Managing late stage PD Flashcards
1
Q
Stages of PD
A
1) Prodromal
- RBD, Depression, constipation, anosmia
- Onset of motor symptoms: Bradykinesia, rigidity, tremor
2) Diagnosis
- Initiation of dopaminergic treatment
3) Maintenance
- Further titratoin of dopaminergic treatment
- Cognitive impairment, urinary symptoms, postural hypotension, pain
4) Complex
- Consider advanced therapies
- Motor fluctuations, dyskinesia
5) Palliative
- Falls, gait disorder
- Dementia, psychosis
2
Q
Motor complications
A
- Fluctuations and dyskinesia
- Occur in 50% after 4-6 years treatment
- Young age
- Disease severity
- Related to disease and treatment duration
- Genetic factors
- Both medications and disease progression lead to motor complications
3
Q
Problems with oral therapies in PD
A
- Swallowing oral therpy- dysphagia in advanced disease
- Stomach- variable absorption of levodopa due to irregular gastric emptying
- Jejunum- competition with dietary amino acids for active transport across the intestinal wall
- Peripheral tissues- reduced levodopa due to peripheral metabolism by AADC and COMT
- Blood brain barrier- Competition for transport across the BBB with large neutral amino acids limits the amount of levodopa reaching the system
- Striatum- conversion of levodopa to dopamine
4
Q
Ax of mo
A
- On/off diaries: limited training/information
- Questionannires
- Inpatient Ax: Expensive and artifical
- Wareable technologies: PKG- Multiple measure in home environment. Not yet proven to be effective
5
Q
tor
Management of motor fluctuations
A
- Fractitionation of total levodopa- lower doses more frequently. NB- increased difficulty in managing and if you just move the times without adjusting the dose then this can lead to dyskinesia
- Address treatable factors
- Delayed gastric emptying
- Constipaton
- Avoid levodopa intake with high protein meals
- Complications of existing drug therapy limiting dose escalation e.g. postural hypotension
6
Q
Adjunctive Tx for motor fluctuations
A
- Dopamine receptor agonists- generally all efficacious (except apomorphine). Ropinerole had slightly less time
- COMT- entacapone generally used, usually stay away from opicapone due to hepatic dysfunction
- MOAB inhibitor- selegilline limited evidence, rasagiline is efficacious
- MOAB-i + Channel blocker- safinamide
- Levodopa infusion- efficacous
- DBS- efficacious
- Choose based off side effect profile
7
Q
Opicapone
A
- OD treatment- helpful for adherence
- Does not cause diarrhoea (caused by entacapone)
- Some improvement in on time when switching from opicapone to entacapone
7
Q
Safinamide
A
- MOAB-I + Glutamate release inhibitor
- Reduced dyskinesia only in those with a high baseline
- Improved on and off period
8
Q
Tx of levodopa-induced dyskinesia
A
- NMDAR (Amantadine)- most effective
- Clozapine- does have good evidence but off license (which is complex due to safety issues) but may be handy if they have dyskinesia
9
Q
Amantadine
A
- Ankle swelling
- Hallucinations + delirium
- Reduces dyskinedia by 40%
- Has long term efficacy
10
Q
Pharmacology of apomorphine
A
- Highly-potent short acting dopamine receptor agonist
- PK- crosses BBB, S/C or IV not orally bioavailble
10
Q
Criteria for non-oral therapies
A
- Motor fluctuations and or dyskinesia
- Refractory tremor
- Despite optimised oral therapy: Typically >5 levodopa doses/day +/- DA/COMT/MOAB-I
- Disease duration >5 years typically- people with atypical PD may initially present with PD but will manifest generally within 5 years. Clear PD
- Levodopa responsive (expect tremor)
- Exlude psychosis/dementia
- Motivated patient
- Relaistic expectations
- No prominent axial symptoms (dysphagia, dysarthria, FOG)
10
Q
Non-motor fluctuations
A
- Neuropsychiatric: Depression, anxiety, apathy, attention, impulse control
- Autonomic: Urinary urgency, sweating, dysphagia, abdo pain, constipation
- Sensory- Pain, visual disturbances, RLS
11
Q
When to give apomorphine pen
A
- Anticipated rescue when required during motor and non-motor off periods
- When absorption of oral levodopa is impaired or the patient has gastroparesis
- To treat delayed ‘On’ periods
- To treat early morning motor problems (akinesia and dystonia)
12
Q
Apomorphine infusion
A
- Patient considers that rescue doses are given to frequently
- Dyskinesias limit further therapy optimisation
- Non-motor symptoms associated with off perioids
- Simplify complex PD dosing regimens to improve convenience and compliance with therapy
- As an alternative to durgical therapy if these are contraindicated
- Absorption or gastric empyting of oral levodopa are impaired
- Can be helpful for IP undergoing complex surgieries where they may be NBM for extended perioids
