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PARKINSON DISEASE
Slow and Shaky. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Level III
Mary L. Wagner, PharmD, MS
CASE SUMMARY
First visit: A 53-year-old woman presents for an evaluation of
new-onset stiffness, tremor, and slowness. The history and physical
exam indicate new-onset PD with nonmotor symptoms of constipation and decreased ability to smell that have preceded the motor
symptoms and diagnosis of PD. The patient also has hypertension
controlled on medication and perimenopausal symptoms of night
sweats, trouble sleeping, and decreased libido that may also be
partly associated with symptoms of PD. Initial treatment options
for a patient diagnosed with early PD are discussed and include a
monoamine oxidase (MAO) type B inhibitor, dopamine agonist, or
levodopa–carbidopa with or without a catechol-O-methyl transferase (COMT) inhibitor.
Second visit: The patient returns 1 year later and describes that
the rasagiline was only partially helpful. After 3 months, she added
pramipexole, which improved her motor symptoms, thinking speed,
and perimenopausal symptoms. However, she developed compulsive
behaviors that were determined to be a side effect of the pramipexole.
These symptoms resolve after stopping the dopamine agonist. The
patient’s seborrhea is a rare sign in mild PD and had not been treated
at the first visit, but it resolved with dopaminergic treatment.
Third visit: The patient’s disease progresses over a 7-year period,
when she returns with the development of motor fluctuations
related to drug–food and drug–drug interactions. She also reports
new-onset RLS. The patient’s hypertension is controlled, but her
risk for osteoporosis has not been adequately evaluated. Students
are asked to make adjustments to the patient’s current therapy
based on the presence of these problems.
QUESTIONS
Problem Identification
1.a. List and assess each one of the patient’s complaints. Determine if there are multiple potential etiologies that could
account for the symptoms.
• Tremor is a symptom of PD.
• Muscle stiffness is a symptom of PD (rigidity).
• Slow movements and taking longer to do things are symptoms
of PD (bradykinesia).
• Constipation is a common premotor symptom and likely to be
a chronic problem because PD patients have decreased gastric
emptying and delayed colon transit time. In addition, the
neurons in the mesenteric plexus of the colon of patients with
PD are thought to degenerate as well. The patient’s constipation also could be aggravated by the calcium channel blocker
and Parkinson’s medications. The patient’s mild constipation
should improve by increasing fiber and fluid intake and physical activity; a mild cathartic may be used as needed.
• Night sweating is most likely a symptom of menopause. It also
may be an autonomic symptom of PD, and the patient should
be asked about sweating at other times of the day.
• Trouble sleeping may be a symptom of menopause, but it could
easily be an associated symptom of PD and more detailed
questions should be asked.
• Irregular menstrual periods are likely to be premenopausal
symptoms and not related to PD.
1.b.Assess the abnormalities in the physical examination and
laboratory findings.
• Seborrhea is suggested by the presence of dry, yellow scales
on the patient’s eyebrows. Seborrhea is sometimes a sign of
PD and may improve with PD treatment. If treatment for
seborrhea is considered necessary, over-the-counter tar-based
dandruff shampoos can be used twice weekly. It is more commonly seen in older patients, more advanced disease, and in
undertreated PD patients.
• Decreased facial expression (masked facies) and decreased eye
blinking are signs of bradykinesia.
• Pill-rolling rest tremor in her right hand is a sign of PD.
• Rigidity is a sign of PD.
• Micrographia is a sign of PD and a consequence of bradykinesia and rigidity.
• Decreased hand agility, as noted by the patient having problems with dressing, cutting food, motor coordination, and
rapid alternating movements, is a symptom of PD.
• Low serum vitamin D concentration is a common problem in
many people with or without PD.
• Total Unified Parkinson Disease Rating Scale (UPDRS) of
seven indicates very mild PD. The UPDRS is a six-part scale in
which each question is assigned a score ranging from 0 to 4 (none
to severe). It evaluates mentation, behavior, and mood (part 1,
4 items); activities of daily living (ADLs) (part 2, 13 items); PD
motor symptoms (part 3, 27 individual scoring items); complications of therapy (part 4); and stage of disease (parts 5 and 6).
• Hamilton depression score of 3 is within the range of normal.
There are 21 questions with a total possible score of 66 (0–6 is
normal and 7–17 is mild depression). In addition, the patient
does not express feelings of depression although sleep dysfunction could be related to either serotonin/noradrenergic
problems or menopause.
1.c. List the cardinal motor and nonmotor symptoms of PD, and
describe which signs and symptoms of PD are present in this
patient.
• The cardinal motor signs of PD are rest tremor, rigidity, bradykinesia (akinesia), gait problems, and postural instability.1 This
patient manifests tremor, rigidity, and bradykinesia. Postural
instability usually occurs late in the course of the disease.
• Nonmotor symptoms that may be seen in PD include psychological disturbances (ie, psychosis, dementia, depression,
anxiety, and behavioral problems), sleep disorders, autonomic
dysfunction (ie, drooling, constipation, sexual dysfunction,
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Parkinson Disease
Margery H. Mark, MD
• Decreased libido may be a nonmotor symptom of PD that
should improve with adequate treatment for PD. It may also be
a symptom associated with menopause. Many women do not
feel comfortable talking about this subject, and many clinicians
fail to ask the patient about these symptoms. With the goal of
minimizing doses of dopamine drugs, it is important to assess
the patient’s functional ability throughout the entire day.
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• Loss of smell is a common premotor symptom of PD.
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urinary problems, sweating, orthostatic hypotension, and seborrhea), speech disturbances, anosmia, and sensory changes.
Some patients develop nonmotor symptoms prior to the onset
of motor symptoms.1–5 This patient reports constipation and
seborrhea. The patient’s symptoms of sleeping problems,
night sweating, and decreased libido may be related to PD or
menopause.
1.d.According to the Hoehn–Yahr Scale, what stage is the
patient’s disease?
Neurologic Disorders
• The patient exhibits early signs of Stage I PD. She has unilateral
and mild symptoms of tremor, rigidity, and bradykinesia without postural abnormalities.
Desired Outcome
2.What are the goals of therapy for patients with PD?
• Currently, there are no therapies that cure PD. Theories
abound and many studies are underway to try to slow the progression of disease; however, no available therapies have been
proven to do so.
• The goals of treatment are to reduce the incidence and severity
of motor and nonmotor symptoms, maintain quality of life,
improve ADLs, and minimize complications of drug therapy.
Therapeutic Alternatives
3.a. What nonpharmacologic alternatives may be beneficial for
the treatment of PD in this patient both now and in the
future?
• It is important to evaluate the potential benefit of referring the
patient to a physical therapist, occupational therapist, speech
therapist, and nutritionist.2–4,6,7
• An exercise program and increased activity during the day
should improve the patient’s constipation. Keeping physically
active may improve daytime alertness, sleep quality, mood,
and overall health. Several studies suggest a neuroprotective
role for exercise in PD.6
• Physical therapy is not needed for this patient now. It will
become important when she develops balance and gait problems because it provides additive symptomatic benefit to
medications.7 A therapist can then teach her skills that would
improve her motion and reduce her risk of falling. It will also
teach her how to exercise in ways that minimize injury. At this
point, she should be able to engage in any exercise regimen
she chooses, and working with a trainer at a gym would be
advantageous.
• Occupational therapy can be helpful for improving her writing
and typing. As her disease progresses, a therapist can provide
information about adaptive equipment for the home, specialized clothing, and personal training that can maximize her
independence, safety, and ADLs.
• Speech therapy is not needed at this time. It may be helpful
in the future to assess the patient’s swallowing and teach her
exercises that improve speech quality.
• Dietary modification should include increased fluids and
fiber-rich foods. Modifying the protein content in meals can
improve nausea and erratic drug absorption, but this is only
an issue for patients taking levodopa. Changing the texture
of foods may minimize the risk of aspiration. These problems
are not currently a concern for this patient, but they should
be kept in mind as the disease progresses. Patients should eat
a balanced diet and take a daily multivitamin. Patients should
make sure that they are eating food rich in folic acid (eg, beans,
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
wheat germ, and nuts) and vitamin B12 (eg, meat, fish, and
cheese).
• Surgical procedures (eg, deep brain stimulation) are effective
for patients with tremor and dyskinesias. This patient is currently not a candidate for surgery because her symptoms are
mild, and she has not exhausted all pharmacologic options.
Patients with significant psychiatric and cognitive problems
should not have the surgery because their outcomes are generally poor.
• Music therapy may improve memory, help with relaxation, and
strengthen voice muscles with singing.
• Other therapies that patients may ask about include: acupuncture, Alexander techniques, applied kinesiology, chelation
therapy, detoxification therapy, healing touch therapy, hypnosis, or ozone therapy to name a few. There is unclear, conflicting, or negative evidence for these therapies.7,8
3.b. Based on the patient’s signs and symptoms, what pharmacotherapeutic alternatives are viable options for her at this
time?
• The agents discussed below may improve the motor symptoms
of PD. It should be noted, however, that motor fluctuations
and associated nonmotor symptoms such as insomnia, constipation, and psychological disturbances are common. These are
difficult to treat because they may be difficult to differentiate
from drug effects and disease progression.9
• Anticholinergics may be somewhat helpful for treating rest
tremor, urinary frequency, excess sweating, and drooling but
less effective for bradykinesia, rigidity, or gait problems. They
are not a good option in this patient because of her constipation. These agents are usually avoided or used with caution in
patients more than 60 years of age because of an increased risk
of confusion, cognitive problems, and hallucinations. Considering that PD patients have an increased risk of dementia,
it is interesting to note that anticholinergic medications have
been associated with a 2.5-fold increase in amyloid plaque
and neurofibrillary tangle densities. This may increase the
risk of cognitive impairment. Patients should receive baseline evaluations for cognition, psychiatric history, and blood
pressure prior to starting therapy. Then monitor patients for
dry mouth, dry eyes, blurred vision, constipation, memory/
cognitive problems, urinary retention, orthostatic hypotension, temperature sensitivity, and sedation. These agents
also decrease gastric acid secretion, delay gastric emptying,
and may decrease the absorption of other medications. They
should be discontinued gradually to avoid withdrawal effects
or worsening of PD symptoms. Although CNS side effects still
occur, glycopyrrolate has poor CNS penetration and may be
helpful for treating sialorrhea and sweating. Not many brand
name anticholinergic products are available because many
companies have discontinued their oral formulations. Available oral products include:
✓Trihexyphenidyl (generic)
✓Benztropine mesylate (generic)
✓Orphenadrine citrate (generic)
✓Glycopyrrolate (Robinul, Robinul Forte)
• Overall, the risk-to-benefit ratio of these drugs is not favorable
in PD.
• MAO-B inhibitors selectively and irreversibly inhibit MAO
type B, which decreases dopamine metabolism. They may
also act by reducing free radical formation and by a variety
of other mechanisms including those that affect apoptosis
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✓Selegiline orally disintegrating tablet (Zelapar)
✓Rasagiline (Azilect)
• Selegiline is primarily metabolized by CYP2B and CYP3A4.
Rasagiline is metabolized by CYP1A2. The metabolites of
selegiline (desmethylselegiline) and rasagiline (aminoindan) are also purported to have neuroprotection properties.
Unlike selegiline, rasagiline is not metabolized to amphetamine which may have neurotoxic and stimulating properties. The disintegrating tablet formulation of selegiline avoids
first-pass metabolism, which improves bioavailability and
decreases amphetamine metabolite concentrations. The hope
that rasagiline would be neuroprotective was diminished
when the ADAGIO study reported that the 1-mg but not
the 2-mg dose met the criteria for possible neuroprotection.
Because of these mixed findings, the FDA did not support the
claim that rasagiline was neuroprotective; however, additional
research continues because patients who initiate treatment
with MAO-B inhibitors may have better outcomes than those
who do not initiate treatment with MAO-B inhibitors. Questions that remain to be answered are how a potential U-shaped
dose–response curve may affect future dosing and outcome, if
administering medication early in the disease helps or hinders
compensatory mechanisms, and if treatment of patients with
early identifiable risk factors should have different outcome
measures. The current UPDRS scale used as the primary
outcome in these studies may not be sensitive enough to
measure changes in patients with early PD possibly leading
to missing mild clinical improvements. The modified version
of the UPDRS scale and new questionnaire related to nonmotor symptoms may be better than the unmodified UPDRS to
measure outcomes in patients with early disease. In 2007, the
Movement Disorder Society (MDS) published a revision of the
UPDRS, known as the MDS-UPDRS. The MDS-UPDRS modifies the original with the following subscales: (1) nonmotor
experiences of daily living (13 items), (2) motor experiences of
daily living (13 items), (3) motor examination (18 items), and
(4) motor complications (6 items).10
• Side effects of selegiline include nausea, confusion, hallucinations, insomnia, headache, jitteriness, orthostatic hypotension,
and dyskinesias. Rasagiline can cause diarrhea, weight loss,
hallucinations, and rash. Elderly patients may be more prone
to the psychiatric side effects. Dyskinesias should improve with
a decrease in concomitant carbidopa/levodopa dose. There is
• A dopamine agonist may be a good option for this patient
because she is young and without psychiatric symptoms. Starting a dopamine agonist should relieve symptoms of PD, delay
the need for carbidopa/levodopa by 4–5 years, and decrease
her risk of developing motor fluctuations by two to three
times. Although some experts contend that use of levodopa
should be delayed, there are equal arguments to the contrary.
The use of a dopamine agonist in preference to carbidopa/
levodopa may result in less motor benefit and greater risk
of hallucinations or somnolence. Levodopa should be used
as initial therapy in the elderly and in those with cognitive
impairment; some experts argue that it is also the preferred
drug even in younger patients. Nevertheless, young patients
may be more likely to develop obsessive–compulsive disorder
(OCD) and impulse-control disorder (ICD), which can occur
with dopamine agonists.
• Dopamine agonists can also be added to carbidopa/levodopa
when patients develop motor complications. They have a
longer duration of action, minimize fluctuations in dopamine
blood concentrations, decrease off-time, improve wearing-off
symptoms, allow for levodopa dose reduction, and improve
ADLs.2,3 Products available include:
✓Bromocriptine (Parlodel)
✓Cabergoline (Dostinex): not approved for use in PD
✓Pramipexole (Mirapex)
✓Pramipexole ER (Mirapex ER)
✓Ropinirole (Requip)
✓Ropinirole XL (Requip XL)
✓Apomorphine (Apokyn): SC injection for “rescue therapy”
✓Rotigotine (Neupro) transdermal ER patch
• Bromocriptine and cabergoline are ergot derivatives. Cabergoline, a very long-acting agonist, is effective for PD but is
very expensive, and the manufacturer sought an indication
for hyperprolactinemia instead of PD. Bromocriptine is the
least potent of all these drugs and has fallen out of current
use. Pramipexole, ropinirole, apomorphine, and rotigotine are
nonergot derivatives.
• Ropinirole is metabolized by CYP1A2, pramipexole is eliminated unchanged in the urine by active tubular secretion, and
rotigotine is metabolized by conjugation and dealkylation. The
metabolism profile differences may be important when identifying potential drug interactions.
• Common class side effects include nausea, vomiting, dyskinesias, somnolence, sedation, hallucinations, nightmares, confusion, and postural hypotension. Dyskinesias caused by adding
any of the dopamine agonists to carbidopa/levodopa may be
improved by decreasing the dose of either drug. In addition,
ergot medications may cause erythromelalgia (painful reddish
discoloration of the skin over the shins) as well as pleuropulmonary, retroperitoneal, and cardiac fibrosis.
• Dopamine agonists have been associated with punding (repetitive, often purposeless, stereotyped behaviors) and ICD such
as an excessive craving for gambling, shopping, sexual activities, hobbies, or eating. The literature quotes a rate of 17% of
OCD and ICD, but many experts feel that this is an underestimate. All patients on dopamine agonists should be asked at
every visit about any change in behavior. Lowering the dose
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Parkinson Disease
✓Selegiline (Eldepryl)
no real tyramine effect with these drugs, which are MAO-Bspecific in therapeutic doses, so there is little concern about
hypertensive crises. The FDA has lifted the caveats regarding
rasagiline and tyramine-containing foods.
CHAPTER 69
(programmed cell death), trophic factors, or signaling pathways. The current agents in this class have a propargyl ring
structure that binds to the glyceraldehyde-phosphate dehydrogenase (GAPDH), an enzyme used in the glycolysis pathway.
They also prevent activation of caspase, an enzyme that cleaves
protein and is important in apoptosis. Clinically, they symptomatically delay the need to start levodopa, allow for a lower
dose of levodopa, decrease off-time, and improve wearing-off
symptoms in patients with motor fluctuations, but their effects
are generally mild. Their neuroprotective effects are possible
but not proven. Safinamide, an investigational drug, has antiglutamate activity which may improve dyskinesia. An MAO-B
inhibitor could be used as initial therapy in this patient for
mild symptomatic effect while delaying the need for carbidopa/levodopa; however, the patient should be informed that
these agents have not been proven to delay progression of the
disease. Since her symptoms are affecting her job performance,
an MAO inhibitor may not be enough to control her symptoms.3 Available agents include:
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SECTION 6
is usually not sufficient, but stopping the medication should
relieve the behaviors. Trials with zonisamide, amantadine,
topiramate, or valproate may be effective in patients refractory
to dose reduction.3
Neurologic Disorders
• Excessive daytime sleepiness may occur in 15% of PD patients,
and 67% of patients have nighttime sleep disturbances. Excessive sleepiness can be aggravated by all dopaminergic drugs;
therefore, patients taking dopamine agonists or carbidopa/
levodopa who are still driving need to be aware of this potentially dangerous side effect. Sleep attacks may occur without
warning in up to 6% of patients. Patients at greatest risk of
sleep attacks are those with a high Epworth Sleepiness Scale
score, long duration of PD, and those taking dopamine agonists with levodopa. Medications may contribute to sleepiness;
however, the pathology of PD may be a large contributor as
the 8-year prevalence rate of daytime sleepiness increased from
6 to 54%. Rather than sacrifice motor performance by reducing or eliminating the offending agonist, addition of modafinil
(Provigil) in doses of 200–600 mg daily (divided BID) may be
helpful. Patients’ driving ability can be assessed using simulated driver’s tests.
• Apomorphine is approved by the FDA for acute end-of-dose
wearing off and unpredictable on/off episodes in patients with
advanced stages of PD. It is used as parenteral (injectable)
rescue therapy because apomorphine’s onset of effect is within
10–20 minutes and its duration is only 60 minutes. Because
it causes nausea and vomiting, premedication with an antiemetic is required initially, but this side effect may wane over
time. Choosing an antiemetic is tricky because many common
antiemetics worsen PD symptoms, and the 5-HT3 antagonists
used for nausea aggravate hypotension. Trimethobenzamide
300 mg three times daily should be taken for 2 days prior to
starting apomorphine and continued for 2 months or until
tolerance to the nausea develops. Apomorphine may also
improve nonmotor symptoms of pain, panic attacks, erectile
dysfunction, or GI symptoms. Domperidone, an antiemetic
not available in the United States (but available in Canada), but
unlike other antiemetics, it is a peripheral blocker of D2 and
D3 and does not decrease central dopamine.
• Rotigotine, a patch formulation providing 24-hour dopaminergic coverage, is approved for both early and advanced
PD. Patients apply the patch once daily to a hairless area on
their abdomen, thigh, hip, flank, shoulder, or upper arm. This
product would be helpful for those who are unable to take oral
medications or have variable absorption due to altered gastric
motility. Patients who are allergic to sulfites may have an allergic reaction to the patch that contains sodium metabisulfite.
To avoid skin burning, the patch should be removed before
patients receive magnetic resonance imaging. Tolerance may
be an issue with higher doses and some patients may benefit
from a patch-free period during the night. It is also unknown
if the continuous delivery of dopamine will lead to fewer motor
complications. Patients often forget they are wearing a patch,
forget that patches are still medications and fail to report their
use to their other physicians, and/or remove them before the
24-hour period, all of which can lead to serious consequences.
• Carbidopa/levodopa is not needed at this time. When her
disease progresses and the dopamine agonist has been maximized, carbidopa/levodopa should be added to the dopamine
agonist. Levodopa decreases morbidity and mortality. Even
though it is metabolized to free radicals, it is unlikely to be
neurotoxic. Some clinicians decide that it is best to delay
levodopa therapy until after other agents have failed. Others
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
decide that levodopa initiation should not be delayed because
it may normalize basal ganglia dysfunction and clinical state.
Products available include:
✓Carbidopa/levodopa (Sinemet)
✓Carbidopa/levodopa controlled release (Sinemet CR)
✓Carbidopa (Lodosyn)
✓Carbidopa/levodopa extended release (Rytary)
✓Carbidopa/levodopa enteral suspension (Duopa)
✓Carbidopa/levodopa/entacapone (Stelevo)
• The sustained-release formulation has a delayed onset from 0.5
to 2 hours and longer duration due to longer absorption compared to the standard (immediate-release) tablets, decreasing
off-time, and improving wearing-off symptoms. Doses need
to be increased about 30% when converting from standard
release to sustained release because the sustained release is
only 70% absorbed. There is concern among some experts that
the generic sustained-release matrix formulation does not act
as reliably as the brand controlled-release, and dose failure
or irregular absorption is not uncommon when a patient is
switched from brand to generic. Bedtime administration may
improve off-symptoms during the night; however, it may be
of no help while patients are asleep and may not last long
enough to cover early morning off periods. Nighttime dosing
of levodopa may also be considered counterproductive because
it is not physiologic.
• Some patients may also need to take standard tablets when
they want a quicker onset of effect, such as the first morning
dose. Making a liquid formulation of carbidopa–levodopa
may be helpful for patients reporting a delayed onset of effect
with standard formulations. Proteins in the diet will compete
with levodopa for transport across the gut wall and blood–
brain barrier; thus, it is best if levodopa is given 0.5 hour
before or 1 hour after eating. Side effects of levodopa include
dyskinesias, orthostatic hypotension, confusion, nausea, and
psychological effects (hallucinations, nightmares, and altered
behavior). ICDs can occur, although less frequently than with
dopamine agonists. Usually 75–100 mg per day of carbidopa
is sufficient to inhibit dopa decarboxylase; however, some
patients may require up to 300 mg to minimize peripheral side
effects of levodopa. Levodopa should be discontinued slowly
to avoid neuroleptic malignant syndrome. Symptoms of PD
that do not respond well to levodopa therapy include balance
problems, freezing, autonomic symptoms, pain disturbances,
cognitive impairment, and psychological complaints.
• Rytary, an extended-release capsule formulation of carbidopa/
levodopa, provides more continuous blood concentrations
and has a longer duration of action than traditional formulations, allowing for a lower dosing frequency and reduction
in off-time. The levodopa/carbidopa combination can be
administered directly to the duodenum via a small tube and
decrease off-time in advanced patients. Doses are not directly
interchangeable with other levodopa preparations. Patients
need extensive education when stating this regimen, and they
will need to take oral medications along with their 16-hour
infusion.
• COMT inhibitors decrease the peripheral catabolism of
levodopa by inhibiting COMT.2,3 Products available include:
✓Tolcapone (Tasmar)
✓Entacapone (Comtan)
• A combination product with carbidopa/levodopa and entacapone (Stalevo) is available to simplify treatment for patients so
69-5
• Side effects of COMT inhibitors include GI disturbances (diarrhea, nausea, and vomiting), anorexia, dyskinesias, sleepiness,
urine discoloration, postural hypotension, and hallucinations.
Dyskinesias should improve with a decrease in the carbidopa/
levodopa dose. In 2010, the FDA issued a safety concern for
entacapone, because of a potential increased risk of cardiovascular disease and prostate cancer. In 2015, the FDA reported
that they found no evidence of an increased risk of myocardial
infarction, stroke, or other cardiovascular events associated
with the use of entacapone or Stalevo. Although one study
found no increased risk of prostate cancer, the data are still
under review with the FDA.
• Tolcapone was associated with several cases of severe liver
failure in initial studies, resulting in three fatalities and has
been removed from the market in some countries. For this
reason, it should be reserved for patients who cannot take or
do not respond to other adjunctive therapies (eg, entacapone).
It should be started at 100 mg daily and increased very slowly.
Serum alanine aminotransferase and aspartate aminotransferase concentrations should be monitored at baseline, then
every 2–4 weeks for 6 months and then periodically for the
remainder of therapy. If the liver function tests exceed two
times the upper limit of normal or there are other signs of
liver dysfunction, discontinue tolcapone. Entacapone has been
associated with two cases of liver dysfunction; however, there
are no guidelines for the monitoring of liver enzymes. This
patient does not need COMT inhibitors at this time because
they are only useful in conjunction with levodopa.
• Amantadine is another option for this patient, albeit lower
on the list, because its benefits are modest. In addition, its
mild anticholinergic properties may worsen the patient’s
constipation. It can be used as initial therapy in an effort to
delay starting levodopa. Some authorities suggest that it protects dopamine neurons from damage due to excitotoxins,
and a retrospective study reported that patients receiving
long-term amantadine had longer survival. It may decrease
off-periods and dyskinesias in patients who develop significant dyskinesias along with modest off-periods. Short-acting
levodopa causes pulsatile stimulation of dopamine receptors,
and it is associated with NMDA receptor changes that result in
motor complications. Amantadine, which antagonizes NMDA
receptors, may reduce these dyskinesias.3 It may also improve
• Side effects of amantadine include nausea, dizziness, insomnia,
livedo reticularis (benign purple mottling of the skin of dependent extremities), peripheral edema, orthostatic hypotension,
hallucinations, and confusion. Its stimulant action may worsen
insomnia and restlessness.2,3
• Nonprescription treatments (dietary supplements)8:
✓Coenzyme Q10 is a dietary supplement with little regulation by the FDA. Evidence is contradictory, and only much
higher doses than what the patient is taking seem to be
associated with any benefit or slowing of PD progression; see
Section 19 for further discussion.
✓Vitamins C and E are recommended for their antioxidant
properties; however, no significant improvements have been
shown compared to placebo. Vitamin C may increase the
concentrations of levodopa, thereby prolonging its action.
Some clinicians feel that vitamins C and E combined have a
synergistic effect, but this is unproven in PD.
✓B vitamin supplements may be warranted in some patients
with PD. Metabolism of levodopa may cause elevated homocysteine concentrations, and therefore greater B vitamin
requirements may be needed to maintain normal homocysteine concentrations in PD patients.
✓Mucuna pruriens (ie, cowage): Cowage contains high concentrations of levodopa and possibly trace amounts of
other chemicals and tryptamines, but long-term benefit is
unknown. Acute psychosis, gastrointestinal effects, and itching are possible side effects.8 It is important to note that the
levodopa in the Mucuna pruriens does not have carbidopa
to help counter the peripheral effects of levodopa, and the
amount of levodopa that is absorbed cannot be controlled.
• Other agents that a patient might purchase include: ashwagandha, choline, kava, chromium, or fava beans. Kava, used for
sleep and relaxation, has been associated with many reports of
severe hepatotoxicity in recent years and has been banned in
several European countries. Patients should be strongly counseled to avoid its use.
Optimal Plan
4.What drug, dosage form, dose, schedule, and duration of
therapy are best for this patient’s current problems?
Parkinson disease:
• There is no established protocol for treating patients with PD
because much depends on the individual symptoms of the
patient as well as the clinician’s views on neuroprotection and
experience with dopamine agonists and other drugs. The best
initial treatment options for this patient diagnosed with early
PD include the following agents.
• MAO type B inhibitor: Rasagiline is preferred over selegiline,
in part because rasagiline is not metabolized to amphetamine
as is selegiline. Although neuroprotection is not proven and
the FDA does not recognize a neuroprotective role for rasagiline, there are still unanswered questions, and it may delay
the need to start more potent medications. Clinicians, after
discussing with the patient the advantages and disadvantages
of starting therapy with rasagiline, choose to start therapy with
rasagiline. Rasagiline should be started at 0.5 mg daily and, if
symptoms continue after 1 month, increase the dose to 1 mg.
Until more is known, there is likely no value in increasing the
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Parkinson Disease
• Some clinicians suggest that COMT inhibitor should be added
when carbidopa/levodopa is first introduced in an effort to
promote more continuous dopamine stimulation, potentially
minimizing long-term complications associated with the more
pulsatile effect of levodopa. Administering levodopa with a
COMT inhibitor every 3 hours provides concentrations that
are similar to a levodopa infusion. However, this polytherapy
regimen may increase adverse effects so many specialists
advise against it. In one report, switching patients from the
sustained-release levodopa to Stalevo improved motor function, improved quality of life, and reduced sleepiness. Both
entacapone and tolcapone inhibit peripheral COMT activity,
but tolcapone may also have central effects. The significance
of this pharmacologic difference is unknown and probably of
no consequence. Tolcapone is much more potent than entacapone and may be more useful for advanced patients.
symptoms of ICD, but further studies are needed. When
stopping amantadine, it should be gradually discontinued to
minimize potential withdrawal effects.
CHAPTER 69
that they do not need as many tablets. COMT inhibitors are
used in conjunction with carbidopa/levodopa in patients with
motor fluctuations to prolong the action of levodopa, increase
on-time, decrease wearing-off effects, improve ADLs, and
allow for levodopa dose reduction.
2
69-6
SECTION 6
dose to 2 mg because data suggest loss of efficacy at this dose.2,9
This patient’s symptoms may have progressed to the point that
they will not be adequately controlled with rasagiline alone.
Neurologic Disorders
• Dopamine agonist: Many clinicians like to start therapy with
a dopamine agonist instead of levodopa because it may delay
the onset of motor fluctuations and still help the patient’s
motor symptoms. Bromocriptine is no longer recommended
for PD. Pramipexole may improve symptoms of depression.2
The following are guidelines for initiating therapy with either
pramipexole or ropinirole.
✓Start pramipexole 0.125 mg PO TID, and increase the dose
gradually every 5–7 days or slower up to 0.75 mg TID. The
dose then can gradually be increased to 4.5 mg, and rarely,
patients may use up to 6 mg per day. Doses should be
reduced if the patient’s creatinine clearance is <60 mL/min.2
✓Alternatively, start ropinirole 0.25 mg PO TID, increasing
weekly or slower by 0.25 mg/dose to an average dose of
3–4 mg TID with some patients using maximum doses of
8 mg TID.2
✓The benefits of a patch formulation in this patient do not
outweigh the long-acting formulations of oral dopamine
agonists; however, if a patch formulation is determined to
be beneficial, rotigotine can be given. It should be applied
once a day. Inform the patient that it should not be placed
on skin that is oily, irritated, or damaged or in a location that
will be rubbed by tight clothing. The patch should be pressed
firmly in place and held for 30 seconds, and the site should
be rotated so the same site is not used more than once every
14 days. Multiple patches may be needed to achieve the
prescribed dose. Start with the 2-mg patch for patients in
the early stages of the disease (as with this patient). The dose
may be increased as needed by 2 mg daily at weekly intervals, up to 6 mg daily for early-stage disease and up to 8 mg
daily for advanced-stage disease.
✓If one dopamine agonist is maximized without improvement, some benefit may be achieved by switching to a
different dopamine agonist. Guidelines on how to switch
dopamine agonists are limited. Some clinicians recommend
a slow taper of the first drug while slowly titrating the second agent. Others suggest a rapid titration based on dose
equivalency because this minimizes patient confusion and
may reduce the risk of uncontrolled PD symptoms. Careful
monitoring of patient behavior and sleepiness is required
when starting these drugs.
• Levodopa/carbidopa with or without a COMT inhibitor: Some
clinicians prefer levodopa over dopamine agonists, especially
in elderly patients with an increased risk of cognitive dysfunction, or even in younger patients who are at risk of OCD or
ICD. Dopamine agonists should be discontinued if the patient
reports any change, development, or increase in compulsive
behavior. When prescribing levodopa, some clinicians prefer
a combination product of levodopa with a COMT inhibitor
for potential pharmacokinetic advantages. Others feel that it is
better to add a COMT inhibitor later in therapy to minimize
GI adverse effects that may occur due to starting two drugs
simultaneously.
• A cost-utility study in advanced patients with motor fluctuations reported that rasagiline with carbidopa–levodopa
or carbidopa–levodopa–entacapone combination product
showed greater effectiveness and less cost from a payer perspective when compared to carbidopa–levodopa monotherapy.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Entacapone with carbidopa–levodopa was effective but more
costly than carbidopa–levodopa alone.10 Although adding an
MAO inhibitor to patients receiving levodopa may improve
motor fluctuations in advanced patients,7 the benefit of adding
an MAO inhibitor with levodopa in early-disease patients is
not well established.
• For this patient, start rasagiline 0.5 mg PO daily, because benefit may outweigh risk considering its symptomatic benefit. If
symptoms continue after 1 month, increase the dose to 1 mg.
If after another month symptoms do not improve, considering
her young age and lack of psychiatric risk factors, add pramipexole 0.125 mg PO TID. If side effects develop (particularly
OCD/ICD) or motor symptoms progress, change the pramipexole to levodopa–carbidopa. Some clinicians avoid dopamine agonists in all age groups because of the risk of OCD/
ICD and because they consider that the risk is underreported.
If a dopamine agonist is used, ask the patient about OCD/
ICD symptoms at each visit and discontinue the agent if these
symptoms develop.
• As more information becomes available, continue to evaluate
the value of rasagiline therapy because the benefit of using an
MAO inhibitor with a dopamine agonist in patients with early
disease is unknown.
Seborrhea:
• The disorder is mild enough to avoid treatment, and it often
improves as the PD symptoms improve. Nonprescription
tar-based dandruff shampoos are often helpful if treatment is
considered necessary. It is helpful to rotate among different
shampoo brands.3
Constipation:
• The patient should continue to increase fluids and fiber in her
diet to minimize constipation. A popular natural concoction to
increase fiber is prune juice, applesauce, and bran. She should
avoid agents with anticholinergic properties. If constipation
does not improve after these measures are taken, add a stool
softener such as docusate and/or other mild laxatives.2,3 It is
important to evaluate constipation because it may be associated with an increased risk of bathroom falls. Excessive straining for a bowel movement can stimulate a vasovagal response
that may cause dizziness, which in turn can cause falls.
Decreased libido:
• Reevaluate this condition after starting medications for PD.
The patient should maintain adequate communication with
her spouse. Refer to her gynecologist to evaluate potential
menopausal symptoms and for counseling if needed. It is
important to ask about this because patients may not volunteer
the information.
Night sweats:
• Refer to gynecologist to evaluate treatment for potential
menopausal symptoms. If unresolved at next visit, consider
autonomic symptoms of PD as the underlying cause.
Trouble sleeping:
• Refer to gynecologist to evaluate potential menopausal symptoms. If unresolved at next visit, consider this to be a symptom
of PD, which is very common. Typically, patients have secondary insomnia, in which they fall asleep easily but awaken
several times during the night because of a disruption in the
sleep cycle related to PD.2,3
69-7
5.Which monitoring parameters should be used to evaluate the
patient’s response to medications and to detect adverse effects?
• The subparts of the UPDRS and patient diaries are used
to measure the patient’s response to therapy and disease
progression.
Patient Education
6.What information should be provided to the patient to ensure
successful therapy, enhance compliance, and minimize adverse
effects?
General information:
• Try to stay as physically active as possible because a good regular exercise regimen is important.
• It is normal to have good days and bad days; do not be anxious
to increase medication doses too quickly. Call your doctor
before adjusting your medication on your own. (Note: Patients
with poor understanding of their symptoms may tend to overdose themselves.)
• It is a good idea to be involved in a PD support group.
• Keep a diary of symptoms and medication times just before
and after clinic visits. This will help the clinicians make dose
adjustments and evaluate changes that were made. Record
when medications start working, when they begin to wear off,
and when dyskinesias occur. Write down a description of how
you feel between doses as well as when you eat and sleep.
• Maintaining good communication with your spouse should
help improve your sex life.
Medication information:
• Rasagiline: The FDA has not approved this medication as neuroprotective (a drug that slows disease progression). Therefore,
the benefit versus risk of taking this drug should be evaluated
at each visit. Notify your healthcare provider if your PD symptoms do not improve or if you experience any new symptoms
after starting this medication. Common side effects with the
medication include diarrhea, weight loss, and hallucinations.
• Pramipexole: The dosage of this medication needs to be
increased slowly to minimize adverse effects such as nausea
or thinking problems. Taking the medication with food will
minimize nausea. The medication may increase the risk of
obsessive–compulsive behaviors; therefore, if you or your
family notices any changes in behavior notify your healthcare
provider. For example, you may find that you are compelled
or feel driven to do regular activities in excess such as eating,
shopping, or hobbies.
• Metamucil: It is important to drink six to eight cups of fluid
daily when taking this bulk-forming laxative. Notify your
healthcare provider if you continue to have problems with
constipation.
• Multivitamin: In addition to a healthy diet, a single once-aday vitamin should be sufficient over multiple single vitamins.
Consider taking a supplement without iron if constipation is
a problem.
■■ CLINICAL COURSE—1 YEAR LATER
Follow-Up Questions
1.What is your assessment of the effectiveness of the PD therapy
the patient is now receiving?
• Rasagiline probably was insufficient to control her motor
symptoms so she started the pramipexole, which improved her
motor symptoms. The UPDRS score dropped 10 points.
• The night sweats and libido improved after additional PD
therapy and hormone replacement therapy.
2.What potential side effects from therapy is the patient now
experiencing?
• The patient is most likely experiencing pramipexole-induced
compulsive behaviors. The symptoms may resolve with dose
reduction but almost always the medication needs to be discontinued as patients often increase the dose again on their own.
3.What adjustments in drug therapy do you recommend for each
of the patient’s problems?
Parkinson disease:
• The compulsive behaviors may improve by reducing the
pramipexole dose or switching to a different dopamine agonist; however, most patients require drug discontinuation. The
pramipexole dose should be reduced to 0.5 mg PO BID while
continuing the same dose of rasagiline. If motor symptoms
increase or the compulsive behaviors do not improve, pramipexole must be discontinued. She is likely to have the same
problems on other dopamine agonists. Trials with amantadine,
zonisamide, topirmate, or valproate may be considered3 but
it is likely the side-effect benefit ratio would eventually favor
switching to Sinemet.
• If motor symptoms are functionally limiting, Sinemet 25/100
should be started, beginning at one-half tablet twice a day.
• Reevaluate the potential benefit of rasagiline at future visits.
Constipation:
• This condition has not improved with daily Metamucil
(psyllium) and diet changes. The patient should continue to
exercise, eat a fiber-rich diet, drink plenty of fluids, and take
Metamucil daily. She should also consider adding another
mild laxative.
• Add a stool softener such as docusate sodium 100 mg daily. If
constipation continues to be a problem, consider increasing
the stool softener to twice a day.
• Mild hyperosmotic laxatives such as magnesium hydroxide
(milk of magnesia) can be used several times a week if needed.
• If constipation continues, polyethylene glycol (eg, Miralax,
Macrogol) is available over the counter and lactulose, sorbitol,
and lubiprostone (Amitiza) are available by prescription for
chronic use. Lactulose may cause more gas and bloating than
lubiprostone. An evidence-based review of polyethylene glycol
(Macrogol) indicates that it is probably effective.5
Seborrhea:
• The patient should begin using a nonprescription dandruff
shampoo if symptoms increase.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Parkinson Disease
• The occurrence of side effects from all medications should
be assessed at each visit. Patients who experience side effects
or unresolved PD symptoms between visits should call their
physicians. Because patients often have difficulty driving, they
may be evaluated via telephone interviews.
• Amlodipine: Monitor your blood pressure and report any signs
of dizziness or lightheadedness. As your PD progresses the
dose of your antihypertensive may need to be decreased.
CHAPTER 69
Outcome Evaluation
69-8
SECTION 6
Menopausal symptoms (insomnia, night sweats, and
decreased libido):
• These symptoms improved with the addition of hormonal
treatment by the patient’s gynecologist. Continue to evaluate
because these symptoms may also be associated with PD.
4.What information should the patient receive about her medical problems and therapy at this visit?
Medical problems:
Neurologic Disorders
• Parkinson disease: You may have a return of symptoms as
the medications are readjusted. Call your physician if your
symptoms are worse when reducing the dopamine agonist
dose because the doctor may want to adjust your medications.
• Constipation: Be patient, because it may take several months
to totally correct constipation. You can use mild laxatives and
glycerin suppositories.
• Seborrhea: It is important to commit to keeping up with good
hygiene because frequent cleansing with soap removes oils from
affected areas and improves seborrhea. It is important to use the
dandruff products as instructed because improper use may delay
improvement. If your symptoms do not improve after several
weeks of regular use, contact your healthcare provider.
Parkinson’s medications added since the last visit:
• Carbidopa/levodopa: Take this medicine with food because it
may minimize nausea in patients who are initiating therapy. It
may discolor your urine and sweat. Contact your doctor if you
notice any new symptoms after starting this medication.
• Docusate sodium: Space this medicine by several hours from
your other medicines because it improves the absorption of
other drugs in the intestine. Do not take this medicine with
mineral oil because it may cause side effects.
• Mild hyperosmotic laxatives such as magnesium hydroxide
(milk of magnesia) can be used several times a week.
• Dandruff shampoo: Purchase a shampoo that has coal tar
(eg, T/Gel), zinc pyrithione (eg, Denorex advanced formula),
salicylic acid (eg, Ionil), salicylic acid/sulfur (eg, Meted), or
selenium sulfide (eg, head and shoulders intensive treatment). After applying the shampoo, leave it on your scalp for
5–10 minutes before washing but avoid contact with your eyes.
Use the shampoo daily until inflammation improves, then
use it two to three times per week. Purchase several different
products with different active ingredients and rotate the use
of these products because coal tar should not be used for long
periods. Using coal tar may increase the risk of sunburn for up
to 24 hours after use.
5.What additional tests could be ordered to assess comorbid
conditions?
• Osteoporosis history: Patient should have a DXA scan to
screen for osteoporosis.
■■ CLINICAL COURSE—7 YEARS LATER
Follow-Up Questions
1.List the patient’s problems at this visit.
• Disease progression with motor fluctuations
✓Morning off-period
✓Wearing off
✓Delayed on
✓Chorea
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
• Sleep problems
• Fatigue
• Constipation
• Hypertension
• 3-kg weight loss
2.List and explain any drugs or foods that could be causing any
drug–drug or drug–food interactions.
• Kava may impair the effects of dopamine resulting in the
patient’s increased off-periods.8
• Cowage can increase the concentration of levodopa, causing
the patient’s dance-like movements (chorea).
• Iron can bind to the levodopa, decreasing the amount of
levodopa absorbed, and iron increases constipation.
• Protein in meals can compete with levodopa for absorption,
leading to slower times to peak dopamine concentrations and
decreased peak dopamine concentrations.8
3.For each of the problems identified, what adjustments in drug
therapy do you recommend?
Motor fluctuations:
• The patient’s motor fluctuations (early wearing off, morning
off, delayed onset, and chorea) are partly due to disease progression and aggravated by drug interactions.
✓Wearing off at the 11:30 am dose: The iron dose taken with
the 11:30 am levodopa is probably binding to the levodopa
and decreasing the amount of levodopa absorbed. The
11:30 am dose may be too close to lunch, resulting in incompletely absorbed levodopa (doses should be spaced from
meals by 30–60 minutes). The patient’s report of fatigue is
not likely due to anemia. She has a normal serum ferritin
concentration and does not need iron supplementation for
her symptoms of fatigue. Iron therapy worsens constipation;
the patient should stop iron therapy, and the serum ferritin
concentration should then be re-checked.
✓The morning off-period (stiff when awakening at night and
off when awakening in the morning) may be related to the
kava impairing the effects of levodopa, and to disease progression because the patient loses the benefit of the sleep
effect on dopamine function. Kava can decrease the effect of
dopamine and cause extrapyramidal effects. Kava increases
off-periods in Parkinson’s patients taking levodopa. The
patient’s symptoms should improve with stopping the kava
and by adjusting the 10 pm PD medications. As the patient’s
disease progresses, she will develop more motor fluctuations
and dyskinesias despite adjustments in the levodopa dosing.
The patient will likely need additional levodopa doses or
the addition of longer acting dopaminergic agents. Adding
a COMT inhibitor, dopamine agonist, or MAO inhibitor
to levodopa each would decrease off-periods. Adding or
switching some of the doses to Sinemet CR also decreases
off-periods. Patients with advanced disease who are astute
enough to recognize on and off changes and can be trusted
not to overdose themselves may be allowed to adjust the
dose and timing of their medication. This patient is currently
on the maximum dose of an MAO inhibitor and previously
had side effects to pramipexole. Although a different dopamine agonist could be tried, the patient is now older and
may have an increased risk of CNS side effects. Addressing
the sleep problem may help preserve or restore the early
morning sleep effect and therefore improve the morning
off-period.
69-9
Sleep problems:
• Sleep problems may due to uncontrolled motor symptoms,
depression, anxiety, frequent urination, menopause, or a sleep
disorder. The patient’s symptoms are consistent with restless legs syndrome (RLS), periodic limb movements of sleep
(PLMS), or REM sleep behavior disorder (RBD). Dopamine
agonists are usually the treatment of choice for RLS; however,
this patient had side effects from pramipexole. A different
dopamine agonist could be tried, but the risk of psychological
side effects may be greater now that she is older. The patient
may also benefit from adding half of a levodopa tablet (50 mg)
30 minutes prior to RLS symptoms starting. If additional
levodopa doses are added between dinner and bedtime, the
patient should check for signs of increased chorea. Other
medications for RLS include opioids and gabapentin, but opioids should be avoided in PD due to an increased fall risk. RBD
is very common in the Lewy-body disease, and patients may
report thrashing and talking in sleep. Low-dose clonazepam is
suggested for RBD.
Fatigue:
• Fatigue is a nonmotor symptom of PD but may also be due to
the patient’s decreased sleep quality from RLS and potential
PLMS that often accompany RLS or just part of the PD itself.
Modafinil could be added if symptoms of fatigue continue after
resolving the sleep problem.
Constipation:
• The patient’s constipation is probably aggravated by the addition of iron. Reevaluate after stopping iron therapy. If it continues to be a problem, consider adding an osmotic laxative
and a stimulant laxative to be used as needed.
Hypertension:
• Her blood pressure appears controlled with verapamil. It is
important to control her blood pressure because uncontrolled
hypertension could be a risk factor for vascular dementia.
Menopausal symptoms:
• The symptoms of decreased libido and night sweats appear to
have resolved without the continued use of hormone therapy.
Osteopenia:
• The patient should have a follow-up DXA scan since it has
been more than 2 years since the last DXA. Patients with PD
Weight loss:
• The patient has a normal BMI of 20 kg/m2, but she should be
monitored for any continued weight loss, which is common in
patients with PD.
Decrease in MoCA:
• The patient has a family history of dementia, and patients with
PD have a 30–60% chance of developing full dementia; the
patient’s two-point drop in the Montreal Cognitive Assessment (MoCA) may not warrant concern, but further evaluation is needed because all PD patients eventually have some
degree of cognitive dysfunction.
• Neuropsychological testing in newly diagnosed untreated
patients with PD found that 24% of patients had problems with
executive function and memory. Memory problems in PD are
different from those in AD. The cognitive dysfunction in PD
is more frontal-lobe mediated. Patients with PD have more
problems with executive function and retrieval of information
that tends to respond with cuing, whereas patients with AD
have more problems with encoding and storage of information. Patients with AD are also more likely to have problems
with language.
• Because the Folstein MMSE test is not a useful measure of cognitive dysfunction in PD, it has been replaced by the MoCA,
which is more sensitive for executive function. Like the MMSE,
it is a 30-point scale test that can be employed rapidly in the
clinic.
• Acetylcholinesterase inhibitors and memantine have been
used in PD patients with dementia, but results are not impressive, and memantine often causes more confusion in these
patients.
• This patient’s decrease in MoCA score may be significant
or related to impaired sleep quality resulting in fatigue and
reduced focus and attention during the exam. The patient
should avoid drugs that worsen cognition (eg, anticholinergics, sedatives, and amantadine), and the MoCA should be
repeated at the next visit when her sleep problems should
have improved. If surgical treatments for PD are considered
in the future, the patient should undergo neuropsychological
testing as part of the evaluation.
4.What information should be provided to the patient to ensure
successful therapy, enhance compliance, and minimize adverse
effects in regards to the medications that have been added
since the last visit?
General:
• Parkinson disease: Your increased off-periods could be due
to disease progression or interactions with the supplement
medications you added. The iron interacts with your levodopa
so less of it is absorbed, resulting in lower concentrations of
dopamine to treat your symptoms. The kava can decrease the
effect of dopamine and Parkinson-like symptoms. The cowage
contains dopamine but does not contain carbidopa, so it does
not work as well as your levodopa/carbidopa. Your symptoms
should improve after discontinuing the iron, kava, and cowage.
Because studies with coenzyme Q10 are not overwhelmingly
positive and it is very expensive, the cost outweighs the benefit
and it should be discontinued.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Parkinson Disease
✓Chorea: The patient reports increased dance-like movements
from 8:30 to 10 am since she has started her OTC supplements. The cowage at 8 am along with her levodopa dose
may be providing too much dopamine resulting in peak
dose chorea. Until additional data are available, there is no
value in taking this supplement because it is not regulated by
the FDA and complicates the proper dosing of levodopa. The
patient should stop the cowage and monitor for improvement in chorea symptoms.
have an increased risk of falling. If this patient has low bone
density, a fall would increase her risk of fracture, disability,
morbidity, and mortality.
CHAPTER 69
✓Delayed onset of carbidopa/levodopa with the 5:30 pm dose:
Taking levodopa with food will delay the time to peak onset
and decrease the amount of levodopa absorbed. If she continues to experience a delayed onset of effect after spacing
the doses by an hour from the meals, she can crush/chew
the standard carbidopa/levodopa or dissolve it in a small
amount of Gatorade to increase the surface area for quicker
absorption that would allow her to not have to get an additional prescription. Another option is to move the dose an
hour earlier.
69-10
SECTION 6
Neurologic Disorders
• In addition, protein in meals can compete with levodopa
for absorption, leading to a longer time for your medication
to take effect and lower dopamine concentrations. Take the
levodopa/carbidopa 30 minutes before meals. Call your physician if your symptoms do not improve or if they worsen. It
is good to read about your condition, but you should talk to
your healthcare professional before taking any new medications. Continue to use a PD diary to record the timing of your
medicine and the effects of your medicine. You should note
how long it takes for your medication to start working, how
long the dose lasts, and if you have any chorea between doses.
You should note any changes in the amount of off time that
you may have.
• Sleep problems: The movements and sensations that occur during the night are possibly due to RBD, RLS, or PLMS. Call your
physician if your symptoms do not improve with stopping the
supplements. You do not need to take the iron for RLS because
your ferritin concentrations are normal.
• Memory: The memory test is within normal limits, but you
have several risk factors for dementia (family history of
dementia, hypertension, and PD). I am going to give you a
questionnaire that will ask questions about how well you plan,
manage time, remember things, and control your emotions
(executive functions). Please complete this with the help of
your family and return at your next visit.
• Exercise: Patients should be encouraged to develop a regular
exercise routine because it has been associated with improved
learning, memory, motor performance, and depression. Exercise can facilitate synaptogenesis, induce neurotropic factors, and enhance neuroplasticity, and increase dopamine
receptors.3
■■ CLINICAL COURSE: ALTERNATIVE THERAPY
Ms Farmer has been taking coenzyme Q10 for about a month before
coming in for reevaluation. Unlike the kava and cowage, which
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
could be actively worsening her symptoms or posing other safety
problems, coenzyme Q10 might actually have some benefit for PD.
Should Ms Farmer continue taking the supplement? See Section
19 (Complementary and Alternative Therapies) in this Instructor’s
Guide for questions and answers about the use of coenzyme Q10
for treatment of PD.
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