Parkinson's Disease Flashcards
What are the different types of PD
- Idiopathic PD (most often)
- Parkinson’s plus (less data on what agents work eg. levodopa):
Multiple system atrophy (aka Shy-Drager syndrome)
Progressive supranuclear palsy
Corticobasal degeneration
Lewy body disease - Parkinsonism (manifestation of the syndrome? Different MOA from idiopathic PD)
Drug-induced, toxin-induced
Vascular
What are the 4 characteristic features of PD
Tremor - resting tremor (not doing anything)
Rigidity - muscular rigidity (cogwheel hypertonic? Increase contraction)
Akinesia - slowness & poverty of movement
Postural instability (gait)
How to diagnose PD?
- 2 of the 3 cardinal signs must be present
- Tremor: resting tremor (disappears with movement), increases with stress
- Rigidity: “ratchet”- like stiffness (cogwheel rigidity); also lead pipe 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.
What features appear at initial presentation of idiopathic PD
- Asymmetric
- Positive response to levodopa or apomorphine
- Postural Instability (& falls)- not present at diagnosis
- Less rapid progression (rapid= H&Y 3 in 3 years)
- Autonomic dysfunction– not present
- Neuroimaging- ??
- Impaired olfaction (?)
- Honeymoon period of 1st 3 yrs whr even w diagnosis, dont need/minimal pharmacological intervention, pt still can lead normal life.
What happens to pt as PD progresses
- Unable to perform basic ADLs (or to perform them safely):
Mobility (walking, using stairs) - increase falls
Feeding self
Grooming, personal hygiene
Toileting
Showering/bathing
Continence (bowel and bladder) - Choking (swallowing problems)
- Pneumonia
- Falls
What is the greatest burden of PD
Costs
What are the features of early/young onset PD <40y/o
- Slower disease progression
- Features:
< Cognitive decline
Earlier motor complications
Dystonia is common initial presentation vs falls & freezing in late-onset - Dopamine agonists used in preference to levodopa
What is goals of tx for PD
No cure
Manage symtpoms
Maintain function and autonomy
No treatment for PD has ever been shown to be “neuroprotective”
What are the classes of drugs for PD Tx
Increase central dopamine, dopaminergic transmission:
- Levodopa + DCI
- Dopamine agonists
- MAO B inhibitors
- COMT inhibitors
Correct imbalance in other pathways
- Anticholinergics
- NMDA antagonists
What is nonpharm tx for PD
PT (help them move):
- Stretching, transfers, posture
- Walking (draw a line or shine a light then they walk towards it to “unfreeze” them)
OT:
- Mobility aids, home &
- Workplace safety
- Speech & swallowing (how big can they swallow? Can crush?)
- Surgery
Which drug is most effective for treating PD smx
Levodopa
Esp bradykinesia & rigidity
Less effective for speech, postural reflex & gait disturbances
Can dopamine be used as a treatment? Why?
No, it does not cross the blood-brain- barrier
SE of levodopa
N/V (take with meals), orthostatic hypotn, drowsiness, sudden sleep onset, hallucinations, psychosis, dsykinesias
How does levodopa work?
Peripheral conversion of levodopa to dopamine: Is catalysed by DOPA decarboxylase, MAO, COMT
Why are DCI (benserazide, carbidopa) added to levodopa?
Increased bioavailability, prevents break down on levodopa outside of BBB
What type of meals affect absorption of levodopa
Absorption ↓ with high fat or high protein meals.
Counselling: space apart from heavy meal.
Does DCI cross BBB?
No
What is dose of levodopa
75-100mg daily
DCI : levodopa
either 1:4 or 1:10
What is the “On-off” phenomenon?
- ON = response to levodopa (helps gain mobility -> so less adherence issues),
- OFF = no response to levodopa
- Unpredictable, not related to dose/dosing interval (cant tweak dosing regimen)
- “throwing a light switch”
- Mechanism unclear
- Difficult to control with meds
What is the “wearing off” complication and how to manage it
- Effect of levodopa wanes before the end of the dosing interval
- Shortened “ON” time
- Associated with disease progression
- Management:
Modify times of administration, and/or
Replace with modified-release preparations at the appropriate time
What is dyskinesias motor complications and how to manage?
- Can be unpredictable like “on-off” even if you flatten the peak dose so add amantadine
- Involuntary, uncontrollable
- Twitching, jerking
- Peak dose dyskinesia
- Dystonia
- Management : add amantadine; replace specific doses with modified-release levodopa
How to dose adjustment when switching btw immediate release and controlled release forms?
IR to CR : generally ↑ dose needed (~25%,-50%)
CR to IR : generally ↓ dose needed
Sustained released forms are useful for __
↓ stiffness upon waking
Examples of sustained released forms
Sinemet SR
Madopar HBS
What DDI with levodopa?
Pyridoxine:
- Cofactor for dopa decarboxylase
- Generally not a problem if levodopa is administered with a DCI but do be aware of the possibility of interactions with High dose B6 for haematological problems or in high potency vit B complex tabs
Iron: Affects absorption of levodopa -> space out administration
Protein: Affects absorption of levodopa -> space out administration
Dopamine antagonists:
- Metoclopramide, prochlorperazine (N&V)
- Antiemetic of choice in PD = domperidone (for GI motility)
- 1st gen antipsychotics - if possible, avoid unless thr is indication then R vs B, which is more pressing issue to tackle
- Risperidone
Examples of dopamine agonists
Cabergoline
Ropinirole
Pramipexole
Peripheral SE of dopamine agonists
N&V
Orthostatic hypotension
Leg edema
Central SE of dopamine agonists
- Hallucinations (usually visual > auditory)
- Somnolence, day-time sleepiness (similar to levo due to similar MOA)
- Compulsive behaviours:
Gambling, shopping, eating, hypersexuality
Act on reward system
Caregivers need to watch out! Then stop drug
CV SE of dopamine agonists
Fibrosis:
- Pulmonary, pericardiac, retro-peritoneal
- May be partially reversible upon withdrawal
- Lower risk with non-ergot agents
Valvular heart disease:
Incidence appears to be greater with ergot-derived agents (∴not used often now)
Dopamine agonists vs levodopa place in therapy?
- < motor complications than levodopa but…
- > hallucinations, sleep disturbances, leg oedema, orthostatic hypotension
- No clinically significant differences in efficacy between agents
- Frequently preferred over levodopa in younger patients: to maximise treatment options and delay the onset of levodopa- induced motor complications (unless rly bothered by tx)
Dopamine agonists place in therapy?
- Monotherapy In Young-onset PD
- Adjunct to levodopa in moderate/severePD
- Management Of Motor Complications Caused By Levodopa -> can give lower dose
- Neuroprotection, disease modification??
Which PD drug is available as transdermal patch?
Rotigotine
Examples of MAO-B inhibitors for PD
Selegiline, rasagiline
What is MAO-Bi place in therapy?
Effective as monotherapy in early stages
Dose of selegiline
5mg OM to BD (second dose in afternoon)
Dose of rasagiline
0.5 to 2mg once daily
DDI with MAOBi
- SSRIs, SNRIs, TCAs: Wash out periods recommended
- Pethidine, tramadol,
- Linezolid
- Dextromethorphan
- Dopamine
- Sympathomimetics : nasal decongest eg. pseudoephedrine, phenylephrine
- Another MAOi
Food interactions with MAOBi
tyramine, cheeses, meat, soy sauce
Among levodopa, dopamine agonists and MAOBi, which has more improvements in motor smx and more motor complications?
Levodopa
Example of Catechol-O-Methyl Transferase Inhibitors (COMT-i)
Entacapone
DDI with entacapone
- Iron, calcium,
- Avoid concurrent nonselective MAOi (but safe with MAO- Bi, caution with selective MAO-Ai)
- any catecholamine drug
- Enhance anticoagulant effect of warfarin
SE of entacapone
Diarrhoea, urine discolouration (orange),
dyskinesia upon initiation, orthostatic hypotn, N/V
Which drug must Entacapone be taken with
Levodopa
Anticholinergics place in therapy
Limited use, primarily used to control temors
Example of anticholinergic used in PD
Benzhexol
NMDA antagonists place in therapy
Adjunctive, manage levodopa-induced dyskinesia
SE of NMDA antagonist
Nausea, light headedness, insomnia, confusion, hallucinations, livedo reticularis
What complementary medicines have shown some effect for PD
Co-enzyme Q10
Creatine
Vit E
Gluthathione
Riboflavin
Lipoic acid
Acetyl carnitine
Curcumin
How to differentiate drug induced parkinsonism vs PD
Smx tend to occur bilaterally in DIP
Withdrawal of the drug usually leads to improvement in 80% of smx in 8wks
Examples of drugs that can induce parkinsonism
High risk:
Typical antipsychotics
Atypical antipsychotics
a-methyldopa
Cinnarizine
Intermediate risk:
Valproate, phenytoin, levetiracetam
Prochlorperazine, metoclopramide
Diltiazem, verapamil
Lithium
