Parkinson's disease

Question 1

Parkinson’s disease : Pathophysiology

Answer 1

1 . Dopaminergic Neuronal Loss:
* Gradual degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc)
* These neurons project to the striatum, a part of the basal ganglia, and play a crucial role in motor control.

2 . Alpha-Synuclein Aggregation:
* Abnormal aggregation of a protein called alpha-synuclein - known as Lewy bodies
* Accumulate in the dopaminergic neurons of the substantia nigra and other regions of the brain

3 . Loss of Dopamine neurotransmitter
* The loss of dopaminergic neurons results in an imbalance in neurotransmitters - low Dopamine levels
* The reduction in dopamine levels contributes to motor dysfunction in Parkinson’s disease

Question 2

Parkinson’s disease : Clinical features

Answer 2

Symptoms are asymmetrical - more affected on one side of the body
Classic triad
1 . Resting tremor - a tremor that is worse at rest, improved with intentional movement
* ‘Unilateral’ , ‘Pinrolling’ tremor

2 . Rigidity resisting passive movement
* ‘Cogwheel’ rigidity

3 . Bradykinesia - slowness of movement
* Micrographia : Handwriting gets smaller
* Shuffling gait : smaller steps when walking
* Difficulty initiating movement
* Hypomimia : Reduced facial movements

4 . General features
* Cognitive impairment and memory issues
* Depression and insomnia
* Loss of smell - ansonia

Question 3

Parkinson’s disease : Diagnosis

Answer 3

1. Clinical diagnosis
2. SPECT imaging

Question 4

Parkinson’s disease : Levodopa

Answer 4

Levodopa + peripheral decarboxylase inhibitor
MOA : synthetic dopamine
Combined with a peripheral decarboxylase inhibitor (e.g., carbidopa benserazide)

• which stops it from being metabolised in the body before it reaches the brain
  Combination therapy:
• Co-beneldopa (levodopa and benserazide)
• Co-careldopa (levodopa and carbidopa)

SE :
1 . Dry mouth, Anorexia, Palpitations
Postural hypotension
2 .End- dose wearing off : Exacerbation of motor sx towards end of dose interval
3 .Peak-dose : Dyskinesia
Dyskinesia refers to abnormal movements associated with excessive motor activity
e.g.

• Dystonia : excessive muscle contraction leads to abnormal postures,
• Chorea : abnormal involuntary movements that can be jerking

Mx of Dyskinesia with Levodopa use : Amantadine is a glutamate antagonist

Question 5

Parkinson’s disease : COMT Inhibitor

Answer 5

COMT(catechol-o-methyltransferase) Inhibitor
e.g. Entacapone

• Entacapone (COMT inhibitor) + Levodopa + Decarboxylase inhibitor

MOA : Entacapone slows break down of levodopa in the brain - extending its duration of action

Question 6

Parkinson’s disease : Dopamine agonist

Answer 6

Dopamine agonist
E.g. Bromocriptine, Cabergoline
MOA : Dopamine agonist, binds and stimulates dopamine receptors
SE :
1. Pulmonary fibrosis
1. Risk of Hallucinations
1. Excess sleepiness

Question 7

Parkinson’s disease : MOAB inhibitor

Answer 7

Monoamine oxidase-B inhibitor
E.g. Selegiline, Rasagiline
MOA : MOAB-inhibitor inhibit breakdown of dopamine in the brain

Question 8

Parkinson’s disease : Management

Answer 8

First line :
1. If > motor sx : Levodopa
2. Otherwise : Dopamine agonist / MOAB inhibitor/COMT inhibitor

Second line :
1. If sx not control despite optimal levodopa : Add adjunct therapy of
* Dopamine agonist / MOAB inhibitor/COMT inhibitor