PH3110 Unit 4 Parkinson's

What is Parkinson's disease?

A progressive neurodegenerative disease where dopamine neurons in the substantia nigra progressively die over many years.

Where do the affected neurons project their axons?

In the striatum (specifically the caudate nucleus and putamen).

What are the major motor symptoms of PD?

Tremor, bradykinesia (slow movements), stiffness, reduced facial expression, and changes in posture/walking.

What percentage of neurons are typically lost by the time of diagnosis?

50-60% of dopaminergic neurons.

Mechanism: Levodopa (L-dopa)

A precursor that crosses the BBB and is converted into dopamine by DOPA decarboxylase to replace lost dopamine.

Mechanism: Carbidopa & Benserazide

AADC (aromatic l-amino acid decarboxylase) inhibitors that do not cross the BBB; they prevent peripheral breakdown of L-dopa to increase its bioavailability in the brain.

Mechanism: MAO-B Inhibitors (Rasagiline, Selegiline)

Inhibit monoamine oxidase-B to prevent the breakdown of dopamine in the brain.

Examples of MAO-B Inhibitors

Rasagiline, Selegiline

Mechanism: COMT Inhibitors (Entacapone, Tolcapone)

Inhibit catechol-O-methyltransferase to prevent the breakdown of both L-dopa and dopamine.

Used as adjuvants to Levodopa to increase "on" time

Examples of COMT Inhibitors

Entacapone, Tolcapone

Mechanism: Dopamine Agonists (Pramipexole, Ropinirole, Rotigotine)

Directly stimulate post-synaptic dopamine receptors in the striatum.

Examples of Dopamine Agonists

Pramipexole, Ropinirole, Rotigotine

Indication: Levodopa

First-line treatment when motor symptoms significantly affect the patient's daily life and quality of life.

Indication: MAO-B Inhibitors

Early-stage PD where symptoms do not affect daily life, or as an adjuvant to Levodopa to reduce "off" time.

Indication: Rotigotine Patch

Used for nocturnal akinesia, restless leg syndrome, or when a patient is Nil By Mouth (NBM) to avoid withdrawal.

Side Effect: Dopamine Agonists

High risk of Impulse Control Disorders (gambling, binge eating, shopping) and hallucinations.

Side Effect: Levodopa (Long-term)

Motor complications including dyskinesias and response fluctuations ("on-off" effects).

What is Dyskinesia?

Involuntary writhing or erratic movements of the face, arms, legs, or trunk.

What is Neuroleptic Malignant-like Syndrome?

A life-threatening condition (hyperthermia, rigidity, altered mental status) caused by abrupt withdrawal of dopamine medication.

Patient Question: What is going on in my brain?

Specific dopamine neurons are dying; the rest of the brain is largely unaffected, but the condition is progressive.

Patient Question: What caused this?

The cause is not fully understood, but it is a mix of genetics (family history) and sporadic environmental factors.

Patient Question: Is there a cure?

There is no cure for Parkinson's, but medications like levodopa can significantly reduce symptoms and help with movement.

Why not just give dopamine?

Dopamine itself cannot cross the blood-brain barrier (BBB), the brain's natural protective shield.

Clinical Advice: Taking L-dopa with food

Nausea is common at the start; taking meds with a cracker can help, but avoid high protein meals which compete with absorption.

Clinical Advice: Constipation

Chronic constipation reduces drug efficacy; management includes fiber, fluid, exercise, and osmotic laxatives.

Scenario: Patient has hallucinations and dyskinesia on L-dopa

Lower the L-dopa dose and consider adding an adjuvant like an MAO-B or COMT inhibitor instead of a dopamine agonist.

Scenario: Patient experiences "wearing-off" before next dose

Increase the frequency of doses (e.g., from 3 times a day to 4 or 5 times) rather than increasing the dose amount.

Why is there poorer symptoms control in a late-stage patient despite levodopa treatment?

1. Levodopa has a higher turnover rate, so unable to store dopamine in synaptic vesicles, so more “off” periods.

2. Fewer surviving neurons, so more dopamine needed to achieve same effect, so more dyskinesias and smaller therapeutic window

What are psychotic symptoms in PD?

Mostly visual hallucinations (e.g., seeing people or objects) and delusions (false beliefs), often caused by medications.

What are a few other complications of Parkinson’s, its medications, including autonomic dysfunction?

Constipation, Hypotension, Swallowing problems and weight loss, Excessive salivation, Sweating, Bladder/sexual problems

NAV (meds), Pain, Sleep disturbances - melatonin imbalance, Aspiration pneumonia, Pressure sores