L4 Antiparkinsons Flashcards
What is the function of basal ganglia and its significance in the pathophysiology of PD?
Facilitates and modulates motor movements initiated by motor cortex
- PD: degeneration of dopaminergic neurons with Lewy body inclusions in substantial nigra, which has dopaminergic projections to basal ganglia
Lewy bodies
aggresome, containing a-synuclein and ubiquitin
What is the main cause of parkinsonism?
PD
- but 10-25% of patients with parkisonian syndromes do not have PD
What are some common differential diagnoses of PD?
Atypical parkinsonian disorders
Diagnosis and diagnostic criteria of PD are based on? (3)
- Presence of clinical features (movement disorders)
- Exclusion of alternative diagnoses
- Neuroimaging
What are the 3 cardinal features of PD?
rest tremors, rigidity, bradykinesia
What is often neglected in PD management?
Non-motor manifestations
- autonomic, neuropsychiatric, olfactory, sensory
- common in PD, more prominent in later stages of PD - cause significant disability
- relatively resistant to, and may be worsened by dopaminergic agents
When will significant disability be experienced over the course of PD?
significant disability 10-15yrs after onsent
Motor fluctuation, dyskinesias and non-motor symptoms are common at later stages:
falls, postural instability, postural hypotension, confusion, dementia, suboptimal nutrition, speech and sleep disorders
What does treatment has to be individualised according to? (6)
age, stage of disease, level of activity, assoc physiological factors, assoc medical conditions, patient factors
Does a patient with early symptomatic PD without complications require any oral medications?
No, if coping well
Non-pharmacologicals for PD
- Physiotherapy and exercise regime (stretching, maintain balance and posture)
- Healthy and balanced diet
- Knowledge on disease
- Social support
What is the gold standard medication used for PD?
Levodopa
Examples of ‘2-in-1’ preparation with levodopa
and peripheral decarboxylase inhibitors
- Levodopa + benserazide = Madopar
- Levodopa + carbidopa = Sinemet
- available as regular form or long acting form (HBS or CR)
What is a potentially serious side effect of levodopa?
Dyskinesia (10%/yr) - chronic SE that is accumulative, does not fade away even if dose is later reduced
What is the most efficacious drug for the symptomatic management of both early and late PD?
Levodopa
What is the dose of levodopa that should be used?
Lowest effective dose! Should be kept to the minimum necessary, to achieve good motor function
Example of an anticholinergic (and dose) used in PD
Artane (trihexyphenidyl) 2-15mg/day
What are the common side effects of anticholinergics and which group of population is the most susceptible to it?
Dry mouth, constipation, urinary retention, sedation, delirium, confusion, halucinations
- ELDERLY
What are the advantages of anticholinergiccs?
- May be effective in controlling tremor
- Peripherally acting agents may be useful in treating sialorrhoea
How are anticholinergic agents used in PD treatment?
symptomatic monotherapy or as an adjunct to levodopa to treat tremors and stiffness
Examples of MAO-B inhibitors used in PD
Selegiline (Jumex), rasagiline
Anticholinergic MOA
Does not act directly on the dopaminergic system, correct the imbalance between acetylcholine and dopamine in PD
MAO-B inhibitors MOA
- inhibit enzyme MAO, interferes with breakdown of dopamine
- lab studies suggest that it may delay the nigral brain cell degeneration
How are MAO-B inhibitors used in PD treatment?
Symptomatic monotherapy, used in early stages
Examples of COMT inhibitors
Entacapone (Comtan) and Tolcapone (Tasmar)
COMT inhibitors MOA
only effective if used with levodopa: blocks an enzyme that converts levodopa into an inactive form, hence more levodopa is available to enter the brain -> increases duration of each dose of levodopa, beneficial in treating ‘wearing off’ responses
What are the side effects of COMT inhibitors? (6)
- increase abnormal movements (bradykinesias)
- liver dysfunction (esp Tolcapone)
- nausea, diarrhea
- urinary discoloration
- visual hallucinations
- daytime drowsiness, sleep disturbances
Dopamine agonists MOA
- act directly on dopamine receptors in the brain to reduce the symptoms of PD: prevent or delay onset of motor complications
Examples of dopamine agonists
- Bromocriptine (Parlodel)
- Pergolide (Celance, Permax)
- Piribedil (Trivastal Retard)
- Ropinirole (Requip)
- Pramipexole (Sifrol)
Is dopamine agonist or levodopa a better class of drug for PD?
Levodopa, still the gold standard
What is a side effect specific to Pergolide
restrictive valvular heart disease
What is a side effect specific to ropinirole, pramipexole
somnolence (incr sleepyness)
Side effects of dopamine agonists (general)
similar to levodopa, fibrosis, arrhythmia
Recognising that levodopa and dopamine agonists have similar SE, which is milder?
Dopamine agonist - can be used in younger patients
In younger patients with PD, which drug class should be commenced first?
Dopamine agonists
How are dopamine agonists used in PD treatment?
symptomatic monotherapy, adjunct to levodopa
What can be considered a therapy to reduce dyskinesia in patients with PD who have motor fluctuations?
Amantadine
Amantadine MOA
- enhance release of stored dopamine
- inhibit presynaptic uptake of catecholamine
- dopamine receptor agonist
- NMDA receptor anatagonist (anti-glutamate)
How are amantadine used in PD treatment
monotherapy or adjunct to levodopa
What is an important function of Amantadine?
Antidyskinetic
Amantadine’s usefulness as anti-PD drug is often limited by
- side effects
- need to screen patient for history of seizures and psychiatric smx
