkinson's Flashcards
Pathophysiology of Parkinson’s Disease
- dopamine deficiency in brain
- imbalance between inhibitory dopamine and excitatory acetylcholine
- loss of dopaminergic cells
- formation of Lewy Bodies
- required 30-80% of nigral cell death before disease manifests clinically
Diagnostic Criteria for Parkinson’s
Bradykinesia (slowness and difficulty initiating voluntary movement)
+ at least one of the following
- limb muscle rigidity
- resting tremor
- postural instability
Levodopa
MOA: precursor to dopamine, crosses BBB
Dosing: 200-300 mg/day -> inc by 100mg/wk -> 800-1000mg/day
CI: Breast feeding, closed angle glaucoma, melanoma
DDI: dopamine antagonists (metoclopramide and APS), MAOIs, high protein intake, pyridoxine
ADE: dyskinesia, On-off, decreased effectiveness over time, psych disturbances, vivid dreams, nausea, ortho hypo, saliva/sweat/urine discoloration, NMS w/ abrupt dc
Carbidopa
MOA: inhibit breakdown of levodopa in the periphery (increases both absorption and T1/2)
Dosing: 70-100mg/day
CI: pregnancy / lactation
ADE
Carbidopa
MOA: inhibit breakdown of levodopa in the periphery (increases both absorption and T1/2)
Dosing: 70-100mg/day
CI: pregnancy / lactation
Sinemet CR
Carbidopa / Levodopa
25/ 100 mg
50 / 200 mg
less bioavailable than IR (consider giving 25% more per day)
pats complain of slowed onset
when switching from IR to CR start with 50% reduction in frequency
Inbrija
Levodopa powder for inhalation
for intermittent treatment of OFF episodes
ADE: somnolence, hallucinations, dyskinesia, COUGH, nausea, URTI, discolored sputum
Tolcapone (Tasmar)
MOA: reversible selective inhibitor of COMT -> prevents breakdown of L-dopa
Dosing: 100mg TID
CI: hepatic disease
DDI: nonselective MAOI, other drugs metabolized by COMT (apomorphine, bitolterol, dobutamine, dopamine, epinephrine, isoetharine, isoproterenol, methyldopa, norepinephrine)
ADE: hepatocellular injury, similar ADE to levodopa
Generally Entacapone is preferred over Tolcapone
Entacapone (Comtan)
MOA: reversible selective inhibitor of COMT -> prevents breakdown of L-dopa
Dosing: 200mg with each dose of levodopa/carbidopa
DDI: nonselective MAOI, other drugs metabolized by COMT (apomorphine, bitolterol, dobutamine, dopamine, epinephrine, isoetharine, isoproterenol, methyldopa, norepinephrine)
ADE: similar to levodopa + brown/orange urine
Stalevo
Carbidopa / Levodopa / Entacapone
12.5 / 50 / 200
25 / 100 / 200
50 / 150 / 200
Selegiline (Eldepryl, Zelapar [transbuccal])
MOA: noncompetitive, selective MAO-Bi -> decrease breakdown of dopamine
- increase L-dopa peak, can dec L- dopa dose up to 50%
Dosing:
-Eldepryl (PO): 5mg QD-BID
-Zelapar (dissolving tablet): 1.25 mg QD - 2.5 mg QD after 6 weeks. no food or drink 5 minutes before/after
DDI: nonspecific MAOI, TCA, SSRI, SNRI, DXM, tyramine containing foods at doses > 10 mg, sympathomimetics
ADE: CNS, GI, hypertensive crisis, serotonin syndrome, insomnia, jitteriness HA
Rasagiline (Azilect)
MOA: noncompetitive, selective MAO-Bi -> decrease breakdown of dopamine
- decrease in free radicals -> may be disease modifying
Dosing: 0.5 mg QD w/ levodopa
- 1 mg as monotherapy
DDI: nonspecific MAOI (2 week washout), TCA, fluoxetine (5 week washout), sympathomimetics
ADE:
-monotherapy: HA, arthralgia, GI upset, falls
- w/ levodopa: dyskinesia, GI upset, HA, weight loss, arthralgia, orthostasis (during first 2 months)
Safinamide (Xadago)
MOA: selective MAOBi
- Na and K channel blocker, dec glutamate release
- adjunct to L-dopa for wearing off symptoms
Dosing: 50mg PO QD -> 2 weeks -> inc to 100mg QD if needed
CI: Child-Pugh class C, do not exceed dose of 50mg in hepatic impairment
ADE: dyskinesia, hallucinations/psychosis, impulse control, behavior change, nausea, daytime somnolence, NMS in withdrawal, retinal pathology
Amantadine (Symmetrel, Gocovri, Osmolex ER)
MOA: not understood, decreases rigidity, tremor, bradykinesia, L-dopa induced dyskinesia
Dose:
-Symmetrel IR: 300 mg/day PO div
-Gocovri ER: 137 mg PO QD 1w -> 274 mg PO QD
- Osmolex ER: 129 mg PO QD 1w -> 322 mg PO QD
CI: CHF, orthostatic hypotension, peripheral edema
DDI: Flumist, Quinine/Quiidine, HCTZ, triamterene
ADE: orthostatic hypotension, hallucinations, sedation, anticholinergic AEs, livedo reticularis - mottling of skin with LE edema (resolves with dc), NMS with abrupt disruption
Pramipexole (Mirapex)
MOA: Dopamine agonist
Dosing:
-IR 0.125mg TID -> MDD 1.5mg TID
-ER 0.375 mg QD -> MD 4.5 mg QD
PK: smoking may decrease levels (induces CYP1A2)
CI: abrupt discontinuation, hepatic disease
ADE: edema, impulsivity, psychosis, N/V, orthostasis, sedation, vivid dreams, pedal edema, plum fibrosis (Ergots), cardiac valvopathy
Ropinirole (Requip)
MOA: Dopamine agonist
PK: smoking may decrease levels (CYP1A2)
Dosing:
IR 0.25 mg TID -> MDD 24mg
ER 2mg QD -> MDD 24mg
CI: abrupt discontinuation, hepatic disease
ADE: edema, impulsivity, psychosis, N/V, orthostasis, sedation, vivid dreams, pedal edema, plum fibrosis (Ergots), cardiac valvopathy
Bromocriptine (Parlodel)
MOA: dopamine agonist
CI: breast feeding, eclampsia, ergot alkaloid hypersensitivity, uncontrolled HTN
DDI: antihypertensive agents, erythromycin
ADE: CNS, GI, pulmonary fibrosis (chest radiograph at BL, once yearly)
Rotigotine (Neupro)
MOA: dopamine agonist, transdermal patch
Dosing: 2mg/24h -> inc weekly by 2mg/24h up to 6mg
-4mg minimum effective dose
DDI: dopamine antagonists (APS and metoclopramide)
ADE: application site reaction, CNS, GI, peripheral edema
Apomorphine (Apokyn)
MOA: stimulates postsynaptic D2 type receptors
- used as needed or for off episodes
Dosing: 2mg SC test dose under medical supervision
-monitor BP pre-dose, 20 min, 40min, 60min
-may increase dose by 1mg every few days as needed up to 6mg
-pretreat with antiemetic (3 days before, continue for 2 months and reassess) -NOT 5HT3 antagonists or antidopaminergic
ADE: N/V dizziness, somnolence, chest pain/pressure, dyskinesia, falls, yawning, rhinorrhea
Non-pharm treatments for Parkinson’s
surgery (deep brain stimulation)
physical therapy and exercise
nutrition
- fluids
- fiber
- omega 3 fatty acids
- occupational therapy and fall precautions
Management of wearing off syndrome
increase frq
switch to CR (decreased frq may require IR morning dose)
adjunctive DA (MAOI/COMT/Amantadine)
Management of OFF NO ON
delayed stomach emptying / decreased absorption?
- inc dose
- inc frq
- take on empty stomach
- use ODT
advanced disease > APO SQ
Management of delayed onset
empty stomach
water
avoid protein
if CR: consider switching off CR or adding IR
Management of peak effect dyskinesia
dec dose
inc frq
add amantadine
use CR Sinemet
add DA agonist
Management of dystonia
add early morning dose
CR at HS
DA agonist
Baclofen
Botox
Management of freezing
inc dose
DA agonist
gait modification
physical therapy
Management of depression in parkinson’s
pramipexole
SSRIs
venlafaxine
Management of dementia in parkinson’s
rivastigmine
Management of insomnia in parkinson’s
eszopiclone
melatonin
Management of excessive daytime sleepiness
modafanil
Management of orthostatic hypotension
fludrocortisone
midodrine
droxidopa
Management of sexual dysfunction
sildenafil
Management of constipation
PEG
probiotics
lubiprostone
Management of urinary frequency
solifenacin
Management of drooling
glycopyrrolate
botox
Management of psychosis
evaluate for other causes (pathological, drug)
simplify regimen
consider atypical antipsychotics
- Quetiapine
- Clozapine
- Pimavanserin tartrate (Nuplazid)
