Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. CHAPTER 16 Antiparkinsonian Drugs

2 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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)

3 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.

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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

6 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Parkinson’s Disease (cont’d)  Classic symptoms include:  Akinesia  Bradykinesia  Rigidity  Tremor  Postural instability

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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

9 Mosby items and derived items © 2011, 2007, 2004 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

10 Mosby items and derived items © 2011, 2007, 2004 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

11 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

12 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Levodopa Therapy (cont’d)  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

13 Mosby items and derived items © 2011, 2007, 2004 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

14 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Therapy for PD (cont’d)  Indirect-acting dopamine-receptor agonists  MAOB inhibitors: selegiline, rasagiline  COMT inhibitors: entacapone, tolcapone  Presynaptic dopamine release enhancer: amantadine

15 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Drug Therapy for PD (cont’d)  Anticholinergic drugs  Benztropine, others  Antihistamines  Diphenhydramine  Nondopamine-receptor agonists  Ergot: bromocriptine  Nonergot: pramipexole, ropinirole, apomorphine  Dopamine replacement drugs  Carbidopa, carbidopa-levodopa

16 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Selective MAOI Therapy: Selegiline  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

17 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Selective MAOI Therapy: Selegiline (cont’d)  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)

18 Mosby items and derived items © 2011, 2007, 2004 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 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

19 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Selective MAOI Therapy: Selegiline (cont’d)  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

20 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

21 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Presynaptic Dopamine Release Enhancer  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

22 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Presynaptic Dopamine Release Enhancer (cont’d)  Amantadine (Symmetrel)  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

23 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. COMT Inhibitors  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

24 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. COMT Inhibitors (cont’d)  Tolcapone (Tasmar)  Has caused severe liver failure  Requires monitoring of liver enzymes  Not used unless other drugs do not work

25 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Direct-Acting Dopamine Receptor Agonists  Nondopamine dopamine receptor agonists (NDDRAs)  Ergot derivatives (bromocriptine and pergolide)  Nonergot drugs (pramipexole, ropinirole, apomorphine)  Dopamine replacement drugs  Levodopa, carbidopa, carbidopa-levodopa (Sinemet)

26 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Direct-Acting Dopamine Receptor Agonists (cont’d)  Nondopamine dopamine receptor agonists (NDDRAs)  Ropinirole (Requip) Newer, nonergot NDDRA Newer, nonergot NDDRA Used for PD and restless leg syndrome Used for PD and restless leg syndrome  Apomorphine (Apokyn) Newer, nonergot dopamine agonist Newer, nonergot dopamine agonist Subcutaneous injection Subcutaneous injection

27 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Direct-Acting Dopamine Receptor Agonists (cont’d)  Direct-acting  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

28 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

29 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

30 Mosby items and derived items © 2011, 2007, 2004 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  Does not relieve bradykinesia (extremely slow movements)

31 Mosby items and derived items © 2011, 2007, 2004 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

32 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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)

33 Mosby items and derived items © 2011, 2007, 2004 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

34 Mosby items and derived items © 2011, 2007, 2004 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

35 Mosby items and derived items © 2011, 2007, 2004 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

36 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. 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

37 Mosby items and derived items © 2011, 2007, 2004 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

38 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  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

39 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  Patient should be taught not to discontinue antiparkinsonian drugs suddenly  Teach patient about what therapeutic and adverse effects to expect with antiparkinsonian drug therapy

40 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc. Nursing Implications (cont’d)  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

41 Mosby items and derived items © 2011, 2007, 2004 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