Parkinson's disease Flashcards
Define Parkinson’s disease
Progressive neurological affect the motor functions
What are the motor symptoms of PD?
Tremor: resting tremors
Rigidity: initial stiffness, slowing of gait
Akinesia/bradykinesia: begins on one side
Postural instability: stooped posture
What are some of the non-motor symptoms of PD
Depression Dementia Psychosis Sleep disorder Urinary dysfunction Dysphasia or sialorrhea Orthostatic hypotension
How would the diagnosis of PD happen?
Clinical criteria of primarily motor symptoms. Exclude neurological damage, hx of provoking drugs, toxins, infections and other similar diseases
What are the first-line drugs used to treat PD? Explain the mechanism
- Levodopa: a dopamine precursor that can bypass BBB
- Carbidopa: Dopa-decarboxylase inhibitor
- Entacapone: COMT inhibitor
What are the first-line drugs used to treat PD? Explain the mechanism
- Levodopa: a dopamine precursor that can bypass BBB, increasing lack of dopamine
- Carbidopa: Dopa-decarboxylase (DDC) inhibitor, blocks Levodopa from being used in periphery
- Entacapone: COMT inhibitor, blocks Levodopa from being metabolised in periphery
Why would you use a combination to treat PD?
synergistic effect
What are the combination drug therapies used in PD Tx?
Levodopa + carbidopa
levodopa + entacapone
levodopa + carbidopa + entacapone
What are some of the non-pharmacological management techniques used in treatment of PD?
- exercise: balance training, physiotherapy
- balanced nutrition
- education, counselling, social support
- carer support
- speech and language therapy, PT
What signs can be used for a differential diagnosis?
- essential tremor (affect 3% of population) producing bilateral moving tremor
- drug induced parkinsonism
SINEMET and KINSON are combinations of which drugs?
Carbidopa and Levodopa
Levodopa can slow progression of PD symptoms, reduces mortality and is well tolerated. What are the drawbacks of the drug?
- limited impact on gait and postural instability
- long-term tx complicated by developing motor complications
- risk of aggravating hallucinations, cognitive impairment and orthostatic hypotension
What is the optimal dose for levodopa initially? How many formulations are there for levodopa?
- 3x per day intially - will increase later on
- 4 formulations (immediate release, controlled release, dispersible tablets, intestinal gel)
What are some side effects of Levodopa
- nausea
- vomiting
- postural hypotension
- sedation
- vivid dreams/hallucinations
- psychosis
What motor complications are associated with Levodopa?
- wearing off
- delayed on
- fluctuations with on/off periods
- dyskinesia (excessive movements from excess dopamine)
Dopamine agonists are another group of drugs that could be used in PD treatment. What is the mode of action?
Directly stimulate dopaminergic receptors in the brain providing a modest effect (compared to Levodopa)
What are the advantages to using dopamine agonists? What
- significant reduction in motor complications
- longer half-life and duration of effect than Levodopa
- ## less frequent administration
What are the advantages to using dopamine agonists? What
- significant reduction in motor complications
- longer half-life and duration of effect than Levodopa
- less frequent administration
- alt. first-line for younger sufferers
Non-ergot dopamine agonists are safer than ergot derivatives. Give examples of DA durgs
- Pramipexole(O, OMR)
- Ropinirole (O)
- Rotigotine (TD patch)
- Apomorphine (parenteral)
What are some of the side effects of DA drugs?
fatigue, nausea, leg oedema, constipation. Others: dizziness, drowsiness, hallucinations. sudden sleep attacks, impulse control disorder.
MAO-B inhibitors are less commonly used to treat PD. Explain the MOA and provide an example drug
- Blocks monoamine oxidase enzymes that degrade dopamine in basal ganglia
- Rasagiline and Selegiline
Explain the rationale of Anticholinergics for PD thx and provide examples
Rationale: dopamine depletion results in overactivity of cholinergic activity so use anti-Ach to combat over excitation
- Benzhexol
- Benztropine
What are some of the side effects of DA drugs? What AEs are specific to ergot derivatives?
impulse control disorders, fatigue, nausea, leg oedema, constipation. Others: dizziness, drowsiness, hallucinations, sudden sleep attacks,
Ergot: Fibrotic reactions and cardiac valve disease
COMT inhibitors may be used in adjunct thx. with levodopa. What is the benefit of the COMT inhibitor? what are the downsides of increasing dosage down the line?
- used mostly in advanced PD and motor complications
- increased “on” times by 1-2 hrs
- reduced “off” time
- selective and reversible
- well tolerated
- Increase freq/severity of dyskinesia, hallucinations, Vs
What are some of the other ways to aid in PD management of symptoms?
- speech thx
- music thx
- counselling
- anti-depressants
- dance thx
