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Parkinson's disease: the interplay of medical and surgical treatment options with physical therapy.

Risk Factors

Although the exact cause of PD is unknown, a combination of risk factors has been described in the literature. After the age of 60, the risk of developing PD is 2-4%, and to a greater degree in men than in women. (4,5,6) Though environmental risk factors, such as exposure to industrial poisons, chemicals and toxins may have role, contact alone is not believed to be sufficient. Rather, such exposure becomes concerning when presented alongside other risk factors. (1,4,5,6) Currently minimal evidence suggests a pure hereditary linkage with PD, genetic linkages do remain a topic of intense research. (1,6) At this time, mutations in various genes, including a-synuclein, parkin, ubiquitin C-terminal hydrolase L1 (UCH-L1), DJ-1, PINK1 and leucine-rich repeat kinase 2 (LRRK2), have been identified and linked to PD. (6,7) Of great interest is the "parkin gene" which appears to be associated with familial, young-onset PD. (6) However, a genetic susceptibility for development of PD is of strongest relevance when combined with environmental triggers, such as herbicides, pesticides and exposure to heavy metals such as manganese. (6,8,9) The aforementioned triggers may explain why the prevalence of PD appears to be greater in rural populations and farming communities. (7,9)

Pathophysiology

PD-related symptoms reflect disruptions to the neurotransmitter balance in the basal ganglia. (8) The disease is primarily characterized by a loss of dopaminergic neurons in the basal ganglia (most commonly the substantia nigra pars compacta) which results in a striatal dopamine deficiency. (8) In the corticothalamic pathway, dopamine serves as an inhibitory neurotransmitter of the globus pallidus internus (GPI) and subthalamic nucleus (STN) wherein excitation of the cerebral cortex and promotion of movement is governed. (10) The dopamine deficiency may also result in an apparent increase in activity in the cholinergic pathways in the basal ganglia, further contributing to PD associated symptoms. (8,10) Currently, the mechanisms underlying the degeneration and death of dopaminergic cells are not fully understood. (9) A current topic of bench research involves the identification of Lewy bodies, potential markers of PD. (9) The mutations represented amidst Lewy body proteins, including ubiquitin and a-synuclein, appear representative of areas of neuronal degeneration, such as the substantia nigra. (9)

Diagnosis and Classification

The diagnosis of PD is complicated, especially in the elderly, as manifestations of the normal aging process can parallel key Parkinson's symptoms. (11) For example, slower motor movements or fixed facial expressions may occur with normal aging or be indicative of PD. (11) Certain medications may also result in symptoms that mimic those commonly associated with PD, such as tremor and rigidity.11 No specific laboratory tests yield a confirmatory diagnosis of PD at this time. (1,5) Rather, diagnosis is usually achieved via a thorough history and clinical exam, as well as through the presence of two of the four following symptoms: bradykinesia, rigidity, resting tremor and postural instability. (8,11) In addition, imaging procedures such as CT, MRI, and PET scans are typically included for purposes of differential diagnosis and for exclusion of alternate pathologies. (5) The Hoehn and Yahr Classification of Disability Scale is a recognized tool used to estimate the stage and severity of the disease (refer to Table 1). Current research efforts are directed toward better identifying the nonmotor symptoms of PD, such as depression, anxiety, and dementia that often predate motor manifestations. (9) Such non-motor symptoms have been shown to significantly impact quality of life (QOL) indices by contributing to heightened disability and greater predisposition for institutionalized care. (9)

Clinical Signs and Secondary Impairments

PD encompasses a clinical tetrad of rigidity, bradykinesia, tremor and impaired postural reactions (1,11) The onset of these clinical signs occurs upon depletion of 60% or more of the dopamine-producing cells in the substantia nigra. (10,12) The expression of these hallmark symptoms differs among individuals. (9,10) Some patients develop a 'tremor dominant' condition, while others develop a 'motor disorder' that manifests through gait disturbance, rigidity and postural instability. (9)

Rigidity can affect all striated muscle and presents as increased resistance to passive range of motion (PROM). (10) Rigidity initially occurs unilaterally, although progression to bilateral involvement is likely. (10,11) Further, the presentation of rigidity may increase with active movement, mental concentration and emotional tension. (10) Two predominant forms of rigidity are most often seen in patients with PD--cogwheel and leadpipe. (10) Cogwheel rigidity is a "jerky" movement experienced in response to passive motion that reflects alterations in muscle tension and relaxation. (10) Leadpipe rigidity, on the other hand, is constant, non-fluctuating, uniform resistance to passive movement.10 The second hallmark sign of PD is bradykinesia or reductions in speed, range and amplitude of both automatic movement and initiation of movement. (10) Severe bradykinesia or akinesia, signifies complete immobility with "freezing episodes" lasting anywhere from a few seconds to many hours. (10) The third clinical sign is tremor or involuntary oscillations occurring at a rate of 4-7 oscillations per second. (10) Tremors represent the firstappearing clinical sign in 70% of cases. (6) Resting, or "pill roll," tremors typically disappear with voluntary movement while postural, or active, tremors occur when a limb is statically maintained against gravity. (10) The fourth hallmark feature of PD is the impairment of postural and balance reactions.10 The risk of falls increases as patients lose the reactive processes needed to adjust posture and regain equilibrium. (10) Instability also reflects patient limitations in protective extension mechanisms, difficulty with feed-forward adjustments and in severe cases, the inability to self-orient to the upright or vertical position. (10) A list of additional clinical manifestations can be found in Table 2.

In addition to the aforementioned clinical signs, a variety of secondary impairments are associated with PD. Many of these secondary impairments can be favorably addressed by physical therapy. Musculoskeletal compromise is revealed through findings of atrophy, weakness, reduced extensibility, limited range of motion, postural deformity and decreased bone density. (10) Cardiopulmonary compromise often results from decreased vital capacity, reduced thoracic expansion and decreased activity tolerance (given decreased cardiac output, tachycardia and hyperpnea). As such, patients have a predisposition for respiratory complications, most notably pneumonia, and should be vigilantly monitored. (10)

Medication Management

The diagnosis of PD does not always necessitate the commencement of pharmacotherapy. (2) Drug therapy, however, is warranted when the disease becomes disabling or when the patient's quality of life is sufficiently affected by symptoms. (2) By resolving the dopamine-acetylcholine imbalance and by restoring normal motor function, the goal of pharmacotherapy is to both alleviate troublesome motor symptoms and increase quality of life for the patient with PD. (10) As is the case with most medication prescription, the risk-benefit ratio must be considered. For the patient with PD, medications are not prescribed with a curative intent, but rather for symptom management. (8) Physical therapy intervention coupled with medical management is hoped to produce better patient outcomes than either variable used alone. (8,10) Therapist should be cognizant that at peak drug effect when bothersome PD-related symptoms are typically at their lowest, adverse drug effects are typically at their greatest. As such, one must consider the timing of medications relative to physical therapy sessions. (10)

Levodopa, approved by the United States Food and Drug Administration (FDA) in 1973, is considered the single-most effective drug for the treatment of rigidity and bradykinesia and remains the "gold standard" by which PD medications are measured. (8,13) Through decarboxylation, levodopa transforms into dopamine. If the beneficial effects of levodopa are to be realized, levodopa must cross the blood-brain barrier prior to conversion. (1,8) Peripheral decarboxylation is minimized through administration of levodopa with carbidopa. These two agents combined in a carbidopa : levodopa ratio of 1:4 or 1:10 is known by the trade name Sinemet [R]. (8) For patients who experience the "wearing off" phenomenon, whereby symptoms worsen for a period of time prior to administration of the next dose, combining carbidopa, levodopa and entacapone (i.e.--Stalevo [R]) may increase the "active period" of levodopa in the brain by 10%. (1) In patients receiving levodopa, the peak effects of drug therapy are noted approximately one hour after oral administration of the medication. (10) Thus, coordination of physical therapy sessions with medication administration should occur to help patients derive maximum benefit from each session. (8,10) Table 3a lists the side effects, indications and interactions of the various carbidopa/levodopa combinations.

Dopamine agonists serve to stimulate the action of dopamine at post-synaptic dopamine receptors. (11) When compared with levodopa, these agents emerge as advantageous in that they do not rely on conversion to an active form by the presynaptic neurons depleted in PD. (13) These agents can be used alone, but are typically used in combination with levodopa, especially in patients who experience end-of-dose akinesia, the on/off effect or who experience a general decrease in the effects of levodopa. (8) Patients who utilize a dopamine agonist along with levodopa have been able to reduce their levodopa dosage as well as reduce on/off time by 8-32%. (13) Given that dopamine agonists have a halflife of several hours, decreased motor complications may be realized in patients with early PD who utilize these agents in combination as opposed to sole use of levodopa. (1,8,11) In March 2007, the dopamine agonist, pergolide (Permax) was removed from the market by the FDA given concerns related to heart valve damage. (1) Later, in March 2008, UCB Inc., the manufacturer of Neupro (rotigotine transdermal system), recalled the drug as a deviation from approved product standards was noted that reduced treatment effectiveness. (1) Table 3b lists the side effects, indications and interactions of commonly used dopamine agonists.

Deficiency of striatal dopamine often leads to excess activity in specific cholinergic pathways in the basal ganglia. (8) Anticholinergics function by acting indirectly on the dopaminergic system by restoring balance between acetylcholine and dopamine. (8,11) Patient outcomes can be optimized when anticholinergics are used in conjunction with levodopa or other antiparkinson drugs. (8) Patients with rigidity, mild cases of PD, or resting tremors typically derive the greatest benefit from use of anticholinergics. (1,8,11) Table 3c lists the side effects, indications and interactions of anticholinergics agonists. Note that adverse drug effects associated with this class of agents can be significant enough in elderly patients to warrant the use of alternate medications. (13)

Monoamine oxidase-B (MAO-B) inhibitors have also been shown to prevent the breakdown of levodopa. (1) As such, MAO-B inhibitors prolong the local effects of dopamine at CNS synapses. (8) Selegiline [R] prolongs the action of levodopa, reducing levodopa dosages by 10-25%. (8) Selegiline [R] is believed to limit free radical production by inhibiting dopamine oxidation, thereby yielding neuroprotective effects. When prescribed in the early stages of PD, these medications may delay the need to initiate Sinemet [R]. (1) When prescribed in the later stages of PD, the medications may, in fact, enhance the effects of Sinemet [R]. (1) Table 3d lists the side effects, indications and interactions of MAO-B inhibitors.

Catechol-O-methyltransferase (COMT) inhibitors are taken in conjunction with levodopa to block the COMT enzyme that degrades levodopa in the periphery, thus allowing greater quantities to cross the blood brain barrier. (1,11) The plasma half-life of levodopa increases approximately 50% when administered with a COMT inhibitor, consequently allowing lower levodopa doses to achieve desired effects. (11) COMT inhibitors also increase "on" time and reduce "off" time in patients with motor fluctuations. (11) Tolcapone, a clinically approved COMT inhibitor for the treatment of PD, assists in managing problematic symptoms through maintenance of dopamine levels. (11) Table 3e lists the side effects, indications and interactions of individual COMT inhibitors.

Other important adjunctive medications, such as Amantadine and Rivastigmine tartrate do not reside in the aforementioned categories. Table 3f lists the side effects, indications and interactions of these medications.

Surgical Treatment--Deep Brain Stimulation

Pharmacotherapy for PD management has significant limitations. After many years of utilizing the "gold standard" treatment, levodopa, many individuals have developed troubling motor fluctuations, severe dyskinesias, refractory tremors, functional interferences from a "wearing off" phenomenon and other unwanted side-effects. (3,14) In light of this, surgically-based techniques, most recently deep brain stimulation (DBS) may be considered. DBS is continuous, high-frequency electrical stimulation administered to targets inclusive of the ventral intermediate nucleus (VIM) of the thalamus, the globus pallidus internus (GPI) and the subthalamic nucleus (STN). This procedure represents an upgrade from earlier surgeries, most notably the pallidotomy. (3,15) DBS was initially approved by the United States FDA in 1997 solely to treat essential tremor. (3) In 2002, DBS was approved as a treatment option for PD for patients with additional symptoms such as rigidity, bradykinesia and dystonia. (3)

In patients with PD, the clinical expression of motor signs reflects underlying abnormalities with the electrical feedback loop in the brain. (3) The current imposed with DBS interrupts this abnormal communication cycle to normalize electrical activity. (3) Not only do tremors improve with this intervention, but problematic bradykinesias, rigidity, dyskinesias, speech, handwriting and dystonias demonstrate favorable results as well. (3) Currently, DBS of the STN is touted as the most effective surgical intervention for PD given outcomes inclusive of decreased patient reliance on antiparkinson medication, lessened "wearing-off" intervals when medications remain utilized and improvement in problematic dyskinesias. (3,16) DBS to the GPI may more specifically reduce patient dystonias and dyskinesias. (3,11,15,16) DBS to both the STN and GPI has been associated with improvements in motor performance, activities of daily living and QOL in patients with advanced PD. (3,11,16) Reductions in essential tremor have been noted in patients receiving DBS to the VIM of the thalamus, with bilateral thalamic stimulation yielding less midline tremors of the jaw, neck and trunk. (3,15) DBS to one cerebral hemisphere generally reduces PD symptoms on the contralateral side of the body. (3) For patients with bilateral symptoms, gait and speech problems, DBS is often administered bilaterally. (3)

DBS is of tremendous benefit in that it is safe, reversible and adjustable. (3) When compared to lesioning techniques, the risk of complications with DBS is considerably less. (15) Through non-invasive adjustment of operating parameters, individualized therapy can be provided to maximize patient benefit and minimize adverse effects. (3) Table 4 indicates candidacy for DBS. Potential complications include infection, stroke hemorrhage, disorientation, depression, poor motivation, post-operative sleepiness and slow mental processing. (3)

Patient selection for DBS usually flows from the multidisciplinary input of a movement disorders neurologist, a functional neurosurgeon and a neuropsychologist. (16) As DBS is an elective surgery, each patient should consider the personal, professional and social factors that may be influenced by this treatment option. (16) While a patient may realistically expect reduced motor fluctuations, dyskinesias and medication requirements post-DBS, a patient's best "on" performance level is unlikely to improve. (16) Long-term studies indicate that PD symptoms remain controlled for many years after implantation of the DBS; even after 5 years, patients remain 50% improved. (3) However, DBS does not prevent complications that occur later in the disease process such as dementia, balance deficits and poor posture. (3)

After the patient has completed the required pre-operative screening tests, the placement of the electronic device begins in stages. (3) The procedure itself takes three to six hours and is performed while the patient is awake to allow for needed communications regarding symptom presence or improvement. (3) During this time, the patient's problematic symptoms are generally at their worst as PD medications are not ingested prior to the operation. (3) Intra-operatively, the DBS electrode is inserted deep into the designated brain target site and a connecting wire is run from the scalp into the chest where it will later be connected to an implantable pulse generator (IPG). (3) The post-surgical hospitalization period is typically 2-3 days. (3) During the first 24 hours, complaints of exhaustion, confusion and mild headache are common. (3) The patient generally returns to the operating room one week later where, under anesthesia, the IPG is attached to the connecting wire. (3) Mild pain medications are administered post-operatively should chest and neck discomfort be experienced.3 Routine outpatient follow-up then occurs to make needed adjustments to the stimulator and medication dosage to optimize outcome. (3)

After implantation, patients should be advised to avoid physical activity that could damage the device or wire and refrain from undergoing chiropractic neck manipulations and receiving ultrasound diathermy. (3) MRIs should be cautiously obtained, when necessary. (3)

Benefits of Physical Therapy

The goals of rehabilitation are multiple and include teaching compensatory strategies, decreasing secondary impairments, minimizing functional disability, and promoting a healthy adjustment to the psychological impact of the disease on QOL. (10) Common impairments often respond favorably to exercise (range, strength, balance, respiratory, aerobic), gait training, functional activities and relaxation techniques. (8,10,11)

Range of motion (ROM) deficits are effectively addressed either manually or mechanically and should utilize functional patterns that incorporate the trunk, scapula or pelvis in order to optimize outcomes. (10) Proprioceptive neuromuscular facilitation (PNF) techniques can be utilized to help accomplish such an objective. Balance activities are also of extreme importance and can occur in multiple fashion, including low velocity weight shifts, movement transitions such as sit to stand and physioball activities that elicit postural reactions and encourage pelvic and trunk mobility. (10) Whenever possible, sensory and environmental conditions should be varied to simulate situations patients may encounter in every day life. (10) Deep breathing exercises should also be incorporated into therapy to increase chest expansion and to improve vital capacity. (10) Diaphragmatic breathing, chest wall expansion and controlled breathing/coughing techniques are warranted in this patient population given the typical presentation of cardiopulmonary deconditioning resulting from decreased mobility and agility. (10) Patients should also be instructed in a regular aerobic exercise program which includes daily ambulation in order to optimize efficiency of oxygen transport, maximize alveolar ventilation, mobilize secretions and provide musculoskeletal benefits. (10) Mobility impairments require appropriate interventions as well and may respond favorably to PNF, neurodevelopmental treatment approaches (NDT), callisthenic exercises, music therapy and the use of verbal, auditory and tactile stimulation. (10) Sensory reinforcement utilized with gait training may improve reciprocal arm swing, contralateral trunk movement, heel strike, toe off, weight transfers, stride length and base of support. (10) Floor markings may help facilitate gait initiation and cessation as well as the ability to turn or change direction. Carrying a bag in one arm may minimize listing during gait, while use of appropriate footwear may further optimize gait mechanics and function. (10)

Collaboration with occupational therapists is also of benefit in obtaining adaptive equipment and suggestions for ADL modifications to improve functional performance. For example, wearing loose fitting clothing with velcro can save energy and facilitate increased independence with dressing. (10) Group activities, including dancing, singing, cooking and exercise, provide both psychomotor and psychologic benefit to participants given the positive support and comfort resulting from group collaboration and exchange.10 Relaxation techniques can also be addressed in the group setting through activities such as yoga, tai chi or water aerobics. (10,11) Education on energy conservation, work simplification, pacing, infection control and therapeutic exercise should reflect the needs of the patient relative to disease progression. (10)

As previously mentioned, physical therapy sessions should be coordinated with medication administration in order to yield maximal effects from the drug. (8) For example, scheduling physical therapy one hour after the administration of the morning dose of levodopa allows maximal pharmacologic and physical therapy benefits to occur simultaneously. During peak drug effect, problematic parkinsonian symptoms are most controlled, thus promoting more complete patient participation in therapy sessions so maximal gains can be achieved. However, when beneficial effects of the medication are at their greatest, so are the adverse effects of the medication. Despite the benefits of antiparkinson medications, many cause orthostatic hypotension. (8) Blood pressure and heart rate should therefore be closely monitored with positional changes to prevent injury related to a syncopal event. (8)

A randomized controlled trial was conducted to ascertain the impact of physical therapy on QOL measures in patients with idiopathic PD (Hoehn and Yahr Stage II) on a stable medication regimen. In the short term, patients who received physical therapy and continued with the medication program reported improved QOL, most notably due to improvements in mobility, comfortable walking speed (CWS) and activities of daily living (ADLs). (12) Long term benefits were also noted, specifically improvement in the CWS score, the Unified Parkinson's Disease Rating Scale (UPDRS) ADL score and UPDRS total score. (12) The absence of regular physical activity increases the risk of falls in patients, with PD, given deteriorations in muscle strength and balance. (17) Rehabilitative interventions can assist patients with PD in maximizing physical performance and activities of daily living and delay, if not prevent, secondary complications. (17)

Conclusion

PD is a progressive disease with no cure. (6, 11) The medical and surgical therapies to date have not been able to avert the development of later, severe symptoms. At this time, it is through the interplay of pharmacotherapy, physical rehabilitation and DBS that patients can receive the individualized therapy necessary to decrease the debilitating symptoms and impairments of PD for improved QOL.

References

(1.) Parkinson's Disease Foundation http:// www.pdf.org Accessed November 20, 2007.

(2.) Nutt, J.G., and Wooten, F.W. (2005) Diagnosis and Initial Management of

(3.) Parkinson's Disease. N Engl J Med. Vol 353(10): 1021-1027. Parkinson's Disease Foundation. www.pdf.org/Publications/Surgery_ for_PD.pdf. Accessed November 20, 2007.

(4.) Libow, LS. (2006) Introduction. Symposium Reporter. Vol 7(7suppl 1): 3.

(5.) NYU Medical Center http://www.med. nyu.edu/patientcare/library Accessed November 25, 2007.

(6.) Parkinson's Disease Society http:// www.parkinsons.org.uk Accessed November 20, 2007.

(7.) Schapira, AHV. (2007) Future Directions in the Treatment of Parkinson's Disease. Movement Disorders. Vol 22(suppl 17): S385-S391.

(8.) Ciccone, CD. Pharmacology in Rehabilitation. F.A. Davis Company: Philadelphia, 1996.

(9.) Noble, C. (2007) Understanding Parkinson's Disease. Nurs Stand. Vol 21(34): 48-56.

(10.) Sullivan, S.B., and Schmitz, T.J. Physical Rehabilitation and Assessment and Treatment. F.A. Davis Company: Philadelphia, 2002. (11.) Pahwa, R. (2006) Understanding Parkinson's Disease: An Update on Current Diagnostic and Treatment Strategies. Symposium Reporter. Vol 7(7 Suppl 2): 4-10.

(12.) Ellis, T. (2005) Efficacy of a Physical Therapy Program in Patients With Parkinson's Disease: A Randomized Controlled Trial. Arch Phys Med Rehabil. Vol 86(4): 626-32.

(13.) Hermanowicz M.D., Neal. (2007) Drug Therapy for Parkinson's Disease. Seminars in Neurology. Vol 27(2): 97-105.

(14.) Volkmann J. (2004) Deep Brain Stimulation for the Treatment of Parkinson's Di sease. J Clin Neurophysiol Vol 21(1): 6-17.

(15.) Uc, EY., Follet, K.A. (2007) Deep Brain Stimulation In Movement Disorders. Seminars in Neurology. Vol 27(2): 170-182.

(16.) Kern DS and Kumar R. (2007) Deep Brain Stimulation. Neurologist. Vol 13(5): 237-52.

(17.) Crizzle, AM., Newhouse, IJ. (2006) Is Physical Exercise Beneficial for Person's With Parkinson's Disease? Clin J Sport Med. Vol 16(5): 422-25.

Amber L. Spitzer, PT, DPT

Ellen Wruble Hakim, PT, DScPT,

MS, CWS, FACCWS

Ellen Wruble Hakim, PT, DScPT, MS, CWS, FACCWS is Vice Chair of the Professional Degree Programs and Director of the Entry-level DPT Program in the Department of Physical Therapy and Rehabilitation Science at the University of Maryland School of Medicine. She serves as a subject matter expert for the APTA's Acute Care Section in efforts to formulate a description of specialty practice.

Amber L. Spitzer, PT, DPT is the Assistant Physical Therapy Supervisor at The Joan and Joel Smilow Cardiopulmonary Rehabilitation and Prevention Center at The Rusk Insitute of Rehabilitative Medicine, NYU Langone Medical Center.
Table 1. Hoehn and Yahr Staging of Parkinson's Disease

Stage I

* Unilateral involvement
* Minimal or no functional impairment
* Friends have noticed changes in posture, locomotion and facial
   expression

Stage II

* Bilateral or midline involvement
* No impairment of balance
* Mild disability

Stage III

* Impaired righting reflexes
* Mild to moderate disability
* Significant slowing of body movements
* Early impairment of equilibrium on walking or standing

Stage IV

* Severely disabled
* Can still walk to a limited extent
* No longer able to live alone

Stage V

* Confinement to bed or w/c unless aided
* Cachectic stage
* Requires constant nursing care

Sources:

1) Hoehn, M and Yahr, M: Parkinsonism: onset, progression
and mortality. Neurology 17(5): 427-24, 1967.

2) O'Sullivan, S.B. and Schmitz, T.J. Physical Rehabilitation and
Assessment and Treatment. F.A. Davis Company: Philadelphia, 2002.

3) Massachusetts General Hospital: Functional and Stereotactic
Neurosurgery 3)
http://neurosurgery.mgh.harvard.edu/Functional/pdstages.htm
Accessed March 29, 2008.

Table 2: Clinical Manifestations

* Poverty of movement
* Fatigue
* Gait impairments
* Mask-like facial expression
* Dsyphagia
* Dysarthria, hypophonia, mutism
* Autonomic nervous system dysfunction
* Visual deficits
* Mental status changes
* Perceptual motor deficits
* Sensory loss

Sources:

1) O'Sullivan, S.B. and Schmitz, T.J. 1) Physical
Rehabilitation and Assessment and Treatment.
F.A. Davis Company: Philadelphia, 2002.

2) Parkinson's Disease Foundation 2) http://www.
pdf.org Accessed March 29, 2008.

Table 3a: Carbidopa/Levodopa combinations

                 AVAILABLE         INITIAL
MEDICATION       DOSES             DOSING      SIDE EFFECTS

Carbidopa/       10/100 mg         25/100 mg   Low blood pressure,
Levodopa         25/100 mg         2-3X/day    nausea, confusion,
(Sinemet         50/200 mg                     dyskinesia, dry mouth,
[R])                                           dizziness

Carbidopa/       10/100 mg         50/200 mg   Low blood pressure,
Levodopa         25/100 mg         2X/day      nausea, confusion,
controlled       50/200 mg                     dyskinesia, dry mouth,
release                                        dizziness
(Sinemet
CR [R])

Carbidopa/       12.5/50/200 mg    12.5/50/    Dyskinesia, nausea,
Levodopa/        25/100/200 mg     200 mg      diarrhea, hyperkinesia,
Entacapone       18.75/75/200 mg               abdominal pain,
(Stalevo         31.25/125/200                 dizziness, harmless
[R])             mg                            discoloration of urine,
                 37.5/150/200 mg               saliva and/ or sweat
                 50/200/200 mg

Carbidopa/       10/100 mg         25/100 mg   Low blood pressure,
Levodopa         25/100 mg         2-3X/day    nausea, confusion,
Orally           25/250 mg                     dyskinesia, dry mouth,
disintegrating                                 dizziness
tablet
(Parcopa
[R])

MEDICATION       INDICATIONS                   INTERACTIONS

Carbidopa/       First course of treatment;    Antacids, antiseizure
Levodopa         converts to dopamine to       drugs,
(Sinemet         manage major symptoms         antihypertensives,
 [R])                                          antidepressants,
                                               high protein
                                               food

Carbidopa/       First course of treatment;    Antacids, antiseizure
Levodopa         converts to dopamine to       drugs,
controlled       manage major symptoms and     antihypertensives,
release          may prolong effectiveness     antidepressants,
(Sinemet CR                                    high protein
[R])                                           food

Carbidopa/       Secondary course of           Same as levodopa/
Levodopa/        treatment; combines           carbidopa, MAO
Entacapone       entacapone with levodopa/     inhibitors, Comtan,
(Stalevo         carbidopa to block COMT       Sinemet, high doses
[R])             enzyme and prolong            (10 mg or more) of
                 levodopa's effectiveness      selegiline

Carbidopa/       First course of treatment;    Antacids, antiseizure
Levodopa         converts to dopamine to       drugs,
Orally           manage major symptoms;        antihypertensives,
disintegrating   also for patients with        antidepressants,
tablet           swallowing difficulties       high protein
(Parcopa                                       food
[R])

Table 3b: Dopamine Agonists

MEDICATION       AVAILABLE                        SIDE EFFECTS*
                 DOSES      DOSING

APOKYN           .02 mL-    .02 mL during    Nausea, vomiting, low
[TM}             .06 mL     "off" periods    blood pressure,
injection                                    sleepiness,
(apomorphine                                 dyskinesias,
hydrochloride)                               hallucinations,
                                             chest pain

Bromocriptine    2.5 mg     2.5 mg 3X/day    Low blood pressure,
(Parlodel        5 mg                        nausea, edema,
[R])                                         confusion, dry mouth,
                                             depression, headaches

Rotigotine       2mg/       One 2 mg         Nausea, application
Transdermal      24hrs      patch a day      site reactions,
System           4 mg/                       somnolence, dizziness,
(Neupro          24hrs                       headache, vomiting,
[R])             6 mg/                       sleep attacks,
                 24hrs                       insomnia.

Pramipexole      .125 mg    .125 mg 3X/      Arthritis, chest pain,
(Mirapex         .25 mg     day              nausea, low blood
[R])             .5 mg                       pressure, sleep
                 1 mg                        disturbances, sedation
                 1.5 mg

Ropinirole       .25 mg     .25 mg 2X/day    Abdominal pain, sleep
(Requip          .5 mg                       disturbances, nausea,
[R])             1 mg                        low blood pressure,
                 2 mg                        sedation
                 3 mg
                 4 mg
                 5mg

Ropinirole       (Once      2 mg taken       Nausea, dizziness,
                 daily)
extended-        2 mg       once a day for   drowsiness, or
release          4 mg       1 to 2 weeks,    sleepiness, headache,
tablets          6 mg       followed by      sudden uncontrolled
(Requip          8 mg       increases of     movements (dyskinesia),
 [R] XL          10 mg      2 mg/day at 1    abdominal pain/
[TM])            12 mg      week or longer   discomfort,
                 14 mg      intervals as     hallucination,
                                             constipation and
                 16 mg      appropriate      increase or decrease in
                 18 mg                       blood pressure and heart
                 20 mg                       rate. Patients should
                 22 mg                       also tell their doctor
                 24 mg                       if they experience new
                                             or increased gambling,
                                             sexual, or other intense
                                              urges while taking
                                              Requip XL. Requip XL
                                              may increase the side
                                              effects of levodopa.

Table 3c: Anticholinergics

                 AVAILABLE    INITIAL
MEDICATION       DOSES        DOSING       SIDE EFFECTS *

Benzotropine     .5 mg        .5 mg 2X/    Confusion, hallucinations,
mesylate                      day          nausea, blurred vision, dry
(Cogentin                                  mouth, urinary retention,
[R])                                       nervousness; not used
                                           long-term due to side
                                           effects

Trihexyphenidyl  1 mg         1-2 mg 2X/   Confusion, hallucinations,
HCL              2 mg         day          nausea, blurred vision, dry
(Artane                                    mouth, urinary retention,
[R])                                       nervousness; not used
                                           long-term due to side
                                           effects

MEDICATION       INDICATIONS                   INTERACTIONS

Benzotropine     Secondary medication;         Anti-histamines,
mesylate         tremor; attempts to restore   Propulside [R],
(Cogentin        balance by inhibiting other   Haldol [R], Thorazine
[R])             enzymes and nerve cells       [R], Symmetrel [R],
                 that may attack dopamine      Clozaril [R], alcohol

Trihexyphenidyl  Secondary medication;         Anti-histamines
HCL              tremor; attempts to restore
(Artane          balance by inhibiting other
[R])             enzymes and nerve cells
                 that may attack dopamine

Table 3d: MAO-B Inhibitors

                    AVAILABLE  INITIAL
MEDICATION          DOSES      DOSING         SIDE EFFECTS *

Selegiline          5 mg       5 mg 2X/       Agitation, insomnia,
(Eldepryl [R],                 day            hallucinations
Carbex [R]                     (max dose)

Selegiline HCI      1.25mg     1.25mg 1X      Dizziness, nausea, pain,
Orally                         daily          headache, insomnia,
disintegrating                                rhinitis, dyskinesias,
tablet                                        back pain, stomatitis,
(Zelapar [R])                                 dyspepsia

Rasagiline          0.5mg      0.5mg 1X       Increased dyskinesias,
(Azilect [R])       1mg        daily          postural hypotension,
                                              headaches, joint pain,
                                              indigestion

MEDICATION          INDICATIONS               INTERACTIONS

Selegiline          Tertiary medication;      Anti-depressants,
(Eldepryl [R],      controls brain's          narcotic painkillers,
Carbex [R]          metabolism of dopamine    decongestants

Selegiline HCI      Adjunct to levodopa in    Anti-depressants,
Orally              patients with             narcotic decongestants
disintegrating      painkillers, "off"        significant
table (Zelapar      periods
[R])

Rasagiline          Signs and symptoms        High tyramine content
(Azilect [R])       of PD as initial          foods (for example,
                    monotherapy and           draft beer, red wine,
                    adjunct to levodopa       aged cheeses, soy sauce
                                              and other products),
                                              narcotic painkillers,
                                              anti-depressants,
                                              decongestants

Table 3e: COMT Inhibitors

               AVAILABLE   INITIAL
MEDICATION     DOSES       DOSING          SIDE EFFECTS *

Entacapone     200 mg      200 mg with     Abdominal pain, back
(Comtan [R])               levodopa;       pain, constipation, nausea,
                           max 8 per day   diarrhea, blood in urine

Tolcapone      100 mg      100 mg 3X/      Abdominal pain, back
(Tasmar [R])   200 mg      day             pain, constipation, nausea,
                                           diarrhea, blood in urine,
                                           liver failure

MEDICATION     INDICATIONS                     INTERACTIONS

Entacapone     Secondary medication; delays    MAO inhibitors
(Comtan [R])   wearing off by prolonging
               effectiveness of levodopa

Tolcapone      Tertiary medication for motor   MAO inhibitors
(Tasmar [R])   fluctuations; limited in
               those who have exhausted other
               treatment options

Other medications

                AVAILABLE       INITIAL
MEDICATION      DOSES           DOSING        SIDE EFFECTS *

Amantadine      100 mg          100 mg 2-3    Dizziness, weakness,
(Symmetrel                      X/day         dry mouth,
[R])                                          constipation, skin
                                              blotches

Rivastigmine    1.5mg           1.5mg 2X      Nausea, vomiting, loss
tartrate        3mg             per day       of appetite, weight
(Exelon         4.5mg                         loss
[R])            6mg
                Patch 10 (9.5
                mg/24 hrs)
                Patch 20 (17.4
                mg/24 hrs)

MEDICATION      INDICATIONS             INTERACTIONS

Amantadine      Secondary medication    Cogentin [R] (benztropine),
(Symmetrel      for tremor and muscle   Disipal [R] (orphenadrine),
[R])            rigidity                Sinemet [R] (levodopa),
                                        Artane [R] (trihexyphenidyl),
                                        amphetamines, alcohol

Rivastigmine    Dementia associated     No known drug-drug
tartrate        with PD                 interactions
(Exelon [R])

* Please note that the side effects listed in the tables that
accompany each class of medication are the most commonly experienced.
Not all individuals will experience such side effects. For many
people who do experience side effects, they can often be effectively
limited or eliminated with careful adjustments to dosage or the timing
of the individual doses. If any side effects are experienced, speak to
the treating physician immediately. For a complete description of each
drug and its possible side effects, please request a "package insert"
from your pharmacist for each drug being used. It is recommended that
all prescriptions be filled at the same pharmacy to avoid interactions
between medications. Interactions can be dangerous and even
life-threatening, so make sure the pharmacist knows of all medications
and supplements being taken--including over-the-counter medications
and supplements.

This chart was originally published on the
Parkinson's Disease Foundation's (PDF) website,
www.pdf.org/en/meds_treatment. It is reprinted, in its entirety,
with permission from PDF. For additional information of Parkinson's
disease, please visit www.pdf.org.

Table 4

Good Candidate for DBS

* Typical PD with tremor
* Good response to levodopa
* Dyskinesias
* Wearing-off spells
* Good general health
* Excellent family support

Poor Candidate for DBS

* Atypical parkinsonism
* Poor response to levodopa
* Memory problems, apathy or
   confusion
* Severe depression or anxiety
* Severe medical problems
* No social support

This chart was originally published on the Parkinson's
Disease Foundation's (PDF) website, www.pdf.org/
pdf/DBS2008.pdf. It is reprinted, in its entirety, with
permission from PDF. For additional information of
Parkinson's disease, please visit www.pdf.org.
COPYRIGHT 2008 American Physical Therapy Association, Acute Care Section
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2008 Gale, Cengage Learning. All rights reserved.

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Author:Spitzer, Amber L.; Hakim, Ellen Wruble
Publication:Acute Care Perspectives
Date:Dec 22, 2008
Words:5420
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