• Bradykinesia
• Muscular rigidity
• Resting limb tremor
• Gait dysfunction and loss of postural reflexes

Also includes nonmotor symptoms such as autonomic dysfunction (bladder and bowel dysfunction, sexual dysfunction, orthostatic hypotension), depression, cognitive difficulties, dementia, sleep disturbances

Dopamine Antagonists

• antipsychotics
• antiemetics
• metoclopramide

n-MPTP

• by-product of synthesis of street heroin

Bradykinesia and at least 2 of the following:

• limb/muscle rigidity
• resting tremor abolished by movement
• postural instability

Bilateral

Mild postural imbalance

Leads to independent life

Bilateral

Postural instability

Requires substantial help

Severe

Patient restricted to bed or wheelchair

• N/V
• Orthostasis
• Hallucinations
• Dyskinesias

• 1st line therapy as monotherapy
• Adjunctive therapy to levodopa/carbidopa

• Treatment of acute, intermittent "off" episodes associated with advanced PD
• Non-ergot dopamine agonist with high affinity for D4 and moderate affinity for D2, D3, and D4
• Given subcutaneously

1st line in patients with mild disease to slow progession and delay need for levdopa

As adjunctive therapy to decrease "wearing off"

Side Effects:

• Insomnia
• Dizziness
• Nausea/Abdominal pain
• Dry mouth

1st line in patients with mild disease to slow progression and delay need for levodopa

Adjunctive therapy to decrease "wearing off"

Side Effects:

• Headache
• Dizziness
• N/V
• Orthostatic hypotension
• Dyskinesias

CI:

• meperidine
• tramadol
• propoxyphene
• sympathomimetic amines
• Dextromethorphan
• MAOIs
• St. Johns wort
• Mirtazepine
• cyclobenzaprine

• Orthostatic hypotension
• Somnolence
• Dyskinesia
• Explosive diarrhea -- less frequent with entacapone
• Urine discoloration
• Liver failure -- less frequent with entacapone
• Must monitor LFTs with tolcapone

2nd line agents used only in combination with levodopa/carbidopa

May decrease "wearing off", on-off times, and motor fluctuations

• stimulates dopamine receptors
• increases dopamine release
• reduces dopamine uptake
• mild anticholinergic activity
• ? neuroprotective effect (NMDA modulation)

• Dry mouth
• Dizziness
• Confusion
• Livedo reticularis
• Insomnia
• Hallucinations
• Nightmares
• Blurred vision
• Depression

? 1st line agent for younger patients or as adjunctive therapy in those with akinesia, rigidity, and tremor

• totaly daily levodopa dose < 600 mg
• no dyskinesias
• concurrent IR carbidopa/levodopa + entacapone
• IR carbidopa/levodopa and end-of-dose "wearing off"

• Trihexyphenidyl
• Benztropine
• Diphenhydramine
• Biperiden
• Procyclidine

• cognitive impairment
• urinary retention
• constipation
• dry mouth
• blurred vision
• flushing

• ? 1st line agent for younger patients with tremors
• adjunctive therapy for tremor