Neuro exam 2- Parkinson's disease
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Dopamine agent used for parkinson's disease
Dopa Decarboxylase inhibitor used for parkinson's
Dopamine Agonist used for Parkinson's
Bromocriptine, Pramipexole, Ropinirole, Rotigotine, Apomorphine
MAO-B inhibitors used for Parkinson's
COMT inhibitors used for Parkinson's
Anticholinergics used for Parkinson's
4 cardinal features in PD Clinical presentations
bradykinesia (slowness of movement; difficulty initiating movement; micrographia; freezing; festinating gait)
Limb muscle rigidity ("cog-wheel" or ratchet-like movement; hypomimia)
Resting tremor ("pill-rolling"; voluntary movement diminishes tremor; absent during sleep)
Dopamine Agonists (Common side effects)
- lower-extremity edema, postural hypotension, dizziness, somnolence, insomnia,
- constipation, asthenia, hallucinations, vivid dreams, dyskinesias, HA, gait
- abnormality, confusion, dystonia, hypertonia, amnesia, urinary frequency
Dopamine Agonist (Warnings/Precautions)
- behavior (binge eating, gambling, uncontrolled shopping, hyper-sexuality)
Combinations:*Sinemet, Sinemet CR,
- - Nausea, dizziness, urine
- discoloration, orthostatic hypotension, HA
- Confusion, hallucinations, delusions, agitation, psychosis, depression, nervousness, somnolence
- Rare but serious- cardiac arrhythmia
Explain about Levodopa
what kind of substance?
95% converted to ------------ in -------
Inactivated by ----------------
- precursor to dopamine, only combo product, Sinemet exist
- dopamine doesnt cross BBB but this does
- 95% converted to dopamine in basal ganglia
- 1 hour half life
inactive by presynaptic re-uptake, MAO, or COMT
Explain about carbidopa
what role in PD treatment?
- Dopa decarboxylase inhibitor
- Lodosyn; stand alone 25mg tablet, combo as Sinemet
- 1) reduce peripheral conversion of levodopa to dopamine by inhibiting dopa decarboxylase
- 2) reduce SE (N/V) of peripheral metabolism of levodopa
- - 75 mg required to inhibit decarboxylase activity
1) what is dosage form available and the brand name refers to them?
2) dose available (IR& CR)
3) starting dose & maintenance dose& pakage insert max dose (both IR & CR)
1)Oral disintergrating tab- Parcopa; IR and CR tabs.
- 2) IR: 10/100,25/100,25/250mg
- CR: 25/100, 50/200
- 3) Initial: IR- 25/100 PO TID; CR- 50/200mg CR PO BID at no less than 6 hour intervals
- Maintenance:IR 400-600
- Max: IR 8 tabs (200/2000)
titration plan for IR & CR (including conversion)
- IR titrate: - after initial dosing, can lower the dose as long as Sx controlled
- lower dose like 25/100 BID or 10/100 BID and don't forget adding Carbidopa!! (need 75mg)
- - inc. 1 tab every 1-2 days up to maintenance (400-600)
- - elderly, pts in dementia- start at lower initial dose & titrate slowly
CR: titrate through 3 days intervals. when switch from IR, increase CR dose by 10-30% (10% first!) greater than IR daily dosing no later than 6 hours (4,6,8 possible while awake.. but ..6hr)
1) half life for IR? and duration for IR?
2) Food interaction for IR & CR
3) when do you switch from IR to CR?
4) In what case, switiching to CR is not good?
5) what do you do if Nausea
6) what's counseling about CR tablet?
- 1) half life of IR: 1-1.5 hour
- IR duration: 5 hours
- 2) food decrease IR absorption(minimize Nausea, Food increase CR absorption.
- 3) when morning Sx exist, may take CR at night. for nausea, to prevent sudden peak concentration of IR (increase 10%!)
- 4) not good option for wearing off
- 5) check carbidopa amount, may increase more if needed. if just start IR, may have food for 3 days to minimize Nausea (only 3 days!!) Change to CR to minimize abrupt peak.
- 6) dont chew or crush. take as whole or halved
what are the contraindications for Sinemet?
- 1) Avoid w/ non selective MAOB inhibitor (phenelzine, tranylcypromine, isocarboxazid, selegiline Transdermal (nardil, parnate, marplan, emsam)
- 2)n pts w/ narrow angle glaucoma
- 3) hx of melanoma or undiagnosed skin lesions
what 's SE for Sinemet?
Tx for severe one?
- common: motor complication/fluctuation / dyskinesias->1) lower levodopa products and add adjucntive drug (MAO-B, COMT-I or dopa agonist) OR 2) may keep same dose and inc. frequency.
- Nausea, orthostatic hypotension, HA, dizziness.
- Hallucination, delusion, agitation, psychosis , depression, nervousness, somnolence, confusion ( due to too much dopamine-> lower dose ? increase frequency but keep the same daily dosing. just lowering peak level)
- Cardiac arrhythmia
what happen if abrupt w/d or dose reduction of sinemet?
Neuro malignant syndrome (NMS)
Requip Requip XL
- ergotomine derived
- pulmonary fibrosis
- less efficacy
special about dosing?
mirapex, Mirapex ER
- Renal dysfunction dose reduced when
- CrCl <50ml/min
ropinirole start dosing
- IR: start 0.25mg PO TID
- ER: 2mg daily
important fact about Neupro?
- Rotigotine comes out as patch
- rotate application daily (not at same place more than once every 14 days)
- application site rxn
1) dosage form?
2) use- when? how? duration of benefit?
4) tx SE?
6) affecting organ?
- 1) SC prn
- 2) off, no-on, delayed on
- to trigger on response w/t 20min. duration of benefit is 1.5 hours
- 3)nausea/vomiting,orthostatic hypotension
- 4) tigan( trimethobenzamide 300mg po tid starting 3 days prior to apokyn and continue for 2 months.
- 5) NO 5HT antagonist: ondansetron(zofran), granisetron (Kytril)
- 6) hepatic renal function decline: caution mild to moderate hepatic impair and renal impairment (renal, use 0.1ml as testing dose)
MAO-B inhibitors (2)?
& it's brand name
- Rasagiline=Eldepryl or zelapar (ODT)
- selegiline = azilect
when is MAO-B inhibitor, Rasagiline used for PD?
mild PD monotherpay in pts w/ no or minimal functional disability
what s role for Selegeiline in PD treatment?
FDA approved for adjunctive use w/ levodopa
what kind of benefit rasagiline have if used in mild early therapy?
- delay levodopa using 9months to 1 yr.
- beneficial effects last about 1 yr
what is benefit of using Rasagiline for adjunctive in combo w/ levodopa (for mild, moderate, severe)?
extend levodopa action by 1 hour in pts with "wearing off"
if add rasagiline to levo therapy, dose adjustment?
lower dose of levodopa by 10% ( it was 25-30% for dopamine agonist)
when is Azilect effective ?
wearingoff (motor complication appears in 1hour), less effective for on-off
how does rasagiline work synergically w/ levodopa? (MOA?)
it prevents metabolism of dopa. (not for better sx control; either to delay dopa use or extend for wearing off)
what do you have to remember from Selegiline?
brand Eldepryl, zelapar(ODT)
lose selectivity over 10mg (if not selective, can't use with levodopa)
when prescribed BID-> means breakfast & lunch!!! (due to insomnia)
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