1. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Chapter 15
Antiparkinson Drugs
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

2. 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)
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

3. Basal Ganglia and Related Structures of the Brain
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

4. Neurotransmitter Abnormality in Parkinson’s Disease
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

5. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

6. Parkinson’s Disease (cont’d)
Classic symptoms include:
Akinesia
Bradykinesia
Rigidity
Tremor
Postural instability
Staggering gait
Drooling
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

7. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

8. 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”
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

9. Classroom Response Question
The “off-on phenomenon” that some patients with Parkinson’s disease (PD) experience is best explained as the
need to take a drug holiday to improve response to medications.
variable response to levodopa, resulting in periods of good control and periods of poor control of PD symptoms.
alternating schedule of medications needed to control PD.
fluctuation of emotions that often occurs with PD.
Correct answer: B
Rationale: Some patients who take levodopa on a long-term basis experience times when their PD symptoms are under control and other times when symptoms are not well controlled.
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

10. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

11. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Levodopa Therapy
Levodopa is a precursor of dopamine
Blood-brain barrier does not allow exogenously supplied dopamine to enter, but does allow levodopa
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

12. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

13. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

14. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

15. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

16. 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)
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

17. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

18. Selective MAOI Therapy (cont’d)
Improve functional ability
Decrease severity of symptoms
Only 50% to 60% of patients show a positive response to therapy
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

19. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

20. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

21. 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 carbidopa-levodopa
Also used as an antiviral for influenza virus infection
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

22. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
COMT Inhibitors
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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

23. COMT Inhibitors (cont’d)
tolcapone (Tasmar)
Has caused severe liver failure
Requires monitoring of liver enzymes
Not used unless other drugs do not work
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

24. Classroom Response Question
Which drug used for the management of the patient with Parkinson’s disease is most likely to cause postural hypotension?
amantadine (Symmetrel)
selegiline (Eldepryl)
tolcapone (Tasmar)
entacapone (Comtan)
Correct answer: A
Rationale: Amantadine, carbidopa-levodopa, and ropinirole are most likely to cause postural hypotension.
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

25. 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)
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

26. Nondopamine Dopamine Receptor Agonists
Directly stimulate dopamine receptors
Activate dopamine receptors and stimulate production of more dopamine
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

27. Classroom Response Question
The beneficial role of the NDDRA ropinirole (Requip) is that it
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.
Correct answer: A
Rationale: The longer that levodopa therapy can be delayed, the longer the benefit of the therapy will be experienced once it is eventually started.
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

28. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

29. Dopamine Replacement Drugs (cont’d)
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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

30. 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)
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

31. 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)
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

32. 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?
Take the medication first thing in the morning.
Limit fluid intake when taking this drug.
The tremors you experience will be reduced within 24 hours of taking this drug.
Do not take this medication at the same time as other medications.
Correct answer: D
Rationale: When anticholinergics are used for the treatment of Parkinson’s disease, these medications should not be taken at the same time as other mediations. The medications should be administered at bedtime. Fluid intake should not be restricted as they cause dry mouth, and it may take several days to weeks for the beneficial effects of the medication to become evident.
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

33. Copyright © 2014 by Mosby, an imprint of Elsevier Inc.
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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

34. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

35. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

36. Nursing Implications (cont’d)
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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

37. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

38. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.

39. 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
Copyright © 2014 by Mosby, an imprint of Elsevier Inc.