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Parkinson's Nurse Navigator A Newsletter for Nurses in Neurology
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Greetings!
The Nurse Navigator is a quarterly e-newsletter focusing on best practices in nursing care for patients with Parkinson's and other related movement disorders. Articles will be written by nurses, mid-levels and specialists with a wide range of experience and expertise. Since many patients rely on nursing care as their primary contact and information source we thought it would be helpful to provide information, tools and insights from fellow practitioners. If you know of other colleagues that would benefit from this newsletter, please do forward it along. Thanks for reading. Sincerely, Colleen Crowley Executive Director 877-980-7500 | colleenc@nwpf.org |
Parkinson's Medications |
Parkinson's disease (PD) - a progressive neurologic movement disorder- caused by degeneration of dopaminergic neurons was first described in medical literature in 1817 by James Parkinson. Since the 1960's significant advances have been made in understanding the pathophysiology, societal effects and treatment of this immobilizing disorder (Pahwa, 2007).
Many individuals - health professionals and lay persons- think of tremulous hands, stooped posture and shuffling gait as representative symptoms in a person diagnosed with Parkinson's disease. An important concept to remember is that this neurodegenerative movement disorder affects all aspects of movement in an individual. As dopamine is depleted all coordination of movement changes. Individuals develop slow or stiffened movement in their face, trunk and extremities. The obvious hallmark changes of "masked face", bradykinesia, rigidity, stooped, shuffling gait and resting tremor are the "tip of the iceberg". Patients can develop life threatening symptoms as the disease progresses. Symptoms including balance problems with resultant falls, worsening coordination of muscles in the gastrointestinal (GI) tract including speech, swallowing and digestion result in aspiration and constipation. Additionally problems with coordination of limb movement may interfere with activities of daily living (ADLs). Effective and appropriate prescription of medications, close monitoring of patients reactions to medications with elimination of ineffective or deleterious medications is prudent for maintaining patient safety (Pahwa, 2007).
The following is a brief discussion including some of the most common side effects and resolution of side effects for Parkinson's medications. Health care providers may be more successful in achieving optimum medication effects and reductions of unwanted side effects when they consider the goals of their patients and the patient's families. The primary goals in medication management are improved efficacy, reduced side effects, and patient safety.
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Dopaminergic Agents |
Classification of common dopaminergic agents used to treat parkinsonian motor symptoms includes levodopa preparation, dopaminergic agonists, catechol-o-methyl-transferase inhibitors and monoamine oxidase inhibitors. When prescribing dopaminergic medicines it is important to note that side effects may be cumulative and a reflection of polypharmacy. However, certain side effects are more significant with certain classes of medicine. The following reviews various medication classes and associated side effect.
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Levodopa therapy |
The cornerstone for pharmaceutical treatment of Parkinson's disease continues to be dopamine enhancement or replacement. The immediate metabolic precursor of dopamine is levodopa which is absorbed through the GI tract. When levodopa alone is ingested orally more than 85% is rapidly metabolized to dopamine in the periphery and very little dopamine is then available to cross the blood-brain barrier. Levodopa can cause profound nausea and vomiting when given alone in adequate amounts to control Parkinson's symptoms. Carbidopa is added to levodopa in a combination tablet to minimize this problem because carbidopa is a peripheral inhibitor of dopa decarboxylase and increases the fraction of unmetabolized levodopa available to cross the blood-brain barrier. This can reduce the level of nausea caused by the levodopa.
Table 2 lists the most common doses of Carbidopa/levodopa tablets (Sinemet ™) used for treatment of PD.
Table 2; Carbidopa/levodopa medication formulation
Medication |
Carbidopa |
Levodopa |
Immediate Release |
10mg |
100mg |
|
25mg |
100mg |
|
25 mg |
250mg |
Slow or Controlled release |
25mg |
100mg |
|
50mg |
200mg |
This medication has a half-life of 0.75 - 1.5 hours, is excreted in the urine (70-80%) and is completely metabolized within approximately 4.5 to 5 hours after ingestion. There are multiple variables that may interfere with absorption and transport of carbidopa/levodopa. Absorption of levodopa in the proximal small intestine depends on gastric emptying, which may be slowed or erratic in PD. Oral liquid formulations (prepared by dissolving carbidopa levodopa tablets in water and ascorbic acid to enhance solubility) can shorten the time to reach peak concentration and onset of effect but do not affect plasma levodopa. Protein also interferes with levodopa absorption at the level of the intestine and blood brain barrier. Therefore, absorption of levodopa is improved if taken one hour before or after a high protein meal.
Nausea is not uncommon especially when initiating levodopa therapy. Taking medicine with food such as crackers or toast can reduce nausea. Initiating therapy at a low dose such as one half tablet and gradual titration to desired dose can be effective in reducing nausea. Fortunately, nausea usually abates after a couple of weeks of regular dosing. Anti-emetic medication used with the initial doses of levodopa may alleviate some of the nausea as patients start therapy (Jankovic, 2007), however it is important to note that many anti-emetics are dopaminergic antagonists and should be avoided in people with Parkinson's disease.
About 18% of individuals will experience orthostatic hypotension with or without use of levodopa. These patients tend to be older, have more advanced PD and had a longer duration of PD symptoms. These individuals are identified because they have a larger range between their highest and lowest sitting systolic and diastolic BPs (Bavard, S2011). Patients and their families need frequent reminders to maintain safety considerations in relationship to all activities. When PD patients rise from a seated to a standing position it's important to stand still for a few moments to let their blood pressure equilibrate before they begin walking. When picking something up off the floor a patient would be less likely to have BP fluctuations if they kneel down instead of bending over to pick something up before they resume a standing posture (Nyholm, 2006).
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COMT Inhibitors |
Catechol-O-methyl transferase (COMT) inhibitors reduce the peripheral metabolism of levodopa allowing greater availability of levodopa resulting in an increased time in the blood stream so levodopa can penetrate the blood-brain barrier (this concept is similar to dopa decarboxylase inhibition by carbidopa). Available COMT inhibitors, tolcapone and entacapone, can extend the functional effect of levodopa experienced as reduced off time in patients experiencing motor fluctuations and therefore, may increase the risk of levodopa side effects. Entacapone is also available in a combination pill carbidopa/levodopa/entacapone (Stalevo™). Unique side effects associated with this class of medicine include diarrhea and transient elevated liver function tests (LFTs). The diarrhea associated with COMT inhibitors may be severe, resistant to medication treatment and occur up to 6-8 weeks after initiation of these medications.
Patients may also experience nausea, vomiting, dyskinesia, sedation, hypotension, headache and constipation. |
Dopamine Agonists |
Dopaminergic agonists activate post synaptic dopaminergic receptors and are used for initial therapy and to manage motor fluctuations in advanced disease. The common dopaminergic medicines used in practice include pramipexole, ropinirole and rotigotine transdermal patch (not currently available in the US). These medications improve symptoms of PD while delaying motor fluctuations and dyskinesia and may be used in all stages of PD either in combination with levodopa or as monotherapy.
The dopamine agonists enhance the effects of dopamine so it is important to consider the side effects of dopamine when prescribing the agonists as mono or adjunctive therapy. Certain side effects are more common or troublesome with dopaminergic agonists than levodopa, namely cognitive difficulties, hallucinations, impulsivity control symptoms, hypotension and sedation. Impulsivity control symptoms are incentive or reward -based repetitive symptoms and include gambling, compulsive shopping or eating and hypersexuality. These patients can be protected against these activities by scheduling frequent office visits and include questions in the review of systems about these activities. Include family members in the interview for their observations of the patient's behaviors. If there are signs of these behavioral problems an adjustment, reduction or elimination of the dopamine agonists' medication will be necessary (Evans, 2009).
The dopamine agonists can have a side effect of sleepiness, including a sudden intense need for sleep. Sedation and daytime sleepiness are also common side effects of levodopa. Individuals with Parkinson's are pre-disposed to sleep disorders so adding the side-effect of sleepiness from medications can contribute to problems with sleep wake cycles. Restorative sleep is essential for all individuals. Patients can benefit from maintaining good sleep hygiene. Patients can improve their sleep by choosing consistent times when they go to bed and awaken - week-ends and holidays included. A sleep environment is best quiet and restful. If there are pets in the household pets should sleep in a separate area (Nyholm, 2007).
Psychosis with hallucinations rarely occurs in untreated Parkinson's patients but may occur in patients receiving dopaminergic therapy especially dopaminergic agonists. Individuals who have had PD greater than 20 years, or who are older are more commonly afflicted with this symptom. The dopamine agonists can trigger or worsen these symptoms in some patients. Patients will rarely initiate discussion about hallucinations so it is important to describe this medication side-effect. It is important to address patient fears and offer reassurance as well as optimal medication adjustments to reduce psychiatric symptoms as much as possible (Nyholm, 2006).
Additionally, the sleep disorders common in Parkinson's patients can also contribute to psychosis and paranoia. Older age, disease severity, sleep disturbance, cognitive impairment, dementia and/or depression are other variables seen in Parkinson's patients who develop psychosis (Poewe, 2001; Zahodne, 2008).
Health care providers will improve patient outcomes by simplifying and reducing the types and amounts of medications as much as the patient will tolerate. When evaluating a patient who is taking multiple medications and you are considering reducing medications consider tapering and stopping the medications with the highest risk-to-benefit ratio first. The anticholinergics are first, then selegiline, dopamine agonists, amantadine and finally COMT inhibitors. Levodopa is reduced last. This is not always possible due to motor dysfunction. If the medication dose cannot be reduced in patients they may need the addition of other classes of medications to control the psychotic symptoms such as hallucinations or paranoid ideation (Nyholm, 2006).
Quetiapine has been used to control psychotic symptoms. One benefit of quetiapine is that the medication can be dosed in small increments and increased gradually to match the patient's needs. The most common side effect is sedation which can be advantageous because many of these patients have sleep disorders that contribute to their psychosis. Quetiapine is very helpful to induce regularly scheduled sleep patterns for PD patients in addition to reducing psychotic or agitated behavior. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. (Friedman, 2002)
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Monoamine-oxidase inhibitors |
Selegiline and rasagiline are monoamine oxidase B inhibitors (MAO-B inhibitors) and are used as adjunctive therapy in patients with Parkinson's. These medications block the metabolism of levodopa by the enzyme monoamine oxidase in the brain, effectively increasing the availability of dopamine in the synaptic cleft. Selegeline (Eldepryl™) and rasagiline (Azilect™) are two available MAO-B inhibitors that differ in their side effect profile. Selegeline is metabolized to an amphetamine so may increase the risk of confusion, hallucinations, agitation and insomnia. As a group MAO B inhibitors should not be used with meperidine; the analgesics tramadol, methadone, and propoxyphene; the antitussive agent dextromethorphan; as well as St. John's wort and cyclobenzaprine. Use of these medicines with MAO B inhibitors is contraindicated due to risk of serotonin syndrome. Serotonin syndrome presents as a clinical triad of behavioral, motor hyperactivity and autonomic symptoms. Cognitive effects range from headache, agitation, confusion, to hallucinations and coma. Autonomic effects include shivering, diaphoresis, hypertension, fever and tachycardia's and motor hyperactivity includes hyper-reflexia with clonus, myoclonus or tremor.
The following table lists other medicines that should be used with Caution along with MAO-B selective inhibitors.
Class of Medication |
Medications |
5-HT |
Triptans |
Anti-depressants |
MAOIs, TCAs, SSRIs, SNRIs, bupropion, trazodone, nefazodone |
Opioids |
Tramadol, fentanyl, pentazocine, buprenorphine, oxycodone, hydrocodone, |
CNS stimulants |
Phentermine, diethylpropion, methamphetmine, amphetamine, sibutramine, methylphenidate |
Herbs |
St. John's Wort, Nutmeg, Yohimbe, tryptophane, |
Others |
Tryptophan, valproate, buspirone, dextromethorphan, chlorpheniramine, risperidone, olanzapine, metoclopramide, lithium, linezolid |
Parkinson's disease as a progressive process will continue to evolve and as patients age they may develop multiple co-morbid chronic illness in addition to PD. Conscientious medication management for PD patients includes frequent evaluation of the patient and their medications. Frequent evaluation of all medication effectiveness, tolerability, patient compliance and the level of patient understanding is important for successful treatment for Parkinson's patients.
There are many medications available to optimize patient mobility but the most important aspect of medication management remains attention to a patient's general health. Medications will work best if the patient maintains the foundation of general good health. This implies that patients and their families need reminders to maintain regular sleep patterns, adequate water intake, regular exercise and balanced regular meals. When health care providers remember that the goal of treatment is to improve quality of life they will likely provide prudent prescription and frequent re-evaluation of medications.
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Author |
Dr. Monique Giroux is the medical director of the Northwest Parkinson's Foundation. She specializes in movement disorders with a focus on rehabilitation and wellness for Parkinson's patients.
Author: Mo Hillstrand, is a nurse practioner in private practice in Achorage Alsaka. She has a Master's degree in Health Care Management from University of Alaska Anchorage 1996 and was recently awarded a Doctorate in Nursing Practice from Vanderbilt University. She specializes in neurology including longterm care of Parkinson's disease. |
References
Bavard, S., Cochen De Cock, V. & Dauvillers, Y. (2011). Dopamine deregulation syndrome in Parkinson's disease and restless legs syndrome. Geriatric Psychology Neruopsychiatric, 1, 227-235.
Evans, A., Strafella, A., Weintraub, D. & Stacy, M. (2009). Impulsive and compulsive behaviors in Parkinson's disease. Movement Disorders, 15, 1561-1570.
Friedman, J., & Factor, S. (2002). Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease. Movement Disorders. DOI: 10.1002/1531-8257(200003)15:2<201: AID-MDS1001>3.0.CO; 2-D
Hubble, J. (2002) Long-term studies of dopamine agonists. Neurology, 26, (Suppl 1):S42-50.
Jankovic, J. & Stacy, M. (2007) Medical management of levodopa-associated motorcomplications in patients with Parkinson's disease. (2007). CNS Drugs. 21, 677-692.
Nyholm, D. (2006). Pharmacokinetic optimization in the treatment of Parkinson's disease: Anupdate. Clinical Pharmacokinetics. 451 09-36.
Pahwa, R. & Lyons, K. (Eds.) (4th Ed.) (2007). Handbook of Parkinson's disease. New York, NY: Informahealthcare.
Powe, W. & Seppi, K. (2001). Treatment options for depression and psychosis in Parkinson's disease. Journal of Neurology. Supplement. 3, II12-1121.
Zahodne, L. & Fernandez, H. (2008). Pathophysiology and treatment of psychosis in Parkinson's disease: A review. Drugs and Aging. 25, 665-682. |
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The Northwest Parkinson's Foundation (NWPF) plays a vital role in helping people with Parkinson's live meaningfully with the disease. A large part of our mission is education, both for the medical professional and for patients, caregivers and families. At both levels we have the opportunity to improve the day-to-day for those touched by this debilitating disease set. With the addition of Dr. Monique Giroux as Medical Director, we have become a recognized leader in professional education as well as patient education.
The NWPF currently serves 25,000 people throughout the Northwest and beyond. Our primary constituency resides in the Northwest (Washington, Oregon, Idaho, Montana and Alaska), home of 70,000+ Parkinson's patients.
This program is generously supported by educational grants from Teva Neuroscience. | |
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