Chapter 16 - The Red Zone

Transcript Chapter 16 - The Red Zone

CHAPTER 16 Antiparkinsonian 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) Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate 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 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 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 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 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 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 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 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 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 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) 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 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 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 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 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 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 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 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) 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 Used for PD and restless leg syndrome  Apomorphine (Apokyn) • • Newer, nonergot dopamine agonist Subcutaneous injection 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 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 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 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) 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 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) 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 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 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 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 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 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 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 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 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 Mosby items and derived items © 2011, 2007, 2004 by Mosby, Inc., an affiliate of Elsevier Inc.