Parkinsons Flashcards
(36 cards)
What dopamine receptors are of most importance in Parkinsons disease?
D1 and D2
What is the pathology of parkinsons disease?
Depigmentation and neuronal loss of dopaminergic neurons in S.Nigra Lewy bodies (composed of alpha synnuclein and ubiquitin, but do not contain tau protein) in the S. Nigra
What is Braak staging?
Progression of pathological stages in PD
Stage 1-2: usually pre-symptomatic with changes in medulla and olfactory bulb leading to anosmia, REM sleep behavioural disturbance
Stage 3-4: changes involve S.Nigra and midbrain, manifests as parkinsons
Stage 5-6: involves cortex of temporal, frontal lobes, leads to neuropsychiatric and congnitive symptoms
Risk factors for parkinsons
Older age
Family history
Genetic syndromes
Possible: Depression, head injury, exposure to pesticides
Genetic syndromes of parkinsons disesase
Most cases sporadic
Glucocerebrosidase gene
SNCA gene
PARK 1 and 2 mutations in alpha synuclein gene
Protective factors of parkinsons
Smoking
Caffine
Possible ibuprofen and physical activity
Main motor features of PD
Tremor - pinrolling, 4Hz, starts unilaterally and spreads contralaterally
Akinesia - small amplitude, slow movements
Decrementing - as tasks is performed over and over speed and amplitude decrease
Rigidity
Postural instability and gait freezing
Main non-motor features of PD
Cognitive dysfunction and dementia Psychosis and hallucinations (typically visual) Mood disorder Sleep disorder (REM sleep disorder) Autonomic dysfunction
Differentials for parkinsonism
Parkinsons disease Dementia with lewy bodies Corticobasal degeneration Multiple systems atrophy Progressive supranuclear palsy Drug induced Normal pressure hydrocephalus
What is the prevalence of dementia in parkinsons?
40%
How do you differentiate between Dementia with Lewy bodies and parkinsons disease dementia?
PDD if dementia develops after 1 year of parkinsons symptoms
If dementia starts within 1 year of parkinsonism can be considered dementia with lewy bodies
Features that suggest an alternative diagnosis for parkinsonism then PD
Early falls Early and severe autonomic dysfunction Cerebellar signs Vertical saccadic eye movements Apraxia/agnosia Exposure to neuroleptics Symmetrical disease
Main drug classes used in treatment of PD
Levodopa - always combined with a peripheral decarboxylase inhibitor to prevent peripheral conversion of dopamine in liver or systemic circulation Dopamine agonists MAO-B inhibitors Anti-cholinergics Amantadine COMT inhibitors
Examples of levodopa drugs
Levodopa + carbidopa = sinemet
Levodpa + benserazide = Madopar
Examples of dopamine agonists
Bromocriptine, pergolide, pramipexole, Ropinirole
Apomorphine has dopamine agonist activity
Main concerning ADR of dopamine agonist
Impulse control disorder
Example of MAO-B inhibitor
Seligiline, Rasagiline
Example of anti-cholinergic
Benztropine, Trihexyphenidyl
Example of COMT inhibitor
Tolcapone, entacapone
Main principles of treatment in parkinsons
Start Levodopa early (most effective)
In young patients can trial dopamine agonist first before levodopa
MAOI-B inhibitors can be considered for those with mild motor symptoms as monotherapy
Early referral for DBS when L-Dopa effect wears off
What is the on-off phenomenum
loss of dopamine storage capacity leads to shorter duration of action levodopa as disease progresses
On is periods with good effect from medications, off is periods of worsening parkinsonism due to wearing off of medications
What are dyskinesias in parkinsons
the effect seen at the peak concentration of the dopamine drug leading to involuntary abnormal movements
Treatment options for on-off and treatment related dyskinesias
Best option is to fractionate L-dopa - give lower doses more frequently
other options: add COMT inhibitor, reduce levodopa doses and add dopamine agonist, amantadine
In severe cases proceed to DBS
Action of COMT inhibitors
Block COMT enzyme which decreases peripheral conversion of Levodopa to an inactive metabolite, and blocks central conversion of Dopamine to inactive metabolite
