Lecture 29: Pathophysiology and pharmacology of Parkinson's

What characterizes the pathophysiology of Parkinson’s disease?

The degeneration of dopaminergic neurons, which produce dopamine needed for smooth and coordinated muscle movements

Where are dopaminergic neurons found, and what happens when they die?

Found in the substantia nigra of the brain

When they die, dopamine levels drop, leading to the movement problems seen in Parkinson’s disease

What protein is abnormally involved in Parkinson’s disease, and what does it form?

The alpha-synuclein protein clumps abnormally inside neurons, forming Lewy bodies that contribute to cell death and brain dysfunction

What are the common motor symptoms of Parkinson’s disease?

Tremor, rigidity, bradykinesia, and gait instability, which significantly impair daily functioning

What are some non-motor symptoms of Parkinson’s disease?

Depression, sleep disorders, cognitive decline, loss of smell, skin and sweating problems, fatigue, freezing, swallowing issues, and constipation

Which dopaminergic pathway is primarily affected in Parkinson’s disease?

The nigrostriatal pathway, which runs from the substantia nigra to the striatum; damage here causes movement problems

What are other dopaminergic pathways affected in Parkinson’s disease, and what functions do they influence?

The ventral tegmental area to the nucleus accumbens and frontal cortex pathways affect mood, motivation, and cognition

What is the most recognizable symptom of Parkinson’s disease?

Tremor, often described as “pill rolling,” though it may not be present in all patients at onset

What is bradykinesia?

Slowness of movement that affects fine motor skills and daily tasks

What is rigidity in Parkinson’s disease?

Increased muscle tone leading to stiffness and resistance to movement, often associated with joint pain

What diagnostic imaging technique is used to assess dopamine activity in Parkinson’s disease?

SPECT (single photon emission computed tomography) imaging, which helps visualize dopamine loss in the brain

What is the main focus of current Parkinson’s disease treatments?

Symptomatic relief and enhancing dopamine transmission in the striatum

What is the most effective pharmacological treatment for Parkinson’s disease?

L-DOPA (levodopa), which acts as a precursor to dopamine

Why is L-DOPA combined with Carbidopa?

Because L-DOPA cannot cross the blood-brain barrier easily

Carbidopa prevents its breakdown before it reaches the brain, reducing side effects like nausea

What long-term complication can result from L-DOPA use?

Dyskinesia, which refers to involuntary, erratic movements

What is end-of-dose deterioration in L-DOPA treatment?

It means the drug’s effects wear off before the next dose is due

What are on/off fluctuations in Parkinson’s disease treatment?

Sudden changes between being able to move (on) and being immobile (off)

What is dopamine dysregulation in Parkinson’s treatment?

When the brain becomes overly sensitive to dopamine, complicating management strategies

What are some emerging therapies for Parkinson’s disease?

Deep brain stimulation, neurotrophic factors, and stem cell therapies, which may offer more effective disease management in the future