Parkinson's Disease CA Flashcards
What is Parkinson’s Disease?
A progressive neurodegenerative disorder that primarily affects movement, but also has non-motor symptoms
Which area of the brain is affected in Parkinson’s Disease?
pars compacta of the substantia nigra, which is part of the basal ganglia
where there is a loss of dopamine-producing neurons
What is dopamine?
a neurotransmitter that is essential for smooth and coordinated muscle movements
Pathophysiology of Parkinson’s Disease
- Degeneration of dopaminergic (dopamine-producing) neurons
- Cause decrease in dopamine, impaired communication between substantia nigra and the striatum, abnormal activity in the motor circuits of the brain - Overactivity of acetylcholine
- Due to reduction in dopamine, which creates an imbalance between dopamine and acetylcholine
- Causing tremors and rigidity - Lewy bodies which disrupts function of neurons
- Lewy bodies: abnormal protein aggregates, made up of a protein called alpha-synuclein that clumps together inside neurons
- Disrupts function of neurons, induces apoptosis
Cardinal signs of Parkinson’s Disease
- Bradykinesia
- Rigidity
- Tremor at rest
- Postural instability (but occurs at a later stage)
Note: diagnosis requires 2 of 3
Clinical features of Parkinson’s Disease
- Tremor
- present at rest
- decreased by action
- common in arms (pill-rolling movements)
- can affect head, jaw and legs
- can be unilateral or bilateral - Rigidity
- Increase in muscle tone
- “Lead Pipe” rigidity: increased resistance in ROM in all limbs
- “Cog-wheel” rigidity: rigidity combined with resting tremor (limbs move with small, jerky movement) - Bradykinesia
- Less movement (hypokinesia or akinesia)
- Delay in initiation of movement (freezing)
- Slow movements
E.g. loss of facial expression (mask face), blinking, arm swinging - Postural and gait abnormality
- flexed posture (legs, arms, trunk and neck)
- slow, short shuffling gait, “festinant gait” - Others
- mask face
- slow monotonous voice
- micrographia
- drooling
- excessive sweating
-urinary urgency and incontinence
- mental depression
- dementia very rare
What is the onset of Parkinson’s Disease like?
Insidious, then unilateral, then bilateral
Risk factors for Parkinson’s Disease
- Old age
- Highly likely: Monozygotic co-twin (identical) with early-onset PD
- Probable: Positive family history
- Possible: Herbicides, pesticides, heavy metals, proximity to industry, rural residence, well water, repeated head trauma
- Possible protective effect: smoking, caffeine
Non-motor features of Parkinson’s Disease
- loss of sense of smell
- aches and pains
- cognitive impairment: executive functions, memory
- mood disorders, depression, anxiety, panic attacks, hallucinations, sleep disorders
- dribbling of saliva (sialorrhoea)
- autonomic symptoms
How is dopamine synthesised and broken down in the body?
Synthesis:
1. L-typrosine converted to L-dopa, catalysed by enzyme tyrosine hydroxylase
- L-dopa converted to dopamine, catalysed by enzyme DOPA decarboxylase
Breakdown:
1. Dopamine converted to homovanillic acid, catalysed by COMT & MAO)
What are the 4 main classes of drugs used to treat Parkinson’s Disease? (A Major Dose of Laughter)
- Anticholinergic agents
e.g. artane, - MAO-B inhibitors
e.g. selegiline, - Dopamine agonists
e.g. bromocriptine, - Levodopa
e.g. madopar
What is Levodopa and how is it usually administered?
- the precursor to dopamine
- usually administered together with peripheral decarboxylase inhibitors (e.g. Carbidopa, or Levodopa+Carbidopa: Sinemet)
- Most efficacious drug for symptomatic mgmt of both early & late PD
Why does Levodopa have to be prepared together with carbidopa?
To address dopamine production in the periphery, reduces adverse side effects
Carbidopa is a dopa decarboxylase inhibitor that does not cross the blood-brain barrier
Hence it blocks the enzyme in the periphery (outside the brain) but not in the brain.
This prevents the premature conversion of levodopa to dopamine in peripheral tissues, thereby reducing peripheral dopamine levels and the associated side effects
Nursing care for Parkinson’s Disease
- Emotional well-being
- Medication compliance
- PT (exercise regime, mobility, balance, freezing)
- OT (ADL and home safety)
- ST (safe feeding)
- Patient education
Why is dopamine not given directly?
Levodopa can cross the blood-brain barrier into the brain unlike dopamine, converted into dopamine once entered the brain
Side effects of the use of levodopa
ST:
- N&V
- Postural hypotension
LT:
- Motor fluctuations
- Tardive Dyskinesia (10%/year, if you take levodopa for 10 years… definitely will have dyskinesia AND it’s irreversible)—–involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips.
Dose of levodopa should be kept to MINIMUM to achieve good motor function
What are COMT inhibitors and how are they used to treat Parkinson’s Disease?
e.g. Entacapone and Tolcapone
Are only effective when used as an adjunct to levodopa
MOA:
- Inhibit dopamine breakdown
- Blocks enzyme that converts levodopa into inactive form
- More levodopa avail to enter brain
Side effects of the use of COMT inhibitors
- Increase in abnormal movements (dyskinesias)
- Liver dysfunction (tolcapone)
- Nausea, diarrhoea
- Urinary discolouration
- Visual hallucinations
- Daytime drowsiness, sleep disturbances
What are MAO-B inhibitors and how are they used to treat Parkinson’s Disease?
e.g. Selegiline
Efficacious as a symptomatic MONOtherapy & may be used in early stages of PD (START WITH SELEGILINE)
MOA: Inhibit dopamine breakdown, may delay nigral brain cell degeneration (neuroprotective function
Side effects of the use of MAO-B Inhibitors
- Mild nausea
- Dry mouth
- Lightheadedness
- Constipation
- Confusion (can occur in elderly people with PD)
- Hallucinations (can occur in elderly people with PD)
What are anticholinergics and how are they used to treat Parkinson’s Disease?
e.g. Trihexyphenidyl (Artane)
Effective in controlling tremors
Peripherally acting agents may be useful in treatment of sialorrhoea (excessive prod of saliva)
May be used as symptomatic MONOtherapy or as adjunct to levodopa to treat tremors and stiffness in PD
MOA: Inhibitors at cholinergic receptors
Side effects of the use of anticholinergics
(esp in elderly)
- Dry mouth
- Sedation
- Constipation
- Urinary retention
- Delirium & confusion
- Hallucinations
What are dopamine agonists and how are they used to treat Parkinson’s Disease?
E.g. Bromocriptine (Parlodel)
Are efficacious as symptomatic monotherapy, may be used as adjunct to levodopa in treatment of PD
In younger PD pts, start with dopamine agonists then levodopa
MOA: Activate dopamine receptors, act directly on dopamine receptors of brain → reduce symptoms of PD
Note: Antiparkinsonian effects not superior to levodopa
Often used before levodopa to prevent/delay onset of motor complications (dyskinesia)
Side effects of the use of dopamine agonists
Similar to levodopa
- ‘Ergot’ derivative - fibrosis
- Pedal edema
- Somnolence (increased sleepiness) with ropinirole, pramipexole
- Arrhythmia
- Pergolide: restrictive valvular heart disease
*rather mild compared to levodopa
How is early symptomatic Parkinson’s Disease without complications managed?
- May not even need oral meds if coping well
- Recommend PT and exercise regime (stretching, maintain balance and posture)
- Healthy and balanced diet
- Knowledge on disease
- Social support
What are some factors that determine the choice of medication?
- Age (Younger pts to start from dopamine agonists)
- Stage of disease
- Level of activity
- Associated psychological factors
- Associated medical conditions
- Patient factors
