IC16 - Parkinson's Disease Flashcards
What are the 4 characteristic features of Parksion disease?
- Tremor at rest
- Rigidity
- Akinesia
- Postural instability
How is diagnosis made for Parkinson’s disease?
Tremor, Rigidity, Akinesia/ bradykinesia
What are the features of the idiopathic PD at initial presentation?
- Asymmetric
- No postural instability
- No autonomic dysfunction
List 2 drugs that patients with idiopathic PD response to at initial presentation.
- Levodopa
- Apomorphine
What are the two neuroimaging techniques that can be used for differential diagnosis?
- MRI
- SPECT, DaT (differentiate essential tremors and other non-dopamine deficiency etiologies)
What are symptoms associated with disease progression of idiopathic PD?
- Unable to perform basic ADLs
- Choking
- Pneumonia
- Falls
What is the pathophysiology behind PD?
- Loss of dopaminergic neurons in substantia nigra
- Misfolded alpha-synuclein formation of Lewy body –> long term expression of alpha-synuclein decrease DA neurotransmission and mediates mitochondrial failure –> neuroinflammation –> activation of microglia
What are the non-motor symptoms of Parkinson disease?
- Cognitive impairments
- Psychiatric symptoms
- Sleep disorders
- Autonomic dysfunction
- Others: fatigue
What are the features of early/ young onset PD?
- < cognitive decline
- earlier motor complications
- Dystonia
What is the preferred agent early/ young onset PD?
Dopamine agonists
What are the two purpose of pharmacological treatments for PD?
- Increase central dopamine, dopaminergic transmission
- Correct imbalance in other pathways
What symptoms is levodopa most effective in treating?
bradykinesia and rigidity
Why is dopamine not recommended in treatment of PD?
It does not cross BBB
What are the side effects of levodopa?
N/V
Hypotension (orhtostatic)
Dorwsiness, sudden sleep onset
Hallucinations, psychosis
Dyskinesias
What is one important counselling point for patients on levodopa?
Eat on empty stomach or with light snacks if cannot tolerate drug S/E.
Absorption of levodopa ________ with high fat or high protein meals.
decreases
What drug is levodopa often give with?
- DOPA decarboxylase inhibitors (benserazide, carbidopa)
DCI ____ cross BBB.
does not
What is the dose of DCI needed to be administered with Levodopa?
75 to 100mg (to saturate dopa)
What is the on-off phenomenon?
Unpredictable response to levodopa and is not related to dose or dosing interval
What is the wearing off phenomenon?
Effects wanes off before end of doing interval
What can be done to manage the wearing off effects?
- Modify times of administration
- Replace with modified release preparations at appropriate time
_____ is an motor complication of levodopa.
Dyskinesia
How can dyskinesia for PD be managed?
- Amantadine
- Replace with specific doses with modified-release levodopa
How can motor complications of levodopa be managed?
- Adjust levodopa dose
- Offer dopamine agonist, MAOB-i, or catechol-O-methyl transferase inhibitors as adjunct
Sustained release form levodopa has ___ bioavailability.
Lower
How can dose adjustment be made when switching between IR and CR levodopa?
IR to CR: increase dose
CR to IR: decrease dose
What is the sustained release forms useful for?
Decrease stiffness
What are some counselling points pertaining to sustained released levodopa?
Do not crush or open capsule
List four DDI with Levodopa.
- Pyridoxine
- Iron
- Protein
- Dopamine antagonists
What is the antiemetic of choice in PD?
Domperidone
What are some ergot derivatives dopamine agonists?
Bromocriptine
Cabergoline
Pergolide
What are some non-ergot derivatives dopamine agonists?
- Ropinirole
- Pramipexole
- Rotigotine
- Apomorphine
Ropinirole is ______ by liver.
metabolised
Dose adjustment is needed for ____ impaired patients for Pramipexole.
Renal (excreted unchanged in urine)
Dopamine agonists have ____ t1/2 and duration of action than levodopa.
longer
What are the peripheral dopaminergic A/E of dopamine agonists?
- N/V
- Orthostatic hypotension
- Leg Oedema
What are the central dopaminergic A/E of dopamine agonists?
- Hallucination
- Somnolence, day-time sleepiness
- Compulsive behaviors
What are the non-dopaminergic A/E of dopamine agonists?
- Fibrosis
- Valvular heart disease
Pertains more for ergot derivatives
What is the MAOi type that have central effects and is used for PD?
MAO-B
List two MAOi medications used for PD.
Selegiline
Rasagiline
Why does selegiline and rasagiline have long duration of action?
Irreversible enzymes inhibitors
MAOB inhibitors are useful in _____ stages of PD as monotherapy.
Early
Which of the MAOB inhibitors is metabolized to amphetamines that are stimulating?
Selegiline
List 7 DDI associated with MAOB-inhibitors?
- SSRIs, SNRIs, TCAs
- Pethidine, tramadol
- Linezolid
- Dextromethorphan
- Dopamine
- Sympathomimetics
- MAOi
What is the most important DFI associated with MAOi?
Food containing tyramine . e.g. cheese or fermented products
What are two examples of COMT?
- Entacapone
- Tolcapone
COMT must be given with ______.
Levodopa
What are the DDI associated with Entacapone?
- Iron. Ca2+
- Concurrent nonselective MAOi (but safe with MAO- Bi, caution with selective MAO-Ai)
- Catecholamine drug
- Enhance anticoagulant effect of warfarin
List 2 side effects of entacapone.
Diarrhoea, urine discolouration (orange)
Which special population should use entacapone with caution?
Hepatic impairment
______ may occur when entacapone is initiated.
Dyskinesia
What is the main purpose of anticholinergic in PD?
Tremor control
What is the use of amantadine?
NMDA anatagonist –> prevent glutamate from binding to NMDA receptor and subsequent cell death
What drug should not be given with amanadine?
Memantine
Which group should use amatadine with caution?
Renal impaired
NMDA antagonists can be _____.
stimulating
What are the six adverse effects of NMDA antagonists?
Nausea, light-headedness, insomnia, confusion, hallucinations, livedo reticularis
Describe drug-induced parkinsonism.
- Bilateral and reversible symptoms
- Acute/ subacute onset
- Uncommon to have rest tremors
- Will have normal uptake of presynaptic markers and reduced uptake of dopamine receptor ligands
List 5 drugs that can cause drug induced parkisonism.
Dopamine D2 receptor blockers
Dopamine depletes
Calcium channel antagonists
Atypical antipsychotics
Antiepileptic
What is the management of drug-induced parkinsonism?
- Anticholinergics
- Amantadine