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

Chapter 15

Antiparkinson Drugs

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)

Basal Ganglia and Related Structures of the Brain

Neurotransmitter Abnormality in Parkinson’s Disease

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

Classic symptoms include: Akinesia Bradykinesia Rigidity Tremor Postural instability Staggering gait Drooling

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”

Classroom Response Question

The “off-on phenomenon” that some patients with Parkinson’s disease (PD) experience is best explained as the

A. need to take a drug holiday to improve response to medications.

B. variable response to levodopa, resulting in periods of good control and periods of poor control of PD symptoms.

C. alternating schedule of medications needed to control PD.

D. fluctuation of emotions that often occurs with PD.

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

Levodopa Therapy

Levodopa is a precursor of dopamine Blood-brain barrier does not allow exogenously

supplied dopamine to enter, but does allow levodopa

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

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

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

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

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)

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

Improve functional ability Decrease severity of symptoms Only 50% to 60% of patients show a positive

response to therapy

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

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

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

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

COMT Inhibitors (cont’d)

tolcapone (Tasmar) Has caused severe liver failure Requires monitoring of liver enzymes Not used unless other drugs do not work

Which drug used for the management of the patient with Parkinson’s disease is most likely to cause postural hypotension?

A. amantadine (Symmetrel)

B. selegiline (Eldepryl)

C. tolcapone (Tasmar)

D. entacapone (Comtan)

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)

Nondopamine Dopamine Receptor Agonists

Directly stimulate dopamine receptors Activate dopamine receptors and stimulate

production of more dopamine

The beneficial role of the NDDRA ropinirole (Requip) is that it

A. appears to delay the start of levodopa therapy.

B. allows for levodopa therapy to begin earlier.

C. improves the patient’s tolerance of parkinsonian symptoms.

D. replaces dopamine in the brain.

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

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

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)

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)

When providing teaching to a patient receiving an anticholinergic for the treatment of Parkinson’s disease, the nurse will include which information?

A. Take the medication first thing in the morning.

B. Limit fluid intake when taking this drug.

C. The tremors you experience will be reduced within 24 hours of taking this drug.

D. Do not take this medication at the same time as other medications.

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

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

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

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

Patient should be taught not to discontinue antiparkinson drugs suddenly

Teach patient about expected therapeutic and adverse effects with antiparkinson drug therapy

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

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

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

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