Nausea is often troublesome, especially at the initiation of apomorphine treatment; accordingly, pretreatment with the anti-emetic trimethobenzamide (300 mg three times daily) for 3 days is recommended before apomorphine is introduced and is then continued for at least 1 month, if not indefinitely. Other adverse effects include dyskinesias, drowsiness, insomnia, chest pain, sweating, hypotension, syncope, constipation, diarrhea, mental or behavioral disturbances, panniculitis, and bruising at the injection site. Apomorphine should be prescribed only by physicians familiar with its potential complications and interactions. It should not be used in patients taking serotonin 5-HT3 antagonists because severe hypotension may result.
Amantadine, an antiviral agent, was by chance found to have relatively weak antiparkinsonism properties. Its mode of action in parkinsonism is unclear, but it may potentiate dopaminergic function by influencing the synthesis, release, or reuptake of dopamine. It has been reported to antagonize the effects of adenosine at adenosine A2A receptors, which may inhibit D2 receptor function. Release of catecholamines from peripheral stores has also been documented. Amantadine is an antagonist of the NMDA-type glutamate receptor, suggesting an antidyskinetic effect.
Peak plasma concentrations of amantadine are reached 1–4 hours after an oral dose. The plasma half-life is between 2 and 4 hours, with most of the drug being excreted unchanged in the urine.
Amantadine is less efficacious than levodopa, and its benefits may be short-lived, often disappearing after only a few weeks of treatment. Nevertheless, during that time it may favorably influence the bradykinesia, rigidity, and tremor of parkinsonism. The standard dosage is 100 mg orally two or three times daily. Amantadine may also help in reducing iatrogenic dyskinesias in patients with advanced disease.
Amantadine has a number of undesirable central nervous system effects, all of which can be reversed by stopping the drug. These include restlessness, depression, irritability, insomnia, agitation, excitement, hallucinations, and confusion. Overdosage may produce an acute toxic psychosis. With doses several times higher than recommended, convulsions have occurred.
Livedo reticularis sometimes occurs in patients taking amantadine and usually clears within 1 month after the drug is withdrawn. Other dermatologic reactions have also been described. Peripheral edema, another well-recognized complication, is not accompanied by signs of cardiac, hepatic, or renal disease and responds to diuretics. Other adverse reactions to amantadine include headache, heart failure, postural hypotension, urinary retention, and gastrointestinal disturbances (eg, anorexia, nausea, constipation, and dry mouth).
Amantadine should be used with caution in patients with a history of seizures or heart failure.
A number of centrally acting antimuscarinic preparations are available that differ in their potency and in their efficacy in different patients. Some of these drugs were discussed in Chapter 8. These agents may improve the tremor and rigidity of parkinsonism but have little effect on bradykinesia. They are more effective than placebo. Some of the more commonly used drugs are listed in Table 28–1.
Treatment is started with a low dose of one of the drugs in this category, the dosage gradually being increased until benefit occurs or until adverse effects limit further increments. If patients do not respond to one drug, a trial with another member of the drug class is warranted and may be successful.
Antimuscarinic drugs have a number of undesirable central nervous system and peripheral effects (see Chapter 8) and are poorly tolerated by the elderly or cognitively impaired. Dyskinesias occur in rare cases. Acute suppurative parotitis sometimes occurs as a complication of dryness of the mouth.