IC17 Parkinson's Disease Flashcards
What are the 4 characterpstic features of PD (which ones are cardinal signs)?
- Tremors (resting)
- Rigidity (lead pipe or cogwheel)
- Akinesia (bradykinesia)
- Postural instability
How do tremors manifest and what should be excluded?
resting tremors that disappear with movement and increases with stress
exclude generalised anxiety that can be triggered by certain activities
What must be present for a PD diagnosis?
Clinical signs, physical exam and history
2/3 of the cardinal signs (T,R,A)
What are the characteristic features of idiopathic PD? Which ones manifest upon diagnosis and which ones show up later on?
Upon dx:
assymetry
Later on:
positive response to levodopa or apomorphine
less rapid progression
may present with impaired olfaction
What are the possible factors that could lead to loss of dopaminergic neurons in PD? (3)
age-related factors
environmental toxins or insults (MPTP-MPP+, pesticides, herbicides)
genetic factors (predisposition to toxins or insults and genetic abnormalities)
Which 2 scoring systems can be used used for PD staging?
Hoehn and Yahr (H&Y)
MDS-UPDRS
What are the 5 non-motor symptoms of PD?
- Cognitive impairment → dementia
- Psychiatric symptoms → depression, psychosis
- Sleep disorders → REM sleep behaviour disorder
- Autonomic dysfunction → constipation, GI motility, sialorrhea and orthostatic hypotension
- Other symptoms → fatigue
Differentiate between the features in early onset PD and typical PD? (3)
slower disease progression
less cognitive decline
earlier motor complications
What are the 2 goals of therapy for PD?
manage symptoms
maintain function and autonomy
no neuroprotective treatment yet
Which 2 symptoms of PD are levodopa good for managing?
rigidity and akinesia
What is an important counselling point for taking levodopa?
Space apart from heavy meal
If got n&v, can take w light snacks
What is the DCI dosing required to saturate DOPA?
75-100mg daily
What are the levodopa to DCI ratios?
Sinemet 1:4 or 1:10
Madopar 1:4
What are the side effects of levodopa (5)
- nausea, vomiting (especially in new treatment)
- orthostatic hypotension
- drowsiness and sudden sleep onset
- hallucinations, psychosis
- dyskinesias (usual onset 3-5 years of starting levodopa)
What is the “on-off” phenomenon in levodopa treatment?
ON refers to levodopa response
OFF refers to no levodopa response
unpredictable and not related to dose or dosing intervals
What is the “wearing off” phenomenon in levodopa treatment?
effect of levodopa wanes before the end of the dosing interval with a shortened ON time, associated with disease progression
How can “wearing off” be managed?
modifying times of administration or replacing with modified-release preparations
How can peak dose dyskinesia be managed?
manage by decreasing dose and increasing frequency
alternatively can be managed by adding amantadine or replacing levodopa with specific doses or MR-levodopa
How should dose of levodopa/DCI be adjusted with switching from IR to CR form?
Increase dose by 25-50%
What are the DDIs with levodopa?
- Pyridoxine (vitamin B) → cofactor for DOPA decarboxylase, possibility of interactions with high dose B6
- Iron → space out administration
- Protein → space out administration
- Dopamine antagonists → such as risperidone, FGA and metoclopramide/prochlorperazine (domperidone is antiemetic of choice in PD)
What dosage forms are rotigotine and apomorphine available in
rotigotine: transdermal patch
apomorphine: SC injection
What are the peripheral dopaminergic side effects of dopamine agonists?
Dopaminergic (peripehral) → nausea, vomiting, orthostatic hypotension, leg edema
What are the central dopaminergic side effects of dopamine agonists?
Dopaminergic (central) → hallucinations (visual > auditory), somnolence, day-time sleepiness, compulsive behaviours (gambling, shopping, eating, hypersexuality)
What are the non-dopaminergic side effects of dopamine agonists?
Non-dopaminergic → fibrosis, valvular heart disease
Compare between the efficacy and side effect profile of dopamine agonists and levodopa
Dopamine agonists result in less motor complications than levodopa
but shows a higher instance of hallucinations, sleep dsiturbances, eg. edema and orthostatic hypotension
What is the place in therapy for dopamine agonists
Monotherapy in young-onset PD
Adjunct to levodopa in moderate to severe PD
Which two dopamine agonists are available as both IR and SR forms?
Pramipexole and Ropinorole
Which neurotransmitters do MAO-A and MAO-B act on
MAO-A (peripheral) → NA and 5-HT
MAO-B (central) → DA
What type of drugs are selegiline and rasagiline?
irreversible MAO-B inhibitors
Describe the half life and duration of action for selegiline and rasagiline
Short half-life of 1.5-4h
Long duration of action due to irreversibility
When are MAO-B inhibitors indicated in PD treatment?
Early stages of disease
Can use as monotherapy
How should selegiline be dosed
0.5mg OM to BD
second dose in the afternoon because metabolite (amphetamine) is stimulating
How should rasagiline be dosed
0.5 to 2mg OD
What are DDIs with MAO-B inhibitors?
SSRIs, SNRIs, TCAs (washout period recommended for these 3)
pethidine, tramadol, linezolid, dextrometorphan, dopamine, sympathomimetics (eg. nasal decongestants like pseudoephedrine and phenylephrine) and other MAOis
What are COMTi drugs
Entacapone
Tolcapone (not used anymore due to ADRs)
How do COMTi drugs help in PD?
They help to decrease “off” time
How should COMTi drugs be administered?
At the same time as levodopa (not effective as monotherapy)
What kind of a COMTi is entacapone
Reversible
What are DDIs with COMTis?
- iron, calcium
- concurrent nonselective MAOi (but safe w MAOBi)
- any catecholamine drug
- warfarin (enhances anticoagulant effect)
What are side effects of COMTis? (3)
diarrhea
urine discolouration (orange)
may cause dyskinesia and potentiate other dopaminergic effects (ortho hypotension, n&v)
In which populations should entacapone be used with caution?
Pts w hepatic impairment
What symptoms do anticholinergics help with
Tremors
What are the side effects of NMDA antagonists? (6)
nausea, light-headedness, insomnia, confusion, hallucinations, livedo reticularis
What is memantine’s place in PD therapy?
Mostly adjunctive to manage levodopa-induced dyskinesia
What are the features of drug-induced parkinsonism
symptoms tend to occur bilaterally
drug withdrawal usually leads to sx improvement
What are high risk drugs that can cause drug-induced parkinsonism?
- Dopamine receptor blockers → typical antipsychotics (eg. haloepridol, prochlorperazine), high dose atypical antipsychotics (eg. risperidone, olanzapine, aripiprazole)
- Dopamine depleters
- Dopamine synthesis blockers → α-methyldopa
