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CHAPTER 16
Antiparkinsonian Drugs
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Parkinson’s Disease (PD)
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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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Parkinson’s Disease (cont’d)
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
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)
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Classic symptoms include:
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Akinesia
Bradykinesia
Rigidity
Tremor
Postural instability
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Parkinson’s Disease (cont’d)


A progressive condition
Rapid swings in response to levodopa occur
(“on-off phenomenon”)
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PD worsens when too little dopamine is present
Dyskinesia occurs when too much dopamine is
present
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Dyskinesia
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
Difficulty in performing voluntary movements
Two common types
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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)
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
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)
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
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As PD progresses, it becomes more difficult
to control it with levodopa
Ultimately, levodopa no longer controls the
PD, and 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
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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)
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Indirect-acting dopamine-receptor agonists
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MAOB inhibitors: selegiline, rasagiline
COMT inhibitors: entacapone, tolcapone
Presynaptic dopamine release enhancer:
amantadine
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Drug Therapy for PD (cont’d)
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Anticholinergic drugs
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Antihistamines
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Diphenhydramine
Nondopamine-receptor agonists
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Benztropine, others
Ergot: bromocriptine
Nonergot: pramipexole, ropinirole, apomorphine
Dopamine replacement drugs

Carbidopa, carbidopa-levodopa
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Selective MAOI Therapy:
Selegiline
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MAOIs break down catecholamines in the
CNS, primarily in the brain
Selegiline is a selective MAOB inhibitor

Causes an increase in levels of dopaminergic
stimulation in the CNS
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Selective MAOI Therapy:
Selegiline (cont’d)
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Selegiline is a newer, potent, irreversible
MAOI that selectively inhibits MAOB
Does 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:
Selegiline (cont’d)
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Used in combination with levodopa or
levodopa-carbidopa
Used as an adjunct when a patient’s
response to levodopa is fluctuating
Allows the dose of levodopa to be decreased

Delays development of unresponsiveness to
levodopa therapy
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Selective MAOI Therapy:
Selegiline (cont’d)
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Improves functional ability
Decreases severity of symptoms
Only 50% to 60% of patients show a positive
response to therapy
Prophylactic selegiline may delay the
development of serious debilitating PD for
9 to 18 years
Rasagiline approved in 2008 with similar
action to selegiline
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Selective MAOI Therapy:
Selegiline (cont’d)

Adverse effects are usually mild


Nausea, lightheadedness, dizziness, abdominal
pain, insomnia, confusion, dry mouth
Doses higher than 10 mg/day may cause more
severe adverse effects, such as hypertensive
crisis
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Presynaptic Dopamine Release
Enhancer

Amantadine (Symmetrel)
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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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Presynaptic Dopamine Release
Enhancer (cont’d)
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Amantadine (Symmetrel)
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Used early in the course of the disease
Usually effective for only 6 to 12 months
Also used as an antiviral for influenza virus
infection
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COMT Inhibitors
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Indirect-acting
Tolcapone (Tasmar) and 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)
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Tolcapone (Tasmar)
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Has caused severe liver failure
Requires monitoring of liver enzymes
Not used unless other drugs do not work
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Direct-Acting Dopamine Receptor
Agonists

Nondopamine dopamine receptor agonists
(NDDRAs)
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Ergot derivatives (bromocriptine and pergolide)
Nonergot drugs (pramipexole, ropinirole,
apomorphine)
Dopamine replacement drugs

Levodopa, carbidopa, carbidopa-levodopa
(Sinemet)
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Direct-Acting Dopamine Receptor
Agonists (cont’d)

Nondopamine dopamine receptor agonists
(NDDRAs)
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Ropinirole (Requip)
• Newer, nonergot NDDRA
• Used for PD and restless leg syndrome
Apomorphine (Apokyn)
• Newer, nonergot dopamine agonist
• Subcutaneous injection
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Direct-Acting Dopamine Receptor
Agonists (cont’d)
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Direct-acting
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Bromocriptine (Parlodel)
Directly stimulate dopamine receptors
Activate dopamine receptors and stimulate
production of more dopamine
Pergolide (Permax) is another direct-acting
drug with a different mechanism of action
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Dopamine Replacement Drugs
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Replacement drugs (presynaptic)
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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)
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Replacement drugs
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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
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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)
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ACh accumulates because of the imbalance
of dopamine
As a result, overstimulation of the cholinergic
excitatory pathways occurs

Muscle tremors and muscle rigidity
 Cogwheel rigidity
 Pill-rolling movement of fingers and head bobbing
while at rest
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Anticholinergic Therapy (cont’d)
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benztropine mesylate (Cogentin)
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
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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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Anticholinergic Therapy:
Indications


Used in the treatment of PD to cause smooth
muscle to relax, resulting in reduced muscle
rigidity and akinesia
Also used to treat drug-induced
extrapyramidal reactions to certain
antipsychotic drugs
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Anticholinergic Therapy:
Adverse Effects
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Drowsiness, confusion, disorientation
Constipation, nausea, vomiting
Urinary retention, pain on urination
Blurred vision, dilated pupils, photophobia,
dry skin
Decreased salivation, dry mouth
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Nursing Implications
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Perform a thorough assessment, nursing
history, and medication history
Include questions about the patient’s:
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CNS
GI and GU tracts
Psychologic and emotional status
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Nursing Implications (cont’d)
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Assess for signs and symptoms of PD
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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)
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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 to minimize GI upset
Encourage patient to force fluids to at least
2000 mL/day (unless contraindicated)
Taking levodopa with MAOIs may result in
hypertensive crisis
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Nursing Implications (cont’d)
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
Patient should be taught not to discontinue
antiparkinsonian drugs suddenly
Teach patient about what therapeutic and
adverse effects to expect with
antiparkinsonian drug therapy
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Nursing Implications (cont’d)
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Levodopa preparations 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)
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Monitor for response to drug therapy
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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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