Parkinson's Disease

Question 1

Levodopa

Answer 1

• Levodopa is used as a shuttle to transport precursor to dopamine across the BBB.
• The precursors are converted to dopamine, which is stored in the surviving nigrostratial nerve terminals.
• It is administered with carbidopa or benzerazide to block peripheral conversion of levodopa to dopamine.
• Adverse effects include nausea, vomiting, postural hypotension, involuntary movements, restlessness and cardiac arrhythmias.

Question 2

Carbidopa

Answer 2

• Administered with levodopa to block peripheral conversion of levodopa to dopamine.
• Metabolism of L-Dopa in GI tract and peripheral tissues is decreased, therefor increasing L-Dopa levels in CNS.
• Carbidopa is highly emetogenic as it stimulates the CTZ.
• Side effects include nausea, abdo pain, constipation, orthostatic hypotension, dizziness, sedation, confusion, and hallucination.

Question 3

Benzerazide

Answer 3

• Blocks peripheral conversion of levodopa to dopamine. Combined with levodopa.

Question 4

Pramipexole or Bromocriptine

Answer 4

• Dopamine agonist.
• Used to delay the onset of L-Dopa therapy and prolong the effective treatment period in patients with deteriorating response.
• Also can be given to those who cannot tolerate L-Dopa.
• Crosses the BBB.
• Potential side effects include somnolence, dyskinesia, nausea, vomiting, orthostatic hypotension, nightmares, hallucination, confusion and dizziness.

Question 5

What is the difference between pramipexole and bromocriptine?

Answer 5

• Bromocriptine is an ergot, so it also targets serotonin receptors.
• Pramipexole is a non-ergot so it does not target serotonin receptors.

Question 6

Entacapone

Answer 6

• COMT inhibitor.
• Inhibits degradation of dopamine.
• Increases the duration of effect of levodopa dose. Can increase peak levels of levodopa, and should be taken with carbidopa/levodopa.
• Can reduce the required dosage of levodopa/carbidopa.

Question 7

Selegiline

Answer 7

• Selective MAOI (MAO-B).
• Reduces degradation of synaptic dopamine and prolonged dopaminergic activity.
• When used as a mono therapy delays the need for L-Dopa by an average of nine months.
• Possible side effects includes nausea, dizziness, abdominal pain, confusion, and exacerbation of L-dopa side effects.

Question 8

Benztropine

Answer 8

• Anticholinergic.
• Used in patients to reduce the side effects of antipsychotic medications. Antipsychotic medications can lead to pseudo-parkinsonism and dystonia.
• Also a second line drug for the treatment of Parkinson’s. Improves tremor but not rigidity or bradykinesia.

Question 9

Amantadine

Answer 9

• Inhibits dopamine reuptake and blocks ACh and glutamate receptors.
• Currently being used to reduce involuntary spasmodic twitching movements. Was used as an anti-viral, now used as an antiparkinsonian drug.
• Effect on Parkinson’s not understood.
• Amantadine is cautioned in renal failure patients and has a narrow TI.
• Side effects include nausea, dizziness, confusion, hallucinations, nightmares, dry mouth, peripheral oedema and livedo reticularis.

Question 10

What is Parkinson’s disease?

Answer 10

• Parkinson’s is a degenerative brain disorder affecting movement, and it is characterized by EPSE symptoms.
• The cause is a deficiency of dopamine, but how this happens is unknown. It is a progressive and incurable disease, and severely affects quality of life.

Question 11

What are the major symptoms of Parkinson’s Disease?

Answer 11

TRAP
- Tremor
- Rigidity
- Akinesia and bradykinesia
- Postural instability
and gait instability (shuffling feet).

Question 12

What are the non-motor related conditions associated with PD?

Answer 12

• Depression and Anxiety
• Cognitive disorders such as dementia
• Sleep abnormalities
• Autonomic dysfunction e.g. constipation
• Sensory e.g. olfactory dysfunction
• Fatigue and weight loss