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

CHAPTER 14
Antiparkinsonian Drugs
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Parkinson’s Disease (PD)
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Chronic, progressive, degenerative disorder
Affects the dopamine-producing neurons in
the brain
Caused by an imbalance of two
neurotransmitters
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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
As long as there are functioning nerve
terminals that can take up dopamine,
symptoms can be partially controlled
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Parkinson’s Disease (cont’d)
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PD is 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 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
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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, then
released as needed
As a result, the 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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As PD progresses, it becomes more and
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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Anticholinergic drugs
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Antihistamines
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benztropine, biperiden, others
diphenhydramine, others
Dopamine-receptor agonists (direct acting)
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bromocriptine, levodopa, pergolide, levodopacarbidopa, others
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Drug Therapy for PD (cont’d)
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Indirect-acting dopamine-receptor agonists
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MAO-B inhibitor: selegiline
COMT inhibitor: entacapone, tolcapone
Miscellaneous drug: amantadine
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Selective Monoamine Oxidase
Inhibitor (MAOI) Therapy
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Selegiline is a newer, potent, irreversible
MAOI that selectively inhibits MAO-B
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
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MAOIs break down catecholamines in the
CNS, primarily the brain
Selegiline is a selective MAO-B inhibitor; it
causes an increase in the levels of
dopaminergic stimulation in the CNS
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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 adjunctive when a patient’s
response to levodopa is fluctuating
Allows the dose of levodopa to be decreased;
delays the development of unresponsiveness
to levodopa therapy
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Selective MAOI Therapy: Selegiline
(cont’d)
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Improvement in functional ability
Decreased 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
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Selective MAOI Therapy: Selegiline
(cont’d)
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Adverse effects usually mild
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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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Dopaminergic Therapy
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Used to provide exogenous replacement of
lost dopamine or to enhance the function of
the few neurons that are still producing their
own dopamine
Goal: to increase levels of dopamine in the
brain and reduce the most detrimental
complications of PD
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Dopaminergic Therapy (cont’d)
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Three categories
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Replacement
Direct acting/replacement
Indirect acting
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Dopaminergic Therapy (cont’d)
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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,
then is converted to dopamine
However, the large doses of levodopa needed to
get dopamine to the brain also cause adverse
effects
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Dopaminergic Therapy (cont’d)
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Replacement drugs (presynaptic) (cont'd)
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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 bloodbrain barrier, where it can be converted to
dopamine
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Dopaminergic Therapy (cont’d)
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Indirect acting: amantadine (Symmetrel)
Causes release of dopamine from the storage sites at
the end of nerve cells that are still intact
Also blocks the 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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Dopaminergic Therapy (cont’d)
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ropinirole (Requip)
Newer, nonergot dopamine agonist
Used for PD, and restless leg syndrome
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Dopaminergic Therapy:
Indications
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Used to increase dopamine levels in the brain
and reduce the severity of PD symptoms
Amantadine also has antiviral effects
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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
They do 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
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Muscle tremors and muscle rigidity
 Cogwheel rigidity
 Pill-rolling movement of fingers and head bobbing
while at rest
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Anticholinergic Drugs
Used for PD
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benztropine mesylate (Cogentin)
trihexyphenidyl (Artane)
biperiden (Akineton)
procyclidine (Kemadrin)
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Anticholinergic Therapy:
Indications
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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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Mask-like 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
Oral doses should be given to minimize GI
upset
Encourage patient to force fluids to at least
2000 mL/day (unless contraindicated)
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Nursing Implications (cont’d)
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Pyridoxine (vitamin B6) in doses greater than
10 mg will reverse the effects of levodopa
Teach patient to avoid foods high in vitamin
B6
Taking levodopa with MAOIs may result in
hypertensive crisis
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Nursing Implications (cont’d)
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Patients should be told not to discontinue
antiparkinsonian drugs suddenly
Teach patients 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 may take weeks with
other drugs
“Drug holidays”
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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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