neuro: pd Flashcards
3 cardinal signs
- Tremor :
- resting tremor (disappears with movement), increases with stress - Rigidity :
- ‘ratchet’-like stiffness (cogwheel rigidity); also leadpipe rigidity - Akinesia /bradykinesia :
-subjective sense of weakness, loss of dexterity, difficulty using
kitchen tools, loss of facial expression, reduced blinking, difficulty
getting out of bed/chair, difficulty turning while walking.
pathology
loss of dopaminergic neurons in substantia nigra
measuring PD
Hoehn and Yahr, staging
Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)
non-motor sx
- cognitive impairment
- psychiatric sx: depression, psychosis
- sleep disorders
- autonomic dysfunction: constipation, gi motility, orthostatic hypoTN, sialorrhea
- fatigue
early/young onset PD
slower disease progression
features:
- less cognitive decline
- earlier motor complications
- dystonia is common initial presentation vs falls and freezing in late-onset
which drug used in preference for early/young onset PD?
dopamine agonists
predictors of more rapid course
- older onset and rigidity
- postural instability/ freezing gait
- dementia
- assoc comorbidities
- male sex
- poor levodopa response
no treatment of pd has been shown to be
neuroprotective
- goal of tx is to manage sx and function
- not to replace dopamine or cure PD
levodopa: w or wo food?
absorption decr w high fat or high protein meals
- separate adm by 2hr
why can’t dopamine be used as a treatment?
does not cross BBB
peripheral conversion of levodopa to dopamine
- catalysed by DOPA decarboxylase, MAO, COMT
- causes n/v, hypotension
Sinemet
1:4 or 1:10
carbidopa:levodopa
Madopar
1:10
beserazide:levodopa
onset of dyskinesia caused by levodopa
3-5yrs of initiating treatment
dose adj when switching from IR to CR levodopa
IR -> CR, incr dose by 25-50%
levodopa ddi
- antidopaminergics: metoclopramide, prochlorpherazine, antipyschotics
- iron, protein
- pyridoxine
dopamine agonists: ergot derivatives
bromocriptine, cabergoline, pergolide
lower F, due to extensive first-pass metabolism
dopamine agonists: non-ergot derivatives
ropinirole, pramipexole, rotigotine (transdermal), apomorphine (sc)
which dop agonist require dose adj for liver impairment?
ropinirole, mainly metabolised by the liver to inactive metabolites
which dop agonist require dose adj for renal impairment?
pramipexole, excreted largely unchanged in the urine
dop agonists adr
dopaminergic, peripheral: n/v, orthostatic hypoTN, leg edema
dopaminergic, central: hallucinations (usually visual > auditory), somnolence, day-time sleepiness, compulsive behaviours eg. gambling, shopping, eating, hypersexuality
non-dopaminergic: fibrosis, valvular heart disease
fibrosis, ergot or non-ergot DA higher risk?
ergot higher risk
- pulmonary, pericardic, retro-peritoneal
- may be partially reversible upon withdrawal
valvular heart disease, ergot or non-ergot DA higher risk?
incidence appears greater w ergot derived agents
when is DA preferred over levodopa?
younger patients, max treatment options and delay onset of levodopa-induced motor complications
DA vs levodopa
< motor complications, but > hallucinations, sleep disturbances, leg oedema,
orthostatic hypotension
DA: place in therapy
Monotherapy in young-onset PD
Adjunct to levodopa in moderate/severe PD
Management of motor complications caused by
levodopa
Rotigotine patch - ______________
Neuroprotection, disease modification??
Not proven
MAO-A
peripheral, NE and 5HT
MAO-B
central, dopamine
MAO-B inhibitors
selegiline, rasagiline
- irreversible, short t1/2 but long duration of action (MOA regeneration time: 14-28d)
MAO-B inhibitors ddi
washout period reco: ssri, snri, tca
pethidine, tramadol
linezolid
dextromethorphan
dopamine
sympathomimetics: nasal decongestants
another MAOi
if pt is taking MAO-B inhibitors, advise to avoid
tyramine (metabolised by MAO-A and MAO-B)-rich food
- aged cheeses, meat, draft beer, fermented food, banana peel
MAO-B inhibitors, place in therapy
mono in early stages, or adjunct in later stages
Comtan
entacapone - selective, reversible COMT inhibitor
must be taken at the same time as levodopa
Stalevo
levodopa, carbidopa, entacapone
entacapone ddi
iron, calcium,
Avoid concurrent nonselective MAOi (but safe with MAOBi,
caution with selective MAO-Ai)
any catecholamine drug
Enhance anticoagulant effect of warfarin
entacapone adr
diarrhea, urine discolouration (orange)
may cause dyskinesia upon initiation: may req a decr in levodopa dose
may also potentiate other dopaminergic effects: orthostatic hypoTN, n/v
caution use of entacapone in
liver impairment
incr glutamataergic activity linked to
development of and maintenance of levodopa-induced dyskinesia
Glutamate actives NMDA receptor activity
which activates processes that encourage cell
death - a/w neurotoxicity
is amantadine taken OM or ON?
2nd dose in afternoon, not at night
- can be stimulating
adr of amantadine
nausea, light-headedness, insomnia, confusion, hallucinations, livedo reticularis
amantadine place in therapy
adjunctive or
management of levodopa-induced dyskinesia
dose adj of amantadine in
renally impaired pt
