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Rx therapy for Parkinson's.

Parkinson's disease, described by James Parkinson in 1817 as shaking palsy, is a chronic progressive disease of unknown cause. In the United States there are about 50,000 to 60,000 newly diagnosed patients per year and approximately 1 million patients who carry the diagnosis. Parkinson's poses significant morbidity.

The substantia nigra is the part of the brain affected in Parkinson's disease. Cells in this area produce dopamine, and once they begin to die the body receives slow signals on muscle control. The result is discoordination in controlling and initiating movements. Patients with Parkinson's may present a wide range of symptoms, depending on how their disease has progressed. Although the hallmark symptom of the disease is a resting tremor, several other motor symptoms are commonly present, including bradykinesia, rigidity and postural instability, among others.

Not-yet-diagnosed patients may present the feeling of an internal tremor but no visible tremor. Recently diagnosed patients may present a unilateral tremor, and patients who are further along in the disease may have a bilateral tremor affecting a large portion of their body as well as other motor complications.

The decision to start therapy is based on the provider's philosophy: symptomatic versus neuroprotective. With neuroprotective therapy, the goal is to protect the neurons from degeneration and death; unfortunately, this type of therapy is still theoretical. Symptomatic therapy is the mainstay in Parkinson's disease and typically is started once the patient has become functionally impaired. Functional impairment is defined as the disease's impact on daily living activities or on the dominant hand.

Once the decision to start therapy has been made, products containing levodopa are usually chosen, since therapy with levodopa is well established with proven efficacy. Levodopa is the metabolic precursor to dopamine and is decarboxylated in the brain to dopamine. It replaces the dopamine that is no longer naturally occurring in large enough quantities to exert the necessary effect for muscle control.

Levodopa is commonly found in combination with carbidopa, which prevents levodopa from being converted in the periphery and allows it to reach the brain. Carbidopa also lessens the adverse drug reactions associated with levodopa, such as nausea and vomiting. Levodopa can be given on its own, but very large quantities are necessary because of peripheral conversion and are generally not well tolerated.

Regular-release carbidopa/levodopa products are initiated before the controlled-release formulations, which are reserved for patients experiencing wearing off. When initiating most medications for Parkinson's disease, the goal is to use the lowest therapeutic dose to minimize side effects. It is also important to realize that therapy is highly individualized.

Levodopa therapy is not without limitations. Although the gastrointestinal disturbances associated with levodopa therapy are uncomfortable, they are generally alleviated by taking the medication with food and disappear with continued use. Central nervous system side effects can be alleviated by a dose reduction or, in severe cases, the medication may need to be discontinued.

Various motor fluctuations, more severe adverse consequences of levodopa therapy, are often present in Parkinson's disease, such as wearing off, dyskinesias and dystonias. This is because of the progressive degeneration of the nigrostriatal dopamine terminals, resulting in a lack of endogenous dopamine and the receptors unable to receive the dopamine that is available.

Wearing off occurs when the most recent dose of levodopa does not last until the next dose takes effect. Changes in medication therapy are typically indicated when wearing off occurs, and this is when a controlled-release product may be preferable because of its longer duration of action. Dyskinesias --involuntary movements--are a direct result of levodopa therapy and usually occur within 30 minutes of the levodopa dose, but they can occur at any time when levodopa is on board. A controlled-release carbidopa/levodopa product may be selected in this situation as well to minimize the peaks and troughs in therapy, thus smoothing out the dose.

Dystonias are sustained abnormal postures that result from prolonged muscle contractions and can occur when the patient is on or off levodopa. If dystonia is occurring during an off period, the controlled-release product will help the patient reach the next dose, such as throughout the night (a dystonia causing a painful intention of the foot often occurs in the morning). If the dystonia is occurring during an on period, then the controlled-release carbidopa/levodopa product will help smooth out the dose and avoid bombardment of the receptor, which results in the receptor turning off instead of being activated.

Even though levodopa therapy has its limitations, it remains the therapy of choice for the treatment of Parkinson's disease. Patients on levodopa therapy walk a fine line between obtaining relief from their Parkinson's symptoms and avoiding unwanted adverse reactions from their medications. When the correct balance is found, the patient is able to enjoy increased functionality and an improved quality of life.

Tara Muzyk, Pharm. D., is a clinical pharmacy writer based in Lebanon, Pa. She has extensive experience as a clinical pharmacist and has served as an associate professor of pharmacy at the University of Southern Nevada College of Pharmacy and as education director for the VA Southern Nevada Healthcare System.
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Title Annotation:Focus
Author:Muzyk, Tara
Publication:Chain Drug Review
Geographic Code:1USA
Date:Jan 19, 2015
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