Parkinson's disease Flashcards
Pathophysiology of parkinson’s
- lewy body protein deposits of alpha-synuclein
- loss of dopaminergic neurons form pars compacta of substantia nigra of the midbrain
- degeneration also occurs in other basal ganglia nuclei
diagnosis
- clinical diagnosis by recognizing physical signs and symptoms
- DAT imaging to assess extent of neuron loss
early onset Parkinsons
strongly linked to genetic factors
- PARK 1 gene - codes for alpha synuclein protein
- inherited AD
- rare but major lewy body protein - PARK 2 - codes for Parkin protein
- Autosomal recessive
- responsible for most cases of juvenile PD
Epidemiology
around twice as common in men
mean age of diagnosis is 65 years
definition of Parkinson’s
Parkinson’s disease is a progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra.. This results in a classic triad of features: bradykinesia, tremor and rigidity. The symptoms of Parkinson’s disease are characteristically asymmetrical.
Clinical features of parkinson’s
patients develop a variety of non specific symptoms prior to motor symptoms
- anaemia (present in 90%)
- Depression + Anxiety
- Aches and pains
- REM sleep behavior disorder
- Autonomic features - urinary urgency, postural hypotension
- Restless leg syndrome
Bradykinesia
- slowing down of movements - progressive fatiguing and reduced amplitude
- difficulty initiating movements
- facial immobility : mask like
- Serpentine stare - reduced frequency of spontaneous blinking - Short shuffling steps with reduced arm movements
Tremor
- presenting symptom in 70% of patients
- unilateral initially spreading to leg
- most marked at rest - reduces in motion
- worse whens stressed or tired
- typically ‘pin rolling’ ie. the thumb and index finger
Rigidity
- lead pipe - stiffnes son passive limb movements
2. cogwheel rigiity - stiffness occurs with tremor
Postural and gait changes
- stooped posture is characteristic
2. shuffling gait - slow turns, reduced stride length and reduced arm swing
Speech and swallowing
- quiet, indistinct flat voice
- drooling
- swallowing difficulty - increased risk of aspirayion pneumonia
Cognitive and psychiatric changes
- cognitive impairment and dementia in 80% of later stages
- visual hallucinations and psychosis
- depression and anxiety are common
Drug-induced parkinsonism
- motor symptoms are generally rapid onset and bilateral
- rigidity and rest tremor are uncommon
Names of anti-Parkinson’s medication
- Levadopa
- Dopamine receptor agonist - Bromocriptine/Ropinirole
- Monoamine Oxidase - B inhibitors
- Amantadine
- Catechol-O-Methyl Transferase inhibitors
- Anti muscarinics
Levodopa ( mechanism of action )
- a precursor of dopamine which is used as a dopamine supplement
- precursor needs to be used because dopamine itself cannot cross the blood-brain barrier
- Administered alongside ‘decarboxylase inhibitor’ ( carbidopa) to inhibit decaboxylase enzyme from converting Ldopa into dopaine peripherally
Positive effects of Levadopa
- improved motor symptoms
- improves activities of daily living
- fewer spec adverse side effects - excess sleepiness/hallucinations etc
Adverse effects of Levadopa
- ‘wearing off effect’ no longer effective in stimulating dopamine terminals// less effective overtime
- dyskinesia ( invol writhing movements )
- Dry mouth
- Anorexia
- Palpitations
- Drowsiness
MOAB inibitors ( mechanism of actions )
- inhibits monoamine oxidase enzyme which breaks down dopamine
- e,g, Selegiline
Catechol-O-Methyl Transferase
- Entacapone, tolcapone
- COMT is an enzyme which transfers methyl group onto dopamine and inactivates it
- this enzyme is inhibited and so more dopamine is avaliable
Dopamine receptor agonist
- Bromoccriptine/ Ropinirole
Dopamine receptor agonist - Adverse side effects
- Pulmonary + Cardiac fibrosis ( obtain ECG, ECHO, ESR and Chest x RAY prior to starting)
- impulse control disorder - complete inhibition
- more likely to cause hallucinations
Anti muscarinics
- block cholinergic receptors
- now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson’s disease
- help tremor and rigidity
e. g. procyclidine, benzotropine
management of parkinson’s
- first-line treatment:
- if the motor symptoms are affecting the patient’s quality of life: levodopa - if the motor symptoms are not affecting the patient’s quality of life:
dopamine agonist (non-ergot derived),
levodopa
monoamine oxidase B (MAO‑B) inhibitor - If a patient continues to have symptoms despite optimal levodopa treatment or has developed dyskinesia then NICE recommend the addition of a
- dopamine agonist,
- MAO‑B inhibitor
- catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct
Amantadine
- mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses
- side-effects include
ataxia
slurred speech
confusion
dizziness and livedo reticularis
