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
