Trientine hydrochloride, another chelating agent, is preferred by many over penicillamine because of the lesser likelihood of drug reactions or neurologic worsening. It may be used in a daily dose of 1–1.5 g. Trientine appears to have few adverse effects other than mild anemia due to iron deficiency in a few patients. Tetrathiomolybdate may be better than trientine for preserving neurologic function in patients with neurologic involvement and is taken both with and between meals. It is not yet commercially available.
Zinc acetate administered orally increases the fecal excretion of copper and can be used in combination with these other agents. The dose is 50 mg three times a day. Zinc sulfate (200 mg/d orally) has also been used to decrease copper absorption. Zinc blocks copper absorption from the gastrointestinal tract by induction of intestinal cell metallothionein. Its main advantage is its low toxicity compared with that of other anticopper agents, although it may cause gastric irritation when introduced.
Liver transplantation is sometimes necessary. The role of hepatocyte transplantation and gene therapy is currently under investigation.
SUMMARY Drugs Used for Movement Disorders Subclass, Drug Mechanism of Action Effects Clinical Applications Pharmacokinetics, Toxicities, Interactions • Levodopa Transported into the central nervous system (CNS) and converted to dopamine (which does not enter the CNS); also converted to dopamine in the periphery Ameliorates all motor symptoms of Parkinson’s disease and causes significant peripheral dopaminergic effects (see text) Parkinson’s disease: Most efficacious therapy but not always used as the first drug due to development of disabling response fluctuations over time Oral • ~6–8 h effect • Toxicity: Gastrointestinal upset, arrhythmias, dyskinesias, on-off and wearing-off phenomena, behavioral disturbances • Interactions: Use with carbidopa greatly diminishes required dosage and is now standard • use with
COMT or MAO-B inhibitors prolongs duration of effect + carbidopa (Sinemet, others): Carbidopa inhibits peripheral metabolism of levodopa to dopamine and reduces required dosage and toxicity; carbidopa does not enter CNS + carbidopa + entacapone (Stalevo): Entacapone is a catechol-O-methyltransferase (COMT) inhibitor (see below) • Ropinirole:
Similar to pramipexole; nonergot; relatively pure D2 agonist • Bromocriptine: • Apomorphine:
Nonergot; subcutaneous route useful for rescue treatment in levodopa-induced dyskinesia; high incidence of nausea and vomiting
DOPAMINE AGONISTS • PramipexoleDirect agonist at D3 receptors, nonergot Reduces symptoms of parkinsonism•smoothsoutfluctuations in levodopa response Parkinson’s disease: Can be used as initial therapy•alsoeffectivein on-off phenomenon Oral•~8heffect•Toxicity: Nausea and vomiting, postural hypotension, dyskinesias, confusion, impulse control disorders, sleepiness • Selegiline:
Like rasagiline, adjunctive use with levodopa; may be less potent than rasagiline • Safinamide:
Also used as adjunct to levodopa in patients with response fluctuations