Parkinson's Disease Symptoms

Parkinson's Disease (PD)

• PD is a neurodegenerative disorder characterized by motor symptoms: tremor at rest, rigidity, postural instability, and bradykinesia.
• Nonmotor symptoms of PD include autonomic dysfunction, sleep disturbances, depression, psychosis, and dementia.

Pathology of PD

• Primary pathology in PD is the degeneration of neurons in the substantia nigra that supply dopamine to the striatum.
• This results in an imbalance between dopamine and acetylcholine.

Treatment of Motor Symptoms

• Motor symptoms are primarily treated with drugs that directly or indirectly activate dopamine receptors.
• Drugs that block cholinergic receptors can also be used.
• Levodopa (combined with carbidopa) is the most effective treatment for motor symptoms.
• Levodopa relieves motor symptoms by converting to dopamine in surviving nerve terminals in the striatum.

Levodopa

• The enzyme that converts levodopa to dopamine is called a decarboxylase.
• Acute loss of response to levodopa occurs in two patterns: gradual wearing off and abrupt loss of effect (“on-off” phenomenon).
• Principal adverse effects of levodopa include nausea, dyskinesias, hypotension, and psychosis.

Interactions with Other Drugs

• First-generation antipsychotic drugs block dopamine receptors in the striatum, negating the effects of levodopa.
• Second-generation antipsychotics like clozapine and quetiapine do not block dopamine receptors and can be used safely to treat levodopa-induced psychosis.
• Combining levodopa with a nonselective MAO inhibitor can result in hypertensive crisis.

Carbidopa

• Carbidopa enhances the effects of levodopa by preventing decarboxylation of levodopa in the intestine and peripheral tissues.
• Carbidopa cannot cross the blood-brain barrier, allowing conversion of levodopa to dopamine in the brain.

Pramipexole

• Pramipexole is an oral nonergot dopamine agonist used as a first-line drug for motor symptoms.
• It can be used alone in early PD and combined with levodopa in advanced PD.