Parkinsons disease Flashcards
What is Parkinsons disease?
Neurodegenerative disease resulting from loss of dopaminergic neurones in the substantia nigra
When does Parkinson’s become clinically apparent?
Not until >,50% of dopaminergic cell activity has been lost
What is Parkinsonism?
Umbrella term for the clinical syndrome involving bradykinesia plus at least 1 of tremor, rigidity, +/or postural instability.
Excluding PD, list 5 causes of Parkinsonism
Drug-induced parkinsonism
Cerebrovascular disease
Lewy body dementia
Multiple system atrophy
Progressive supranuclear palsy.
Name 2 drugs that can cause Parkinsonism
Antipsychotics
Metoclopramide
What triad of symptoms characterises Parkinson’s?
Resting tremor
Bradykinesia
Rigidity
What are the aetiological causes of Parkinson’s?
Idiopathic (most common)
Genetic (minority)
Describe epidemiology of Parkinsons
Mean age ~65y
M > F
Describe 3 features of bradykinesia in Parkinsons disease
Short, shuffling steps + reduced arm swing
Difficulty + slowness initiating movement
Poverty of movement (hypokinesia)
Describe the tremor in PD
Most marked at rest, 3-5 Hz
Worse when stressed or tired
Improves with voluntary movement/ action/ mental concentration
“Pill rolling”: thumb + index finger
Usually asymmetrical
Describe the rigidity in Parkinson’s disease
Lead-pipe: constant resistance felt when limb is passively flexed in the presence of hypertonia without tremor
OR
Cogwheel: regular intermittent relaxation of tension felt when limb is passively flexed in the presence of tremor + hypertonia.
List 6 autonomic/ non-motor symptoms seen in Parkinsons
Postural hypotension + falls
Constipation
Urinary frequency/ urgency
Dribbling of saliva
Sexual dysfunction
Anosmia
How can you screen for postural instability?
Pull test
Tendency to fall backwards after a sharp pull from the examiner.
Give 2 ways in which energy/ sleep if affected in Parkinson’s
REM sleep behaviour disorder
Fatigue
List 5 signs of Parkinsons
Mask like facies/ Hypomimia Flexed posture Quiet voice Smaller hand writing (micrographia) Drooling of saliva
Describe the gait in PD
Stooped Shuffling Small-stepped gait Reduced arm swing Difficulty initiating walking
What 2 features describe the onset of PD?
INSIDIOUS
Unilateral
What is meant by the terms “on” and “off” in relation to a PD patient?
ON: moving well, may have dyskinesias
OFF: stiff + bradykinetic
What psychological pathologies may arise with PD?
Depression
Dementia
Psychosis
How does drug-induced Parkinsonism differ?
Motor Sx are usually rapid onset + bilateral
Rigidity + rest tremor uncommon
Describe diagnosis of PD
Refer urgently to a specialist
Clinical dx
Response to dopaminergic therapy is supportive
What neuroimaging investigation can be used to differentiate PD from essential tremor?
DaTSCAN: single photon emission computed tomography (SPECT) using
123 I‑FP‑CIT
List 5 drug classes for managing PD
Levodopa + dopa-decarboxylase inhibitor
Dopamine agonists
MAO-B inhibitors
COMT inhibitors
Anticholinergics
What is the first line treatment if the motor symptoms are affecting the patient’s quality of life in PD?
Levodopa + carbidopa
What is the first line treatment if the motor symptoms are NOT affecting the patient’s quality of life in PD?
Dopamine agonist (non-ergot derived)
or
Levodopa
or
Monoamine oxidase B (MAO‑B) inhibitor
Why must a dopamine decarboxylase inhibitor be given with Levodopa?
Prevents peripheral metabolism of levodopa to dopamine outside of the brain + hence reduces side effects
Give 3 advantages of Levodopa treatment
Most effective Tx for motor Sx
More improvement in ADLs
Fewer adverse effects e.g. excessive sleepiness, hallucinations, + impulse control disorders
Give a disadvantage of Levodopa treatment
More motor complications e.g. dyskinesia
List 5 common adverse effects of Levodopa
Dry mouth
Anorexia
Palpitations
Postural hypotension
Psychosis
Which adverse effects are due to the difficulty in achieving a steady dose of levodopa?
End-of-dose wearing off: Sx worsen towards end of dosage interval= decline of motor activity
On-off phenomena: large variation in motor performance (normal function during on vs weakness + reduced mobility during off)
Dyskinesias at peak dose: dystonia, chorea + athetosis
If a patient acutely cannot take levodopa orally, what must be given? Why?
Dopamine agonist patch as rescue medication
To prevent acute dystonia
Name 2 monoamine oxidase B inhibitors
Selegiline
Rasagiline
Give 2 advantages of MAO B inhbitors
Less motor complications
Less adverse effects e.g. excessive sleepiness, hallucinations, + impulse control disorders
Give a disadvantage of MAO B inhibitors
Less improvement in motor Sx + daily functioning
What is the MOA of MAO-B inhibitors?
Inhibit breakdown of dopamine secreted by the dopaminergic neurons
Name 2 dopamine agonists (non-ergot)
Ropinirole
Pramipexole
Give an advantage of dopamine agonists (non ergot)
Less motor complications
Give 2 disadvantages of dopamine agonists (non ergot)
Less improvement in motor Sx + daily functioning
More adverse effects e.g. excessive sleepiness, hallucinations, + impulse control disorders
Why are ergot dopamine agonists no longer used first line? Name 2
Risk of pulmonary, retroperitoneal + cardiac fibrosis with long-term use and need for additional monitoring.
Cabergoline, Bromocriptine
If ergot derived dopamine receptor agonists are used in PD, what must be performed?
Echocardiogram, ESR, creatinine + CXR obtained prior to Tx
Patients should be closely monitored
Which drugs can be used as adjuncts to levodopa if a patient continues to have symptoms or has developed dyskinesia?
Dopamine agonist
MAO‑B inhibitor
Catechol‑O‑methyl transferase (COMT) inhibitor
Amantadine
Name 2 COMT inhibitors
Entacapone
Opicapone
What is the mechanism of action of COMT inhibitors?
prevent peripheral degradation of levodopa, allowing a higher concentration to cross the BBB
hence used as adjunct
What are the benefits of adjunctive COMT in PD?
More improvement in motor Sx + daily functioning
Lower risk of hallucinations than other drug classes.
What are the disadvantages of adjunctive COMT in PD?
More adverse effects such as excessive sleepiness + impulse control disorders
What is the probable mechanism of action of amantidine?
Increases dopamine release
Inhibits uptake at dopaminergic synapses
List 6 side effects of Amantadine
Confusion
Constipation
Dizziness
Dry mouth
Slurred speech
Livedo reticularis
What complications can arise due to missing/ not absorbing Parkinson’s medication?
Acute akinesia
Neuroleptic Malignant Syndrome
Give 3 factors increasing risk for impulse control disorders
Dopamine agonist therapy
Hx of previous impulsive behaviours
Hx of alcohol consumption and/or smoking
What drug can be used to manage drooling in Parkinson’s?
Glycopyrronium bromide
Describe management of excessive daytime sleepiness in PD
No driving
Medication adjustment
Modafinil if alternative strategies fail.
Describe management of orthostatic hypotension in PD
Medication review
If Sx persist: Midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance)
What class of drugs can be used to treat drug-induced parkinsonism? What do they do? Give 2 examples
Anti-muscarinics, block cholinergic receptors
Help reduce tremor + rigidity
Procyclidine
Benzotropine
