Parkinson Disease Flashcards
What is PD?
It is a disease of unknown etiology characterised by tremor, rigidity, bradykinesia and postural and gait abnormalities
When do PD occur?
Middle to late life (*incidence increases with age - 2-10% diagnosed at 50)
- after 50, common in 70-80s
Which gender has a higher chance of getting PD?
Both sex have the same incidence
What is the onset of PD?
Insidious/gradual and progress from unilateral to bilateral for idiopathic PD
What are the cardinal signs of PD?
- Bradykinesia
- less movement = hypokinesia/akinesia
- delay in initiation of movements = freezing
- once start = slow movements (bradykinesia)
- e.g. loss of facial expression, blinking, arm swinging
- Tremor
- primarily at rest, decrease during activity and increase during stress
- 4-6Hz
- common in arms (pill-rolling tremor on hands)
- can affect head, jaw & legs
- can be unilateral/bilateral
- Rigidity
- increase muscle tone
- affect both flexor and extensor muscle groups (but flexors are affected more)
- known as “lead pipe” rigidity (increase resistance in whole ROM): muscle resistance
- rigidity with resting tremor = cogwheel phenomenon (stop and go sensation due to alternating resistance and relaxation)
What are the other signs of PD?
- Postural and gait abnormality
A) flexed/stopped posture (legs, arm, trunk and neck)
B) slow, short, shuffling gait (“festinant gait”/“chasing their central of gravity”)
C) doesn’t stop upon propulsion/retropulsion - Masked/emotionless face
- Decreased arm swing
- Hypovolemic speech (slow,motionless voice)
- Swallowing difficulty
- Micrographia - handwriting that progressively gets smaller
- Drooling of saliva
- Excessive sweating
- Urinary problems/urgency/incontinence (start hesitancy)
- Mental depression
- Dementia (rare)
- Postural instability at late stage
What is the pathphysiology behind PD?
Loss of neurons -> decrease DA in striatum -> imbalance DA (inhibitory NT) and ACh (excitatory NT) -> extra pyramidal tract impairment (loss of inhibition by direct pathway and stimulation of indirect pathway) -> Parkinsonism
What are the ways that pharm therapy can help with PD motor symptoms?
- Increase synthesis of DA
- L tyrosine synthesises to L dopa via tyrosine hydroxylase (rate limiting enzyme in DA production)
- L dopa then synthesises to DA via DOPA decarboxylase
- Decrease breakdown of DA
- DA is broken down into homovanillic acid via catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)
- D1 & D2 receptor agonist
What is the gold standard for PD treatment?
Levodopa
How does levodopa help with PD?
It increases DA synthesis by increasing precursor to increase dopaminergic tone
What are the SE of levodopa?
Short term:
1. Nausea
2. Vomiting
3. Postural hypotension
Long term:
1. Motor fluctuations (feel like sometimes med is working and sometimes not working; may also feel worsening of non-motor symptoms - anxiety & pain)
2. Dyskinesia (most worrying AE)
- due to continuous supply of DA = post synaptic plasticity disrupted = disruption in D1 & D2 receptor = more likely to get dyskinesia
- increase by 10% each year pt takes levodopa (even after discontinuation, dyskinesia will continue)
What is added into levodopa to prevent SE due to excessive DA in PNS?
Peripheral decarboxylase inhibitors - carbidopa
Levodopa + carbidopa = sinemet
Without peripheral decarboxylase inhibitors, levodopa can convert to DA even in periphery but cannot enter the brain as it is not easy for DA to pass through the BBB
What medication can be used in early and late stage of PD and is the most efficacious?
Levodopa
What is the implication for levodopa?
Keep dosage to minimum to achieve good motor function (want to avoid dyskinesia)
Name the medications that fall under COMT inhibitors
Entacapone & Tolacapone
