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

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Presentation transcript:

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

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

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.