Parkinsons

Question 1

What is the mechanism of action of L-DOPA (levodopa)

Answer 1

It is converted to dopamine in the dopaminergic neurons which then stimulates dopamine receptors in the striatum so that the direct pathway of movement is active and the indirect pathway is inhibited

Question 2

what does L-DOPA have to be administrated with?

Answer 2

A decarboxylase inhibitor (e.g. carbidopa) to limit peripheral decarboxylation to dopamine which would cause symptoms of nausea and vomiting

Question 3

Side effects of L-DOPA

Answer 3

mostly dyskinesias (involuntary muscle movements)
Choreiform, ballistic and dystonic movements
Hallucinations

Question 4

Why do you get the side effects associated with L-DOPA

Answer 4

Excessive dopaminergic stimulation

Question 5

Explain the half life of L-DOPA

Answer 5

Short half-life (90 mins) and pulsatile dosing (DuoDopa – duodenal pump)

Question 6

Why is L-DOPA only effective for a bit?

Answer 6

As it doesnt prevent the dopaminergic neuron in the substantia nigra pars compacta dying

Question 7

Give some examples of Direct Dopamine Receptor Agonists used to treat the symptoms of parkinsons

Answer 7

Prampipexole (Mirapexin)
Ropinirole (eg Adartel, Requip)
Rotigotine (Neupro)

Question 8

What are the benefits of Direct Dopamine Receptor Agonists

Answer 8

No metabolic conversion, bypasses nigrostriatal neurons
Longer half-life than L-DOPA
Monotherapy or adjunct therapy
May delay or reduce motor fluctuations and dyskinesias

Question 9

What are the adverse effects of Direct Dopamine Receptor Agonists

Answer 9

Nausea, vomiting – activation of peripheral dopamine receptors
Dizziness, postural hypotension
Headache
Drowsiness and somnolence
Dyskinesias
Confusion, hallucinations, paranoia
Pulmonary and retroperitoneal fibrosis, pleural effusion and pleural thickening; Raynaud’s phenomenom

Question 10

Describe Raynard’s phenomenon

Answer 10

Is excessively reduced blood flow in response to cold or emotional stress, causing discoloration of the fingers, toes, and occasionally other areas.

Question 11

Give some examples of inhibitors of dopamine metabolism used to treat the symptoms of parkinsons

Answer 11

• Selegiline
• Rasagiline
• Entacapone
• Tolcapone

Question 12

What is the mechanism of action of selegiline

Answer 12

Irreversible MAO-B inhibitor so inhibits dopamine metabolism in the brain

Question 13

Necessary lifestyle changes with Selegiline

Answer 13

Low tyramine diet (no cheese)

Question 14

Why are anticholinergics used to treat the symptoms of parkinsons?

Answer 14

Because Dopamine depletion causes cholinergic overactivity

Question 15

What are anticholinergics effective at treating

Answer 15

Mainly for tremor and to lesser degree, rigidity

Question 16

What are the side effects of the anticholinergics?

Answer 16

Dry Mouth
Sedation
Delirium
Confusion
Hallucinations
Constipations
Urinary retention

Question 17

Give an example of an antiviral agent used to treat parkinsons

Answer 17

Amantidine

Question 18

What is the function of Amantidine

Answer 18

Antiviral agent

PD benefit found accidentally

Question 19

What is the mechanism of action of amantidine

Answer 19

Enhancing release of stored dopamine
Inhibiting presynaptic reuptake of catecholamines
Dopamine receptor agonism
NMDA receptor blockade – autonomic psychiatric

Question 20

What is the function of Memantine

Answer 20

NMDA receptor antagonist

Question 21

What is memantine used for

Answer 21

Used to treat cognitive defects in alzhiemers disease

so it is beneficial for parkinsons related dementia

Question 22

The mechanism of action is unclear for memantine - explain?

Answer 22

Normalize glutamatergic synaptic transmission
Enhance dopamine release
Neuroprotective

Question 23

What is deep brain stimulation and when is it used in parkinsons?

Answer 23

1. Electrical pulse generator implanted into regions controlling motor output
2. Usually only after drugs not longer effective

Question 24

What is the Restorative (only experimental) treatment for parkinsons

Answer 24

Transplantation – stem cells
Gene therapy
Neurotrophic factors – to surviving cells

Question 25

What is the non-motor management of parkinsons

Answer 25

Cognitive therapy
Speech therapy
Physiotherapy
Dietician (bowel, swallowing)
Psychologist (depression)