Module 4.3.2 (Management of Parkinsons) Flashcards
What are the principles of treatment?
ps: You must have bradykinesia plus either tremor or rigidity for a Parkinson’s diagnosis to be considered.
- Maintain function as long as possible with minimum medication
- Individualise therapy according to disease stage and main symptoms
What examples DDI and COMT inhibitors that are used with levodopa for therapy of PD?
DDI: carbidopa and benserazide
COMT-I: entecapone
Examples of ergot and non-ergot dopamine agonists?
Ergot: bromocriptine, cabergoline
Non-ergot: pramipexole, rotigotine (patch), apomorphine (inje)
Examples of MAO-B inhibitors?
- Selegiline, rasagiline, safinamide
What is preferred 1st line therapy for parkinsons? What is it given with?
Levodopa
- Always with DDI (>75 mg benserazide or carbidopa daily)
Why is levodopa/DDI 1st line therapy? What is the AE?
Greatest benefit with the least adverse effects
- especially in elderly and cognitive decline
> improves bradykinesia (slowness of movement) and rigidity, reduces mortality; less effective for tremor
> ADRs: orthostatic hypotension, neuropsychiatric effects, hallucinations and confusion, impulse control disorders, dopamine dysregulation syndrome (compulsive overuse)
Long term levodopa syndrome develops within 5 years of starting LD, what are the two major complications of this? Who is more likely to occur in?
1. Motor fluctuations
> Wearing OFF, delayed ON and ON-OFF swings
2. Drug-induced chorea/dyskinesias
> involuntary erratic, writhing motions usually affecting face, arms, legs or trunk
Especially in patients with earlier onset PD, more severe disease, higher LD dose, longer duration of disease
What happens with increased duration with levodopa therapy?
TI window narrows
- Spend more time ‘off’ and experiencing dyskinesias than their ‘on’ state
Describe the “Wearing OFF” stage of LD. How to manage?
- End of dose failure = earliest and most common motor complication
- Re-emergence of sx before next LD dose is due
> related to the progressive loss of neuronal storage capacity and short half life of LD
- first sign = early morning tremor and immobillity = improves afterr 1st morning dose
Management
- Smaller, more frequent doses (upto 5-6) doses per day
- Add a dopamine agonist (or switch)
- Use CR product –> bedtime dose at first, then during the day
- Take on an empty stomach, reduce protein intake
- Add a COMT inhibitor
- Add rasgiline or selegiline
When does ON-OFF swings occur when using LD? How to amnage?
- Occur in advanced PD, after extended therapy with LD
- Rapid and sudden motor fluctuations unrelated to timing of last LD dose
> exact emchanism unclear; therapeutic challenge
Management
- DBS (deep brain stimulation)
Continuous dopaminergic therapy –> continous infusion + boluses
> SC apomorphine
> Duodenal levopdopa continuous infusions
- LD/CD gel given via percutaneous endoscopic gastronomy (PEG) tube into duodenum or jejunum
- Reduces the fluctuations in concentrations due to erratic or delayed gastric emptying
- Used only for uncontrolled advance disease with severe motor fluctuations, very expensive :(
What is meant by ‘freezing’ in PD? How to manage?
… issa motor complication
- Sudden freezing of gait
- Feet are stuck, difficulty initiating steps or turning
- Exacerabted by stress or when obstacles are encountered
- Symptom of disease or drug-related event
Management
- Increase dopaminergic needs
- Physiotherapy
What are dyskinesias/peak dose dyskinesias? How to manage?
…issa motor complication
Inability to control muscles giving rise to uncoordinated flailing of the arms or legs, or chorea, rapid repetitive movment of the limbs, face, tongue, mouth and neck
> not painful but very distressing
Management
- Decrease LD dose (even though may worsen PD)
- Smaller and more frequent LD doses
- Add amantadine
- Add dopamine agonists or increase dose
- Switch dopamine agonists
How to treat advanced PD?
Combination therapy often required
What are examples of dopamine agonists used to treat advanced PD? Are they used on its own?
Rarely use as 1st line monotherapy (rotigotine (patch) for NBM patient, pramipexole for once-daily dosing); otherwise add on.
- Pramipexole (preferred oral agent)
- Rotigotine (transdermal patch)
- Apomorphine SC injection prn or continuous infusion
> rescue medication for severe fluctuations refractory to conventional therapy
> effective within 5-10 minutes
> requires admission to specialised clinic or hosptial for intiation of therapy
> VERY emotgenic –> domeperidone required
AE of dopamine agonists? Which patients to avoid in? What to warn patients about?
> AE of dopamine agonists are 15% worse than levodopa
hallucinations and confusion common, impulse control disorder (ICD), sudden sleep onset, dopamine dysregulation syndrome
- ICD: problem gambling, hypersexuality, overspending, binge eating, inappropriate internet use, punding
> avoid in patients with history of ICDs or similar, warn patients and carers, monitor behaviour
> If ICD develop, stop DA, taper gradually to avoid withdrawal syndrome
