chapter 12

Antiparkinson Drugs
Objectives
AFTER STUDYING THIS CHAPTER, THE STUDENT WILL BE ABLE TO:

1. Describe major characteristics of Parkinsons 4. Discuss the use of antiparkinson drugs in

disease. special populations.
2. Differentiate the types of commonly used 5. Apply the nursing process with clients
antiparkinson drugs. experiencing parkinsonism.
3. Discuss therapeutic and adverse effects of
dopaminergic and anticholinergic drugs.

Critical Thinking Scenario

Mr. Rod was diagnosed with Parkinsons disease 1 week ago. His symptoms included slow, shuffling gait;
stooped posture; fine tremor at rest; and mask-like facial expression. His physician started him on levodopa
500 mg tid and benztropine (Cogentin) 1 mg hs. You are a home health nurse visiting Mr. Rod.

Reflect on:
 How can Parkinsons disease affect Mr. Rods ability to function normally?

 How does each medication work to restore the balance of neurotransmitters?

 What assessment data will you collect to evaluate whether the antiparkinson medications are effective?

 What assessment data should be collected to detect adverse effects of antiparkinson drugs?

PARKINSONS DISEASE
P arkinsons disease (also called parkinsonism) is a chronic,
progressive, degenerative disorder of the central nervous
system (CNS) characterized by abnormalities in movement
and posture (tremor, bradykinesia, joint and muscular rigid-
ity). It occurs equally in men and women, usually between
50 and 80 years of age. Classic parkinsonism probably results
from destruction or degenerative changes in dopamine-
producing nerve cells. The cause of the nerve cell damage
is unknown; age-related degeneration, genetics, and ex-
posure to toxins (eg, carbon monoxide, organophosphate
pesticides) are possible etiologic factors. Early-onset parkin-
sonism (before 45 years) is thought to have a genetic com-
ponent. Signs and symptoms of the disease also may occur
with other CNS diseases, brain tumors, and head injuries
and with the use of typical or traditional antipsychotic
drugs (eg, phenothiazines). Use of the newer atypical
antipsychotic drugs may reduce the incidence of drug-induced
parkinsonism.
202
The basal ganglia in the brain normally contain substan-
tial amounts of the neurotransmitters dopamine and acetyl-
choline. The correct balance of dopamine and acetylcholine is
important in regulating posture, muscle tone, and voluntary
movement. People with Parkinsons disease have an imbalance
in these neurotransmitters, resulting in a decrease in inhibitory
brain dopamine and a relative increase in excitatory acetyl-
choline. Imbalances of other neurotransmitters (eg, gamma
aminobutyric acid [GABA], glutamate, norepinephrine, and
serotonin) also occur.
ANTIPARKINSON DRUGS
Drugs used in Parkinsons disease increase levels of dopamine
(levodopa, dopamine agonists, monoamine oxidase [MAO]
inhibitors, catechol-O-methyltransferase [COMT] inhibitors)
or inhibit the actions of acetylcholine (anticholinergic agents)
in the brain. Thus, the drugs help adjust the balance of neuro-
transmitters.

Dopaminergic Drugs
Levodopa, carbidopa, amantadine, bromocriptine, pergolide,
pramipexole, ropinirole, selegiline, entacapone, and tolcapone
increase dopamine concentrations in the brain and exert
dopaminergic activity, directly or indirectly. Levodopa is the
mainstay of drug therapy for idiopathic parkinsonism. Car-
bidopa is used only in conjunction with levodopa. The other
drugs are used as adjunctive agents, usually with levodopa.
Anticholinergic Drugs
Anticholinergic drugs are discussed in Chapter 21 and are de-
scribed here only in relation to their use in the treatment of
Parkinsons disease. Only anticholinergic drugs that are cen-
trally active (ie, those that penetrate the bloodbrain barrier)
are useful in treating parkinsonism. Atropine and scopolamine
are centrally active but are not used because of a high incidence
of adverse reactions. In addition to the primary anticholinergic
drugs, an antihistamine (diphenhydramine) is used for parkin-
sonism because of its strong anticholinergic effects.
Mechanisms of Action
Dopaminergic drugs increase the amount of dopamine in the
brain by various mechanisms. Amantadine increases dopamine
release and decreases dopamine reuptake by presynaptic
nerve fibers. Bromocriptine, pergolide, pramipexole, and
ropinirole are dopamine agonists that directly stimulate post-
synaptic dopamine receptors. Levodopa is a precursor sub-
stance that is converted to dopamine. Selegiline blocks one of
the enzymes (MAO-B) that normally inactivates dopamine.
Entacapone and tolcapone block another enzyme (COMT) that
normally inactivates dopamine and levodopa. Anticholinergic
drugs decrease the effects of acetylcholine. This decreases
the apparent excess of acetylcholine in relation to the amount
of dopamine.
Indications for Use
Entacapone, levodopa, pergolide, pramipexole, ropinirole,
selegiline, and tolcapone are indicated for the treatment of
idiopathic or acquired parkinsonism; carbidopa is used only
to decrease peripheral breakdown of levodopa. Some of the
other drugs have additional uses. For example, amantadine
is also used to prevent and treat influenza A viral infections.
Bromocriptine is also used in the treatment of amenorrhea
and galactorrhea associated with hyperprolactinemia.
Anticholinergic drugs are used in idiopathic parkinsonism
to decrease salivation, spasticity, and tremors. They are used
primarily for people who have minimal symptoms or who
cannot tolerate levodopa, or in combination with other anti-
parkinson drugs. Anticholinergic agents also are used to
relieve symptoms of parkinsonism that can occur with the use
CHAPTER 12 ANTIPARKINSON DRUGS 203
of antipsychotic drugs. If used for this purpose, a course of
therapy of approximately 3 months is recommended because
symptoms usually subside by then even if the antipsychotic
drug is continued.
Contraindications to Use
Levodopa is contraindicated in clients with narrow-angle
glaucoma, hemolytic anemia, severe angina pectoris, transient
ischemic attacks, or a history of melanoma or undiagnosed
skin disorders, and in clients taking MAO inhibitor drugs. In
addition, levodopa must be used with caution in clients with
severe cardiovascular, pulmonary, renal, hepatic, or endocrine
disorders. Bromocriptine and pergolide are ergot derivatives
and therefore are contraindicated in people hypersensitive
to ergot alkaloids or those with uncontrolled hypertension.
Selegiline, entacapone, and tolcapone are contraindicated in
people with hypersensitivity reactions to the drugs. Tolcapone
is contraindicated in people with impaired liver function.
Anticholinergic drugs are contraindicated in clients with
glaucoma, gastrointestinal obstruction, prostatic hypertrophy,
urinary bladder neck obstruction, and myasthenia gravis. The
drugs must be used cautiously in clients with cardiovascular
disorders (eg, tachycardia, dysrhythmias, hypertension) and
liver or kidney disease.
INDIVIDUAL ANTIPARKINSON DRUGS
Dopaminergic antiparkinson drugs are described in this sec-
tion; names, routes, and dosage ranges are listed in Drugs at
a Glance: Antiparkinson Drugs.
Levodopa (Larodopa, Dopar) is the most effective drug
available for the treatment of Parkinsons disease. It relieves
all major symptoms, especially bradykinesia and rigidity.
Although levodopa does not alter the underlying disease
process, it may improve a clients quality of life.
Levodopa acts to replace dopamine in the basal ganglia of
the brain. Dopamine cannot be used for replacement therapy
because it does not penetrate the bloodbrain barrier. Levodopa
readily penetrates the CNS and is converted to dopamine by the
enzyme amino acid decarboxylase (AADC). The dopamine is
stored in presynaptic dopaminergic neurons and functions like
endogenous dopamine. In advanced stages of Parkinsons dis-
ease, there are fewer dopaminergic neurons and thus less stor-
age capacity for dopamine derived from levodopa. As a result,
levodopa has a shorter duration of action and drug effects wear
off between doses.
In peripheral tissues (eg, liver, kidney, gastrointestinal
tract), levodopa is extensively metabolized by decarboxy-
lase, whose concentration is greater in peripheral tissues
than in the brain. It is metabolized to a lesser extent by the
enzyme COMT. Consequently, most levodopa is metabo-
lized in peripheral tissues and large amounts are required to
obtain therapeutic levels of dopamine in the brain. Peripheral
metabolism of levodopa can be reduced (and the amounts
 204 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM

Drugs at a Glance: Antiparkinson Drugs

Generic/Trade Name Routes and Dosage Ranges

Dopaminergic Agents
Levodopa (Larodopa)
Carbidopa (Lodosyn)
Levodopa/carbidopa (Sinemet)
Amantadine (Symmetrel)
Bromocriptine (Parlodel)
Entacapone (Comtan)
Pergolide (Permax)
Pramipexole (Mirapex)
Ropinirole (Requip)
Selegiline (Eldepryl)
Tolcapone (Tasmar)
Anticholinergic Agents
Benztropine (Cogentin)
Biperiden (Akineton)
Diphenhydramine (Benadryl)
Procyclidine (Kemadrin)
Trihexyphenidyl (Trihexy)
PO 0.51 g/d initially in 3 or 4 divided doses, increase gradually by no more than 0.75 g/d, every 37 d.
The rate of dosage increase depends mainly on the clients tolerance of adverse effects, especially
nausea and vomiting. Average maintenance dose, 36 g/d; maximum dose, 8 g/d. Dosage must be
reduced when carbidopa is also given (see carbidopa, below).
PO 70100 mg/d, depending on dosage of levodopa; maximum dose, 200 mg/d
Clients not receiving levodopa: PO 1 tab of 25 mg carbidopa/100 mg levodopa 3 times daily or 1 tab of
10 mg carbidopa/100 mg levodopa 3 or 4 times daily, increased by 1 tablet every day or every other day
until a dosage of 8 tablets daily is reached.
Sinemet CR PO 1 tab twice daily at least 6 h apart initially, increased up to 8 tablets daily and q4h intervals
if necessary
Clients receiving levodopa: Discontinue levodopa at least 8 h before starting Sinemet. PO 1 tab of 25 mg
carbidopa/250 mg levodopa 3 or 4 times daily for clients taking >1500 mg levodopa or 1 tab of 25 mg
carbidopa/100 mg levodopa for clients taking <1500 mg levodopa
PO 100 mg twice a day
PO 1.25 mg twice a day with meals, increased by 2.5 mg/d every 24 wk if necessary for therapeutic benefit.
Reduce dose gradually if severe adverse effects occur.
PO 200 mg with each dose of levodopa/carbidopa, up to 8 times (1600 mg) daily
PO 0.050.1 mg/d at bedtime, increased by 0.050.15 mg every 3 d to a maximum dose of 6 mg/d
if necessary
PO wk 1, 0.125 mg 3 times daily; wk 2, 0.25 mg 3 times daily; wk 3, 0.5 mg 3 times daily; wk 4, 0.75 mg
3 times daily; wk 5, 1 mg 3 times daily; wk 6, 1.25 mg 3 times daily; wk 7, 1.5 mg 3 times daily
Renal impairment: Creatinine clearance (Crcl) > 60 mL/min, 0.125 mg 3 times daily initially, up to a maxi-
mum of 1.5 mg 3 times daily; Crcl 3559 mL/min, 0.125 mg 2 times daily initially, up to a maximum of
1.5 mg 2 times daily; Crcl 1534 mL/min, 0.125 mg once daily, up to a maximum of 1.5 mg once daily
PO wk 1, 0.25 mg 3 times daily; wk 2, 0.5 mg 3 times daily; wk 3, 0.75 mg 3 times daily; wk 4, 1 mg
3 times daily
PO 5 mg twice daily, morning and noon
PO 100200 mg 3 times daily; maximum dose, 600 mg daily
PO 0.51 mg at bedtime initially, gradually increased to 46 mg daily if necessary
Parkinsonism, PO 2 mg 34 times daily
Drug-induced extrapyramidal reactions, PO 2 mg 13 times daily, IM 2 mg repeated q30min if necessary to
a maximum of 8 mg in 24 h
PO 25 mg 3 times daily, gradually increased to 50 mg 4 times daily if necessary
Adults: Drug-induced extrapyramidal reactions, IM, IV 1050 mg; maximal single dose, 100 mg; maximal
daily dose, 400 mg
Children: Drug-induced extrapyramidal reactions, IM 5 mg/kg per day; maximal daily dose, 300 mg
PO 5 mg twice daily initially, gradually increased to 5 mg 34 times daily if necessary
PO 12 mg daily initially, gradually increased to 1215 mg daily, until therapeutic or adverse effects occur
Adults: Drug-induced extrapyramidal reactions, PO 1 mg initially, gradually increased to 515 mg daily if
necessary

reaching the brain can be increased) by giving the AADC in-
hibitor, carbidopa. The combination of levodopa and car-
bidopa greatly increases the amount of available levodopa, so
that the levodopa dosage can be reduced by approximately
70%. The two drugs are usually given together in a fixed-dose
formulation called Sinemet. When carbidopa inhibits the de-
carboxylase pathway of levodopa metabolism, the COMT
pathway becomes more important (see entacapone and tol-
capone, COMT inhibitors, below).
Levodopa is well absorbed from the small intestine after
oral administration, reaches peak serum levels within 30 to
90 minutes, and has a short serum half-life (1 to 3 hours).
Absorption is decreased by delayed gastric emptying, hyper-
acidity of gastric secretions, and competition with amino
acids (from digestion of protein foods) for sites of absorp-
tion in the small intestine. Levodopa is metabolized to
30 or more metabolites, some of which are pharmacologi-
cally active and probably contribute to drug toxicity; the
metabolites are excreted primarily in the urine, usually within
24 hours.
Because of side effects and recurrence of parkinsonian
symptoms after a few years of levodopa therapy, levodopa is
often reserved for clients with significant symptoms and
functional disabilities. In addition to treating Parkinsons dis-
ease, levodopa also may be useful in other CNS disorders in
which symptoms of parkinsonism occur (eg, juvenile Hunt-
ingtons chorea, chronic manganese poisoning). Levodopa
relieves only parkinsonian symptoms in these conditions.

Carbidopa (Lodosyn) inhibits the enzyme AADC. As a
result, less levodopa is decarboxylated in peripheral tissues;
more levodopa reaches the brain, where it is decarboxylated
to dopamine; and much smaller doses of levodopa can be
given. Carbidopa does not penetrate the bloodbrain barrier.
Although carbidopa is available alone, it is most often given
in a levodopa/carbidopa fixed-dose combination product
called Sinemet.
Amantadine (Symmetrel) is a synthetic antiviral agent
initially used to prevent infection from influenza A virus.
Amantadine increases the release and inhibits the reuptake of
dopamine in the brain, thereby increasing dopamine levels.
The drug relieves symptoms rapidly, within 1 to 5 days, but
it loses efficacy with approximately 6 to 8 weeks of continu-
ous administration. Consequently, it is usually given for 2- to
3-week periods during initiation of drug therapy with longer-
acting agents (eg, levodopa), or when symptoms worsen.
Amantadine is often given in conjunction with levodopa.
Compared with other antiparkinson drugs, amantadine is
considered less effective than levodopa but more effective
than anticholinergic agents.
Amantadine is well absorbed from the gastrointestinal
tract and has a relatively long duration of action. It is excreted
unchanged in the urine. Dosage must be reduced with im-
paired renal function to avoid drug accumulation.
Bromocriptine (Parlodel) and pergolide (Permax) are
ergot derivatives that directly stimulate dopamine receptors
in the brain. They are used in the treatment of idiopathic
Parkinsons disease, with levodopa/carbidopa, to prolong ef-
fectiveness and allow reduced dosage of levodopa. Pergolide
has a longer duration of action than bromocriptine and may
be effective in some clients unresponsive to bromocriptine.
Adverse effects are similar for the two drugs.
Entacapone (Comtan)and tolcapone (Tasmar) are COMT
inhibitors. COMT plays a role in brain metabolism of
dopamine and metabolizes approximately 10% of peripheral
levodopa. By inhibiting COMT, entacapone and tolcapone in-
crease levels of dopamine in the brain and relieve symptoms
more effectively and consistently. Although the main mecha-
nism of action seems to be inhibiting the metabolism of lev-
odopa in the bloodstream, the drugs may also inhibit COMT in
the brain and prolong the activity of dopamine at the synapse.
These drugs are used only in conjunction with levodopa/
carbidopa, and dosage of levodopa must be reduced.
Entacapone is well absorbed with oral administration and
reaches a peak plasma level in 1 hour. It is highly protein
bound (98%), has a half-life of about 2.5 hours, and is me-
tabolized in the liver to an inactive metabolite. Dosage must
How Can You Avoid This Medication Error?
Mr. Evans, a client with Parkinsons disease, has carbidopa/
levodopa (Sinemet) 25/100 ordered tid. Your pharmacy supplies
you with Sinemet 25/250. You administer 1 tablet to Mr. Evans for
his morning dose.
CHAPTER 12 ANTIPARKINSON DRUGS 205
be reduced by 50% in the presence of impaired liver function.
The parent drug and the metabolite are 90% excreted through
the biliary tract and feces; 10% is excreted in the urine. Adverse
effects include confusion, dizziness, drowsiness, hallucina-
tions, nausea, and vomiting. These can be reduced by lower-
ing the dose of either levodopa or entacapone. Although there
were few instances of liver enzyme elevation or hemoglobin
decreases during clinical trials, it is recommended that liver
enzymes and red blood cell counts be done periodically.
Tolcapone is also well absorbed with oral administration.
Its elimination half-life is 2 to 3 hours and it is metabolized
in the liver. Diarrhea was a common adverse effect during
clinical trials. Because of several reports of liver damage and
deaths from liver failure, tolcapone should be used only in
clients who do not respond to other drugs. When used, liver
aminotransferase enzymes (serum alanine aminotransferase
[ALT] and aspartate aminotransferase [AST]) should be
monitored every 2 weeks for 1 year, then every 4 weeks for
6 months, then every 2 months. Tolcapone should be dis-
continued if ALT and AST are elevated, if symptoms of liver
failure occur (anorexia, abdominal tenderness, dark urine,
jaundice, clay-colored stools), or if parkinsonian symptoms
do not improve after 3 weeks of taking tolcapone.
Pramipexole (Mirapex) and ropinirole (Requip) are newer
drugs that also stimulate dopamine receptors in the brain.
They are approved for both beginning and advanced stages
of Parkinsons disease. In early stages, one of the drugs can
be used alone to improve motor performance, to improve
ability to participate in usual activities of daily living, and to
delay levodopa therapy. In advanced stages, one of the drugs
can be used with levodopa and perhaps other antiparkinson
drugs to provide more consistent relief of symptoms between
doses of levodopa and allow reduced dosage of levodopa.
These drugs are not ergot derivatives and may not cause some
adverse effects associated with bromocriptine and pergolide
(eg, pulmonary and peritoneal fibrosis and constriction of
coronary arteries).
Pramipexole is rapidly absorbed with oral administration.
Peak serum levels are reached in 1 to 3 hours after a dose and
steady-state concentrations in about 2 days. It is less than 20%
bound to plasma proteins and has an elimination half-life of
8 to 12 hours. Most of the drug is excreted unchanged in the
urine; only 10% of the drug is metabolized. As a result, renal
failure may cause higher-than-usual plasma levels and possi-
ble toxicity, but hepatic disease is unlikely to alter drug effects.
Ropinirole is also well absorbed with oral administration.
It reaches peak serum levels in 12 hours and steady-state
concentrations within 2 days. It is 40% bound to plasma pro-
teins and has an elimination half-life of 6 hours. It is metab-
olized by the cytochrome P450 enzymes in the liver to
inactive metabolites, which are excreted through the kidneys.
Less than 10% of ropinirole is excreted unchanged in the
urine. Thus, liver failure may decrease metabolism, allow
drug accumulation, and increase adverse effects. Renal fail-
ure does not appear to alter drug effects.
Selegiline (Eldepryl) increases dopamine in the brain by
inhibiting its metabolism by MAO. MAO exists in two types,
 206 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM
Nursing Notes: Apply Your Knowledge
Mr. Simmons has had Parkinsons disease for 4 years and, de-
spite treatment with Sinemet, his functional abilities continue
to decline. His physician prescribes a tricyclic antidepressant.
He comes to the clinic 3 weeks later complaining of constipa-
tion and difficulty voiding. Are these symptoms related to his
medications?
MAO-A and MAO-B, both of which are found in the CNS
and peripheral tissues. They are differentiated by their rela-
tive specificities for individual catecholamines. MAO-A acts
more specifically on tyramine, norepinephrine, epinephrine,
and serotonin. It is the main subtype in gastrointestinal mucosa
and the liver and is responsible for metabolizing dietary tyra-
mine. If MAO-A is inhibited in the intestine, tyramine in var-
ious foods is absorbed systemically rather than deactivated. As
a result, there is excessive stimulation of the sympathetic ner-
vous system and severe hypertension and stroke can occur.
This life-threatening reaction can also occur with medications
that are normally metabolized by MAO.
MAO-B metabolizes dopamine; in the brain, most MAO
activity is due to type B. At oral doses of 10 mg/day or less, se-
legiline inhibits MAO-B selectively and is unlikely to cause se-
vere hypertension and stroke. At doses higher than 10 mg/day,
however, selectivity is lost and metabolism of both MAO-A and
MAO-B is inhibited. Doses above 10 mg/day should be avoided
in Parkinsons disease. Selegiline inhibition of MAO-B is irre-
versible and drug effects persist until more MAO is synthesized
in the brain, which may take several months.
In early Parkinsons disease, selegiline may be effective
as monotherapy. In advanced disease, it is given to enhance
the effects of levodopa. Its addition aids symptom control and
allows the dosage of levodopa/carbidopa to be reduced.
Nursing Process
Assessment
Assess for signs and symptoms of Parkinsons disease and
drug-induced extrapyramidal reactions. These may include
the following, depending on the severity and stage of pro-
gression:
Slow movements (bradykinesia) and difficulty in chang-
ing positions, assuming an upright position, eating, dress-
ing, and other self-care activities
Stooped posture
Accelerating gait with short steps
Tremor at rest (eg, pill rolling movements of fingers)
Rigidity of arms, legs, and neck
Mask-like, immobile facial expression
Speech problems (eg, low volume, monotonous tone,
rapid, difficult to understand)
Excessive salivation and drooling
Dysphagia
Excessive sweating
Constipation from decreased intestinal motility
Mental depression from self-consciousness and embar-
rassment over physical appearance and activity limita-
tions. The intellect is usually intact until the late stages of
the disease process.
Nursing Diagnoses
Bathing/Grooming Self Care Deficit related to tremors
and impaired motor function
Impaired Physical Mobility related to alterations in balance
and coordination
Disturbed Body Image related to disease and disability
Deficient Knowledge: Safe usage and effects of anti-
parkinson drugs
Imbalanced Nutrition: Less Than Body Requirements
related to difficulty in chewing and swallowing food
Risk for Injury: Dizziness, hypotension related to adverse
drug effects
Planning/Goals
The client will:
Experience relief of excessive salivation, muscle rigidity,
spasticity, and tremors
Experience improved motor function, mobility, and self-
care abilities
Experience improvement of self-concept and body image
Increase knowledge of the disease process and drug therapy
Take medications as instructed
Avoid falls and other injuries from the disease process or
drug therapy.
Interventions
Use measures to assist the client and family in coping with
symptoms and maintaining function. These include the
following:
Provide physical therapy for heel-to-toe gait training,
widening stance to increase balance and base of support,
other exercises.
Encourage ambulation and frequent changes of position,
assisted if necessary.
Help with active and passive range-of-motion exercises.
Encourage self-care as much as possible. Cutting meat;
opening cartons; giving frequent, small meals; and allow-
ing privacy during mealtime may be helpful. If the client
has difficulty chewing or swallowing, chopped or soft
foods may be necessary. Velcro-type fasteners or zippers
are easier to handle than buttons. Slip-on shoes are easier
to manage than laced ones.
Spend time with the client and encourage socialization
with other people. Victims of Parkinsons disease tend to
become withdrawn, isolated, and depressed.

Schedule rest periods. Tremor and rigidity are aggravated
by fatigue and emotional stress.
Provide facial tissues if drooling is a problem.
Evaluation
Interview and observe for relief of symptoms.
Interview and observe for increased mobility and partic-
ipation in activities of daily living.
Interview and observe regarding correct usage of med-
ications.
PRINCIPLES OF THERAPY
Goals of Treatment
The goals of antiparkinson drug therapy are to control symp-
toms, maintain functional ability in activities of daily living,
minimize adverse drug effects, and slow disease progression.
Drug Selection
Choices of antiparkinson drugs depend largely on the type of
parkinsonism (idiopathic or drug induced) and the severity of
symptoms. In addition, because of difficulties with levodopa
therapy (eg, adverse effects, loss of effectiveness in a few
years, possible acceleration of the loss of dopaminergic neu-
rons in the brain), several drug therapy strategies and combi-
nations are used to delay the start of levodopa therapy and,
once started, to reduce levodopa dosage.
CLIENT TEACHING GUIDELINES
Antiparkinson Drugs
General Considerations
Beneficial effects of antiparkinson drugs may not occur for
a few weeks or months; do not stop taking them before
they have had a chance to work.
Do not take other drugs without the physicians knowl-
edge and consent. This is necessary to avoid adverse
drug interactions. Prescription and nonprescription drugs
may interact with antiparkinson drugs to increase or de-
crease effects.
Avoid driving an automobile or operating other poten-
tially hazardous machinery if vision is blurred or drowsi-
ness occurs with levodopa.
Change positions slowly, especially when assuming an
upright position, and wear elastic stockings, if needed, to
prevent dizziness from a drop in blood pressure.
Self- or Caregiver Administration
Take antiparkinson drugs with or just after food intake to
prevent or reduce anorexia, nausea, and vomiting.
CHAPTER 12 ANTIPARKINSON DRUGS 207
1. For drug-induced parkinsonism or extrapyramidal
symptoms, an anticholinergic agent is the drug of choice.
2. For early idiopathic parkinsonism, when symptoms
and functional disability are relatively mild, several
drugs may be used as monotherapy.
a. An anticholinergic agent may be the initial drug of
choice in clients younger than 60 years of age, espe-
cially when tremor is the major symptom. An anti-
cholinergic relieves tremor in approximately 50%
of clients.
b. Amantadine may be useful in relieving bradykinesia
or tremor.
c. A dopamine agonist may improve functional dis-
ability related to bradykinesia, rigidity, impaired
physical dexterity, impaired speech, shuffling gait,
and tremor.
3. For advanced idiopathic parkinsonism, a combination
of medications is used. Two advantages of combination
therapy are better control of symptoms and reduced
dosage of individual drugs.
a. An anticholinergic agent may be given with levodopa
alone or with a levodopa/carbidopa combination.
b. Amantadine may be given in combination with
levodopa or other antiparkinson agents.
c. A dopamine agonist is usually given with levodopa/
carbidopa. The combination provides more effective
relief of symptoms and allows lower dosage of lev-
odopa. Although all four of the available dopamine
agonists are similarly effective, the newer agents
(pramipexole and ropinirole) may cause fewer or
less severe adverse effects than bromocriptine and
pergolide.
Do not crush or chew Sinemet CR. It is formulated to
be released slowly; crushing or chewing destroys this
feature.
Take or give selegiline in the morning and at noon. This
schedule decreases stimulating effects that may interfere
with sleep if the drug is taken in the evening.
Decrease excessive mouth dryness by maintaining an
adequate fluid intake (20003000 mL daily if not con-
traindicated) and using sugarless chewing gum and hard
candies. Both anticholinergics and levodopa may cause
mouth dryness. This is usually a therapeutic effect in
Parkinsons disease. However, excessive mouth dryness
causes discomfort and dental caries.
Report adverse effects. Adverse effects can often be re-
duced by changing drugs or dosages. However, some ad-
verse effects usually must be tolerated for control of
disease symptoms.
 208 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM
d. The levodopa/carbidopa combination is probably the
most effective drug when bradykinesia and rigidity
become prominent. However, because levodopa be-
comes less effective after approximately 5 to 7 years,
many clinicians use other drugs first and reserve levo-
dopa for use when symptoms become more severe.
e. Selegiline may be given with levodopa/carbidopa.
Although evidence is limited and opinions differ,
selegiline may have a neuroprotective effect and
slow the loss of dopaminergic neurons in the brain.
f. Entacapone is used only with levodopa/carbidopa.
However, in contrast to AADC inhibitors, which
increase the bioavailability of levodopa without
increasing its plasma half-life, simultaneous admin-
istration of COMT and AADC inhibitors signifi-
cantly increases the plasma half-life of levodopa.
Tolcapone should be used only when other drugs
are ineffective, because of its association with liver
failure.
Selegiline and entacapone may both be used with
levodopa/carbidopa because entacapone acts periph-
erally and selegiline acts in the brain. Inhibition of
levodopa/dopamine metabolism is a valuable addition
to levodopa as an exogenous source of dopamine.
4. When changes are made in a drug therapy regimen, one
change at a time is recommended so that effects of the
change are clear.
Drug Dosage
The dosage of antiparkinson drugs is highly individualized.
The general rule is to start with a low initial dose and gradually
increase the dosage until therapeutic effects, adverse effects,
or maximum drug dosage is achieved. Additional guidelines
include the following.
1. The optimal dose is the lowest one that allows the
client to function adequately. Optimal dosage may not
be established for 6 to 8 weeks with levodopa.
2. Doses need to be adjusted as parkinsonism progresses.
3. Dosage must be individualized for levodopa and car-
bidopa. Only 5% to 10% of a dose of levodopa reaches
the CNS, even with the addition of carbidopa. When
carbidopa is given with levodopa, the dosage of levo-
dopa must be reduced by approximately 75%. A daily
dose of approximately 70 to 100 mg of carbidopa is re-
quired to saturate peripheral amino acid decarboxylase.
A levodopa /carbidopa combination is available in
three dosage formulations (10 mg carbidopa /100 mg
levodopa, 25 mg carbidopa/100 mg levodopa, and
25 mg carbidopa /250 mg levodopa) of immediate-
release tablets (Sinemet) and two dosage formulations
(25 mg carbidopa/100 mg levodopa, 50 mg carbidopa/
200 mg levodopa) of sustained-release tablets (Sinemet
CR). Various preparations can be mixed to administer
optimal amounts of each ingredient. Sinemet CR is not
as well absorbed as the short-acting form, and a client
being transferred to Sinemet CR needs a dosage increase
of approximately one third.
4. With levodopa, dosage should be gradually increased to
the desired therapeutic level. In addition, therapeutic
effects may be increased and adverse effects decreased
by frequent administration of small doses.
5. With pramipexole and ropinirole, dosage is started at
low levels and gradually increased over several weeks.
When the drugs are discontinued, they should be ta-
pered in dosage over 1 week. With pramipexole, lower
doses are indicated in older adults and those with renal
impairment; with ropinirole, lower doses may be needed
with hepatic impairment.
6. When combinations of drugs are used, dosage adjust-
ments of individual components are often necessary.
When levodopa is added to a regimen of anticholin-
ergic drug therapy, for example, the anticholinergic
drug need not be discontinued or reduced in dosage.
However, when a dopaminergic drug is added to a
regimen containing levodopa/carbidopa, dosage of
levodopa/carbidopa must be reduced.
Use in Children
Safety and effectiveness for use in children have not been es-
tablished for most antiparkinson drugs, including the cen-
trally acting anticholinergics (all ages), levodopa (<12 years),
and bromocriptine (<15 years). However, anticholinergics
are sometimes given to children who have drug-induced
extrapyramidal reactions.
Because parkinsonism is a degenerative disorder of adults,
antiparkinson drugs are most likely to be used for other pur-
poses in children. Amantadine for influenza A prevention or
treatment is not recommended for neonates or infants
younger than 1 year of age but may be given to children 9 to
12 years of age.
Use in Older Adults
Dosage of amantadine may need to be reduced because the
drug is excreted mainly through the kidneys and renal function
is usually decreased in older adults. Dosage of levodopa/
carbidopa may need to be reduced because of an age-related
decrease in peripheral AADC, the enzyme that carbidopa
inhibits.
Anticholinergic drugs may cause blurred vision, dry mouth,
tachycardia, and urinary retention. They also decrease sweat-
ing and may cause fever or heatstroke. Fever may occur in any
age group, but heatstroke is more likely to occur in older adults,
especially with cardiovascular disease, strenuous activity, and
high environmental temperatures. When centrally active anti-
cholinergics are given for Parkinsons disease, agitation, men-
tal confusion, hallucinations, and psychosis may occur. In
addition to the primary anticholinergics, many other drugs
have significant anticholinergic activity. These include some

antihistamines, including those in over-the-counter cold reme-
dies and sleep aids; tricyclic antidepressants; and phenothiazine
antipsychotic drugs. When an anticholinergic is needed by an
older adult, dosage should be minimized, combinations of
drugs with anticholinergic effects should be avoided, and
clients should be closely monitored for adverse drug effects.
Older clients are at increased risk of having hallucinations
with dopamine agonist drugs. In addition, pramipexole dosage
may need to be reduced in older adults with impaired renal
function.
Use in Renal Impairment
Amantadine is excreted primarily by the kidneys and should be
used with caution in clients with renal failure. With pramipex-
ole, clearance is reduced in clients with moderate or severe
renal impairment and lower initial and maintenance doses
are recommended. With ropinirole and entacapone, no dosage
adjustments are needed for renal impairment.
Use in Hepatic Impairment
Ropinirole should be used cautiously in hepatic impairment
and dosage may need to be reduced. With tolcapone, ele-
NURSING
ACTIONS Antiparkinson Drugs
NURSING ACTIONS
1. Administer accurately
a. Give most antiparkinson drugs with or just after food;
entacapone can be given without regard to meals.
b. Do not crush Sinemet CR and instruct clients not to chew
the tablet.
c. Do not give levodopa with iron preparations or multivitamin-
mineral preparations containing iron.
d. Give selegiline in the morning and at noon.
2. Observe for therapeutic effects
a. With anticholinergic agents, observe for decreased tremor,
salivation, drooling, and sweating.
b. With levodopa and dopaminergic agents, observe for im-
provement in mobility, balance, posture, gait, speech, hand-
writing, and self-care ability. Drooling and seborrhea may be
abolished, and mood may be elevated.
CHAPTER 12 ANTIPARKINSON DRUGS 209
vated liver enzymes and a few deaths from liver failure have
been reported. In clients with noncirrhotic liver disease,
dosage reductions are not needed. In clients with hepatic
cirrhosis, however, tolcapone metabolism is impaired and
plasma drug levels are high. Dosage should be reduced and
maintenance dosage should be less than the 600 mg daily
recommended for noncirrhotic clients. In addition, liver
transaminase enzymes should be monitored frequently.
Although liver failure has not been associated with enta-
capone, periodic measurements of liver transaminase en-
zymes are recommended.
Home Care
The home care nurse can help clients and caregivers under-
stand that the purpose of drug therapy is to control symp-
toms and that noticeable improvement may not occur for
several weeks. Also, the nurse can encourage clients to con-
sult physical therapists, speech therapists, and dietitians to
help maintain their ability to perform activities of daily liv-
ing. In addition, teaching may be needed about preventing
or managing adverse drug effects. Caregivers may need to
be informed that most activities (eg, eating, dressing) take
longer and require considerable effort by clients with
parkinsonism.
RATIONALE/EXPLANATION
To prevent or reduce nausea and vomiting
Crushing and chewing destroys the controlled-release feature of
the formulation.
Iron decreases absorption of levodopa.
To decrease central nervous system (CNS) stimulating effects that
may interfere with sleep if the drug is taken in the evening
Decreased salivation and sweating are therapeutic effects when
these drugs are used in Parkinsons disease, but they are adverse
effects when the drugs are used in other disorders.
Therapeutic effects are usually evident within 23 weeks, as levo-
dopa dosage approaches 23 g/d, but may not reach optimum
levels for 6 months.
(continued )
210 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM
NURSING ACTIONS
3. Observe for adverse effects
a. With anticholinergic drugs, observe for atropine-like effects,
such as:
(1) Tachycardia and palpitations
(2) Excessive CNS stimulation (tremor, restlessness, con-
fusion, hallucinations, delirium)
(3) Sedation and drowsiness
(4) Constipation, impaction, paralytic ileus
(5) Urinary retention
(6) Dilated pupils (mydriasis), blurred vision, photophobia
b. With levodopa, observe for:
(1) Anorexia, nausea, and vomiting
(2) Orthostatic hypotensioncheck blood pressure in both
sitting and standing positions q4h while the client is awake.
(3) Cardiac arrhythmias (tachycardia, premature ventricu-
lar contractions) and increased myocardial contractility
(4) Dyskinesiainvoluntary movements that may involve
only the tongue, mouth, and face or the whole body
(5) CNS stimulationrestlessness, agitation, confusion,
delirium
(6) Abrupt swings in motor function (onoff phenomenon)
c. With amantadine, observe for:
(1) CNS stimulationinsomnia, hyperexcitability, ataxia,
dizziness, slurred speech, mental confusion, hallucinations
(2) Livedo reticularispatchy, bluish discoloration of skin
on the legs
RATIONALE/EXPLANATION
These effects may occur with usual therapeutic doses but are not
likely to be serious except in people with underlying heart disease.
This effect is most likely to occur with large doses of trihexyphenidyl
(Artane) or benztropine (Cogentin). It may occur with levodopa.
These are most likely to occur with benztropine. The drug has anti-
histaminic and anticholinergic properties, and sedation is attributed
to the antihistamine effect.
These effects result from decreased gastrointestinal motility and
muscle tone. They may be severe because decreased intestinal
motility and constipation also are characteristics of Parkinsons
disease; thus, additive effects may occur.
This reaction is caused by loss of muscle tone in the bladder and
is most likely to occur in elderly men who have enlarged prostate
glands.
Ocular effects are due to paralysis of accommodation and relax-
ation of the ciliary muscle and the sphincter muscle of the iris.
These symptoms usually disappear after a few months of drug ther-
apy. They may be minimized by giving levodopa with food, gradu-
ally increasing dosage, administering smaller doses more frequently
or adding carbidopa so that dosage of levodopa can be reduced.
This effect is common during the first few weeks but usually sub-
sides eventually. It can be minimized by arising slowly from supine
or sitting positions and by wearing elastic stockings.
Levodopa and its metabolites stimulate beta-adrenergic receptors
in the heart. People with pre-existing coronary artery disease may
need a beta-adrenergic blocking agent (eg, propranolol) to counter-
act these effects.
Dyskinesia eventually develops in most people who take levo-
dopa. It is related to duration of levodopa therapy rather than
dosage. Carbidopa may heighten this adverse effect, and there is
no way to prevent it except by decreasing levodopa dosage. Many
people prefer dyskinesia to lowering drug dosage and subsequent
return of the parkinsonism symptoms.
This is more likely to occur with levodopa/carbidopa combination
drug therapy.
This fluctuation may indicate progression of the disease process.
It often occurs after long-term levodopa use.
Compared with other antiparkinson drugs, amantadine produces
few adverse effects. The ones that occur are mild, transient, and
reversible. However, adverse effects increase if daily dosage ex-
ceeds 200 mg.
This is a benign but cosmetically unappealing condition. It usually
occurs with long-term use of amantadine and disappears when the
drug is discontinued.
(continued )

NURSING ACTIONS
d. With bromocriptine and pergolide, observe for:
(1) Nausea
(2) Confusion and hallucinations
(3) Hypotension
e. With pramipexole and ropinirole, observe for:
(1) Nausea
(2) Confusion, hallucinations
(3) Dizziness, drowsiness
(4) Dyskinesias
(5) Orthostatic hypotension
f. With selegiline, observe for:
(1) CNS effectsagitation, ataxia, bradykinesia, confusion,
dizziness, dyskinesias, hallucinations, insomnia
(2) Nausea, abdominal pain
g. With entocapone and tolcapone, observe for:
(1) Anorexia, nausea, vomiting, diarrhea, constipation
(2) Dizziness, drowsiness
(3) Dyskinesias and dystonias
(4) Hallucinations
(5) Orthostatic hypotension
4. Observe for drug interactions
a. Drugs that increase effects of anticholinergic drugs:
(1) Antihistamines, disopyramide (Norpace), thiothixene
(Navane), phenothiazines, and tricyclic antidepressants
b. Drugs that decrease effects of anticholinergic drugs:
(1) Cholinergic agents
c. Drugs that increase effects of levodopa:
(1) Amantadine, anticholinergic agents, bromocriptine,
carbidopa, entacapone, pergolide, pramipexole, ropinirole,
selegiline, tolcapone
(2) Tricyclic antidepressants
(3) Monoamine oxidase type A (MAO-A) inhibitors, in-
cluding isocarboxazid (Marplan), phenelzine (Nardil), and
tranylcypromine (Parnate)
CHAPTER 12 ANTIPARKINSON DRUGS 211
RATIONALE/EXPLANATION
These symptoms are usually mild and can be minimized by start-
ing with low doses and increasing the dose gradually until the de-
sired effect is achieved. If adverse effects do occur, they usually
disappear with a decrease in dosage.
These effects occurred more commonly than others during clinical
trials.
These effects occurred more commonly than others during clinical
trials.
These drugs have anticholinergic properties and produce additive
anticholinergic effects.
These drugs counteract the inhibition of gastrointestinal motility
and tone, which is a side effect of anticholinergic drug therapy.
These drugs are often used in combination for treatment of Parkin-
sons disease.
These drugs potentiate levodopa effects and increase the risk of
cardiac arrhythmias in people with heart disease.
The combination of a catecholamine precursor (levodopa) and
MAO-A inhibitors that decrease metabolism of catecholamines can
result in excessive amounts of dopamine, epinephrine, and norepi-
nephrine. Heart palpitations, headache, hypertensive crisis, and
stroke may occur. Levodopa and MAO-A inhibitors should not be
given concurrently. Also, levodopa should not be started within
3 weeks after an MAO-A inhibitor is discontinued. Effects of
MAO-A inhibitors persist for 13 weeks after their discontinuation.
These effects are unlikely to occur with selegiline, an MAO-B in-
hibitor, which more selectively inhibits the metabolism of dopamine.
However, selectivity may be lost at doses higher than the recom-
mended 10 mg/d. Selegiline is used with levodopa.
(continued )
 212 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM
NURSING ACTIONS
d. Drugs that decrease effects of levodopa:
(1) Anticholinergics
(2) Alcohol, benzodiazepines (eg, diazepam [Valium]),
antiemetics, antipsychotics such as phenothiazines, haloperi-
dol (Haldol), and thiothixene (Navane)
(3) Oral iron preparations
(4) Pyridoxine (vitamin B6)
e. Drugs that decrease effects of dopaminergic antiparkinson
drugs:
(1) Antipsychotic drugs
(2) Metoclopramide
How Can You Avoid This Medication Error?
Answer: This medication error occurred because the wrong dose
of levodopa was given to Mr. Evans. When administering a combi-
nation product, it is important that the dosage be correct for each
medication. In this situation, the Sinemet provided contained 25 mg
of carbidopa and 250 mg of levodopa. When administering Sinemet
25/250, you give the patient 250 mg of levodopa rather than the
100 mg that was ordered. Call the pharmacy and request that
Sinemet 25/100 be provided.
Nursing Notes: Apply Your Knowledge
Answer: Yes. Both Sinemet and tricyclic antidepressants have
anticholinergic side effects, including urinary retention and con-
stipation. When these medications are given together, enhanced
anticholinergic effects are seen. Tachycardia and palpitations
can also occur. Refer Mr. Simmons to his physician to see if
another antidepressant with fewer anticholinergic side effects
could be used.
Review and Application Exercises
1. Which neurotransmitter is deficient in idiopathic and
drug-induced parkinsonism?
2. How do the antiparkinson drugs act to alter the level of the
deficient neurotransmitter?
RATIONALE/EXPLANATION
Although anticholinergics are often given with levodopa for in-
creased antiparkinson effects, they also may decrease effects of
levodopa by delaying gastric emptying. This causes more levo-
dopa to be metabolized in the stomach and decreases the amount
available for absorption from the intestine.
The mechanisms by which most of these drugs decrease effects of
levodopa are not clear. Phenothiazines block dopamine receptors
in the basal ganglia.
Iron binds with levodopa and reduces levodopa absorption, possi-
bly by as much as 50%.
Pyridoxine stimulates decarboxylase, the enzyme that converts
levodopa to dopamine. As a result, more levodopa is metabo-
lized in peripheral tissues, and less reaches the CNS, where anti-
parkinson effects occur. This interaction does not occur when
carbidopa is given with levodopa.
These drugs are dopamine antagonists and therefore inhibit the
effects of dopamine agonists.
3. What are the advantages and disadvantages of the various
drugs used to treat parkinsonism?
4. Why is it desirable to delay the start of levodopa therapy
and, once started, reduce dosage as much as possible?
5. What is the rationale for various combinations of anti-
parkinson drugs?
6. What are the major adverse effects of antiparkinson drugs,
and how can they be minimized?
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