47 Drug Therapy for

Parkinsons Disease and

Anticholinergics
LEARNING OBJECTIVES
After studying this chapter, you should be able to:
1 Describe major characteristics and manifestations of Parkinsons disease.
2 Understand the pathophysiology of Parkinsons disease.
3 Describe the types of commonly used antiparkinson drugs.
4 Identify the prototype and describe the action, use, adverse eects, contraindications,
and nursing implications for the dopamine receptor agonists.
5 Identify the prototype and describe the action, use, adverse eects, contraindications, and
nursing implications for the catechol-O-methyltransferase (COMT) inhibitors.
6 Identify the prototype and describe the action, use, adverse eects, contraindications, and
nursing implications for a COMT inhibitor and decarboxylase inhibitor/dopamine precursor.
7 Implement the nursing process in the care of patients undergoing drug therapy for
Parkinsons disease.
8 Describe the general characteristics of anticholinergic drugs.
9 Identify the prototype and describe the action, use, adverse eects, contraindications, and
nursing implications for belladonna alkaloids and derivatives.
10 Identify the prototype and describe the action, use, adverse eects, contraindications, and
nursing implications for centrally acting anticholinergic drugs.
11 Identify the prototype and describe the action, use, adverse eects, contraindications, and
nursing implications for anticholinergic medications used for gastrointestinal and urinary
disorders.
12 Implement the nursing process in the administration of anticholinergic agents.

Clinical Application Case Study

Lee Stokes is a 61-year-old man who visits his primary health care provider. He is experienc-
ing pill-rolling movement of the right hand and ngers; slow, stooped movement; a shuf-
ing gait with absence of arm movement; and excessive salivation. His physician diagnoses
Mr. Stokes with Parkinsons disease and starts him on levodopa/carbidopa (Sinemet) 25 mg
carbidopa/100 mg levodopa four times a day and benztropine mesylate at bedtime.

862
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics 863

KEY TERMS
Akinesia: rigid limbs
Anticholinergic drug: drug that inhibits the actions of acetylcholine in the brain

Antimuscarinic drug: drug that interacts with muscarinic cholinergic receptors in the brain, secretory glands, heart, and
smooth muscle to produce an anticholinergic response
Basal ganglia: area in the midbrain that controls smooth voluntary movement

Bradykinesia: inability to move

Catechol-O-methyltransferase inhibitor: medication that inhibits the metabolism of levodopa in the periphery

Cycloplegia: Paralysis in the ciliary muscle of the eye

Dopamine receptor agonist: drug that corrects the neurotransmitter imbalance by increasing levels of dopamine

Extrapyramidal reactions: movement disorders such as tardive dyskinesia (inability to initiate movement), akathisia
(inability to remain motionless), dystonia, and drug-induced parkinsonism that may occur with use of antiparkinsonism and
antipsychotic drugs
Hypertensive crisis: severe increase in blood pressure that can lead to a stroke

Muscarinic receptors: located in the most internal organs, including the cardiovascular, respiratory, gastrointestinal (GI),
and genitourinary systems. When activated by acetylcholine, the affected cells may be excited or inhibited in their functions
Mydriasis: pupil dilation

Nicotinic receptors: located in motor nerves and skeletal muscle; when activated by acetylcholine, the cell membrane
depolarizes and produces muscle contraction
O time: periods of the day when the medication is not working well, causing worsening of parkinsonian symptoms

Parkinsons disease: chronic, progressive, degenerative disorder of the central nervous system characterized by resting
tremor, bradykinesia, rigidity, and postural instability
Parkinsonism: often dened as a parkinsonian syndrome that is idiopathic (having no known cause), although some
atypical cases have a genetic origin
Quaternary amines: anticholinergic drugs that carry a positive charge and are lipid insoluble; they do not readily cross
the cell membranes, are poorly absorbed from the GI tract, and do not cross the bloodbrain barrier
Substantia nigra: region of the midbrain with dopamine cells

Tertiary amines: anticholinergic drugs that are unchanged lipid-soluble molecules, able to cross cell membranes
readily, and are well absorbed from the GI tract and conjunctiva, and they cross the bloodbrain barrier

The rst part of this chapter discusses Parkinsons disease and
the medications administered to decrease the symptoms of the
disease. The second part discusses anticholinergic drugs admin-
istered to decrease secretions and prevent urinary urgency.
Overview of Parkinsons Disease
Parkinsons disease (also called parkinsonism) is a chronic,
progressive, degenerative disorder of the central nervous system
(CNS) characterized by resting tremor, bradykinesia, rigidity,
and postural instability. Manifestations of Parkinsons disease
also may occur with other CNS diseases, brain tumors, and head
injuries. Drugs that deplete dopamine stores or block dopamine
receptors, including the older antipsychotic drugs (phenothia-
zines and haloperidol), reserpine, and metoclopramide, can
produce movement disorders such as secondary parkinsonism
(which also involves extrapyramidal reactions; see Chap. 55).
Treatment can be pharmacologic, nonpharmacologic, and/or
surgical.
The Parkinsons Disease Foundation estimates that approxi-
mately 1 million people in the United States are living with
Parkinsons disease (2010a). This value includes about 60,000
people who are diagnosed each year with the disease, with 96%
older than 50 years of age. Parkinsons disease occurs slightly
more often in men than in women and in Caucasian and
Hispanic/Latino people than in African Americans.
Etiology
The cause of the nerve cell damage is unknown; age-related
degeneration, genetics, and exposure to environmental toxins
864 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
TABLE 47.1
Drugs Administered for the Treatment of Parkinsons Disease
Drug Class Prototype
Dopamine receptor agonist Levodopa/carbidopa
Catechol-O-methyltransferase Tolcapone
(COMT) inhibitors
COMT inhibitor and decarboxylase Levodopa, carbidopa, and
inhibitor/dopamine entacapone (Stalevo)
precursor
are possible etiologic factors. A total of nine genetic linkages
and four genes have been associated with Parkinsons disease,
including mutations of alpha-synuclein and parkin genes.
A high incidence of mutations in the parkin-2 gene has been
associated with early-onset parkinsonism.
Pathophysiology
Idiopathic parkinsonism results from progressive destruction
of or degenerative changes in dopamine-producing nerve
cells in the substantia nigra in the basal ganglia, the area
in the midbrain that controls smooth voluntary movement.
The basal ganglia in the brain normally contain substantial
amounts of the neurotransmitters dopamine and acetylcho-
line. The correct balance of dopamine and acetylcholine is
important in regulating posture, muscle tone, and voluntary
movement. People with Parkinsons disease have an imbal-
ance in these neurotransmitters, resulting in a decrease in
inhibitory brain dopamine and a relative increase in excita-
tory acetylcholine.
Clinical Manifestations
The rst symptom of Parkinsons disease is often a resting
tremor that begins in the ngers and thumb of one hand
(pill-rolling movements), eventually spreading over one
side of the body and progressing to the contralateral limbs.
Other common symptoms include inability to move (brad-
ykinesia), rigid limbs (akinesia), shufing gait, stooped pos-
ture, mask-like facial expression, and a soft speaking voice.
Less common manifestations may include depression, per-
sonality changes, loss of appetite, sleep disturbances, speech
impairment, or sexual difculty. Approximately 15% to
20% of people with Parkinsons disease develop dementia.
The severity of disease manifestations usually worsen over
time. However, disease progression is often quite gradual,
Other Drugs in the Class
Amantadine (Symmetrel)
Apomorphine hydrochloride (Apokyn)
Bromocriptine mesylate (Parlodel, Cycloset)
Cabergoline (Dostinex)
Pramipexole dihydrochloride (Mirapex, Mirapex ER)
Rasagiline (Azilect)
Ropinirole (Requip)
Rotigotine-transdermal (Neupro)
Selegiline hydrochloride (Eldepryl)
Entacapone
and patients may retain near-normal functional abilities for
several years.
Drug Therapy
Drugs used in Parkinsons disease include dopamine recep-
tor agonists, which help correct the neurotransmitter
imbalance by increasing levels of dopamine, and catechol-
O-methyltransferase (COMT) inhibitors, which inhibit the
metabolism of levodopa in the periphery. See Table 47.1. (The
older belladonna alkaloids and the newer centrally acting anti-
cholinergic agents inhibit the actions of acetylcholine in the
brain. As previously stated, these medications are discussed
later in this chapter.)
Clinical Application 47-1
A nurse is providing patient teaching to Mr.
Stokes and his family. The family inquires about
the progression of Parkinsons disease. What
does the nurse tell the patient and the family
with regard to disease progression?
Dopamine Receptor Agonists
Levodopa (L-dopa), the original prototype dopamine receptor
antagonist, was developed in the 1960s. It is routinely admin-
istered with the drug carbidopa; therefore, the combination
medication is discussed as the prototype. Levodopa/
carbidopa (Sinemet, Sinemet CR, Parcopa) is well estab-
lished as the most effective drug for the symptomatic treatment
of idiopathic Parkinsons disease. (Carbidopa is used only in
conjunction with levodopa.) The combination is particularly
effective for the management of akinetic symptoms.
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics 865

Pharmacokinetics Levodopa is well absorbed from the small intestine after

oral administration, reaches peak serum levels within 30
In peripheral tissues (e.g., gastrointestinal [GI] tract, liver),
to 90 minutes, and has a short serum half-life (13 hours).
levodopa is metabolized extensively by the enzyme aromatic
Absorption is decreased by delayed gastric emptying, hypera-
amino acid decarboxylase (AADC) and to a lesser extent
cidity of gastric secretions, and competition with amino acids
by catechol-O-methyltransferase (COMT). Because most
(from digestion of protein foods) for sites of absorption in
levodopa is metabolized in peripheral tissues, large doses are
the small intestine. Pyridoxine (vitamin B6) promotes the
required to obtain therapeutic levels of dopamine in the brain.
breakdown of levodopa, reducing its effectiveness. Levodopa
These large amounts increase adverse drug effects. To reduce
is metabolized to 30 or more metabolites, some of which are
levodopa dosage and decrease adverse effects, carbidopa, an
pharmacologically active and probably contribute to drug tox-
AADC inhibitor, is given to decrease the peripheral metabo-
icity; the metabolites are excreted primarily in the urine, usu-
lism of levodopa. The combination of levodopa and carbidopa
ally within 24 hours.
greatly increases the amount of available levodopa, so that
levodopa dosage can be reduced by approximately 70%. When
carbidopa inhibits the decarboxylase pathway of levodopa
Action
metabolism, the COMT pathway becomes more important Dopaminergic drugs increase the amount of dopamine in the
(see Catechol-O-Methyltransferase Inhibitors for a discussion brain by various mechanisms (Fig. 47.1). If levodopa is admin-
of entacapone and tolcapone). istered alone, large doses must be taken to produce therapeutic

Levodopa increases
availability of l-DOPA, the
precursor from which
dopamine is synthesized by
AADC

Carbidopa inhibits breakdown Bromocriptine, pramipexole,

of levodopa by AADC in the ropinirole, and rotigotine-
GI tract and liver so that more transdermal directly stimulate
levodopa enters the brain postsynaptic dopamine
receptors

INCREASE BRAIN DOPAMINE

Amantadine increases Entacapone decreases Selegiline and rasagiline

dopamine release and blocks breakdown of dopamine decrease breakdown of
reuptake of dopamine into by COMT dopamine by MAO-B
presynaptic neurons

Figure 47.1 Mechanisms by which dopaminergic drugs increase dopamine in the brain. AADC,
amino acid decarboxylase; COMT, catechol-O-methyltransferase; MAO-B, monoamine oxidase B.
866 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
effects. Carbidopa combined with levodopa prevents the
decarboxylation of the levodopa, which makes levodopa
more available for transportation to the brain. Levodopa is
the metabolic precursor of dopamine, and after levodopa
crosses the bloodbrain barrier, it converts to dopamine in
the brain. This is thought to be the mechanism whereby the
drug relieves symptoms of Parkinsons disease. Carbidopa does
not cross the bloodbrain barrier and does not affect levodopa
metabolism.
Use
Levodopa/carbidopa is a treatment of idiopathic Parkinsons
disease, postencephalitic and arteriosclerotic parkinsonism,
and parkinsonism related to carbon dioxide and manganese
intoxication. Prescribers may also order levodopa to reduce the
symptoms of restless leg syndrome (RLS). People with RLS, also
known as Ekboms syndrome, experience paresthesias of the
muscles, particularly in the calf and thighs, creating the urge to
move. Movement relieves the paresthesia, which returns when
the person is at rest or trying to sleep. The disorder may result
in insomnia; mental distress; and, in some cases, suicide.
Levodopa and carbidopa are usually given together in a
xed-dose formulation called Sinemet. Table 47.2 gives doses
of this combination and other dopamine receptor agonists used
to treat Parkinsons disease.
Use in Children
Safety and effectiveness for use in children have not been
established for most antiparkinson drugs. Parkinsonism is a
degenerative disorder of adults, and antiparkinson drugs are
most likely to be used in children for other purposes such as
the stimulation of growth hormone in children with Downs
syndrome.
Use in Older Adults
It may be necessary to reduce dosages of levodopa/carbidopa
because of an age-related decrease in peripheral AADC, the
enzyme that carbidopa inhibits. The risk of hallucinations is
increased in older patients who take dopamine agonist drugs.
Use in Patients With Renal Impairment
Caution is necessary with the use of levodopa/carbidopa in
patients with renal failure. Dosage adjustments are required.
Use in Patients With Hepatic Impairment
With levodopa, cautious use in patients with hepatic impair-
ment is warranted, and dosage reduction may be necessary.
Reduced dosages are indicated with severe hepatic impair-
ment. It is important to monitor liver transaminase enzymes
frequently to assess for liver impairment. At the earliest sign of
hepatotoxicity, drug withdrawal is essential, and there should
be no reinstatement.
Use in Patients With Critical Illness
Caution is necessary with the use of levodopa in patients with
severe neurological, cardiac, or hepatic injuries. Dosage adjust-
ment to the lowest level required for therapeutic effects is
essential.
Use in Patients Receiving Home Care
The home care nurse can help patients and caregivers under-
stand that the purpose of drug therapy is to control symptoms
and that noticeable improvement may not occur for several
weeks. Also, the nurse can encourage patients to consult physi-
cal therapists, speech therapists, and dietitians to help maintain
their ability to perform activities of daily living. In addition,
teaching about preventing or managing adverse drug effects
may be necessary. Caregivers may need to be informed that
most activities (e.g., eating, dressing) take longer and require
considerable effort by patients with parkinsonism.
Adverse Eects
Because of the adverse effects and recurrence of parkinson-
ism symptoms after a few years of levodopa therapy, levodopa
is usually reserved for patients with signicant symptoms and
functional disabilities. The most common CNS adverse effects
are headache and anxiety. Older patients may experience prob-
lems such as hallucinations, dementia, and drowsiness. The
most severe adverse effect is depression with suicidal tendencies.
Cardiovascular adverse effects include ectopic beats, tachy-
cardia, anginal pain, palpitations, hypotension, vasoconstric-
tion, dyspnea, bradycardia, and a widened QRS. The medication
can cause orthostatic hypotension. This effect is common dur-
ing the rst few weeks but usually subsides. Concurrent admin-
istration of nonselective monoamine oxidase (MAO) inhibitors
(used in the treatment of depression) and levodopa can result
in extreme elevations in blood pressure or hypertensive crisis.
(MAO exists in two types, MAO-A and MAO-B, both of
which are found in the CNS and peripheral tissues.)
In addition, some patients report anorexia, bruxism, and
nausea and vomiting. Other less common adverse effects are
piloerection, azotemia, and gangrene with prolonged use.
Dermatologic effects such as hypersensitivity, anaphylaxis, and
urticaria occur less frequently.
Contraindications
Contraindications to the use of levodopa/carbidopa include a
known hypersensitivity to the drug. The drug can dilate pupils
and raise intraocular pressure; thus, narrow-angle glaucoma
is also a contraindication. Levodopa may activate malignant
melanoma; people with suspicious skin lesions or a history of
melanoma should not take it. To avoid the severe hypertension
that may occur with concurrent use of some MAO inhibitors
and levodopa, it is essential that MAO inhibitors be discontin-
ued 14 days prior to beginning levodopa therapy. In addition,
use of levodopa warrants caution in patients with severe car-
diovascular, pulmonary, renal, hepatic, or endocrine disorders;
depression; and peptic ulcer disease.
Nursing Implications
Preventing Interactions
The administration of levodopa/carbidopa with an MAO
inhibitor can precipitate a hypertensive crisis. Postural hypo-
tension occurs with the administration of tricyclic antide-
pressants and levodopa/carbidopa. Methyldopa combined
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics 867

TABLE 47.2
DRUGS AT A GLANCE: Dopamine Receptor Agonists
Pregnancy
Drug Category Routes and Dosage Ranges

Adults Children

Levodopa/ C 1 tablet containing 10 mg carbidopa and 100 mg Safety and efcacy not
carbidopa levodopa or 25 mg carbidopa and 100 mg levodopa established
(Sinemet, Sinemet PO 3 times per day; increased by 1 tablet daily or every
CR, Parcopa) other day up to 6 tablets/d
Patients who are switched from levodopa alone to levo-
dopa/carbidopa: 1 tablet containing 25 mg carbidopa
and 250 mg levodopa PO 34 times per day; the dosage
is adjusted by 1/21 tablet per day (initial dose should
be 20%25% of initial dose of levodopa)
Amantadine C Antiparkinson: 100 mg PO 2 times per day (maximum Safety and efcacy have not been
hydrochloride dosage 400 mg/d) established in children under
(Endantadine, Antiviral: 200 mg/d or 100 mg 2 times per day PO for 10 d the age of 1 y
Symmetrel) after exposure, for the duration of known inuenza A 19 y: 4.48.8 mg/kg/d PO in one
or two divided doses not to
exceed 150 mg/d
912 y: 100 mg PO 2 times per day
Apomorphine hydro- C Off time: Monitor blood pressure with administration: Safety and efcacy not
chloride (Apokyn) 0.2 mL or 2 mg subcutaneous; if no response, adminis- established
ter 0.4 mL or 4 mg if well tolerated administer 0.3 mL
or 30 mg; may increase by 1 mg every day
Max dose: 0.6 mL as a single injection; max of 5 injections/d
Bromocriptine mesylate C 1.252.5 mg PO daily (max dosage: 100 mg/d in divided Safety and efcacy not
(Parlodel, Cycloset) doses) established
Cabergoline (Dostinex) B 0.5 mg PO daily; may increase up to 2.5 mg daily (max Safety and efcacy not
dosage 5 mg/d) established
Pramipexole dihydro- C 0.125 mg PO 3 times per day gradually increase every 57 Safety and efcacy not
chloride (Mirapex, d to a max dose of 1.5 mg 3 times per day established
Mirapex ER) Extended release: 0.375 mg PO daily, may increase after
5 d up to a max dose of 4.5 mg/d
Restless leg syndrome: 0.125 mg taken 23 h before bed,
dose can be increased every 47 d
Renal impairment:
CrCl 3560 mL/min: same titration schedule dosed
2 times/d (max dose: 1.5 mg 2 times per day)
CrCl 1535 mL/min (max dosage 1.5 mg/d)
Rasagiline (Azilect) C 1 mg PO daily as monotherapy; 0.51 mg/d PO Safety and efcacy not
Hepatic impairment: 0.5 mg PO daily established
Ropinirole hydrochlo- C 0.25 mg PO 3 times per day; titrate up by 0.25 mg/dose Safety and efcacy not
ride (Requip, 3 times per day every week to a target dose of 1 mg established
Requip XL) 3 times per day; may be increased by 1.5 mg/d every
week (max dosage: 9 mg/d) and then 3 mg/d to a max
dosage of 24 mg/d
Extended release: 2 mg/d for 12 wk then increase by
2 mg/d at 1 wk intervals; max dosage 24 mg/d
Restless leg syndrome: 0.25 mg 13 h before bedtime for
2 d, increase or 0.5 mg for the rst week, then increase
by 0.5 mg every week to a max dosage of 4 mg
Selegiline hydrochlo- C 5 mg PO 2 times per day with breakfast and lunch; Safety and efcacy not
ride (Eldepryl) dosages >10 mg/d are associated with increased risk of established
toxicity due to MAO inhibition
Geriatric dosage: Start with 5 mg in the morning
868 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
BOX 47.1 Drug Interactions:
Levodopa/Carbidopa
Drugs That Increase the Eects of Levodopa/
Carbidopa
Monoamine oxidase inhibitors
Increase the risk of hypertensive crisis
Drugs That Decrease the Eect of Levodopa/
Carbidopa
Anticholinergics
Increase anticholinergic eects by delaying gastric
emptying
Pyridoxine (vitamin B6)
Stimulates decarboxylase, the enzyme that converts
levodopa to dopamine, causing metabolism in the pe-
ripheral tissues and decreasing medication distribu-
tion to the central nervous system
Phenytoin, papaverine, tricyclic antidepressants,
benzodiazepines
Decrease drug ecacy
with levodopa increases CNS effects. Dysrhythmic effects are
increased when combined with halogenated general anesthet-
ics. Several drugs interact with levodopa/carbidopa, increas-
ing or decreasing its effects (Box 47.1). A high-protein meal
increases the effects of levodopa/carbidopa, and kava decreases
the effects of the drug.
Administering the Medication
The nurse ensures that:
Levodopa/carbidopa is administered with or just after
food or following a meal to reduce nausea and vomiting.
Sinemet CR is not crushed.
Levodopa is not given with iron preparations or multivi-
taminmineral preparations that contain iron.
Levodopa/carbidopa is not administered with a high-
protein diet. Adequate hydration is also necessary.
In addition, the nurse should ensure a temperature-controlled
environment; this prevents hyperpyrexia.
QSEN Safety Alert
When administering levodopa, carbidopa, and other
medications for Parkinsons disease, it is important
that medications be given to the patient on time.
Timing of medication administration is critical for
optimal therapeutic eect.
Assessing for Therapeutic Eects
With levodopa and other dopaminergic agents, the nurse
observes for improvement in mobility, balance, posture, gait,
speech, handwriting, and self-care ability. Elimination of drool-
ing and seborrhea may occur. Mood elevation may result. After
2 to 5 years, the medication may lose its overall effectiveness,
and the dosage may need to be increased. The nurse needs to be
aware of symptoms such as ataxic gait, tremors of the hands and
ngers, drooling, and mask-like facial expressions.
Assessing for Adverse Eects
The nurse assesses for anorexia, nausea, and vomiting. These
symptoms usually disappear after a few months of levodopa/
carbidopa therapy. As previously stated, giving the drug with
food minimizes these effects. The nurse also assesses the
patients blood pressure in the sitting and standing positions to
identify signs of orthostatic hypotension. This effect, too, com-
monly dissipates a few weeks after beginning therapy. Levodopa
and its metabolites stimulate beta-adrenergic receptors in the
heart. Patients with preexisting coronary artery disease may
take propranolol (Inderal) to counteract cardiac dysrhythmia
effects. It is necessary to assess the patient for dyskinesia. The
involuntary movements of the tongue, mouth, and face are
common adverse effects. Decreasing the dose of the medica-
tion decreases dyskinesia.
Patient Teaching
Box 47.2 identies patient teaching guidelines for levodopa/
carbidopa.
Other Drugs in the Class
Amantadine hydrochloride (Endantadine, Symmetrel) is an
antiparkinson and antiviral agent (see Chap. 21). It increases
the dopamine release in the nigrostriatal pathway of patients
with Parkinsons disease. It is absorbed in the GI tract with an
onset of action of 36 to 48 hours, a peak of action of 1.5 to
8 hours, and a half-life of 10 to 25 hours. It crosses the pla-
centa and enters the breast milk. It is excreted unchanged in
the urine. The most common adverse effects of amantadine are
dizziness, light-headedness, and insomnia. The nurse instructs
the patient to report swelling of the ngers or ankles, difculty
walking, urinary retention, tremors, slurred speech, or thoughts
of suicide to the health care provider. It is important not to
discontinue this drug abruptly.
BOX 47.2 Patient Teaching Guidelines
for Levodopa/Carbidopa
Take the medication as prescribed.
Do not crush the sustained-release preparation.
pyridoxine.
Do not take multivitamin preparations containing
tion
Understand that there are adverse eects of medica-
such as drowsiness, dizziness, and orthostatic
hypotension.
pressure.
Change positions slowly to prevent drop in blood
Avoid alcohol.
vomiting.
Take the medication with food to prevent nausea and
Do not take the medication with a high-protein meal.
rate,
Report fainting, light-headedness, irregular heart
uncontrolled facial movements, urinary reten-
tion, nausea, and vomiting to the prescriber.
such
Notify the prescriber of any increase in symptoms
as static gait, altered mobility, and pill rolling.
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics
Apomorphine hydrochloride (Apokyn) is an antiparkinson
agent administered for off time, or off episodes, of drug effects.
Parkinsons diseaseto assist in diminishing the symptoms of
hypomobility. Off time is the period when the medication
is not adequately controlling the patients symptoms. Patients
who suffer from off time episodes have advanced Parkinsons when movements are poorly controlled. Because it has not
disease. Administration is subcutaneous. Doses are incremen-
tal, generally ranging from 20 to 40 mg. The most common
dosage is 30 mg, or 0.3 mL, and the maximum dosage is 60 mg.
The patients blood pressure must be monitored for hyperten-
sive crisis during the administration. When apomorphine is
administered to patients with a known cardiac history, periodic
electrocardiogram results should be monitored as well as serum
electrolytes.
Bromocriptine mesylate (Parlodel, Cycloset) is an ergot
derivative that directly stimulates dopamine receptors in the
brain. It is used in the treatment of idiopathic Parkinsons
disease, with levodopa/carbidopa, to prolong effectiveness
and to allow reduced dosage of levodopa. Administration to
patients with a history of myocardial infarction with residual
dysrhythmia requires caution.
Cabergoline, a synthetic ergot, is a long-acting dopamine
agonist approved by the U.S. Food and Drug Administration
(FDA) for use in hyperprolactinemia. This medication has an
unlabeled use: to improve motor symptoms of parkinsonism.
However, the higher dosage required to treat parkinsonism is
associated with the development of serious heart valve damage
due to brosis.
Pramipexole (Mirapex) and ropinirole (Requip) stimu-
late dopamine receptors in the brain. The FDA has approved
their use in both early and late stages of Parkinsons dis-
ease. In early stages, one of these drugs can be used alone
to improve motor performance, improve ability to partici-
pate in usual activities of daily living, and delay levodopa
therapy. In advanced stages, one of these 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, which are not ergot derivatives, may not cause some
adverse effects associated with bromocriptine (e.g., pul-
monary and peritoneal brosis, 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. The drug is
less than 20% bound to plasma proteins and has an elimina-
tion half-life of 8 to 12 hours. Most of the drug is excreted
unchanged in the urine; only 10% is metabolized. As a result,
renal failure may cause higher-than-usual plasma levels and
possible toxicity. However, hepatic disease is unlikely to alter
drug effects.
Ropinirole is also well absorbed with oral administration. It
reaches peak serum levels in 1 to 2 hours and steady-state con-
centrations within 2 days. It is 40% bound to plasma proteins
and has an elimination half-life of 6 hours. It is metabolized by
the cytochrome P450 enzymes in the liver to inactive metabo-
lites, which are excreted through the kidneys. Less than 10%
of ropinirole is excreted unchanged in the urine. Thus, hepatic
failure may decrease metabolism, allow drug accumulation, and
869
increase adverse effects. Renal failure does not appear to alter
Rasagiline (Azilect) is an irreversible MAO inhibitor. It
is indicated for initial treatment for idiopathic parkinsonism
and as an adjunct therapy with levodopa to reduce off time
been determined to be selective for MAO-B in humans, care
must be taken to avoid tyramine-containing foods as well as
sympathomimetic medications to prevent hypertensive crisis.
In addition, rasagiline has the potential to increase seroto-
nin neurotransmission. When given with other drugs that
enhance stimulation of serotonergic receptors (e.g., antide-
pressants, St. Johns wort, dextromethorphan, and meperi-
dine), serotonin syndrome, a potential fatal CNS toxicity
reaction characterized by hyperpyrexia and death, can occur.
Rasagiline should be discontinued at least 14 days before
beginning treatment with most antidepressants or other
MAO inhibitors. Fluoxetine should be discontinued at least
5 weeks before initiating rasagiline, due to its long half-life.
Rasagiline is well absorbed orally, metabolized in the liver,
and excreted primarily by the kidney. It is contraindicated
with foods containing tyramine or sympathomimetic amine
containing medications (e.g., nonprescription cold prepara-
tions and anesthetics) because of the risk of hypertensive
crisis and with antidepressants (e.g., tricyclic antidepressants,
selective serotonin reuptake inhibitors, serotoninnorepi-
nephrine reuptake inhibitors, mirtazapine), meperidine, and
dextromethorphan because of the potential for inducing sero-
tonin syndrome.
Selegiline (Eldepryl) inhibits metabolism of dopamine
by MAO, which exists in two types (as previously stated).
These types are differentiated by their relative specicities for
individual catecholamines. MAO-A acts more specically on
tyramine, norepinephrine, epinephrine, and serotonin. This
enzyme is the main subtype in GI mucosa and in the liver and
is responsible for metabolizing dietary tyramine. If MAO-A
is inhibited in the intestine, tyramine in various foods is
absorbed systemically rather than deactivated. As a result,
there is excessive stimulation of the sympathetic nervous sys-
tem, and severe hypertension and stroke can occur. This is
sometimes called the cheese reaction because aged cheeses
are high in tyramine. This life-threatening reaction can also
occur with some medications (e.g., sympathomimetics) that
are normally metabolized by MAO. MAO-B metabolizes
dopamine; in the brain, most MAO activity is due to type B.
At oral dosages of 10 mg/d or less, selegiline inhibits MAO-B
selectively and is unlikely to cause severe hypertension and
stroke. However, at dosages greater than 10 mg/d, selectiv-
ity is lost and metabolism of both MAO-A and MAO-B is
inhibited. Dosages greater than 10 mg/d should be avoided
in patients with Parkinsons disease. Selegiline inhibition of
MAO-B is irreversible, 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 (level A). In advanced disease, prescrib-
ers order the drug to enhance the effects of levodopa. Its
addition aids symptom control and allows the dosage of
levodopa/carbidopa to be reduced. Once proposed to have
870 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System

neuroprotective properties, authorities now believe that

Clinical Application 47-2
there is insufcient evidence to recommend the use of sele-
giline to confer neuroprotection in patients with Parkinsons Mr. Stokes has been having o time symptom
disease (level U). development. His neurologist orders rasagiline
(Azilect). He develops an upper respiratory viral
infection with a cough. He begins to take dex-
NCLEX Success tromethorphan hydrobromide (Robitussin) every
4 hours. What is Mr. Stokes at risk for developing?
1. The daughter of a 75-year-old woman states to the par-
What symptom does the nurse assess Mr. Stokes
ish nurse that she has noticed her mother rolling her
for when combining rasagiline and dextrometho-
ngers together on her right hand. The nurse observes
rphan hydrobromide?
the patient and determines she is pill rolling, which
is characteristic of Parkinsons disease. Which of the
following factors contributes to the development of
central nervous system symptom of pill rolling? Catechol-O-Methyltransferase
A. decrease ring of the sinoatrial node Inhibitors
B. conversion of angiotensin I to angiotensin II
C. increase in excitatory acetylcholine
Tolcapone (Tasmar) is the prototype COMT inhibi-
D. inux of potassium through the cell membrane
tor. COMT plays a role in brain metabolism of dopamine
2. A 65-year-old woman has been taking levodopa for and metabolizes approximately 10% of peripheral levodopa.
several weeks for symptoms of Parkinsons disease. By inhibiting COMT, tolcapone increases levels of dopa-
Which of the following symptoms indicates that she is mine in the brain and relieves symptoms more effectively and
not receiving an adequate dose for the treatment of her consistently.
symptoms?
A. edema of the feet and ankles Pharmacokinetics
B. widened QRS complex
Tolcapone is absorbed rapidly and is highly protein bound. It is
C. static gait
metabolized in the liver and possesses a 2 to 3 hour half-life. It
D. increased intraocular pressure
crosses the placenta and enters the breast milk. It is excreted in
3. The 56-year-old man is taking levodopa/carbidopa for the feces and urine.
Parkinsons disease. During the therapy, he becomes
light-headed and dizzy. Which of the following is a
Action
potentially serious adverse effect of the drug treatment?
A. orthostatic hypotension The main mechanism of action of tolcapone seems to be inhib-
B. diminished uid volume iting the metabolism of levodopa in the bloodstream, thus
C. hematuria increasing the plasma concentration and duration of action of
D. jaundice the drug. It may also inhibit COMT in the brain and prolong
the activity of dopamine at the synapse.
4. A 52-year-old man is taking selegiline for the treat-
ment of Parkinsons disease. He consumes port wine
Use
cheese and crackers at a party. Which of the following
symptoms does he develop? Tolcapone is useful for the treatment of signs and symptoms of
A. ataxic gait idiopathic Parkinsons disease. Administration is only in con-
B. melena junction with levodopa/carbidopa, and a reduction in levodopa
C. cardiac dysrhythmia dosage is required. If a patient does not show a clinical benet
D. hypertension within 3 weeks of starting treatment, discontinuation of tol-
capone is necessary.
5. A 48-year-old man with severe akinesia develops severe Table 47.3 presents dosage information for tolcapone and
symptoms of parkinsonism following the administration other drugs in its class.
of his antiparkinson medications. This condition occurs
only one to two times per month. Which of the follow- Use in Older Adults
ing medications is the mans prescriber most likely to When administering tolcapone to geriatric patients, it is
order? important to reduce the dosage and adjust it slowly to prevent
A. bromocriptine mesylate (Parlodel) adverse effects.
B. apomorphine hydrochloride (Apokyn) Use in Patients With Renal Impairment
C. cabergoline (Dostinex)
D. pramipexole dihydrochloride (Mirapex, Mirapex ER) Caution is warranted in administration of tolcapone to patients
with renal impairment because it is excreted in the urine.
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics 871

TABLE 47.3
DRUGS AT A GLANCE: Catechol-O-Methyltransferase (COMT) Inhibitors
Pregnancy
Drug Category Routes and Dosage Ranges

Adults Children

Tolcapone (Tasmar) C 100 mg PO 3 times per day (max dose: 200 mg Safety and efcacy
3 times per day) not established
Entacapone (Comtan) C 200 mg PO administered with each dose of Safety and efcacy
levodopa/carbidopa up to 8 times per day not established

Use in Patients With Hepatic Impairment Assessing for Adverse Eects

If liver values are greater than two times the upper limit of
normal, discontinuation of tolcapone is necessary. Patients
with moderate to severe hepatic impairment should not take
tolcapone at doses exceeding 100 mg three times per day. The
FDA has issued a BLACK BOX WARNING stating that
patients who take tolcapone risk potentially fatal acute fulmi-
nant liver failure. It is important to monitor liver function tests
before therapy begins and every 2 weeks thereafter.
The nurse assesses for disorientation and confusion, light-
headedness, and orthostatic hypotension. It is necessary to take
blood pressure lying down, sitting, and standing up. Frequent
monitoring of liver enzymes is essential.
Patient Teaching
Box 47.3 presents patient teaching guidelines for tolcapone.

Other Drugs in the Class

Adverse Eects
Tolcapone produces adverse effects in several major body systems,
including the CNS, cardiovascular system, dermatological sys-
tem, GI system, and respiratory system. The most severe adverse
effect is fulminant liver failure, which may be fatal. CNS adverse
effects include disorientation, confusion, hallucinations, and psy-
chosis. Dizziness and orthostatic hypotension may also occur.
Contraindications
Contraindications to tolcapone include a hypersensitivity to the
drug. Other contraindications are liver disease, nontraumatic
rhabdomyolysis, hyperpyrexia, and confusion. Caution is war-
ranted with hypertension, hypotension, and renal impairment.
Nursing Implications
Preventing Interactions
It is essential that tolcapone and other COMT medications not
be administered with MAO inhibitors due to the risk of hyper-
tensive crisis.
Administering the Medication
It is necessary to administer tolcapone in conjunction with lev-
odopa/carbidopa and to monitor the patients response to the
Entacapone is well tolerated and safer than tolcapone, and
thus, prescribers more commonly order entacapone. This
COMT inhibitor is well absorbed after oral administration
and reaches a peak plasma level in 1 hour. It is highly pro-
tein bound (98%), has a half-life of about 2.5 hours, and is
metabolized in the liver to an inactive metabolite. Dosage
must be reduced by 50% in the presence of impaired liver
function. The parent drug and metabolite are 90% excreted
through the biliary tract and feces, and 10% of excretion
occurs in the urine. Adverse effects include confusion, dizzi-
ness, drowsiness, hallucinations, nausea, and vomiting, which
can be reduced by lowering the dose of either levodopa or
entacapone. Although clinical trials report few instances of
liver enzyme elevation or hemoglobin decreases, it is recom-
mended that liver enzymes and red blood cell counts be meas-
ured periodically.
BOX 47.3 Patient Teaching
Guidelines for Tolcapone
Take the medication exactly as prescribed.
2Doweeks.
not stop the medication abruptly; taper it over

medication. The addition of the drug may require a decrease in carbidopa.

the levodopa dosage. Abrupt withdrawal of tolcapone can lead
to serious complications. Tapering over 2 weeks is necessary to
prevent adverse effects.
Assessing for Therapeutic Eects
The decrease or absence of symptoms of Parkinsons disease
such as improved gait and mobility, diminished tremors, and
rigidity is indicative of tolcapones therapeutic effectiveness.
Take the medication in conjunction with levodopa/
Use barrier contraceptives while using this medication.
Do not breast-feed while taking the medication.
tral
Use caution when operating machinery due to cen-
nervous system depression.
Use hard candy to decrease dry mouth.
Have liver function tests as scheduled.
872 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
NCLEX Success
6. An elderly woman is taking tolcapone. She has noticed
that her skin is yellow. The nurse assesses which of
the following?
A. intake of carrots
B. temperature related to infection
C. sclera
D. amount of urine output
7. A 35-year-old woman has begun to take tolcapone
in addition to levodopa/carbidopa for Parkinsons
disease. Which of the following is the priority nursing
intervention?
A. arrange to assess the patient for hypertension early in
the morning
B. evaluate the patients ability care for herself
C. have the patient take levodopa/carbidopa 2 hours
after tolcapone
D. instruct the patient to report tea-colored urine to the
prescriber
Catechol-O-Methyltransferase
Inhibitor and Decarboxylase
Inhibitor/Dopamine Precursor
One antiparkinson drug is a combination of levodopa,
carbidopa, and entacapone (Stalevo). This chapter
discusses this medication in a separate class because it com-
bines medications from two separate classes. Administration of
Stalevo allows for greater convenience and improved Parkinson
symptom management. Use of the drug combination provides
the patient with the convenience of one medication.
Pharmacokinetics
The combination drug Stalevo has the same pharmacokinetics
as those of levodopa/carbidopa and entacapone.
Action
Levodopa is the metabolic precursor of dopamine. Depleted in
Parkinsons disease, levodopa is circulated in the plasma and
crosses the bloodbrain barrier, where it is converted to dopa-
mine by the striatal enzymes. Carbidopa inhibits the peripheral
plasma breakdown of levodopa by inhibiting decarboxylation,
thus increasing levodopa. Entacapone is a reversible and selec-
tive inhibitor of COMT. It alters the pharmacokinetics of levo-
dopa, allowing for more sustained levodopa serum levels and
increased concentrations for absorption across the bloodbrain
barrier.
Use
Stalevo is used for the treatment of idiopathic Parkinsons
disease. Table 47.4 presents dosage information for Stalevo.
Comparison of Pharmacokinetic Prole of
Levodopa Throughout the Day Between
Levodopa/Carbidopa/Entacapone and
Levodopa/Carbidopa When Administered
Four or Five Times Daily
by KUOPPMANKI, M., KORPELA, K., MARTTILA,
R., VI KAASINEN, HARTIKAINEN, P., LYYTINEN, J.,
KAAKKOLA, S., HANNINEN, J., LOYTTYNIEMI, E.,
KAILAJARVI, M., RUOKONIEMI, P., ELLMEN, J.
Eur J Clin Pharmacol 2009, 65(5),443455
Epub 2009 Feb 20
This study compared the plasma levodopa concentrations
after repeated doses of levodopa/carbidopa/entacapone
and levodopa/carbidopa. The results of the study revealed
that 100 to 150 mg of levodopa/carbidopa/entacapone
administered four to ve times per day provided a better
pharmacokinetic prole than levodopa/carbidopa.
IMPLICATIONS FOR NURSING PRACTICE: Based on this
study, symptom control was better than with levodopa/
carbidopa and entacapone than levodopa/carbidopa
alone. Thus, the administration of levodopa/carbidopa,
entacapone provides better symptom control in Par-
kinsons patients due to the fact the trough values of
levodopa were higher with the combination medication.
Use in Patients With Renal Impairment
It is necessary to administer Stalevo with caution in patients
with severe renal impairment. Dosage reduction to prevent fur-
ther renal insufciency may be warranted.
Use in Patients With Hepatic Impairment
Cautious administration of Stalevo is also necessary in patients
with hepatic impairment because the medication is metabo-
lized in the liver.
Adverse Eects
Stalevo may affect the GI, dermatologic, respiratory, and
cardiovascular systems. GI adverse effects include diarrhea as well
as nausea, vomiting, bruxism, dry mouth, and excess salivation.
The development of diarrhea is indicative of drug-induced coli-
tis, and it is necessary to discontinue Stalevo if diarrhea occurs.
Also, the risk of melanoma may increase. As with other anti-
parkinson medications, hypotension is a risk, along with heart
attack, stroke, and cardiovascular death. The FDA is conducting
an ongoing review of data to assess whether patients are at risk for
cardiovascular events when taking this drug (U.S. FDA, Stalevo
[carbidopa/levodopa and entacapone], 2010). Also, there is an
increased risk of cardiovascular events in patients who received
Stalevo versus those who received Sinemet. However, the study
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics 873

TABLE 47.4
DRUGS AT A GLANCE: Catechol-O-Methyltransferase Inhibitor and
Decarboxylase Inhibitor/Dopamine Precursor
Pregnancy
Drug Category Routes and Dosage Range

Adults Children

Levodopa/carbidopa/
entacapone (Stalevo)
C Dosing forms: Levodopa 50 mg/carbidopa 12.5 mg/ Safety and efcacy not
entacapone 200 mg PO daily established
Levodopa 75 mg/carbidopa 18.75 mg/entacapone
200 mg
Levodopa 100 mg/carbidopa 25 mg/entacapone
200 mg
Levodopa 125 mg/carbidopa 31.25 mg/entacapone
200 mg
Levodopa 150 mg/carbidopa 37.5 mg/entacapone
200 mg
Levodopa 200 mg/carbidopa 50 mg/entacapone
200 mg

shows that the risk of cardiovascular events is not statistically
signicant, but studies of the drug are continuing. The FDA is
evaluating clinical data that the administration of Stalevo may
increase the male patients risk of developing prostate cancer.
One trial has compared Stalevo with carbidopa and levodopa.
Unexpectedly, the study has revealed that a greater number of
patients taking Stalevo have prostate cancer (U. S. Food and
Drug Administration. FDA Drug Safety Communication, 2010).
Contraindications
Contraindications to the use of Stalevo include a known sen-
sitivity to the levodopa, carbidopa, or entacapone. The con-
current use of MAO inhibitors, or use within 14 days, is also
a contraindication. Levodopa may trigger melanoma; there-
fore, patients with a history of melanoma should not receive
Stalevo. Also, it is important to note that ergot-derived dopa-
mine agonists administered with Stalevo have been associated
with brotic complications such as pleural effusion, pleural
thickening, and pulmonary inltrates.
Nursing Implications
Preventing Interactions
The administration of catecholamines such as epinephrine,
dopamine, and methyldopa enhances the action of entaca-
pone, one of the components of Stalevo.
Administering the Medication
Patients whose medication regime is being changed to Stalevo
should be administered levodopa and the adjunctive entaca-
pone. The levodopa dose should be adjusted prior to the con-
version to Stalevo therapy. The dose should be individualized
based on the therapeutic response. The presence of dyskinesia
necessitates a dosage adjustment. The dose may be adjusted
by changing the strength or adjusting the dosing intervals.
Fractionated doses are not recommended, and only one tablet
should be administered at each dosing interval. The maximum
daily dose is eight 50-, 75-, 100-, 125-, and 150-mg tablets and
only six 200-mg tablets. (Patients who take more than 600 mg/d
of levodopa should not switch directly to Stalevo.) Patients
should swallow the tablets wholenot crushed, broken, or
chewed. Stalevo can be administered without regard to meals.
To prevent uctuation in levodopa absorption, it is necessary to
distribute protein intake throughout the day. People should take
iron, iron supplements, and multivitamins that contain minerals
separately from Stalevo.
Assessing for Therapeutic Eects
The decrease or absence of Parkinsons symptoms such as
muscle rigidity, excessive salivation, pill rolling, and tremors
is indicative of Stalevos therapeutic effectiveness.
Assessing for Adverse Eects
The nurse assesses the patients cardiovascular status, includ-
ing heart rate and blood pressure, to determine alterations in
cardiovascular symptoms. It is also necessary to assess for chest
pain, confusion, and weakness of extremities related to cere-
brovascular accident or myocardial infarction. In addition, the
nurse assesses the patients skin for unusual skin lesions and
checks the patients fecal elimination for drug-induced colitis.
Patient Teaching
Patient education for Stalevo is the same as the patient educa-
tion for the drugs individual components: levodopa, carbidopa,
and entacapone (see Box 47.2). With entacapone, the nurse
instructs the patient to report hallucinations and diarrhea. It
is also necessary to tell the patient that his or her urine may
become brownish-orange. This is a normal reaction to the
medication and is not harmful. In addition, the nurse tells the
patient to protect against falls due to orthostatic hypotension;
patients can stand up slowly.
874 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System

Decient knowledge: safe usage and effects of antiparkin-

Clinical Application 47-3
Mr. Stokes prescriber switches him from
levodopa/carbidopa to levodopa/carbidopa/
entacapone. He asks his nurse what the dier-
ence is between the medication he once took
and what he is now taking. What patient educa-
tion does the nurse provide?
NCLEX Success
8. A 76-year-old woman is taking levodopa/carbidopa/
entacapone (Stalevo). Which of the following is the
priority nursing intervention?
A. administering with a high-protein meal
B. administering with meals only
C. assessing for diarrhea
D. assessing for constipation
9. An elderly man begins taking levodopa/carbidopa/enta-
capone (Stalevo). Which of the following symptoms
warrants a change in the dosage?
A. dilated pupils
B. static gait
C. edema
D. nausea
The Nursing Process
Assessment
Assess for signs and symptoms of Parkinsons disease and
drug-induced extrapyramidal reactions, such as the follow-
ing, depending on the severity and stage of progression:
Slow movements (bradykinesia) and difculty in
changing positions, assuming an upright position, eat-
ing, dressing, and other self-care activities
Stooped posture
Accelerating gait with short steps
Tremor at rest (e.g., pill-rolling movements of ngers)
Rigidity of arms, legs, and neck
Mask-like, immobile facial expression
Speech problems (e.g., low volume, monotonous tone,
rapid, difcult 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.
sonism drugs
Imbalanced nutrition: less than body requirements related
to difculty in chewing and swallowing food
Risk for falls: related to altered gait
Planning/Goals
The patient will
Experience relief of excessive salivation, muscle rigidity,
spasticity, and tremors
Experience improved motor function, mobility, and
self-care abilities
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
Nursing Interventions
The nurse will
Use measures to assist the patient and family in coping
with symptoms and maintaining function. These include
the following:
Arrange for physical therapy for heel-to-toe gait
training, widening stance to increase balance and base
of support, and other exercises
Encourage ambulation and frequent changes of posi-
tion, assisted if necessary
Help with active and passive range-of-motion exercises
Encourage self-care as much as possible
It may help to cut meat; open cartons; give frequent, small
meals; and allow privacy during mealtime.
If the patient has difculty chewing or swallowing,
chopped or soft foods may be necessary.
Hook-and-loop-type fasteners or zippers are easier to
handle than buttons.
Slip-on shoes are easier to manage than laced ones.
Spend time with the patient 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.
Provide appropriate patient teaching related to drug
therapy (see Boxes 47.2 and 47.3).
Evaluation
Interview and observe for relief of symptoms.
Interview and observe for increased mobility and partici-
pation in activities of daily living.
Interview and observe regarding correct usage of
medications.
Overview of Anticholinergic Drugs

Nursing Diagnoses Anticholinergic drugs inhibit the actions of acetylcholine

Bathing/grooming self-care decit related to tremors and in the brain and affect the parasympathetic nervous system.
impaired motor function Most anticholinergic drugs interact with muscarinic cho-
Impaired physical mobility related to alterations in linergic receptors in the brain, secretory glands, heart, and
balance and coordination smooth muscle and are sometimes called antimuscarinic
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics
TABLE 47.5
Common Tertiary Amine and Quaternary Amine
Anticholinergic Drugs
Tertiary Amines
Atropine
Benztropine mesylate (Cogentin)
Darifenacin hydrobromide (Enablex)
Dicyclomine hydrochloride (Bentyl)
Flavoxate hydrochloride (Urispas)
l-Hyoscyamine (Anaspaz)
Oxybutynin chloride (Ditropan)
Scopolamine hydrobromide
Solifenacin succinate (Vesicare)
Tolterodine tartrate (Detrol, Detrol LA,
and Oxytrol)
Trihexyphenidyl hydrochloride (Trihexy)
drugs. When given at high doses, a few anticholinergic drugs
are also able to block nicotinic receptors in autonomic gan-
glia and skeletal muscles. Glycopyrrolate is an example of
such a medication. This drug class includes belladonna alka-
loids and their derivatives, such as atropine, and many syn-
thetic substitutes.
Most anticholinergic medications are either tertiary
amines or quaternary amines (Table 47.5). Tertiary amines are
uncharged lipid-soluble molecules. Atropine and scopolamine
are tertiary amines and therefore are able to cross cell mem-
branes readily. They are well absorbed from the GI tract and
conjunctiva, and they cross the bloodbrain barrier. Tertiary
amines are excreted in the urine.
Quaternary amines carry a positive charge and are lipid
insoluble. Some belladonna derivatives and synthetic anti-
cholinergics are quaternary amines. Consequently, they do not
readily cross cell membranes. They are poorly absorbed from the
GI tract and do not cross the bloodbrain barrier. Quaternary
amines are excreted largely in the feces.
Clinical Use
The widespread effects of anticholinergic drugs limit their
clinical usefulness. Consequently, several synthetic drugs have
been developed in an effort to increase selectivity of action on
particular body tissues, especially to retain the antispasmodic
and antisecretory effects of atropine while eliminating its
adverse effects. This effort has been less than successfulall
the synthetic drugs produce atropine-like adverse effects when
doses are sufcient.
Some synthetic drugs are used for antispasmodic effects in
GI disorders and overactive urinary bladder. Another group of
synthetic drugs includes centrally active anticholinergics used
in the treatment of Parkinsons disease; these drugs balance
the relative cholinergic dominance that causes the movement
875
Quaternary Amines
Glycopyrrolate (Robinul)
Ipratropium bromide (Atrovent)
Methscopolamine bromide (Pamine)
Tiotropium bromide (Spiriva)
Trospium chloride (Sanctura)
disorders associated with parkinsonism. Specic body systems
and conditions in which anticholinergic medications are
administered are listed in Table 47.6.
Drug Therapy
Anticholinergic drugs act by occupying receptor sites on tar-
get organs innervated by the parasympathetic nervous system,
thereby leaving fewer receptor sites free to respond to ace-
tylcholine (Fig. 47.2). Parasympathetic response is absent or
decreased, depending on the number of receptors blocked by
anticholinergic drugs and the underlying degree of parasympa-
thetic activity. Because cholinergic muscarinic receptors are
widely distributed in the body, anticholinergic drugs produce
effects in a variety of locations, including the CNS, heart,
smooth muscle, glands, and the eye.
Specic effects on body tissues and organs include the
following:
CNS stimulation followed by depression, which may
result in coma and death. This is most likely to occur
with large doses of anticholinergic drugs that cross the
bloodbrain barrier (atropine, scopolamine, and antipar-
kinson agents).
Decreased cardiovascular response to parasympathetic
(vagal) stimulation that slows heart rate. Atropine is the
anticholinergic drug most often used for its cardiovascu-
lar effects. According to Advanced Cardiac Life Support
(ACLS) protocol, atropine is the drug of choice to treat
symptomatic sinus bradycardia. Low doses (less than
0.5 mg) may produce a slight and temporary decrease in
heart rate; however, moderate to large doses (0.51 mg)
increase heart rate by blocking parasympathetic vagal
stimulation. Although the increase in heart rate may be
therapeutic in bradycardia, it can be an adverse effect
in patients with other types of heart disease because
876 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System

TABLE 47.6
Body System and Indication of Anticholinergic Use
Body System Indication for Anticholinergic Use

Cardiac Bradycardia, heart block with hypotension and shock: increases heart rate and prevent vagal
stimulation
Gastrointestinal Peptic ulcer disease, gastritis, pylorospasm, and diverticulitis: relieves pain and relaxes gastrointestinal
smooth muscle
Irritable bowel, colitis: reduces frequent bowel movements and abdominal discomfort
Genitourinary Urinary incontinence and frequency: reduces urinary muscle spasm
Cystitis, urethritis, and prostatitis: decreases pain and frequency
Enuresis, paraplegia, and neurogenic bladder: increases bladder capacity
Otolaryngology Head and neck surgery and bronchoscopy: reduces respiratory tract secretions
Ophthalmology Mydriatic and cycloplegic effects: dilate pupils
Respiratory Asthma, chronic bronchitis: produces bronchodilation
Metabolic Mushroom poisoning and organophosphate pesticide poisoning: reduces cholinergic stimulation;
salivation, urination, defecation, bronchial secretions, laryngospasm, and bronchospasm

atropine increases the myocardial oxygen demand.
Atropine usually has little or no effect on blood pressure.
Large doses cause facial ushing because of dilation of
blood vessels in the neck.
Bronchodilation and decreased respiratory tract secre-
tions. Anticholinergics block the action of acetyl-
choline in bronchial smooth muscle when given by
inhalation. This action reduces intracellular guanosine
monophosphate (GMP), a bronchoconstrictive sub-
stance. When anticholinergic drugs are given systemi-
cally, respiratory secretions decrease and may become
Synapse
Presynaptic vesicles
containing acetylcholine
Muscarinic
Nerve ending receptor
Table 47.7 lists the various anticholinergic medications.
viscous, resulting in mucous plugging of small respiratory
passages. Administering the medications by inhalation
decreases this effect while preserving the benecial bron-
chodilation effect.
Antispasmodic effects in the GI tract due to decreased
muscle tone and motility. The drugs have little inhibitory
effect on gastric acid secretion with usual doses and insig-
nicant effects on pancreatic and intestinal secretions.
Mydriasis and cycloplegia in the eye. Normally,
anticholinergics do not change intraocular pressure, but
with narrow-angle glaucoma, they may increase intraoc-
ular pressure and precipitate an episode of acute glau-
coma. When the pupil is fully dilated, photophobia may
be uncomfortable, and reexes to light and accommoda-
tion may disappear.
Miscellaneous effects. These include decreased secretions
from salivary and sweat glands; relaxation of ureters, uri-
nary bladder, and the detrusor muscle; and relaxation of
smooth muscle in the gallbladder and bile ducts.

Belladonna Alkaloid and Derivatives

Atropine sulfate, the prototype of the anticholinergic

drugs, is a naturally occurring belladonna alkaloid that can be
extracted from the belladonna plant or prepared synthetically. It
is usually prepared as atropine sulfate, a salt that is very soluble in
Anticholinergic Effector
target organ water. Atropine sulfate is also classied as a muscarinic antagonist.
drug

Figure 47.2 Mechanism of action of anticholinergic drugs.
Anticholinergic (antimuscarinic) drugs prevent acetylcholine
from interacting with muscarinic receptors on target eec-
tor organs, thus blocking or decreasing a parasympathetic
response in these organs.
Pharmacokinetics
Atropine is well absorbed from the GI tract and distributed
throughout the body. It crosses the bloodbrain barrier to enter
the CNS, where large doses produce stimulant effects and toxic
doses produce depressant effects. The drug is also absorbed
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics 877

TABLE 47.7
Anticholinergic Medications
Drug Class Prototype Other Drugs in the Class

Belladonna alkaloids and derivatives
Centrally acting anticholinergic agents
Gastrointestinal antisecretory/
antispasmodic
Urinary antispasmodic
Atropine sulfate
Benztropine mesylate (Cogentin)
Dicyclomine hydrochloride (Bentyl)
Oxybutynin chloride (Ditropan,
Ditropan XL, Oxytrol)
Homatropine bromide (Isopto Homatropine)
Hyoscyamine sulfate (Anaspaz)
Ipratropium bromide (Atrovent)
Scopolamine hydrobromide
Tiotropium bromide (Spiriva)
Trihexyphenidyl hydrochloride (Trihexy)
Glycopyrrolate (Robinul)
Darifenacin hydrobromide (Enablex)
Flavoxate hydrochloride (Urispas)
Solifenacin succinate (Vesicare)
Tolterodine tartrate (Detrol and Detrol LA)
Trospium chloride (Sanctura)

systemically when applied locally to mucous membranes. It
is metabolized in the liver. The pharmacologic effects last for
about 4 hours, except for ocular effects, which may last for
7 to 14 days. Atropine is rapidly excreted in the urine.
Action
Atropine competitively blocks the effects of acetylcholine at
muscarinic cholinergic receptors that mediate the effects of para-
sympathetic postganglionic impulses. It also prevents the action
of acetylcholine in the CNS. Atropine depresses the salivary and
bronchial secretions, dilates the bronchi, inhibits vagal inu-
ences on the heart, relaxes the GI and genitourinary tracts, and
inhibits gastric acid secretion. In addition, it relaxes the pupil of
the eye and prevents the accommodation for near vision.
Use
In the past, atropine was used to control the symptoms of
Parkinsons diseaseto relieve tremors and decrease rigidity. The
development of the centrally acting anticholinergic agents has
replaced the use of atropine for Parkinsons disease. Impaired renal
or hepatic function is a contraindication to the use of atropine.
The most common use of atropine is the restoration of cardiac
rate and arterial pressure during anesthesia when vagal stimula-
tion produced by intraabdominal traction causes a decrease in
pulse rate, lessening the degree of atrioventricular block when
increased vagal tone is a factor. Atropine also relieves bradycar-
dia and syncope due to hyperactive carotid sinus reex. It also
serves as an antidote for cardiac collapse with an overdose of
parasympathomimetic drugs also know was cholinergic agents
and cholinesterase inhibitors such as physostigmine.
Also, practitioners administer atropine in the preanesthesia
stage to reduce respiratory tract secretions.
In addition, atropine is an antidote for mushroom poisoning
(Amanita muscaria). Symptoms of muscarinic poisoning include
salivation, lacrimation, visual disturbances, bronchospasm,
diarrhea, bradycardia, and hypotension. Atropine prevents
the poison from interacting with muscarinic receptors, thus
reversing the toxic effects. Muscarinic poisoning can also occur
from cholinergic agonist drugs, cholinesterase inhibitor drugs,
and insecticides that contain organophosphates.
Table 47.8 presents dosage information for atropine sulfate
and the other belladonna alkaloids.
Use in Children
Systemic anticholinergics, including atropine, have essen-
tially the same indications in children of all ages as in adults.
Anticholinergic drugs cause the same adverse effects in chil-
dren as in adults. However, the effects may be more severe in
children, who are especially sensitive to these drugs. Facial
ushing is common, and skin rashes may occur. In addition, the
administration of atropine sulfate to children can cause hyper-
pyrexia or atropine fever.
Use in Older Adults
It is necessary to administer atropine cautiously in the geriatric
population. In older adults, CNS reactions are more likely to
occur.
Use in Patients With Critical Illness
When atropine is administered for cardiovascular symptoms,
it is necessary to monitor the patients cardiac status with an
electrocardiogram.
Adverse Eects
Atropine sulfate may adversely affect several body systems.
Cardiovascular adverse effects include bradycardia (low doses)
and with tachycardia (high doses). CNS adverse effects include
blurred vision, mydriasis, cycloplegia, photophobia, and
increased intraocular pressure. In the geriatric population, nerv-
ousness, weakness, confusion, or excitement are common. The
most severe GI adverse effect is paralytic ileus. Genitourinary
effects are urinary hesitancy and retention. The patient may also
complain of decreased sweating, which leads to heat prostration.
878 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
TABLE 47.8
DRUGS AT A GLANCE: Belladonna Alkaloids and Derivatives
Drug
Atropine sulfate (AtroPen,
Sal-Tropine)
Ophthalmic atropine
(Isopto Atropine)
Homatropine bromide (Isopto
Homatropine)
Hyoscyamine sulfate (Anaspaz)
Ipratropium bromide
(Atrovent, Atrovent HFA)
Scopolamine
Tiotropium bromide (Spiriva)
Pregnancy
Category Routes and Dosage Ranges
Adults
C PO, IM, Sub-Q, IV 0.40.6 mg
IM, Sub-Q, or IV 0.40.6 mg prior to
induction. Use 0.4-mg dose with
cyclopropane anesthesia.
IV 0.5 mg (up to 3 mg) every 35 min
PRN
IV titrate large doses of 23 mg as needed
until signs of atropine toxicity appear
and cholinergic crisis is controlled.
For refraction: Instill 1 or 2 drops of
1% solution into eye(s) 1 h before
refraction
C For refraction: Instill 12 drops of 2%
solution or 1 drop of 5% solution into
eye before procedure. May repeat at
510 min intervals as needed.
For uveitis: Instill 1 or 2 drops of 2% or
5% solution 24 times daily or every
34 h as needed.
C PO, SL 0.1250.25 mg 3 or 4 times
daily before meals and at bedtime. PO
(timed- release formula): 0.375
0.75 mg every 12 h; IM, IV, Sub-Q:
0.250.5 mg every 6 h
B Bronchodilation: 2 puffs (36 mcg) of
aerosol 4 times daily. Additional
inhalations may be needed. Do not
exceed 12 puffs/24 h. Solution for
inhalation: 500 mcg, 3 or 4 times
daily.
2 sprays/nostril of 0.03% spray 2 or 3
times daily
Rhinorrhea: 2 sprays/nostril of 0.06%
spray 34 times daily
C 0.40.8 mg daily. PO
0.320.65 mg Sub-Q, IM
0.320.65 mg IV diluted in sterile
water for injection
Transdermal: Apply disk 4 h before
antiemetic effect is needed.
Replace every 3 d.
For refraction: Instill 1 or 2 drops into
eye 1 h before refracting.
For uveitis: Instill 1 or 2 drops into
eye(s) up to 3 times daily.
C Bronchodilation: Inhalation of con-
tents of one capsule
(18 mcg) daily using the
HandiHaler inhalation device
Children
PO, IM, Sub-Q, IV:
716 lb: 0.1 mg
1624 lb: 0.15 mg
2440 lb: 0.2 mg
4065 lb: 0.3 mg
6590 lb: 0.4 mg
under 90 lb: 0.40.6 mg
0.1 mg (newborn) to 0.6 mg (12 y)
given Sub-Q 30 min prior to surgery
For refraction: Instill 12 drops of
0.5% solution twice daily for
13 d before procedure.
For refraction: Instill 1 drop of
2% solution into eye before
procedure. May repeat every
10 min as needed
For uveitis: Instill 1 drop of
2% solution 24 times daily.
Children under 2 y: half of the
previous dose
Children 210 y: PO 0.062
0.125 mg every 68 h
Rhinorrhea: 2 sprays/nostril of
0.03% spray 34 times per day
Preoperative and antiemetic: 6 mcg/
kg/dose Sub-Q, IM, or IV (max
dose: 0.3 mg/dose) every 68 h
Motion sickness: Children
>12 y: 12 tablets PO 1 h prior to
exposure
Apply 1 transdermal disk behind ear
at least 4 h prior to exposure every
3 d as needed
For refraction and iridocyclitis: Instill
1 drop of 0.25% to eye twice daily
for 2 d before procedure
Safety and efcacy have not been
established.
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics
Overdose of atropine or other anticholinergic drugs produces
the usual pharmacologic effect such as decreased secretions,
increased heart rate, relaxation of the bronchial smooth mus-
cle, and decreased GI and genitourinary tone in severe and
exaggerated forms. The anticholinergic overdose syndrome
is characterized by hyperthermia; hot, dry, ushed skin; dry
mouth; mydriasis; delirium; tachycardia; paralytic ileus; and
urinary retention. Myoclonic movements and choreoathetosis
may be evident. Seizures, coma, and respiratory arrest may also
occur. Treatment involves use of activated charcoal to absorb
the ingested drug. Hemodialysis, hemoperfusion, peritoneal
dialysis, and repeated doses of charcoal are not effective.
Physostigmine salicylate (Antilirium), an acetylcholinester-
ase inhibitor, is a specic antidote for overdose of anticholiner-
gics. It is usually given intravenously at a slow rate of injection,
because rapid administration may cause bradycardia, hypersali-
vation (with subsequent respiratory distress), and seizures. The
adult dose is 2 mg (no more than 1 mg/min), and the pediatric
dose is 0.5 to 1 mg (no more than 0.5 mg/min). Repeated doses
may be given if life-threatening dysrhythmias, convulsions, or
coma occurs with anticholinergic overdose. However, the ben-
et of repeat dosing must be balanced against the risk of phys-
ostigmine overdose. Excessive administration of physostigmine
can precipitate a cholinergic crisis, leading to seizures and dys-
rhythmias. Atropine is the antidote for physostigmine overdose.
Diazepam or a similar drug may be given for excessive CNS
stimulation (e.g., delirium, excitement) that accompanies
anticholinergic toxicity. Ice bags, cooling blankets, and tepid
sponge baths may help reduce fever. Articial ventilation and
cardiopulmonary resuscitative measures are used if excessive
depression of the CNS causes coma and respiratory failure.
Infants, children, and the elderly are especially susceptible to
the toxic effects of anticholinergic drugs.
Contraindications
Contraindications to the use of atropine include a known
hypersensitivity to anticholinergic agents. Other contraindica-
tions include glaucoma, stenosing peptic ulcer, pyloroduodenal
obstruction, bronchial asthma, and bladder neck obstruction,
as well as hepatic or renal disease.
Nursing Implications
Preventing Interactions
Drugs that increase the anticholinergic effects of atropine
include amantadine, antihistamines, tricyclic antidepressants,
quinidine, disopyramide, and procainamide. Some herbs also
increase the effectiveness of atropine (Box 47.4).
BOX 47.4 Herb and Dietary
Interactions: Atropine Sulfate
Herbs and Foods That Increase the Eects of
Atropine Sulfate
Aloe
Cascara
Senna
879
Administering the Medication
Prior to administering atropine, the nurse assesses for hyper-
sensitivity to anticholinergic agents, glaucoma, stenosing
peptic ulcer, paralytic ileus, bronchial asthma, bladder neck
obstruction, and cardiac dysrhythmias. The patient should be
well hydrated and the environment should be cool to protect
from hyperpyrexia. If the patient has a history of urinary reten-
tion, the patient should void before administration of the drug.
Assessing for Therapeutic Eects
The nurse assesses the heart rate if atropine is administered
for bradycardia. In preoperative patients, the nurse assesses for
diminished secretions, particularly when the drug is admin-
istered for head and neck surgery. Patients with Parkinsons
disease or Parkinson-like syndromes require assessment for
decreased spasticity and tremors.
Assessing for Adverse Eects
The nurse assesses for the following conditions, which may
indicate a severe anticholinergic reaction:
Changes in rate, quality, and rhythm of the heart that
indicates ventricular tachycardia
Urinary retention
Bowel sounds for signs of paralytic ileus
Photophobia, mydriasis, blurred vision, and increased
intraocular pressure
Dry mouth
Increased temperature. Elderly people and children are
prone to hyperpyrexia due to suppression of perspiration
and heat loss.
Patient Teaching
Box 47.5 identies patient teaching guidelines for atropine
sulfate.
Other Drugs in the Class
Homatropine hydrobromide is a semisynthetic derivative of
atropine used as eye drops to produce mydriasis and cycloplegia.
BOX 47.5 Patient Teaching Guidelines
for Atropine Sulfate
Avoid excessive high temperatures.
Drink water frequently.
Rinse the mouth frequently.
Maintain good dental hygiene.
Use hard candy to decrease dry mouth.
Void before taking the medication.
Visit the ophthalmologist regularly.
less
Notify your prescriber is uid intake is greater or
than urine output.
Notify your prescriber if you develop a fever.
Notify your prescriber if weakness becomes severe.
ness is impaired.
Avoid the use of machinery if visual acuity or alert-
880 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
Compared with atropine, homatropine may be preferable,
because its ocular effects do not last as long.
Hyoscyamine (Anaspaz) is a belladonna alkaloid used in GI
and genitourinary disorders characterized by spasm, increased
secretion, and increased motility. It has the same effects as
other atropine-like drugs.
Ipratropium (Atrovent) is an anticholinergic drug chemically
related to atropine. When given as a nasal spray, it is useful in
treating rhinorrhea due to allergy or the common cold. When
given in inhaled or aerosol form to patients with chronic obstruc-
tive pulmonary disease (COPD), it is benecial as a bronchodila-
tor. Using the respiratory route instead of the systemic route to
administer anticholinergic drugs results in less thickening of res-
piratory secretions and therefore a reduced incidence of mucus-
plugged airways.
Scopolamine has similar uses, adverse effects, and peripheral
effects when compared with atropine but is different with regard
to its central effects. When scopolamine is given parenterally,
it depresses the CNS and causes amnesia, drowsiness, euphoria,
relaxation, and sleep. Effects of the drug appear more quickly
and disappear more readily than those of atropine. Scopolamine
also is used in motion sickness. It is available as oral tablets and
as a transdermal adhesive disk that is placed behind the ear.
The disk (Transderm-V) protects against motion sickness for
72 hours.
Tiotropium bromide (Spiriva HandiHaler) is a dry pow-
der in capsule form intended for oral inhalation with the
HandiHaler inhalation device. This long-acting, antimus-
carinic, anticholinergic, quaternary ammonium compound
inhibits M3 receptors in smooth muscle, resulting in bron-
chodilation. Tiotropium is indicated for daily maintenance
treatment of bronchospasm associated with COPD. It is not
indicated for acute episodes of bronchospasm (i.e., rescue
therapy). Tiotropium is eliminated via the renal system, and
patients with moderate to severe renal dysfunction should be
carefully monitored for drug toxicity. No dosage adjustments
are required for older patients or patients with hepatic impair-
ment or mild renal impairment.
NCLEX Success
10. A 62-year-old man is admitted to the cardiac inten-
sive care unit. He is in sinus bradycardia with a rate
of 48 beats per minute. What is the drug of choice for
sinus bradycardia?
A. atropine sulfate
B. epinephrine (Adrenalin)
C. isoproterenol (Isuprel)
D. dopamine (Intropin)
11. A hospice patient has loud gurgling respirations that
are audible without a stethoscope. Which of the fol-
lowing medications is the drug of choice to decrease
the secretions?
A. trihexyphenidyl (Trihexy)
B. tolterodine (Detrol LA)
C. tiotropium bromide (Spiriva HandiHaler)
D. scopolamine
12. After a man takes atropine sulfate, he becomes
nonresponsive and his respiratory rate drops. Based
on these symptoms, what medication is administered?
A. dicyclomine (Bentyl)
B. dopamine (Intropin)
C. physostigmine salicylate (Antilirium)
D. diazepam (Valium)
Centrally Acting Anticholinergics
Older anticholinergic drugs such as atropine are rarely used to
treat Parkinsons disease because of their undesirable peripheral
effects (e.g., dry mouth, blurred vision, photophobia, constipa-
tion, urinary retention, tachycardia). Newer, centrally acting
synthetic anticholinergic drugs are more selective for mus-
carinic receptors in the CNS and are designed to produce fewer
adverse effects. The prototype centrally acting anticholinergic
agent is benztropine mesylate (Cogentin).
Pharmacokinetics
Benztropine is administered orally and parenterally. The oral form
has an onset of action of 60 minutes and a 6- to 10-hour duration of
action. The parenteral form has an onset of action in 15 minutes
and a similar duration of action. The drug is absorbed from the
GI tract and metabolized in the liver. It crosses the bloodbrain
barrier and the placenta. It is unknown how the drug is excreted.
Action
The anticholinergic activity of benztropine takes place in
the CNS. Experts believe that the drug helps normalize the
imbalance of cholinergic and dominergic neurotransmission in
the basal ganglia of the brain to reduce rigidity, akinesia, and
tremor. It suppresses the secondary symptoms of parkinsonism
such as excessive salivary secretions and drooling.
Use
Benztropine mesylate is used for adjunctive therapy of all forms
of parkinsonism: arteriosclerotic, idiopathic, and postencepha-
litic. It is also administered to control extrapyramidal disorders
such as tardive dyskinesia due to neuroleptic drugs (phenothia-
zines). In addition, it is commonly used as a supplement with
trihexyphenidyl, carbidopa, or levodopa. Table 47.9 lists the
dosages of the centrally acting anticholinergic agents.
Use in Older Adults
Use of benztropine in older adults requires caution. Prescribers
and nurses must adhere strictly to dosing regulations. Patients
older than 60 years of age can develop increased sensitivity to
the CNS effects of all anticholinergic medications.
Adverse Eects
CNS adverse effects of benztropine include disorientation,
confusion, hallucinations, memory loss, psychoses, agita-
tion, euphoria, light-headedness, depression, giddiness, and
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics 881

TABLE 47.9
DRUGS AT A GLANCE: Centrally Acting Anticholinergics
Pregnancy
Drug Category Routes and Dosages

Adults Children

Benztropine
mesylate (Cogentin)
Trihexyphenidyl (Trihexy)
C 0.51 mg PO, IM, IV at bedtime; may increase up to Safety and efcacy have not
6 mg given at bedtime or in 24 divided doses. been established.
For acute dystonia: IM, IV 12 mg; may repeat if
needed. For prevention: PO 12 mg
C 12 mg PO; increase by 2-mg increments at Safety and efcacy have not
3- to 5-d intervals until a total of 610 mg is given been established.
daily in divided doses 34 times daily at mealtimes
and bedtimes.
PO 1 mg initially. Increase as needed to control symptoms.

heaviness of the limbs. With the administration of high Assessing for Therapeutic Eects
doses, an inability to move certain muscle groups may occur. The nurse assesses for decreased rigidity and tremor. Also, he
Peripheral anticholinergic effects include tachycardia, palpita- or she assesses for a decrease in oral secretions and an absence
tion, hypotension, orthostatic hypotension, blurred vision, dry of drooling.
mouth, urinary retention, decreased sweating, and elevated
temperature. Assessing for Adverse Eects
The nurse monitors the patients intake and output. If difculty
Contraindications with urination results, a dosage reduction may be necessary. The
nurse assesses for signs and symptoms of paralytic ileus such as
There are several contraindications to the use of benztropine
intermittent constipation, abdominal pain, diminished bowel
mesylate. Glaucoma is a problem because the drug can increase
sounds on auscultation, and distention. It is also necessary to assess
intraocular pressure. GI obstruction, prostatic hypertrophy,
the heart rate for tachycardia. In addition, the nurse assesses the
and urinary bladder neck obstruction are other complications
inability to move certain muscle groups. Checking the patients
because of the drugs effect on smooth muscle and sphincter
ambulation for signs of muscle weakness and unsteady gait helps.
tone. Also, myasthenia gravis is a contraindication, because
blockade of acetylcholine receptor sites at neuromuscular syn- Patient Teaching
apses exacerbates muscle weakness.
Box 47.6 identies patient teaching guidelines for benztropine.
Caution is necessary in patients with cardiovascular
disorders (e.g., tachycardia, dysrhythmias, and hyperten-
sion) because parasympathetic blockade may allow a harmful
increase in sympathetic dominance. Also, caution is warranted BOX 47.6 Patient Teaching Guidelines
in elderly patients with preexisting cognitive impairments for Benztropine Mesylate
because acetylcholine is an important neurotransmitter in
memory function. Take the medication as prescribed.
Avoid excessive high temperatures.
Nursing Implications cations,
Avoid alcohol, sedatives, and over-the-counter medi-
including cough and cold remedies.
Preventing Interactions Drink water frequently.
Benztropine has the same interactions as atropine. Phenothiazines Rinse the mouth frequently.
and tricyclic antidepressants combined with benztropine Maintain good dental hygiene.
mesylate can cause confusion, hallucinations, and paralytic ileus. Use hard candy to decrease dry mouth.
Administering the Medication
Void before taking the medication.
Visit the ophthalmologist regularly.
If the patient is experiencing GI upset, it is necessary to admin-
ister benztropine with food. The drug may be taken before
than
Notify your prescriber if uid intake is greater or less
urine output.
meals in the presence of a dry mouth and after meals if drooling Notify your prescriber of if you develop a fever.
or nausea occurs. The use of ice chips or lozenges to counter- Notify your prescriber if weakness becomes severe.
act symptoms of dry mouth may help. The patient should void
prior to the administration of the medication. Dosage reduc-
ness is impaired.
Avoid the use of machinery if visual acuity or alert-

tion during the summer months may be necessary.

882 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System
Other Drugs in the Class
Trihexyphenidyl (Trihexy) is used in the treatment of
parkinsonism and extrapyramidal reactions caused by some
antipsychotic drugs. This drug relieves smooth muscle spasm
by a direct action on the muscle and by inhibiting the parasym-
pathetic nervous system. It supposedly has fewer adverse effects
than atropine, but approximately half of the recipients report
mouth dryness, blurring of vision, and other adverse effects
common to anticholinergic drugs. Trihexyphenidyl requires
the same precautions as other anticholinergic drugs and is con-
traindicated in glaucoma.
Clinical Application 47-4
Mr. Stokes has been prescribed benztropine
mesylate (Cogentin) 3 mg PO at bedtime. He
resides in Wisconsin and lives there for much of
the year, but he spends the winter months in Cor-
pus Christi, Texas.
The nurse should educate Mr. Stokes regard-
ing the administration of benztropine mesylate
(Cogentin). What specic guidelines are impor-
tant to mention?
What adverse eect is Mr. Stokes at risk for
during the time he spends in Corpus Christi?
NCLEX Success
13. A 46-year-old woman is taking benztropine mesylate
(Cogentin). The nurse teaches her which of the
following?
A. avoid overheating and stay well hydrated
B. double the dose with excess secretions
C. report diarrhea to the prescriber
D. administer benztropine with phenothiazines
14. A patient is taking benztropine mesylate (Cogentin)
and reports gastrointestinal upset following admin-
istration of the medication. The nurse teaches the
patient to do what?
A. take the medication prior to eating
B. take the medication before bed
C. take the medication with food
D. take the medication with Maalox
Gastrointestinal Anticholinergics
(Antisecretory/Antispasmodic)
Dicyclomine hydrochloride (Bentyl) and glycopyrrolate
(Robinul) are older medications previously administered for the
treatment of peptic ulcer disease. The use of these medications
has declined with the advent of the proton pump inhibitors.
However, they are still prescribed for irritable bowel syndrome.
Dicyclomine hydrochloride (Bentyl) is the prototype
GI anticholinergic medication.
Pharmacokinetics
Dicyclomine is available for oral and parenteral administration.
Its onset of action in 1 to 2 hours, and its duration of action is
4 hours. It is metabolized in the liver and excreted by the kid-
neys. The drug crosses the placenta and enters the breast milk.
Action
Dicyclomine is a GI smooth muscle relaxant. It competitively
blocks the effects of acetylcholine at muscarinic choliner-
gic receptors that mediate the effects of the parasympathetic
postganglionic impulses.
Use
Prescribers order dicyclomine for the treatment of irritable
bowel syndrome. Table 47.10 gives the dosage information for
this drug and related agents.
Use in Older Adults
The onset of adverse effects is increased in elderly people. Use
of dicyclomine in older patients requires caution.
Adverse Eects
Adverse effects of dicyclomine are blurred vision, dry mouth,
altered taste perception, nausea, vomiting, dysphagia, urinary
hesitancy, urinary retention, and irritation at the injection site.
Contraindications
Dicyclomine possesses the same contraindications as the
belladonna derivatives and the centrally acting anticholiner-
gics. Contraindications to the belladonna derivatives include
hypersensitivity, glaucoma, some ulcers, bronchial asthma,
urinary bladder neck obstruction, and hepatic or renal disease.
Contraindications to the use of centrally acting anticholiner-
gics also include glaucoma, GI obstruction, and urinary bladder
neck obstruction, as well as prostatic hypertrophy and myas-
thenia gravis.
Nursing Implications
Preventing Interactions
Dicyclomine has interactions similar to those of the previous
anticholinergics. The combination of antipsychotic agents with
dicyclomine results in decreased effectiveness of the antipsy-
chotic medications. Tricyclic antidepressants and amantadine
combined with dicyclomine produces increased anticholinergic
effects. If dicyclomine is administered with digoxin or atenolol,
there is a greater reduction in the heart rate or blood pressure
then if the medications are administered alone.
Administering the Medication
As with the other anticholinergic medications, it is necessary
to have the patient void before taking dicyclomine. With the
intramuscular preparation, it is important that the patient is
switched to the oral form as soon as possible because of the
increased anticholinergic effects of the parenteral formulation.
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics 883

TABLE 48.10
DRUGS AT A GLANCE: Gastrointestinal Anticholinergics (Antisecretory/
Antispasmodic)
Pregnancy
Drug Category Routes and Dosage Ranges

Adults Children

Dicyclomine
hydrochloride (Bentyl)
Glycopyrrolate (Robinul)
B 2040 mg PO before meals and at bedtime Safety and efcacy have not been
20 mg IM before meals and at bedtime established.
B 12 mg PO 2 or 3 times daily Not recommended in children under the
0.10.2 mg IM, IV age of 12 y for antisecretory use
0.004 mg/kg IM 3060 min before Younger than 2 y: 0.004 mg/lb IM
anesthesia 3060 min before anesthesia 212 y:
0.0020.004 mg/lb IM 3060 min before
anesthesia

Assessing for Therapeutic Eects Action

If dicyclomine is working, the patient reports a decrease in
abdominal pain.
Assessing for Adverse Eects
The nurse assesses for altered taste perception, dry mouth,
nausea, and vomiting, as well as for urinary retention.
Administering the parenteral preparation requires assessment
for injection site irritation.
Patient Teaching
Patient teaching for dicyclomine is the same as for atropine and
benztropine (see Boxes 47.5 and 47.6).
Urinary Antispasmodics
Anticholinergic drugs are the drugs of choice for their anti-
spasmodic effects on smooth muscle to relieve the symptoms
of urinary incontinence and frequency that accompany an
overactive bladder. In infections such as cystitis, urethri-
tis, and prostatitis, the drugs decrease the frequency and
pain of urination. The drugs are also given to increase blad-
der capacity in enuresis, paraplegia, and neurogenic bladder.
Oxybutynin (Ditropan, Ditropan XL, Oxytrol), the pro-
totype, is a urinary antispasmodic that is available in oral and
transdermal forms.
Oxybutynin acts directly to relax the smooth muscle and
inhibits the effects of acetylcholine at muscarinic receptors.
A less potent anticholinergic than atropine, oxybutynin is
more potent as an antispasmodic and devoid of antinicotinic
activity at the skeletal neuromuscular junctions or autonomic
ganglia.
Use
Oxybutynin is administered for the relief of bladder insta-
bility associated with voiding in patients with uninhibited
neurogenic and reex neurogenic bladder. The extended-
release tablets decrease the symptoms of overactive blad-
der, incontinence, urgency, and frequency. Table 47.11
gives dosage information for oxybutynin and other urinary
antispasmodics.
Use in Children
The FDA has approved the use of the extended-release formu-
lation of oxybutynin for the treatment of symptoms of detru-
sor muscle overactivity associated with neurological conditions
such as spina bida in children 6 years and older.
Use in Older Adults
In older adults, the dosage of oxybutynin should not exceed
2.5 mg PO two to three times per day.

Pharmacokinetics Use in Patients With Renal Impairment

The oral preparation of oxybutynin has an onset of action
30 to 60 minute, a peak of 3 to 6 hours, and a duration of action
of 6 to 10 hours. The transdermal preparation has an onset
of action of 24 to 48 hour, a variable peak, and a duration of
action of 96 hours. The medication is metabolized in the liver
and is excreted in the urine. It crosses the placenta and may
enter the breast milk.
The use of oxybutynin in the presence of renal impair-
ment requires caution because of its elimination in the
urine.
Use in Patients With Hepatic Impairment
The use of oxybutynin in the presence of hepatic impairment
requires caution because it is metabolized by the liver.
884 SECTION 10 Drugs Aecting the Autonomic and Central Nervous System

TABLE 48.11
DRUGS AT A GLANCE: Urinary Antispasmodics
Pregnancy
Drug Category Routes and Dosages

Adults Children

Oxybutynin (Ditropan, B 5 mg PO 2 or 3 times daily; max Children >5 y: 5 mg PO daily

Ditropan XL, Oxytrol)
Darifenacin hydrobromide
(Enablex)
Flavoxate hydrochloride
(Urispas)
Solifenacin succinate (Vesicare)
Tolterodine tartrate (Detrol,
Detrol LA)
Trospium chloride (Sanctura,
Sanctura XR)
dose 5 mg 4 times daily. Extended
release: 5 mg PO daily up to
30 mg/daily
TDS: Apply TDS every 34 d.
Geriatric Patient: 2.5 mg
PO 23 times per day
C 7.5 mg PO once daily. May increase
to 15 mg if needed to control
symptoms.
B 100200 mg PO 3 or 4 times daily.
Reduce when symptoms improve.
C 5 mg once PO daily. May increase
to 10 mg once daily if needed to
control symptoms.
C 2 mg PO twice daily. May decrease
to 1 mg when symptoms improve.
Reduce doses to 1 mg PO twice
daily in presence of hepatic
impairment.
C 20 mg PO twice daily at least 1 h
before meals or on an empty
stomach
(max dosage 5 mg 3 times per day)
>6 y: extended release 5 mg PO daily;
dosage may be adjusted in 5 mg
increments up to a max dose of 20 mg/d
Safety and efcacy have not been
established.
Safety and efcacy have not been
established.
Safety and efcacy have not been
established.
Safety and efcacy have not been
established.
Safety and efcacy have not been
established.

Adverse Eects is required in the metabolism of oxybutynin. The inhibition

The adverse effects of oxybutynin are consistent with the
previous anticholinergic agents discussed in this chapter.
The most commonly reported CNS adverse effects include
drowsiness, dizziness, and blurred vision. Other adverse effects
are dry mouth, nausea, urinary hesitancy, and decreased
sweating.
Contraindications
Contraindications to oxybutynin are hypersensitivity to the
medication, pyloric or duodenal ulcer, obstructive intestinal
lesions, intestinal atony, megacolon, colitis, obstructive uropa-
thies, glaucoma, myasthenia gravis, cardiovascular instability,
and urinary retention.
Nursing Implications
Preventing Interactions
Use of oxybutynin in combination with phenothiazines results
in increased anticholinergic effects. The phenothiazines inhibit
the cytochrome 450 enzyme CYP3A4 in the liver. This enzyme
of the enzyme results in a greater amount of oxybutynin that
has not undergone rst-pass metabolism contributing to oxybu-
tynin toxicity. This same effect occurs if haloperidol is admin-
istered with oxybutynin. Also, use of oxybutynin together with
haloperidol reduces the effect of the haloperidol and results in
the development of tardive dyskinesia. Administration of oxy-
butynin with amantadine or nitrofurantoin leads to increased
toxicity of oxybutynin.
Administering the Medication
It is important that the extended-release medication is not cut,
crushed, or chewed.
Assessing for Therapeutic Eects
The nurse assesses for patient reports of decreased urinary
incontinence, urgency, and frequency.
Assess for Adverse Eects
The nurse assesses for CNS depression. He or she also assesses
for urinary hesitancy and retention as well as for impotence.
In addition, it is necessary to assess for allergic reactions to the
medication such as urticarial reactions.
 CHAPTER 47 Drug Therapy for Parkinsons Disease and Anticholinergics
BOX 47.7 Patient Teaching Guidelines
for Oxybutynin Chloride
orTakechew
the medication as prescribed; do not cut, crush,
extended-release tablets.
the
Apply the transdermal patch to dry intact skin over
abdomen, hip, or buttock every 3 to 4 days (twice
weekly). Remove the old system before applying a new
one. Select a new site when applying a new system.
Have periodic bladder examinations to evaluate the
therapeutic response.
Drink water frequently.
Rinse the mouth frequently.
Maintain good dental hygiene.
Use hard candy to decrease dry mouth.
Avoid excessive high temperatures.
than
Notify your prescriber if uid intake is greater or less
urine output.
Notify your prescriber if you develop a fever.
Patient Teaching
Box 47.7 identies the patient teaching guidelines for oxybutynin.
Other Drugs in the Class
Darifenacin (Enablex) is a competitive, antimuscarinic,
anticholinergic agent with selective afnity for M3 receptors
involved in contraction of the urinary bladder. Darifenacin
is indicated for the treatment of overactive bladder, reducing
symptoms of urge incontinence, urgency, and frequency. After
oral administration, darifenacin is 98% protein bound and
extensively metabolized in the liver by enzymes CYP3A4 and
CYP2D6. A small group of people (~7% Caucasian and 2%
African American) are poor metabolizers of the drug and may
require reduced dosages to avoid adverse effects. Dosage should
also be reduced in people with moderate hepatic dysfunction
and avoided in those with severe hepatic impairment.
Flavoxate (Urispas) was developed specically to counter-
act spasm in smooth muscle tissue of the urinary tract. It has
anticholinergic, local anesthetic, and analgesic effects. Thus,
the drug relieves dysuria, urgency, frequency, and pain with
genitourinary infections, such as cystitis and prostatitis.
Solifenacin (Vesicare) is a competitive, antimuscarinic,
anticholinergic agent indicated for the treatment of overactive
bladder with symptoms of urgency, urge incontinence, and fre-
quency. Solifenacin is well absorbed after oral administration,
98% bound to plasma proteins, and extensively metabolized
in the liver by CYP3A4 enzymes. Dosages should be reduced
in people with moderate renal or hepatic impairment, and
solifenacin is not recommended for those with severe hepatic
impairment. Solifenacin may prolong QT intervals, especially
at higher dosages, potentially resulting in dysrhythmias.
Tolterodine (Detrol and Detrol LA) is a competitive
antimuscarinic, anticholinergic agent that inhibits blad-
der contraction, decreases detrusor muscle pressure, and
delays the urge to void. It is used to treat urinary frequency,
urgency, and urge incontinence. Tolterodine is more selective
885
for muscarinic receptors in the urinary bladder than in other
areas of the body, such as the salivary glands, and therefore,
anticholinergic adverse effects are less marked. Reduced doses
(1 mg) are recommended for patients with hepatic dysfunction.
Tolterodine is also available in an extended-release form.
Trospium chloride (Sanctura) is an antimuscarinic, anti-
cholinergic drug for treatment of urgency, urge incontinence, and
urinary frequency associated with overactive bladder. Trospium
reduces the tone of smooth muscle in the bladder, exerting an
antispasmodic effect. Because of its quaternary structure, less
than 10% of an orally administered dose is absorbed, and food
further delays absorption. Therefore, it is recommended that the
medication be taken at least 1 hour before meals or on an empty
stomach. Absorbed trospium is eliminated by a combination of
glomerular ltration and active tubular secretion. Trospium has
the potential for interaction with other drugs that are eliminated
by active tubular secretion (e.g., digoxin, procainamide, pancuro-
nium, morphine, vancomycin, metformin, tenofovir), resulting in
increased serum concentration of either trospium or the coadmin-
istered drug because of competition for the urinary tubular pump.
Reduced dosages of trospium are recommended for patients with
renal insufciency and those older than 75 years of age who may
be less able to tolerate the adverse effects of anticholinergic drugs.
The Nursing Process
Assessment
Assess the patients condition in relation to disorders
for which anticholinergic drugs are used (i.e., check for
bradycardia or heart block, diarrhea, dysuria, abdominal
pain, and other disorders). If the patient reports or medi-
cal records indicate a specic disorder, assess for signs and
symptoms of that disorder (e.g., Parkinsons disease).
Assess for disorders in which anticholinergic drugs are
contraindicated (e.g., glaucoma, prostatic hypertrophy,
reux esophagitis, myasthenia gravis, hyperthyroidism).
Assess use of other drugs with anticholinergic effects, such
as antihistamines (histamine1 receptor antagonists), anti-
psychotic agents, and tricyclic antidepressants.
Nursing Diagnoses
Impaired urinary elimination: decreased bladder tone and
urine retention
Constipation related to slowed gastrointestinal function
Disturbed thought processes: confusion, disorientation,
especially in older adults
Decient knowledge: drug effects and accurate usage
Risk for injury related to drug-induced blurred vision and
photophobia
Risk for noncompliance related to adverse drug effects
Risk for altered body temperature: hyperthermia
Planning/Goals
The patient will
Receive or self-administer the drugs correctly
Experience relief of symptoms for which anticholinergic
drugs are given