Parkinson's Disease: Clinical Features and Therapeutics

Question 1

Key features of PDD (instead of PD)

Answer 1

• visuospatial function
• hallucination
• aggression/anxiety
• amnestic, language deficits

Question 2

How to image PD and what is observed?

Answer 2

Fluorodopa (18-F)

Bilateral loss of DA signal

Question 3

Neurotransmitters involved in PD?

Answer 3

DA, ACh, excitatory amino acids (serotonin, NA, adenosine, opioids)

Question 4

Motor symptoms of PD?

Answer 4

• tremor, rigidity, bradykinesia ]- responsive to medication
• loss of postural reflexes
• shuffling gait
• freezing episodes
• hypomimia (masked facies)

Question 5

Non-motor symptoms of PD?

Answer 5

• neuropsychiatric: hallucinations, confusion, depression (50%)
• autonomic: bladder, bowel, hypotension
• sleep: restless legs, REM sleep behaviour disorders

Question 6

Trend of PD symptoms over time?

Answer 6

Get worse

Early stages (motor) -> Late stages (non-motor)

Question 7

PD management (NICE Guidelines)?

Answer 7

• physiotherapy
• occupational therapy
• speech and language therapist
• specialist nursing care
• exercise/movement (e.g. yoga, tai chi)
• pharmacological

Question 8

Overview of TYPES of pharmacological management of PD?

Answer 8

• indirect agonists (L-DOPA, Amantadine)
• direct DA agonists (apomorphin, ropinirole)
• enzyme blockers (sinemet, selegiline, entacapone)
• anticholinergics
• cell therapy (foetal cell transplant)
• treat secondary symptoms

Question 9

Indirect DA agonists in PD?

Answer 9

• L-DOPA]- gold standard, given w/ enzyme blockers

- amantadine (increased DA release with unknown MOA)

Question 10

L-DOPA absorption features?

Answer 10

Protein load (in food) may interfere w/ absorption because L-DOPA also relies on amino acid tranporters

Question 11

L-DOPA response features?

Answer 11

Benefits wear off.

Requires surviving neurons. As PD progresses, L-DOPA is less effective

Low dose: no response

High dose: diskinesia

Question 12

Advice concerning L-DOPA and young pts?

Answer 12

Young onset PD: give DA agonist (keep L-DOPA for future use)

Question 13

Side effects of DA agonists?

Answer 13

• N&V
• gambling
• hypotension
• somnolence and “sleep attacls”

Question 14

When to use DA agonists?

Answer 14

Early stage PD, to delay the introduction of L-DOPA

Late stage: to reduce the dose of L-DOPA

(NB: if the effect wanes, add L-DOPA)

Question 15

Examples and MOA of enzyme blockers for PD?

Answer 15

• Sinemet: DOPA-decarboxylase inhibitor
• Selegiline: MAO inhibitor
• Entacapone: COMT inhibitor

Question 16

Overview of cell therapy for PD?

Answer 16

Foetal Cell Transplant: extract DA neurons from aborted foetuses and transplant into striatum

Question 17

Overview of treating secondary symptoms in PD?

Answer 17

• ANS features: reduce BP (fluids/salt/fludrocortisone); bladder freq/urgency (desmopressin); drooling (anticholinergics)
• cognitive (ID triggers for depression/anxiety/dementia/hallucinations)
• sleep (avoid drugs, treat depression, sleep hygiene)

[NB: be aware of carer fatigue]