Parkinsons Flashcards
What are the 3 cardinal symptoms of PD?
Tremor (resting tremor), rigidity and akinesia/bradykinesia.
Diagnosis is where 2 of the 3 cardinal signs must be present.
How does PD affect basic ADL?
- mobility issues (walking, using the stairs)
- feeding oneself
- grooming, personal hygiene
- toileting
- showering
- continence (bowel and bladder)
What is the goal of managing PD?
- manage symptoms
- maintain function and autonomy
(no treatment for PD is neuroprotective)
What are the 4 classes of medications used to treat PD motor symptoms?
- levodopa + DCI
- dopamine agonists
- MAOB-inhibitors
- COMT inhibitors
- anticholinergics
- NMDA antagonists
What are some non motor symptoms of PD?
- dementia
- depression/psychosis
- sleep disorders
- sialorrhoea (salivation)
What agent is preferred in early/young onset PD?
Dopamine agonists in preference to levodopa
What are the non-pharmacological treatments used in PD?
- physiotherapy
- occupational therapy
- speech therapy and swallowing
- surgery
What is the most effective drug for treatment of PD symptoms?
Levodopa
Why can’t dopamine be used as a treatment?
Does not cross the BBB
How is levodopa converted to dopamine?
You want it to occur in the brain.
However, peripheral conversion of levodopa to dopamine can occur, catalyzed by DOPA decarboxylase, MAO and COMT -> causes nausea/vomiting and hypotension.
What is the absorption of levodopa affected by?
Absorption decreases with high fat or high protein meals. Separate administration by 2 hours.
What are DOPA decarboxylase inhibitors?
Benserazide and carbidopa
What are the adverse effects of levodopa?
- nausea/vomiting (from peripheral conversion)
- orthostatic hypotension
- drowsiness, sudden sleep onset
- hallucinations, psychosis
- dyskinesia (within 3-5 years of initiating levodopa)
What is the on-off phenomenon for levodopa?
On - response to levodopa
Off - no response to levodopa
(unpredictable)
What is the wearing off phenomenon for levodopa?
effect of levodopa wanes before the end of the dosing interval -> modify time of administration or replace with modified release preparations
How do we manage dyskinesia from levodopa?
add amantadine; replace specific doses with modified release levodopa
How is the bioavailabilty like for sustained release levodopa?
Lower bioavailability than immediate release -> need to adjust doses when converting vice versa.
What are the 4 drug interactions for levodopa?
- Pyridoxine: cofactor for dopa decarboxylase. take note if high dose B6 for haematological problems or in high potency vit B complex tabs
- Iron: affects absorption of levodopa -> space out
- Protein (food and protein powder) -> affect absorption, space out
- Anti-dopaminergic drugs: metoclopramide, prochlorperazine (antiemetic of choice in PD is domperidone); FGA and risperidone
What are examples of dopamine agonists?
Ergot derivatives:
- bromocriptine
- cabergoline
- pergolide
Non-ergot derivatives:
- ropinirole
- pramipexole
- rotigotine (transdermal) -> used in dysphagia in PD patients
- apomorphine (SC)
What special elimination parameters do we need to take note for ropinirole and pramipexole?
Ropinirole: mainly metabolized by the liver to inactive metabolites -> adjust in hepatic impairment
Pramipexole: excreted largely unchanged in the urine -> dose adjust acc to renal function
What are the adverse effects of dopamine agonists?
Dopaminergic: nausea, vomiting orthostatic hypotension leg edema hallucinations somnolence day time sleepiness compulsive behaviours
Non-dopaminergic:
fibrosis (lower risk with non ergot agents)
valvular heart disease (lower risk for non ergot agents)
What is the place in therapy for dopamine agonists?
Preferred over levodopa in younger patients to maximize treatment options and delay the onset of levodopa-induced motor complications. (used as monotherapy in young onset PD)
adjunct to levodopa in moderate/severe PD
What are examples of MAOB-inhibitors?
Selegiline and rasagiline -> both irreversible enzyme inhibitors -> short half life but long duration of action
Place in therapy for MAOB-i?
effective as monotherapy in early stages;
adjunct in later stages
What is selegiline metabolized to?
To amphetamines which are stimulating and have no effect on MAOB.
Is rasagiline metabolized to amphetamines?
NO
What are the drug interactions for MAOBi?
SSRI, SNRI and TCAs -> washout period is recommended
What is a counselling point for MAOB-i?
Avoid tyramine rich foods
What are examples of COMTi?
Entacapone and tolcapone
What is the place in therapy for COMTi?
- Not effective without concurrent levodopa treatment.
- decreases “off” time
What are some drug interactions of entacapone?
- iron, calcium
- avoid concurrent MAOi
- catecholamine drug
- enhance anticoagulant effect of warfarin
What are the adverse effects of entacapone?
- diarrhoea
- urine discolouration (orange)
- use with caution in hepatic impairment, but monitoring of LFTs generally not required
- may cause dyskinesia upon initiation -> may require a lowering of levodopa dose
- may potentiate orthostatic hypotension and nausea/vomiting
What is the difference between tolcapone and entacapone?
- more potent and longer duration of effect than entacapone
- however, causes liver issues -> need to monitor LFTs
What is the place in therapy for anticholinergics in PD?
- primarily used to control tremors
What are examples of NMDA antagonists in PD?
- amantadine
- memantine
What are the adverse effects of NMDA antagonists?
- nausea
- light-headedness
- insomnia
- confusion
- hallucinations
- livedo reticularis
What is the place in therapy for NMDA antagonists?
- used as an adjunct to levodopa to manage levodopa-induced dyskinesias
What are the two types of parkinsonism?
- vascular parkinsonism
- drug-induced parkinsonism
What drugs can cause drug-induced parkinsonism?
- dopamine receptor blockers (FGA antipsychotics eg haloperidol and prochlorperazine, amisulpride & SGA at higher doses eg risperidone, olanzapine and aripiprazole)
- cinnarizine
- valproate
How to treat drug induced parkinsonism?
Remove offending drug
What is Parkinson Hyperpyrexia Syndrome (PHS)?
- caused by changes in dopaminergic treatment
How to manage PHS?
- If cause is reduced dopaminergic medications, reinstate previous treatment and increase dose of levodopa gradually.
- Dantrolene and bromocriptine
What are some complications of PD?
- aspiration pneumonia (impaired swallowing)
- dopamine agonist withdrawal
- psychosis
- dyskinesia
