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 The leading web portal for pharmacy resources, news, education and careers June 24, 2017
Pharmacy Choice - Parkinsons Disease Disease State Management - June 24, 2017

Parkinsons Disease Disease State Management

Parkinson's Disease and Levodopa Therapy
by Tara Muzyk, Pharm D

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 50,000-60,000 newly diagnosed patients per year and approximately 1 million patients who carry the diagnosis. Parkinson's disease poses significant morbidity.

The substantia nigra is the part of the brain effected 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 disease may present with a wide range of symptoms depending on how their disease has progressed. Although the hallmark symptom of Parkinson's is a resting tremor, there are several other motor symptoms which are commonly present, including: bradykinesia, rigidity, and postural instability, among other symptoms.

Not yet diagnosed patients may present with the feeling of an internal tremor but no visible tremor. Whereas recently diagnosed patients may present with a unilateral tremor and patients who are further along in their disease may have a bilateral tremor effecting 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 but unfortunately this type of therapy is still theoretical. Symptomatic therapy is the mainstay in Parkinson's disease and is typically started once the patient has become functionally impaired. Functional impairment is defined as the impact the disease has on the activities of daily living 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 which 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 due to 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 who are 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. The central nervous system side effects may 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 due to the progressive degeneration of the nigrostriatal dopamine terminals resulting in a lack of endogenous dopamine and the receptors not being able to receive the dopamine which is available. Wearing off occurs when the last dose of levodopa is not lasting 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 due to its longer duration of action. Dyskinesias are involuntary movements which occur with the dose of levodopa. They are a direct result of levodopa therapy and usually occur within 30 minutes of the levodopa dose but 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 which result from prolonged muscle contractions and can occur when the patient is on or off of 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 which results in a painful intortion of the foot often occurs during the morning hours). If the dystonia is occurring during an "on" then the controlled release carbidopa/levodopa product will help to 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.

References
  1. Parkinson J. An Essay on the Shaking Palsy, Sherwood, Neely, and Jones, London 1817.
  2. Parkinson J. An Essay on the Shaking Palsy, Sherwood, Neely, and Jones, London 1817.
  3. Shulman, LM, Singer, C, Bean, JA, Weiner, WJ. Internal tremor in patients with Parkinson's disease. Mov Disord 1996; 11:3.
  4. Sinemet® Package Insert. Princeton, NJ; Bristol-Myers Squibb Co.; 2009 Jan
  5. Sinemet® CR Package Insert. Princeton, NJ; Bristol-Myers Squibb Co.; 2009 Jan
  6. Quinn, N. Drug treatment of Parkinson's disease. BMJ 1995; 310:575
  7. Olanow, CW, Watts, RL, Koller, WC. An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines. Neurology 2001; 56:S1.
  8. National Institute of Neurological Disorders and Stroke. Dystonias Fact Sheet. http://www.ninds.nih.gov/disorders/dystonias/detail_dystonias.htm (17 Dec 2014)

Links - Parkinson's Disease
Parkinson's Disease Foundation, Inc. is a national, non-profit organization, chartered in the state of New York with offices in New York City and Chicago.

National Parkinson Foundation, Inc. attempts to educate general medical practitioners to detect the early warning signs of Parkinson's disease.

Parkinson's Disease Learning Center Links and information

Parkinson Foundation of Canada is a not for profit, national charitable organization. The Society raises money through corporate sponsorships, public donations, and planned gifts.

Parkinson's Action Network is the unified advocacy voice of the Parkinson's community, fighting for a cure within five years.

If you would like to contact us please go to our Contact Page.

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