Chapter 15

Antiparkinson Drugs

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 Parkinson’s Disease (PD)
 Chronic, progressive, degenerative disorder
 Affects dopamine-producing neurons in the brain
 Caused by an imbalance of two
neurotransmitters
 Dopamine
 Acetylcholine (ACh)

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Basal Ganglia and Related Structures
of the Brain

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Neurotransmitter Abnormality in
Parkinson’s Disease

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 Parkinson’s Disease (Cont.)
 Symptoms occur when about 80% of the
dopamine stored in the substantia nigra of the
basal ganglia is depleted.
 Symptoms can be partially controlled as long as
there are functioning nerve terminals that can
take up dopamine.

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 Parkinson’s Disease (Cont.)
 Classic symptoms include:
 Akinesia
 Bradykinesia
 Rigidity
 Tremor
 Postural instability
 Staggering gait
 Drooling

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 Parkinson’s Disease (Cont.)
 A progressive condition
 Rapid swings in response to levodopa occur
(“on–off phenomenon”)
 PD worsens when too little dopamine is present.
 Dyskinesia occurs when too much dopamine is
present.
 “Wearing-off phenomenon”
 PD-associated dementia

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 Audience Response System Question

The “off–on phenomenon” that some patients with PD

experience is best explained as the

A. need to take a drug holiday to improve response to medications.

B. variable response to levodopa, resulting in periods of good control
and periods of poor control of PD symptoms.
C. alternating schedule of medications needed to control PD.
D. fluctuation of emotions that often occurs with PD.

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 Dyskinesia
 Difficulty in performing voluntary movements
 Two common types:
 Chorea: irregular, spasmodic, involuntary movements
of the limbs or facial muscles
 Dystonia: abnormal muscle tone leading to impaired
or abnormal movements

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 Pharmacology Overview
 PD is thought to be caused by an imbalance of
dopamine and Ach, with a deficiency of
dopamine in certain areas of the brain.
 Drug therapies are aimed at increasing the
levels of dopamine or antagonizing the effects of
Ach.
 Unfortunately, current drug therapy does not
slow the progression of the disease but rather is
used to slow the progression of symptoms.

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 Selective MAOI Therapy
 MAOIs break down catecholamines in the CNS,
primarily in the brain.
 Selegiline (Eldepryl) and rasagiline (Azilect) are
selective MAO-B inhibitors.
 Cause an increase in levels of dopaminergic
stimulation in the CNS
 Do not elicit the “cheese effect” of the nonselective
MAOIs used to treat depression (if 10 mg or less is
used)

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 Rasagiline (Azilect) and Selegiline
(Eldepryl)
 Used as monotherapy or used as adjuncts with
levodopa
 Contraindications
 Known drug allergy
 Concurrent use with meperidine
 Adverse effects

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 Dopamine Modulator
 amantadine (Symmetrel)
 Antiviral drug used for treatment of influenza
 Indirect acting
 Causes release of dopamine and other
catecholamines from their storage sites in the
presynaptic fibers of nerve cells within the basal
ganglia that have not yet been destroyed by the
disease process
 Blocks the reuptake of dopamine into the nerve fibers
 Result: higher levels of dopamine in the synapses
between nerves and improved dopamine
neurotransmission between neurons
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 Dopamine Modulator (Cont.)
 amantadine (Symmetrel) (Cont.)
 Used early in the course of the disease
 Usually effective for only 6 to 12 months
 Used to treat dyskinesia associated with carbidopa–
levodopa
 Common adverse effects associated with amantadine
are relatively mild and include dizziness, insomnia,
and nausea.
 Drug interactions: increased anticholinergic adverse
effects when given with anticholinergic drugs

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 Catechol Ortho-Methyltransferase
(COMT) Inhibitors
 tolcapone (Tasmar), entacapone (Comtan)
 Block COMT, the enzyme that catalyzes the
breakdown of the body’s catecholamines
 Prolong the duration of action of levodopa;
reduce wearing-off phenomenon
 Adverse effects: GI upset; urine discoloration;
can worsen dyskinesia that may already be
present. Tolcapone has been associated with
cases of severe liver failure.

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 Levodopa Therapy
 Levodopa is a precursor of dopamine.
 Blood–brain barrier does not allow exogenously
supplied dopamine to enter but does allow
levodopa to enter.

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 Direct-Acting Dopamine Receptor
Agonists
 Nondopamine dopamine receptor agonists
(NDDRAs)
 Ergot derivatives: bromocriptine (Parlodel)
 Nonergot drugs: pramipexole (Mirapex), ropinirole
(Requip), and rotigotine (Neupro)
 All of the NDDRAs work by direct stimulation of
presynaptic and/or postsynaptic dopamine
receptors in the brain.

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 Bromocriptine (Parlodel)
 Works by activating presynaptic dopamine
receptors to stimulate the production of more
dopamine
 Bromocriptine: also inhibits the production of the
hormone prolactin, which stimulates normal
lactation and can be used to treat women with
excessive or undesired breast milk production
(galactorrhea) and for treatment of prolactin-
secreting tumors

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 Bromocriptine (Parlodel) (Cont.)
 Caution when used for patients with peripheral
vascular disease
 Adverse reactions: GI upset, dyskinesias, sleep
disturbances
 Drug interactions: erythromycin and adrenergic
drugs

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 Ropinirole (Requip) and
Rotigotine (Neupro)
 Also used to treat a disorder known as restless
legs syndrome, a nocturnal movement of the
legs that disrupts sleep

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 Dopamine Replacement Drugs
 Replacement drugs (presynaptic)
 Levodopa: biologic precursor of dopamine required by
the brain for dopamine synthesis
 Work presynaptically to increase brain levels of
dopamine
 Levodopa is able to cross the blood–brain barrier, and
then it is converted to dopamine.
 However, large doses of levodopa needed to get
dopamine to the brain also cause adverse effects.

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Dopamine Replacement Drugs (Cont.)
 Replacement drugs
 Carbidopa is given with levodopa.
 Carbidopa does not cross the blood–brain barrier and
prevents levodopa breakdown in the periphery.
 As a result, more levodopa crosses the blood–brain
barrier, where it can be converted to dopamine.

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 Levodopa Therapy
 Levodopa is taken up by the dopaminergic
terminal, converted into dopamine, and then
released as needed.
 As a result, neurotransmitter imbalance is
controlled in patients with early PD who still have
functioning nerve terminals.

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 Levodopa Therapy (Cont.)
 As PD progresses, it becomes more difficult to
control it with levodopa.
 Ultimately, levodopa no longer controls the PD,
and the patient is seriously debilitated.
 This generally occurs between 5 and
10 years after the start of levodopa therapy.

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 Levodopa Therapy (Cont.)
 Dopamine must be administered orally as
levodopa dopamine cannot pass through the
blood–brain barrier.
 Levodopa is the biologic precursor of dopamine
and can penetrate into the CNS.
 Adverse effects: confusion, involuntary
movements, GI distress, hypotension, and
cardiac dysrhythmias

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 Levodopa, Carbidopa Therapy
 Contraindicated in cases of angle-closure
glaucoma
 Use cautiously in patients with open-angle
glaucoma
 Adverse effects: cardiac dysrhythmias,
hypotension, chorea, muscle cramps, and GI
distress
 Interactions: pyridoxine and dietary protein

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 Carbidopa–Levodopa (Sinemet)
 Carbidopa (Lodosyn): adjunct to treat nausea
associated with Sinemet
 Sinemet CR: increases “on” time and decreases
“off” time
 Drug interactions occur with tricyclic
antidepressants and other drugs
 Carbidopa–levodopa: best taken on an empty
stomach; to minimize GI side effects, it can be
taken with food

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 Anticholinergic Therapy
 Anticholinergics block the effects of ACh
 Used to treat muscle tremors and muscle rigidity
associated with PD
 These two symptoms are caused by excessive
cholinergic activity.
 Does not relieve bradykinesia (extremely slow
movements)

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 Anticholinergic Therapy (Cont.)
 SLUDGE: Ach is responsible for causing
increased salivation, lacrimation (tearing of the
eyes), urination, diarrhea, increased GI motility,
and possibly emesis (vomiting).
 Anticholinergics have the opposite effects: dry
mouth or decreased salivation, urinary retention,
decreased GI motility (constipation), dilated
pupils (mydriasis), and smooth muscle
relaxation.

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Anticholinergics and Other Drugs Used
for Treatment of PD
 benztropine (Cogentin)
 trihexyphenidyl
 Antihistamines: diphenhydramine (Benadryl)

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 Benztropine (Cogentin)
 Anticholinergic drug used for PD and
extrapyramidal symptoms from antipsychotic
drugs
 Caution during hot weather or exercise because
it may cause hyperthermia
 Adverse effects: tachycardia, confusion,
disorientation, toxic psychosis, urinary retention,
dry throat, constipation, nausea, and vomiting
 Anticholinergic syndrome
 Avoid alcohol
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 Audience Response System Question

Which drug used for the management of the patient with

PD is most likely to cause postural hypotension?

A. amantadine (Symmetrel)
B. selegiline (Eldepryl)
C. tolcapone (Tasmar)
D. entacapone (Comtan)

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 Audience Response System Question

When providing teaching to a patient receiving an

anticholinergic for the treatment of PD, the nurse will
include which information?

A. Take the medication first thing in the morning.

B. Limit fluid intake when taking this drug.
C. The tremors you experience will be reduced within 24 hours
of taking this drug.
D. Do not take this medication at the same time as other
medications.

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 Nursing Implications
 Perform a thorough assessment, nursing history,
and medication history.
 Include questions about the patient’s:
 CNS
 GI and GU tracts
 Psychologic and emotional status

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 Nursing Implications (Cont.)
 Assess for signs and symptoms of PD
 Masklike expression
 Speech problems
 Dysphagia
 Rigidity of arms, legs, and neck
 Assess for conditions that may be
contraindications

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 Nursing Implications (Cont.)
 Administer drugs as directed by manufacturer
 Provide patient education regarding PD and the
medication therapy
 Inform patient not to take other medications with
PD drugs unless he or she checks with
physician

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 Nursing Implications (Cont.)
 When starting dopaminergic drugs, assist
patient with walking because dizziness may
occur
 Administer oral doses with food to minimize GI
upset
 Encourage patient to force fluids to at least 3000
mL/day (unless contraindicated)
 Taking levodopa with MAOIs may result in
hypertensive crisis

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 Nursing Implications (Cont.)
 Patient should be taught not to discontinue
antiparkinson drugs suddenly
 Teach patient about expected therapeutic and
adverse effects with antiparkinson drug therapy

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 Nursing Implications (Cont.)
 Entacapone may darken the patient’s urine and
sweat.
 Therapeutic effects of COMT inhibitors may be
noticed within a few days; it may take weeks
with other drugs.

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 Nursing Implications (Cont.)
 Monitor for response to drug therapy:
 Improved sense of well-being and mental status
 Increased appetite
 Increased ability to perform ADLs, to concentrate, and
to think clearly
 Less intense parkinsonian manifestations, such as
less tremor, shuffling gait, muscle rigidity, and
involuntary movements

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 Case Study

A patient has been diagnosed with PD. Medication therapy

is started for this patient. The nurse should teaching the
patient and care giver that pharmacologic therapy of PD?

A. The medication should be stopped when the patient’s

symptoms improve.
B. Alcohol, over-the-counter drugs, and herbals are to be
avoided unless approved by the prescriber.
C. A common side effect of anticholinergics is drooling.
D. Improvements in symptoms are expected within 5 days
of medication therapy.

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 Case Study (Cont.)

The patient diagnosed with PD has been started on

dopaminergic replacement drug therapy with carbidopa–
levodopa, it is most important for the nurse to

A. assess the patient for dizziness and syncope when the

patient is walking.
B. administer the medication first thing in the morning.
C. administer the medication on an empty stomach.
D. omit protein from the patient’s diet.

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 Case Study (Cont.)

The patient has now been ordered an oral disintegrating

form of the MAO-B inhibitor drug selegiline. When
administering the drug, the nurse should

A. tell the patient to take the medication with liquids.

B. tell the patient to take the medication with a meal.
C. assess the patient for hypertension, a common side
effect of this medication.
D. tell the patient to place oral disintegrating dosage forms
on the tongue, and do not swallow dosage form until it is
completely melted.

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