The severity of dyskinesias associated with levodopa therapy increases with

The severity of dyskinesias associated with levodopa

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by MAO and COMT. The severity of dyskinesias associated with levodopa therapy increases with increasing concentrations.Inhibition of peripheral dopa decarboxylase by carbidopa greatly increases the fraction of administered levodopa that remains unmetabolized and available to cross the blood-brain barrier. Levodopa/carbidopa (#148) is available as Sinemet, Parcopa,Rytary and Duopa.Parcopa is a rapidly dissolving formulation of carbidopa/levodopa. It dissolves on the tongue andis swallowed with saliva (patients with Parkinson’s disease often have trouble swallowing tablets). It costs about 50% more than the generic standard formulation. Sinemet is available as immediate & sustained release tablets (Sinemet; Rytary), and combined with Entacapone [Stalevo]. Rytary capsules contain a combination of immediate- and extended-release beads. The extended-release products produce a greater reduction in “off” time and fewer daily doses (3 x daily vs 5 x daily. Duopa is available as an enteral suspension administered through a nasojejunaltube for patients with advanced Parkinson’s disease.c. Side effects are dose-dependent, reversible, and most related to levels of dopamine, both in the CNS and periphery.(1) Most common early in therapy are anorexia, nausea, and vomiting (80% of patients on levodopa; 20% of patients on Sinemet), caused by stimulation of medullary emetic 22
CNS: Motion Disorderscenter by dopamine. Minimize by giving in divided doses with or immediately after meals. (Warning: high protein meals interfere with the transport of levodopa).(2) Abnormal involuntary dystonic movements (dyskinesia) are common in 50%-80% of patients after 1-4 months of treatment. They include faciolingual tics, grimacing, & rocking movements of arms, legs, or trunk (think of the motions of Michael J Fox as you watched him recently on TV). Dietary factors and erratic gastric emptying may complicate the response to levodopa, producing an "on-off" or "yo-yo” phenomenon. Protein in food competes for the intestinal levo-aminoacid pump responsible for the absorption of levodopa. Patients may switch within seconds from a state of relatively good mobility to one of severe Parkinsonism. Giving smaller doses more frequently may be of benefit.(3) Behavioral disturbances, characterized by anxiety, depression, confusion and delirium, occur in 15% of patients taking levodopa. Elderly patients receiving levodopa & anticholinergic drugs are particularly vulnerable. Atypical antipsychotic agents that have a low affinity for dopamine D2receptors (aripiprazole, olanzapine, quetiapine, risperidone) may be helpful in counteracting behavioral complications. (4) Cardiovascular changes reflect alpha- and beta-adrenergic responses to increased plasma levels of dopamine....a) Sinus tachycardia and PVCs have occurred. Patients with preexisting disturbances of cardiac conduction are most likely to be affected. Propranolol is an effective treatment.b) Orthostatic hypotension occurs in 30% of patients early in therapy for unknown reasons.(5) Endocrine: Dopamine inhibits the secretion of prolactin (by stimulating release of a prolactin inhibitor factor).

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