neuro: pd

Question 1

3 cardinal signs

Answer 1

1. Tremor :
   - resting tremor (disappears with movement), increases with stress
2. Rigidity :
   - ‘ratchet’-like stiffness (cogwheel rigidity); also leadpipe rigidity
3. 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.

Question 2

pathology

Answer 2

loss of dopaminergic neurons in substantia nigra

Question 3

measuring PD

Answer 3

Hoehn and Yahr, staging

Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)

Question 4

non-motor sx

Answer 4

• cognitive impairment
• psychiatric sx: depression, psychosis
• sleep disorders
• autonomic dysfunction: constipation, gi motility, orthostatic hypoTN, sialorrhea
• fatigue

Question 5

early/young onset PD

Answer 5

slower disease progression

features:
- less cognitive decline
- earlier motor complications
- dystonia is common initial presentation vs falls and freezing in late-onset

Question 6

which drug used in preference for early/young onset PD?

Answer 6

dopamine agonists

Question 7

predictors of more rapid course

Answer 7

• older onset and rigidity
• postural instability/ freezing gait
• dementia
• assoc comorbidities
• male sex
• poor levodopa response

Question 8

no treatment of pd has been shown to be

Answer 8

neuroprotective
- goal of tx is to manage sx and function
- not to replace dopamine or cure PD

Question 9

levodopa: w or wo food?

Answer 9

absorption decr w high fat or high protein meals
- separate adm by 2hr

Question 10

why can’t dopamine be used as a treatment?

Answer 10

does not cross BBB

Question 11

peripheral conversion of levodopa to dopamine

Answer 11

• catalysed by DOPA decarboxylase, MAO, COMT
• causes n/v, hypotension

Question 12

Sinemet

Answer 12

1:4 or 1:10
carbidopa:levodopa

Question 13

Madopar

Answer 13

1:10
beserazide:levodopa

Question 14

onset of dyskinesia caused by levodopa

Answer 14

3-5yrs of initiating treatment

Question 15

dose adj when switching from IR to CR levodopa

Answer 15

IR -> CR, incr dose by 25-50%

Question 16

levodopa ddi

Answer 16

• antidopaminergics: metoclopramide, prochlorpherazine, antipyschotics
• iron, protein
• pyridoxine

Question 17

dopamine agonists: ergot derivatives

Answer 17

bromocriptine, cabergoline, pergolide

lower F, due to extensive first-pass metabolism

Question 18

dopamine agonists: non-ergot derivatives

Answer 18

ropinirole, pramipexole, rotigotine (transdermal), apomorphine (sc)

Question 19

which dop agonist require dose adj for liver impairment?

Answer 19

ropinirole, mainly metabolised by the liver to inactive metabolites

Question 20

which dop agonist require dose adj for renal impairment?

Answer 20

pramipexole, excreted largely unchanged in the urine

Question 21

dop agonists adr

Answer 21

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

Question 22

fibrosis, ergot or non-ergot DA higher risk?

Answer 22

ergot higher risk
- pulmonary, pericardic, retro-peritoneal

• may be partially reversible upon withdrawal

Question 23

valvular heart disease, ergot or non-ergot DA higher risk?

Answer 23

incidence appears greater w ergot derived agents

Question 24

when is DA preferred over levodopa?

Answer 24

younger patients, max treatment options and delay onset of levodopa-induced motor complications

Question 25

DA vs levodopa

Answer 25

< motor complications, but > hallucinations, sleep disturbances, leg oedema, orthostatic hypotension

Question 26

DA: place in therapy

Answer 26

􀂇 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

Question 27

MAO-A

Answer 27

peripheral, NE and 5HT

Question 28

MAO-B

Answer 28

central, dopamine

Question 29

MAO-B inhibitors

Answer 29

selegiline, rasagiline - irreversible, short t1/2 but long duration of action (MOA regeneration time: 14-28d)

Question 30

MAO-B inhibitors ddi

Answer 30

washout period reco: ssri, snri, tca pethidine, tramadol linezolid dextromethorphan dopamine sympathomimetics: nasal decongestants another MAOi

Question 31

if pt is taking MAO-B inhibitors, advise to avoid

Answer 31

tyramine (metabolised by MAO-A and MAO-B)-rich food - aged cheeses, meat, draft beer, fermented food, banana peel

Question 32

MAO-B inhibitors, place in therapy

Answer 32

mono in early stages, or adjunct in later stages

Question 33

Comtan

Answer 33

entacapone - selective, reversible COMT inhibitor must be taken at the same time as levodopa

Question 34

Stalevo

Answer 34

levodopa, carbidopa, entacapone

Question 35

entacapone ddi

Answer 35

iron, calcium, 􀂱 Avoid concurrent nonselective MAOi (but safe with MAOBi, caution with selective MAO-Ai) 􀂱 any catecholamine drug 􀂱 Enhance anticoagulant effect of warfarin

Question 36

entacapone adr

Answer 36

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

Question 37

caution use of entacapone in

Answer 37

liver impairment

Question 38

incr glutamataergic activity linked to

Answer 38

development of and maintenance of levodopa-induced dyskinesia Glutamate actives NMDA receptor activity which activates processes that encourage cell death - a/w neurotoxicity

Question 39

is amantadine taken OM or ON?

Answer 39

2nd dose in afternoon, not at night - can be stimulating

Question 40

adr of amantadine

Answer 40

nausea, light-headedness, insomnia, confusion, hallucinations, livedo reticularis

Question 41

amantadine place in therapy

Answer 41

adjunctive or management of levodopa-induced dyskinesia

Question 42

dose adj of amantadine in

Answer 42

renally impaired pt