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Drugs Used In Parkinson Disease (Drugs increasing DA function (Levodopa…
Drugs Used In Parkinson Disease
Signs and symptoms: bradykinesia, muscle rigidity, and resting tremor
Pathology involves the degeneration of nigrostriatal dopamine tracts with imbalance between dopamine (decreased) and ACh (increased)
The pharmacological strategy is to restore normal dopamine and decrease ACh activity at muscarinic-R in the striatum
Drugs increasing DA function
Levodopa
Prodrug converted to DA by aromatic amino acid decarboxylase (AAAD)
Given with carbidopa
Side-effect: dyskinesias, "on-off" effects, psychosis, hypotension, vomiting
Tolcapone and Entacapone
COMT converts L-dopa to 3-O-methyldopa, a partial agonist at dopamine-R
Inhibit COMT and enhance levodopa uptake and efficacy
Tolcapone is hepatotoxic
Selegiline
MAOb-selective inhibitor (no tyramine interactions)
Initial treatment and adjunct to levodopa
Side effects: dyskinesias, psychosis, insomnia
Dopamine-R agonists
Pramipexole and Ropinirole
Bromocriptine (use: prolactinemia and acromegaly)
Side effects: dyskinesia and psychosis
Drugs decreasing ACh function
Benztropine and Trihexyphenidyl (muscarinic blockers)
Actions: ↓ tremor and rigidity but have little effects on bradykinesia
Side effects: atropine-like
Amantadine
Antiviral, which block muscarinic-R and ↑ dopamine release
Side effects: atropine-like and livedo reticularis