12 Parkinson's Disease Medication

Question 1

Pathology of Parkinson’s Disease

Answer 1

Degeneration of Substantia Nigra affecting the Nigro-striatal pathway. Loss of dopaminergic neurons. Presence of Lewy bodies.

Motor symptoms: bradykinesia, rigidity, resting tremor, postural instability

Non motor symptoms:
cognitive impairment, mood disorders, postural hypotension, constipation, speech and swallowing problems, drooling, and unexplained pain

In Parkinsonism, only motor symptoms are manifested.

Question 2

Levodopa

Answer 2

Mechanism:

• Dopamine precursor increase central dopamine synthesis
• 80% of patients showed initial improvement
• effectiveness declines and increase in fluctuation response
• “on- off” effect with peak-dose dyskinesia and end of dose akinesia

It is better to delay the start of L DOPA treatment

Undesirable effects:
Nausea and vomiting, sedation, postural hypotension
psychosis, hallucination, dyskinesia

Question 3

Carbidopa, Benserazide

Answer 3

Mechanism:

• DOPA decarboxylase inhibitor
• cannot cross BBB
• inhibit peripheral conversion of L DOPA to DA
• more DA for brain

levodopa + carbidopa (SINEMET) levodopa + benserazide (MADOPAR)

Undesirable effects:
Nausea and vomiting, sedation, postural hypotension
psychosis, hallucination, dyskinesia

Question 4

Apomorphine

Answer 4

Mechanism:

• D1 and D2
• for emergency relief of off periods
• s.c.

Undesirable effects: nausea and vomiting, dyskinesia, psychological disturbances, orthostatic hypotension, constipation, fibrotic side effects ( Ergot only), peripheral digital vasospasm ( Ergot only)

Question 5

Amantadine

Answer 5

Mechanism:

• stimulate release of dopamine, block reuptake, and directly stimulate DA receptors
• anti-viral drug against influenza

Question 6

Benztropine, trihexyphenidyl

Answer 6

Mechanism:

• anti- muscarinics
• Ach-DA balance hypothesis in striatum
• cholinergic neurons in striatum excite GABAergic neurons
• effective in early stage
• for improving tremor and rigidity
• good for managing antipsychotics-induced Parkinsonism

Undesirable effects: dry mouth, constipation, impaired vision, urinary retention…(typical undesirable-effect profile for antimuscarinic drugs), confusion, dementia (memory impairment)

NOT good for patients showing sign of dementia

Question 7

Selegiline, rasagiline

Answer 7

Mechanism:

• MAO-B Inhibitors ( slow down metabolism of DA)
• neuroprotective effects (stabilise mitochondrial membrane and protect against neurotoxins)
• used alone or concurrently with L DOPA

Question 8

Selegiline, rasagiline

Answer 8

Mechanism:

• MAO-B Inhibitors ( slow down metabolism of DA)
• neuroprotective effects (stabilise mitochondrial membrane and protect against neurotoxins)
• used alone or concurrently with L DOPA

Selegiline metabolised to methamphetamine while rasagiline doesn’t

Undesirable effects:
Nausea and vomiting, sedation, postural hypotension
psychosis, hallucination, dyskinesia

Question 9

Entacapone, tolcapone

Answer 9

Mechanism:

• COMT inhibitors
• entacapone only works peripherally
• tolcapone works centrally and peripherally
• concurrently used with L DOPA

Undesirable effects:
nausea and vomiting, reddish discoloration of urine, other similar to DA overproduction, risk of hepatotoxicity (tolcapone only)