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Drugs for Parkinson's disease.

James Parkinson first described he symptoms of the disease that now bears his name in 1817 (Schapira, Agid et al., 2009). The Parkinson's Disease Foundation (PDF) (2010a) estimates approximately 1 million people in the United States are living with Parkinson's disease (PD). This includes about 60,000 Americans who are diagnosed each year, with 96% of them over age 50. Although no known cure exists for PD, a variety of treatment modalities is available to help patients manage symptoms, and maintain function and quality of life (Snyder & Adler, 2007). Pharmacologic therapy is key to the management of PD. The five most common drug categories for treating this disease will be explored.

Pathophysiology Review

Parkinson's disease is a slowly progressive neurogenerative movement disorder charterterized by the loss of dopamine-producing cells in the substantia nigra portion of the basal ganglia of the brain. The neurotransmitter dopamine carries messages to the brain to control movement; its loss causes the symptoms of PD. Although the loss of neuronal cells in the substantia nigra can account for the progressive features of PD, studies suggest PD also includes "extensive involvement in many neuronal systems outside of the dopaminergic nigrostriatal" systems (Schapira, Agid et al., 2009, p. 1092). It now is being considered a multisystem disease even though the exact pathology for the non-motor symptoms of PD is not well understood.

Symptoms of PD

Parkinson's disease is characterized by both motor and non-motor symptoms. Primary motor symptoms will affect the majority of patients with PD; they include a resting tremor, bradykinesia, rigidity, and postural instability. About 70% of patients will develop resting tremors, which are an early sign of the disease process (PDE 2010b). Secondary motor symptoms also are considered hallmarks of PD, but they may not affect all patients. They include stooped posture, dystonia, fatigue, impaired fine motor movement, drooling, muscle cramping, poverty of movement, sexual dysfunction, micrographia, loss of facial expression (mask-like facial expression), akathisia, and speech problems. Patients with PD also may demonstrate non-motor symptoms as secondary symptoms of the disease. Non-motor symptoms include memory problems or complaints of slower thinking, fear, anxiety, pain, confusion, dementia, sleep problems, constipation, skin problems, depression, loss of energy and/or fatigue, and urinary difficulties. In addition, they may demonstrate compulsive behaviors, which are described as excessive gambling, sexual activity, eating and shopping, abuse of medication, and repetitive activities (PDF, 2010b).

Pharmacologic Treatment for PD

The goal of pharmacologic treatment in PD is management of disease symptoms. Medications may be adjusted or changed as symptoms progress or as response to medication changes for the individual patient. The majority of drugs are used to control the motor symptoms of PD, as treatment efforts for the non-motor symptoms of PD currently is lacking or patients demonstrate poor response to attempted therapies (Chan, Cordato, & O'Rourke, 2008).

Levodopa

Levodopa has been used for over 40 years for treating the symptoms of PD and is still considered gold standard therapy. It replaces the dopamine lost as part of the disease process (Abbruzzese, 2008).

Levodopa provides relief for the motor symptoms of PD within 1530 minutes of administration. It helps by temporarily restoring striatal dopaminergic neurotransmission by stimulating postsynaptic striatal dopamine receptors (LeWitt, 2008). Carbidopa often is added to the regimen to prevent levodopa from being converted to dopamine in the brain, thus allowing more of the levodopa to reach the brain (PDF, 2010c). New research also suggests early dopamine replacement can have long-term benefit with the motor symptoms of PD (Schapira, Emre, Jenner, & Poewe, 2009). Carbidopalevodopa is marketed under four brand names in the United States: Sinemet [R], Sinemet CR [R] (Sinemet controlled release), Parcopa [R] (an orally disintegrating tablet), and Stalevo [R] (a combination product of carbidopa-levodopa and entacapone) (PDE 2010c).

Although levodopa is considered the primary treatment for patients with PD, it is not without adverse effects and other concerns. For example, the clinical benefits of levodopa start to decline after the first year of use; acknowledged decline is about 10% per year of use (Abbruzzese, 2008). Levodopa's steady response for motor symptoms lasts only about 5-7 years before the patient begins to experience poor response to treatment (Chan et al., 2008). The symptoms of this wearing off (called off hours) can be demonstrated in motor fluctuations, dyskinesias, and hyperkinesias. As the disease progresses, the duration response to the drug is shortened; the drug does not last as long and may require more frequent dosing (Abbruzzese, 2008). Common adverse effects of drug therapy include postural hypotension, nausea, and vomiting. Vivid dreams, nightmares, and hallucinations are usually dose-related and more common in patients with cognitive disorders. A rare side effect is cardiac rhythm disturbance; patients with a history of myocardial infarction must be monitored carefully while taking the drug. Previously mentioned compulsive behavior and medication abuse can be related both to pathology and drug therapy. These are seen less frequently with levodopa than other PD drug therapies (Abbruzzese, 2008).

Patients taking levodopa should not take the drug with high-protein meals because high-protein foods can decrease the absorption and bioavailability of the drug. Foods or supplements high in pyridoxine ([B.sub.6]) also should not be consumed, as pyridoxine can inhibit the action of the drug. Although levodopa can be taken with food to help with the gastrointestinal side effects, it can compete with amino acids for absorption. The patient thus can start the drug with food and then slowly alter the dose time to take at least 30 minutes before a meal; this allows the gastrointestinal effects to become more tolerable. In addition, taking the medication on an empty stomach will increase its absorption. Neuroleptic malignant syndrome is a medical emergency that may occur when the drug is withdrawn abruptly. The patient should be educated about the need to take the drug consistently, not only to manage symptoms but also to avoid serious adverse effects (Edmunds & Mayhew, 2009).

Dopamine Agonists

Dopamine agonist drugs help in managing PD by stimulating the parts of the brain that receive dopamine, helping the brain perceive it is receiving dopamine, and therefore satisfying the brain's need for dopamine. These drugs also are considered first-line drug therapy for PD along with levodopa (PDE 2010c). The hypothesis in the use of the dopamine agonist drugs is that continuous dopaminergic stimulation will help prevent dyskinesias and motor fluctuations that occur with PD progression as well as with levodopa therapy (Antonini & Barone, 2008; Schapira, Agid et al., 2009). Research also demonstrates dopamine agonists may be neuroprotective agents in PD (Chwieduk & Curran, 2010).

Antonini and Barone (2008) suggested a treatment algorithm starting with a dopamine agonist or MAO-B inhibitor for first-line therapy, except in the older adult or a patient with cognitive impairment, and then adding levodopa as a second-line drug. Dopamine agents marketed in the United States are bromocriptine (Parlodel [R]), pramipexole (Mirapex [R]), ropinirole (Requip [R], Requip XL [R]), and apomorphine (Apokyn [TM] injection) (Edmunds & Mayhew, 2009; PDE 2010a). Pergolide (Permax [R]) was removed from the market due to cardiovascular side effects, and rotigotine transdermal system (Neupro [R]) was removed from the market due to concern of deviation from approved product standards (PDF, 2010c). Reported adverse effects for this drug category are headache, somnolence, back pain, nausea, vomiting, edema, and nightmares (Chwieduk & Curran, 2010; Edmunds & Mayhew, 2009). When a dopamine agonist is used with levodopa as adjunctive therapy, the dose of levodopa may need to be titrated downward (Edmunds & Mayhew, 2009).

Amantadine (Symmetrel [R]) is an anti-viral dopamine agonist used as a secondary medication for PD treatment in patients experiencing muscle rigidity and tremors. It usually is added to other drug therapy and is not used as a solo or primary drug therapy (PDE 2010c). When amantadine is added to carbidopa-levodopa therapy, it can help prolong the on time and decrease the tremors, dyskinesias, and muscle fatigue (Snyder & Adler, 2007). The greatest therapeutic effect is noted when the drug is added to levodopa therapy. The drug should not be discontinued abruptly; doing so can cause a Parkinsonian crisis or neuroleptic malignant syndrome. Patients with liver or renal dysfunction and older adults may require dosage adjustment and close monitoring (Edmunds & Mayhew, 2009).

Anti-Cholinergic Drugs

Anti-cholinergic drugs, such as benzotropine (Cogentin [R]) and tri-hexphenidyl hydrochloride (Artane [R]), are used in PD to help decrease the activity of acetylcholine, thus balancing the production of dopamine and acetylcholine. Acetylcholine is a neurotransmitter which also controls movement; anti-cholinergic drugs play a small role in treatment of mild, early resting tremors associated with PD. They can cause blurred vision, dry mouth, and urinary retention, and cannot be used with other drugs. They are rarely used as primary drug therapy (PDE 2010c).

COMT Inhibitors

Catechol-O-methyltransferase (COMT) inhibitors are used as adjuncts to carbidopa-levodopa therapy to improve motor fluctuations and block the breakdown of levodopa, therefore allowing a larger amount of levodopa to reach the brain (Chan et al., 2008; PDF, 2010c). Evidence indicates adding COMT inhibitors to levodopa therapy can reduce the end-of-dose failure patients experience as the effect of levodopa decreases, and also decrease the motor fluctuations (Chan et al., 2008; Damier, Viallet, Ziegler, Bourdeix, & Rerat, 2008). Two COMT inhibitors marketed in the United States are entacapone (Comtan [R]) and tolcapone (Tasmar [R]). Stalevo [R] is a combination therapy of carbidopa-levodopa with entacapone (PDF, 2010c). Adverse effects of entacapone therapy include occasional increases in dyskinesias, gastrointestinal upset, dizziness, and drowsiness. Stalevo is under evaluation by the U.S. Food and Drug Administration for possible links to an increased risk of prostate cancer (National Center for Biotechnology Information [NCBI], 2010). Adverse effects of tolcapone include dizziness, drowsiness, excessive dreaming, nausea, vomiting, diarrhea, and increased sweating. Tolcapone can cause life-threatening liver damage; patients taking this drug must be monitored carefully (NCBI, 2008).

Monoamine Oxidase Type-B inhibitors

Monoamine oxidase type-B (MAO-B) inhibitors can be used in early- or late-stage PD. In early-stage PD, they help delay the need for carbidopa-levodopa therapy. In late-state PD, they are added to carbidopa-levodopa therapy to help prevent the breakdown of the drug, allowing more medication to reach the brain (PDF, 2010c). MAO-B is an enzyme found in the brain, particularly in the neurons of the hypothalamus; it has a major role in the metabolism of dopamine in the brain. By inhibiting the MAO-B enzyme, these drugs can help conserve the available dopamine in the early stage of PD and also allow lower doses of carbidopa-levodopa in late-stage PD (Chen & Ly, 2006, Palmese & Grauer, 2004). MAO-B inhibitors thus help improve the symptomatic motor effects of PD. They also are being studied for possible neuroprotective benefits, which have been demonstrated at this time only in experimental laboratory models (Chen & Ly, 2006). MAO-B inhibitors available in the United States are selegiline (Eldepryl [R], Carbex [R]), selegiline oral disintegrating tablet (Zelapar [R]), and rasagiline (Azilect [R]) (PDF, 2010c). In clinical trials, patients with PD treated with rasagiline and estacapone had a significant reduction in the total number of off hours each day, hours when levodopa therapy was not controlling symptoms (Chen & Ly, 2006, Perez-Neri, Montes, & Rios, 2009).

Freezing is a common symptom of PD as well as a symptom of loss of levodopa effects. It is described by patients as ambulating and having the feeling that their feet are suddenly stuck or glued to the floor, which can increase the risk of falling. Patients taking rasagiline had fewer episodes of freezing during walking; there was no difference in freezing with the use of selegiline (Chen & Ly, 2006). Adverse effects of MAO-B inhibitors include arthralgia, increases in systolic blood pressure, angina, depression, and delirium. Postural hypotension can occur in older adults taking MAO-B inhibitors with levodopa-carbidopa (Chen & Ly, 2006). Unlike MAO-A inhibitors whose activity takes place in the gastrointestinal tract, MAO-B activity occurs in the brain, so there is no risk of hypertension when taking these drugs with tyramine-rich foods (Chen & Ly, 2006; Palmese & Grauer, 2004).

The Role of the Nurse

Drug therapy for PD has advanced since 1961, when levodopa was first used for treating the disease. Drug therapy is aimed at managing symptoms and maintaining function and quality of life. Therapy choices will be dependent on a variety of factors, such of age of the patient, onset of symptoms, severity of symptoms, and other chronic disease states and their treatment requirements (Snyder & Adler, 2007). The nurse's role in the treatment of PD is to be aware of the motor and non-motor symptoms of PD, and educate the patient regarding disease process, treatment options, and drug therapy. The patient and family also should be taught drug therapy will be adjusted based on progression of the disease and emergence of symptoms. Assisting the patient with PD to manage the symptoms of the disease as well as the adverse effects of the drug therapy can also help to improve motor function, prevent injury, and maintain autonomy.

References

Abbruzzese, G. (2008). Optimising levodopa therapy. Neurological Science, 29(Suppl. 5), S377-S379.

Antonini, A., & Barone, P. (2008). Dopamine agonist-based strategies in the treatment of Parkinson's disease. Neurological Science, 29(Suppl. 5), S371-S374.

Chan, K.Y., Cordato, D.J., & O'Rouke, F. (2008). Management for motor and non-motor complications in late Parkinson's disease. Geriatrics, 63(5), 22-27.

Chen, J.J., & Ly, A.V. (2006). Rasagiline: A second-generation monoamine oxidase typeB inhibitor for the treatment of Parkinson's disease. American Journal of Health-System Pharmacists, 63(10), 915-928.

Chwieduk, C.M., & Curran, M.P. (2010). Parmipexole extended release in Parkinson's disease. CNS Drugs, 24(4), 327-336.

Damier, R, Viallet, F., Ziegler, M., Bourdeix, I., & Rerat, K. (2008). Levodopa/DDCI and entacapoine is the preferred treatment for Parkinson's disease patients with motor fluctuations in routine practice: A retrospective, observational analysis of a large French cohort. European Journal of Neurology, 15(7), 643-648. Doi: 10.111/j. 14681331.2008.02165

Edmunds, M.W., & Mayhew, M. S. (2009). Pharmacology for the primary care provider. St. Louis, MO: Mosby Elsevier.

LeWitt, P.A. (2008). Levodopa for the treatment of Parkinson's disease. New England Journal of Medicine, 359(23), 2468-2476.

National Center for Biotechnology Information (NCBI). (2010). Entacapone. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000168

National Center for Biotechnology Information (NCBI). (2008). Tolcapone. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001039

Palmese, D.A., & Grauer, A. (2004). Rasagiline an oral irreversible MAO-B inhibitor for the treatment of Parkinson's disease. Formulary, 39(5), 255-258.

Parkinson's Disease Foundation (PDF). (2010a). Statistics on Parkinson's. Retrieved from http://www.pdf.org/en/ parkinson_statistics

Parkinson's Disease Foundation (PDF). (2010b). Symptoms. Retrieved from http://www.pdf.org/en/symptoms

Parkinson's Disease Foundation (PDF). (2010c). Medications & treatments. Retrieved from http://www.pdf.org/en/ meds_treatments

Perez-Neri, I., Montes, S., & Rios, C. (2009). Inhibitory effect of dehydroepiandresterone on brain monoamine oxidase activity: In vivo and in vitro studies. Life Sciences, 85( 17-18), 652-656.

Schapira, A.H., Agid, Y., Barone, P., Jenner, P., Lemke, M.R., Poewe, W. Tolosa, E. (2009). Perspectives on recent advances in the understanding and treatment of Parkinson's disease. European Journal of Neurology, 16(10), 1090-1099.

Schapira, A.H., Emre, M., Jenner, R, & Poewe, W. (2009). Levodopa in the treatment of Parkinson's disease. European Journal of Neurology, 16(9), 982-989.

Snyder, C.H., & Adler, C.H. (2007). The patient with Parkinson's disease: Part I-treating the motor symptoms; part II-treating the nonmotor symptoms. Journal of the American Academy of Nurse Practitioners, 19(4), 179-197.

Lisa A. Cranwell-Bruce, MS, RN, FNP-C, APRN, is a Clinical Instructor, FNP Track Specialty Facilitator, Byrdine F. Lewis School of Nursing, College of Health and Human Sciences, Georgia State University, Atlanta, GA.

Note: The author and all MEDSURG Nursing Editorial Board members reported no actual or potential conflict of interest in relation to this continuing nursing education article.

Answer/Evaluation Form: Drugs for Parkinson's Disease Deadline for Submission: December 31, 2012

OBJECTIVES

This continuing nursing educational (CNE) activity is designed for nurses and other health care professionals who are interested in drugs for Parkinson's disease. For those wishing to obtain CNE credit, an evaluation follows. After studying the information presented in this article, the nurse will be able to:

1. Define the pathophysiology and symptoms of Parkinson's disease.

2. Describe the pharmacologic treatments available for Parkinson's disease.

3. Discuss the role of the nurse in the pharmacologic management of patients with Parkinson's disease.

CNE Instructions

1. Persons wishing to obtain CNE credit must read the article and complete the answer/evaluation form. Evaluations can be submitted two ways:

* AMSN's Online Library: Complete your evaluation online and print your CNE certificate immediately. Simply go to www.amsn.org/library

* See #3.

2. Upon completion of the answer/evaluation form, a certificate for 1.0 contact hour(s) and 60 Pharmacology Minutes will be awarded.

Fee: AMSN Member: Free

Regular: $15.00

3. Persons without access to the Internet may photocopy and send the answer/evaluation form along with a check or credit card order payable to AMSN to MEDSURG Nursing, CNE Series, East Holly Avenue Box 56, Pitman, NJ 08071-0056. Test returns must be postmarked by December 31, 2012. A CNE certificate will be provided by mail.

Fee: AMSN Member: $10.00

Regular: $15.00

This independent study activity is co-provided by AMSN and Anthony J. Jannetti, Inc. (AJJ).

AJJ is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation (ANCC-COA).

Anthony J. Jannetti, Inc. is a provider approved by the California Board of Registered Nursing, Provider Number, CEP 5387.

This article was reviewed and formatted for contact hour credit by Dottie Roberts, MSN, MACI, RN, CMSRN, OCNS-C [R], MEDSURG Nursing Editor; and Rosemarie Marmion, MSN, RN-BC, NE-BC, AMSN Education Director.

ANSWER FORM

1. If you applied what you have learned from this activity into your practice, what would be different?
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2. By completing this activity, I was able
   to meet the following objectives:

   a. Define the pathophysiology and
      symptoms of Parkinson's disease.          1    2    3   4    5
   b. Describe the pharmacologic treatments
      available for Parkinson's disease.        1    2    3   4    5
   c. Discuss the role of the nurse in the
      pharmacologic management of patients
      with Parkinson's disease.                 1    2    3   4    5

3. The content was current and relevant.        1    2    3   4    5

4. The objectives could be achieved using
   the content provided.                        1    2    3   4    5

5. This was an effective method to learn
   this content.                                1    2    3   4    5

6. I am more confident in my abilities since
   completing this material.                    1    2    3   4    5

7. The material was (check one) ___new
   ___review for me

8. Time required to complete the reading
   assignment: _____minutes

I verify that I have completed this activity: _________________

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Title Annotation:CNE SERIES
Author:Cranwell-Bruce, Lisa A.
Publication:MedSurg Nursing
Date:Nov 1, 2010
Words:3095
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