1. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 14 Antiparkinsonian Drugs

2. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Parkinson’s Disease (PD)  Chronic, progressive, degenerative disorder  Affects the dopamine-producing neurons in the brain  Caused by an imbalance of two neurotransmitters  Dopamine  Acetylcholine (ACh)

3. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.

4. Parkinson’s Disease (cont’d)  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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6. Parkinson’s Disease (cont’d)  PD is 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 is present

7. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate 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

8. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate 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

9. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Levodopa Therapy (cont’d)  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

10. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Levodopa Therapy (cont’d)  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

11. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate 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

12. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Therapy for PD (cont’d)  Anticholinergic drugs  benztropine, biperiden, others  Antihistamines  diphenhydramine, others  Dopamine-receptor agonists (direct acting)  bromocriptine, levodopa, pergolide, levodopa- carbidopa, others

13. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Therapy for PD (cont’d)  Indirect-acting dopamine-receptor agonists  MAO-B inhibitor: selegiline  COMT inhibitor: entacapone, tolcapone  Miscellaneous drug: amantadine

14. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Selective Monoamine Oxidase Inhibitor (MAOI) Therapy  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)

15. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Selective MAOI Therapy: Selegiline  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

16. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Selective MAOI Therapy: Selegiline (cont’d)  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

17. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Selective MAOI Therapy: Selegiline (cont’d)  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

18. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Selective MAOI Therapy: Selegiline (cont’d)  Adverse effects 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

19. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Dopaminergic Therapy  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

20. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Dopaminergic Therapy (cont’d)  Three categories  Replacement  Direct acting/replacement  Indirect acting

21. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Dopaminergic Therapy (cont’d)  Replacement drugs (presynaptic)  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

22. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Dopaminergic Therapy (cont’d)  Replacement drugs (presynaptic) (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

23. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Dopaminergic Therapy (cont’d)  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

24. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Dopaminergic Therapy (cont’d)  ropinirole (Requip)  Newer, nonergot dopamine agonist  Used for PD, and restless leg syndrome

25. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Dopaminergic Therapy: Indications  Used to increase dopamine levels in the brain and reduce the severity of PD symptoms  Amantadine also has antiviral effects

26. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. 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  They do not relieve bradykinesia (extremely slow movements)

27. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Anticholinergic Therapy (cont’d)  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

28. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Anticholinergic Drugs Used for PD  benztropine mesylate (Cogentin)  trihexyphenidyl (Artane)  biperiden (Akineton)  procyclidine (Kemadrin)

29. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. 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

30. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Anticholinergic Therapy: Adverse Effects  Drowsiness, confusion, disorientation  Constipation, nausea, vomiting  Urinary retention, pain on urination  Blurred vision, dilated pupils, photophobia, dry skin  Decreased salivation, dry mouth

31. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate 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

32. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Assess for signs and symptoms of PD  Mask-like expression  Speech problems  Dysphagia  Rigidity of arms, legs, and neck  Assess for conditions that may be contraindications

33. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. 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

34. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  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)

35. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Pyridoxine (vitamin B 6 ) in doses greater than 10 mg will reverse the effects of levodopa  Teach patient to avoid foods high in vitamin B 6  Taking levodopa with MAOIs may result in hypertensive crisis

36. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Patients should be told not to discontinue antiparkinsonian drugs suddenly  Teach patients about what therapeutic and adverse effects to expect with antiparkinsonian drug therapy

37. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Levodopa preparations may darken the patient’s urine and sweat  Therapeutic effects may take weeks with other drugs  “Drug holidays”

38. Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. 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