Transcript Pharmacology and the Nursing Process, 4th ed. Lilley/Harrington

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’d)


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’d)

Classic symptoms include:

Akinesia
 Bradykinesia
 Rigidity
 Tremor
 Postural instability
 Staggering gait
 Drooling
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Parkinson’s Disease (cont’d)


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”
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Classroom Response Question
The “off-on phenomenon” that some patients with
Parkinson’s disease (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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Levodopa Therapy


Levodopa is a precursor of dopamine
Blood-brain barrier does not allow exogenously
supplied dopamine to enter, but does allow
levodopa
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Levodopa Therapy (cont’d)


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’d)



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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Drug Therapy for PD



Aimed at increasing levels of dopamine as long
as there are functioning nerve terminals
remaining
Antagonizes or blocks the effects of ACh
Slows the progression of the disease
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Drug Therapy for PD (cont’d)

Indirect-acting dopamine-receptor agonists



Monoamine oxidase B (MAO-B) inhibitors: selegiline,
rasagiline
Catechol ortho-methyltransferase (COMT) inhibitors:
entacapone, tolcapone
Dopamine modulator: amantadine
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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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Selective MAOI Therapy (cont’d)



Used in combination with levodopa or
carbidopa-levodopa
Used as adjuncts when a patient’s response to
levodopa is fluctuating
Allow the dose of levodopa to be decreased

Delay development of unresponsiveness to levodopa
therapy
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Selective MAOI Therapy (cont’d)



Improve functional ability
Decrease severity of symptoms
Only 50% to 60% of patients show a positive
response to therapy
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Selective MAOI Therapy (cont’d)

Adverse effects are usually mild


Dizziness, insomnia, nausea, diarrhea, chest pain,
headache, weight loss
Doses higher than 10 mg/day may cause more
severe adverse effects, such as hypertensive crisis
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Dopamine Modulator

amantadine (Symmetrel)

Indirect acting
 Causes release of dopamine from storage sites at the
end of nerve cells that are still intact
 Blocks reuptake of dopamine into the nerve endings,
allowing more to accumulate both centrally and
peripherally
 Does not stimulate dopamine receptors directly
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Dopamine Modulator (cont’d)

amantadine (Symmetrel)




Used early in the course of the disease
Usually effective for only 6 to 12 months
Used to treat dyskinesia associated with carbidopalevodopa
Also used as an antiviral for influenza virus infection
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COMT Inhibitors


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
Indirect acting
tolcapone (Tasmar), entacapone (Comtan)
Inhibit COMT, the enzyme responsible for the
breakdown of levodopa, the dopamine precursor
Prolong the duration of action of levodopa;
reduce wearing-off phenomenon
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COMT Inhibitors (cont’d)

tolcapone (Tasmar)



Has caused severe liver failure
Requires monitoring of liver enzymes
Not used unless other drugs do not work
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Classroom Response Question
Which drug used for the management of the patient with
Parkinson’s disease is most likely to cause postural
hypotension?
A.
B.
C.
D.
amantadine (Symmetrel)
selegiline (Eldepryl)
tolcapone (Tasmar)
entacapone (Comtan)
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Direct-Acting Dopamine Receptor
Agonists

Nondopamine dopamine receptor agonists
(NDDRAs)



Ergot derivatives (bromocriptine)
Nonergot drugs (pramipexole, ropinirole)
Dopamine replacement drugs

Levodopa, carbidopa, carbidopa-levodopa (Sinemet)
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Nondopamine Dopamine Receptor
Agonists


Directly stimulate dopamine receptors
Activate dopamine receptors and stimulate
production of more dopamine
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Classroom Response Question
The beneficial role of the NDDRA ropinirole (Requip) is that
it
A.
B.
C.
D.
appears to delay the start of levodopa therapy.
allows for levodopa therapy to begin earlier.
improves the patient’s tolerance of parkinsonian symptoms.
replaces dopamine in the brain.
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Dopamine Replacement Drugs

Replacement drugs (presynaptic)



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’d)

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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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’d)

benztropine mesylate (Cogentin)



Also used to treat extrapyramidal symptoms caused
by use of antipsychotic drugs
trihexyphenidyl (generic only)
Antihistamines also have anticholinergic
properties

diphenhydramine (Benadryl)
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Classroom Response Question
When providing teaching to a patient receiving an
anticholinergic for the treatment of Parkinson’s disease, 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’d)

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’d)



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’d)
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


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’d)


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’d)


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’d)

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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