Pharmacology and Treatment of Basal Ganglia Disorders

Question 1

Parkinson’s Disease:
What occurs neurologically in the 6 stages of it?

What are the main symptoms?

Why does it cause HYPOkinesia?

Why does it cause Rigidity and Tremor?

What can cause it?

What is used to diagnose it?

What is the difference in movement with Parkinson’s and Huntington’s?

Answer 1

• o Stage 1-2; early degeneration, sleep & olfaction disturbance
  o Stage 3-4; loss of 50-80* nigrostriatal neurons, motor symptoms begin
  o Stage 5-6; presence of Lewy Bodies, psychiatric symptoms begin
• Rigidity, Resting Tremor, HYPOkinesia, Bradykinesia, Psychiatric symptoms
• Due to loss of Dopaminergic neurons (less inhibition of inhibitory GABAnergic neurons)
• Disturbances of other transmitter systems; ↑ACh
• Pesticides, Genetics, Oxidative stress, Neuroinflammation, Drug-induced (Anti-psychotics, Lithium, Antiepileptics, Antiemetics)
• DAT (Dopamine Transporter) scan
• o Parkinson’s = HYPOkinesia
  o Huntington’s = HYPERkinesia

Question 2

What is the first line of treatment for Parkinson’s?

What is given with the L-DOPA to increase its effectiveness? What does this prevent?
→ What does this enzyme do?

What are the short term side-effects of L-DOPA?

What are the long term side-effects of L-DOPA?

Answer 2

• L-DOPA (Levodopa)
• Benserazide/Carbidopa to peripherally inhibit Dopa Decarboxylase; they can’t cross the BBB to PREVENT SYSTEMIC EFFECTS
  → Converts L-DOPA to Dopamine in the blood
• • Impulse Control Disorder - Hypersexuality, Pathological Gambling, Punding
  • Postural Hypotension
  • Confusion, Visual hallucinations, Delusions
  • Insomnia, Vivid dreams, Nightmares, Inversion of Sleep-Wake cycle
  • N&V, Loss of appetite
• Peak-dose Dyskinesia, Dystonia, Unpredictable on/off periods of drug response, Confusion, Visual hallucinations, Dementia

Question 3

What other treatment options are there? Give detail on what they do and any potential adverse effects/AEs. Give an example.

Answer 3

Dopamine D2/3 agonists:
o e.g. Bromocriptine, Ropinirole, Pramipexole
o 50% of patients respond to these alone
o AEs; N&V, Psychiatric symptoms

Dopamine release drugs:
o e.g. Amantadine
o ↑Dopamine release
o Less effective than L-DOPA, but its AEs are less severe

MAOB Inhibitor:
o e.g. Selegiline
o Low risk of hallucinations, Less AEs

COMT Inhibitor:
o e.g. Entacapone
o Slows down L-DOPA elimination
o Low risk of hallucinations, Less AEs

Antimuscarinics:
o e.g. Benzatropine, Procyclidine
o Used in early stages for younger people to reduce tremor and rigidity
o Not to be used in elders due to causing Memory problems, Confusion
o AEs; Dry mouth, Impaired vision, Urinary retention

Question 4

What is the last treatment option? What occurs with it? When is it used?

Answer 4

Deep Brain Stimulation:
o Implantation of electrodes and foetal nigral tissue into striatum
o Only used for those with ADVANCED Parkinson’s whose symptoms aren’t well controlled by medication