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dopa and thereby alter the plasma pharmacokinetics of levodopa, leading to more sustained plasma levels and more constant dopaminergic stimulation of the brain Two such agents, tolcapone and entacapone, are currently available and may be used as an adjunct to levodopa-carbidopa in patients with response fluctuations or an otherwise inadequate response and who either have failed with other adjunctive therapies or are not candidates for such therapies Treatment results in reduced response fluctuations, with a greater period of responsiveness to administered levodopa Tolcapone is given in a dosage of 100 mg or 200 mg three times daily, and entacapone is given as 200 mg with each dose of Sinemet (levodopa-carbidopa) With either preparation, the dose of Sinemet taken concurrently may have to be reduced by up to one-third to avoid side effects such as dyskinesias, confusion, hypotension, and syncope Diarrhea is sometimes troublesome Because rare cases of fulminant hepatic failure have followed its use, tolcapone should be avoided in patients with preexisting liver disease Serial liver function tests should be performed at 2-week intervals for the first year and at longer intervals thereafter in patients receiving the drug as recommended by the manufacturer Hepatotoxicity has not been reported with entacapone, which is therefore the preferred agent, and serial liver function tests are not required Stalevo is the commercial preparation of levodopa combined with both carbidopa and entacapone It is best used in patients already stabilized on equivalent doses of carbidopa/ levodopa and entacapone It is priced at or below the price of the individual ingredients (ie, carbidopa/levodopa and entacapone) and has the added convenience of requiring fewer tablets to be taken daily It is available in three strengths: Stalevo 50 (125 mg of carbidopa, 50 mg of levodopa, and 200 mg of entacapone), Stalevo 100 (25 mg of carbidopa, 100 mg of levodopa, and 200 mg of entacapone), and Stalevo 150 (375 mg of carbidopa, 150 mg of levodopa, and 200 mg of entacapone) 7 Atypical antipsychotics Confusion and psychotic symptoms, which may be iatrogenic, often respond to atypical antipsychotic agents, which have few extrapyramidal side effects and do not block the effects of dopaminergic medication Olanzapine, quetiapine, and risperidone may be tried, but the most effective of these agents is clozapine, a dibenzodiazepine derivative Clozapine may rarely cause marrow suppression, and weekly blood counts are therefore necessary for patients taking it The patient is started on 625 mg at bedtime and the dosage increased to 25 100 mg/d as needed In low doses, it may also improve iatrogenic dyskinesias.
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The full listing for this exercise is shown in Example A-60.
High-frequency thalamic stimulation is effective in suppressing the rest tremor of Parkinson s disease, and chronic bilateral stimulation of the subthalamic nuclei or globus pallidus internus may benefit all the major features of the disease Electrical stimulation of the brain has the advantage over ablative procedures of being reversible and of causing minimal or no damage to the brain, and is therefore the preferred surgical approach to treatment There is no evidence that the natural history of Parkinson s disease is affected
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Pahwa R et al Practice Parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidencebased review): Report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology 2006 Apr 11;66(7):983 95 [PMID: 16606909] Samii A et al Parkinson s disease Lancet 2004 May 29;363 (9423):1783 93 [PMID: 15172778] Suchowersky O et al Practice Parameter: Neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology 2006 Apr 11;66(7):976 82 [PMID: 16606908] Tolosa E et al The diagnosis of Parkinson s disease Lancet Neurol 2006 Jan;5(1):75 86 [PMID: 16361025] Wu SS et al Treatment of Parkinson s disease: what s on the horizon CNS Drugs 2005;19(9):723 43 [PMID: 16142989]
Gradual onset and progression of chorea and dementia or behavioral change Family history of the disorder Responsible gene identified on chromosome 4
Example A-60. One solution to Exercise 20-2
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Physical therapy or speech therapy helps many patients The quality of life can often be improved by the provision of simple aids to daily living, eg, rails or banisters placed strategically about the home, special table cutlery with large handles, nonslip rubber table mats, and devices to amplify the voice
Huntington s disease is characterized by chorea and dementia It is inherited in an autosomal dominant manner and occurs throughout the world, in all ethnic groups, with a prevalence rate of about 5 per 100,000 The gene responsible for the disease is on the short arm of chromosome No 4 At 4p163 there is an expanded and unstable CAG trinucleotide repeat; repeat length may have an effect on rate of progression
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