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

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

CHAPTER 14CHAPTER 14

Antiparkinsonian DrugsAntiparkinsonian Drugs


Parkinson’s Disease (PD)Parkinson’s Disease (PD)

Chronic, progressive, degenerative disorderChronic, progressive, degenerative disorder Affects the dopamine-producing neurons in Affects the dopamine-producing neurons in

the brainthe brain Caused by an imbalance of two Caused by an imbalance of two

neurotransmittersneurotransmitters DopamineDopamine Acetylcholine (ACh)Acetylcholine (ACh)


Parkinson’s Disease (cont’d)Parkinson’s Disease (cont’d)

Symptoms occur when about 80% of the Symptoms occur when about 80% of the dopamine stored in the substantia nigra of the dopamine stored in the substantia nigra of the basal ganglia is depletedbasal ganglia is depleted

As long as there are functioning nerve As long as there are functioning nerve terminals that can take up dopamine, terminals that can take up dopamine, symptoms can be partially controlledsymptoms can be partially controlled



Symptoms include:Symptoms include: BradykinesiaBradykinesia RigidityRigidity TremorTremor Postural instabilityPostural instability



PD is a progressive conditionPD is a progressive condition Rapid swings in response to levodopa occur Rapid swings in response to levodopa occur

(“on-off phenomenon”)(“on-off phenomenon”) PD worsens when too little dopamine is presentPD worsens when too little dopamine is present Dyskinesia occurs when too much is presentDyskinesia occurs when too much is present


DyskinesiaDyskinesia

Difficulty in performing voluntary movementsDifficulty in performing voluntary movements Two common typesTwo common types

Chorea: irregular, spasmodic, involuntary Chorea: irregular, spasmodic, involuntary movements of the limbs or facial musclesmovements of the limbs or facial muscles

Dystonia: abnormal muscle tone leading to Dystonia: abnormal muscle tone leading to impaired or abnormal movementsimpaired or abnormal movements


Levodopa TherapyLevodopa Therapy

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

exogenously supplied dopamine to enter, but exogenously supplied dopamine to enter, but does allow levodopadoes allow levodopa


Levodopa Therapy (cont’d)Levodopa Therapy (cont’d)

Levodopa is taken up by the dopaminergic Levodopa is taken up by the dopaminergic terminal, converted into dopamine, then terminal, converted into dopamine, then released as neededreleased as needed

As a result, the neurotransmitter imbalance is As a result, the neurotransmitter imbalance is controlled in patients with early PD who still controlled in patients with early PD who still have functioning nerve terminalshave functioning nerve terminals


Levodopa Therapy (cont’d)Levodopa Therapy (cont’d)

As PD progresses, it becomes more and As PD progresses, it becomes more and more difficult to control it with levodopamore difficult to control it with levodopa

Ultimately, levodopa no longer controls the Ultimately, levodopa no longer controls the PD, and patient is seriously debilitatedPD, and patient is seriously debilitated

This generally occurs between 5 and This generally occurs between 5 and 10 years after the start of levodopa therapy10 years after the start of levodopa therapy


Drug Therapy for PDDrug Therapy for PD

Aimed at increasing levels of dopamine as Aimed at increasing levels of dopamine as long as there are functioning nerve terminals long as there are functioning nerve terminals remainingremaining

Antagonizes or blocks the effects of AChAntagonizes or blocks the effects of ACh Slows the progression of the diseaseSlows the progression of the disease


Drug Therapy for PD (cont’d)Drug Therapy for PD (cont’d)

Anticholinergic drugsAnticholinergic drugs benztropine, biperiden, othersbenztropine, biperiden, others

AntihistaminesAntihistamines diphenhydramine, othersdiphenhydramine, others

Dopamine-receptor agonists (direct acting)Dopamine-receptor agonists (direct acting) bromocriptine, levodopa, pergolide, levodopa-bromocriptine, levodopa, pergolide, levodopa-

carbidopa, otherscarbidopa, others


Drug Therapy for PD (cont’d)Drug Therapy for PD (cont’d)

Indirect-acting dopamine-receptor agonistsIndirect-acting dopamine-receptor agonists MAO-B inhibitor: selegilineMAO-B inhibitor: selegiline COMT inhibitor: entacapone, tolcaponeCOMT inhibitor: entacapone, tolcapone Miscellaneous drug: amantadineMiscellaneous drug: amantadine


Selective Monoamine Oxidase Selective Monoamine Oxidase Inhibitor (MAOI) TherapyInhibitor (MAOI) Therapy

Selegiline is a newer, potent, irreversible Selegiline is a newer, potent, irreversible MAOI that selectively inhibits MAO-BMAOI that selectively inhibits MAO-B

Does not elicit the “cheese effect” of the Does not elicit the “cheese effect” of the nonselective MAOIs used to treat depression nonselective MAOIs used to treat depression (if 10 mg or less is used)(if 10 mg or less is used)


Selective MAOI Therapy: SelegilineSelective MAOI Therapy: Selegiline

MAOIs break down catecholamines in the MAOIs break down catecholamines in the CNS, primarily the brainCNS, primarily the brain

Selegiline is a selective MAO-B inhibitor; it Selegiline is a selective MAO-B inhibitor; it causes an increase in the levels of causes an increase in the levels of dopaminergic stimulation in the CNSdopaminergic stimulation in the CNS


Selective MAOI Therapy: Selegiline Selective MAOI Therapy: Selegiline (cont’d)(cont’d)

Used in combination with levodopa or Used in combination with levodopa or levodopa-carbidopalevodopa-carbidopa

Used as an adjunctive when a patient’s Used as an adjunctive when a patient’s response to levodopa is fluctuatingresponse to levodopa is fluctuating

Allows the dose of levodopa to be decreased; Allows the dose of levodopa to be decreased; delays the development of unresponsiveness delays the development of unresponsiveness to levodopa therapyto levodopa therapy



Improvement in functional abilityImprovement in functional ability Decreased severity of symptomsDecreased severity of symptoms Only 50% to 60% of patients show a positive Only 50% to 60% of patients show a positive

response to therapyresponse to therapy Prophylactic selegiline may delay the Prophylactic selegiline may delay the

development of serious debilitating PD for development of serious debilitating PD for 9 to 18 years9 to 18 years



Adverse effects usually mildAdverse effects usually mild Nausea, lightheadedness, dizziness, abdominal Nausea, lightheadedness, dizziness, abdominal

pain, insomnia, confusion, dry mouthpain, insomnia, confusion, dry mouth Doses higher than 10 mg/day may cause more Doses higher than 10 mg/day may cause more

severe adverse effects, such as hypertensive severe adverse effects, such as hypertensive crisiscrisis


Dopaminergic TherapyDopaminergic Therapy

Used to provide exogenous replacement of Used to provide exogenous replacement of lost dopamine or to enhance the function of lost dopamine or to enhance the function of the few neurons that are still producing their the few neurons that are still producing their own dopamineown dopamine

Goal: to increase levels of dopamine in the Goal: to increase levels of dopamine in the brain and reduce the most detrimental brain and reduce the most detrimental complications of PDcomplications of PD


Dopaminergic Therapy (cont’d)Dopaminergic Therapy (cont’d)

Three categoriesThree categories ReplacementReplacement Direct acting/replacementDirect acting/replacement Indirect actingIndirect acting



Replacement drugs (presynaptic)Replacement drugs (presynaptic) Work presynaptically to increase brain levels of Work presynaptically to increase brain levels of

dopaminedopamine Levodopa is able to cross the blood-brain barrier, Levodopa is able to cross the blood-brain barrier,

then is converted to dopaminethen is converted to dopamine However, the large doses of levodopa needed to However, the large doses of levodopa needed to

get dopamine to the brain also cause adverse get dopamine to the brain also cause adverse effectseffects



Replacement drugs (presynaptic) (cont'd)Replacement drugs (presynaptic) (cont'd) Carbidopa is given with levodopaCarbidopa is given with levodopa Carbidopa does not cross the blood-brain barrier, Carbidopa does not cross the blood-brain barrier,

and prevents levodopa breakdown in the peripheryand prevents levodopa breakdown in the periphery As a result, more levodopa crosses the blood-As a result, more levodopa crosses the blood-

brain barrier, where it can be converted to brain barrier, where it can be converted to dopaminedopamine



Indirect acting: amantadine (Symmetrel)Indirect acting: amantadine (Symmetrel) Causes release of dopamine from the storage sites at Causes release of dopamine from the storage sites at

the end of nerve cells that are still intactthe end of nerve cells that are still intact Also blocks the reuptake of dopamine into the nerve Also blocks the reuptake of dopamine into the nerve

endings, allowing more to accumulate both centrally endings, allowing more to accumulate both centrally and peripherallyand peripherally

Does not stimulate dopamine receptors directlyDoes not stimulate dopamine receptors directly



Indirect acting: COMT inhibitorsIndirect acting: COMT inhibitors tolcapone (Tasmar) and entacapone tolcapone (Tasmar) and entacapone

(Comtan)(Comtan) Inhibit COMT, the enzyme responsible for the Inhibit COMT, the enzyme responsible for the

breakdown of levodopa, the dopamine breakdown of levodopa, the dopamine precursorprecursor



Direct acting: bromocriptine (Parlodel)Direct acting: bromocriptine (Parlodel) Directly stimulates the dopamine receptorsDirectly stimulates the dopamine receptors Able to activate dopamine receptors and stimulate Able to activate dopamine receptors and stimulate

the production of more dopaminethe production of more dopamine Pergolide (Permax) is another direct-acting drug with Pergolide (Permax) is another direct-acting drug with

a different mechanism of actiona different mechanism of action



ropinirole (Requip)ropinirole (Requip) Newer, nonergot dopamine agonistNewer, nonergot dopamine agonist Used for PD, and restless leg syndromeUsed for PD, and restless leg syndrome


Dopaminergic Therapy:Dopaminergic Therapy:IndicationsIndications

Used to increase dopamine levels in the brain Used to increase dopamine levels in the brain and reduce the severity of PD symptomsand reduce the severity of PD symptoms

Amantadine also has antiviral effectsAmantadine also has antiviral effects


Dopaminergic Therapy:Dopaminergic Therapy:Adverse EffectsAdverse Effects

Vary according to drug usedVary according to drug used Tolcapone has caused liver failureTolcapone has caused liver failure

Need to monitor liver enzymesNeed to monitor liver enzymes Used only when other drugs failUsed only when other drugs fail


Anticholinergic TherapyAnticholinergic Therapy

Anticholinergics block the effects of AChAnticholinergics block the effects of ACh Used to treat muscle tremors and muscle Used to treat muscle tremors and muscle

rigidity associated with PDrigidity associated with PD These two symptoms are caused by These two symptoms are caused by

excessive cholinergic activityexcessive cholinergic activity They do not relieve bradykinesia (extremely They do not relieve bradykinesia (extremely

slow movements)slow movements)


Anticholinergic Therapy (cont’d)Anticholinergic Therapy (cont’d)

ACh accumulates because of the imbalance ACh accumulates because of the imbalance of dopamineof dopamine

As a result, overstimulation of the cholinergic As a result, overstimulation of the cholinergic excitatory pathways occursexcitatory pathways occurs Muscle tremors and muscle rigidityMuscle tremors and muscle rigidity Cogwheel rigidityCogwheel rigidity Pill-rolling movement of fingers and head bobbing Pill-rolling movement of fingers and head bobbing

while at restwhile at rest


Anticholinergic Drugs Anticholinergic Drugs Used for PDUsed for PD

benztropine mesylate (Cogentin)benztropine mesylate (Cogentin) trihexyphenidyl (Artane)trihexyphenidyl (Artane) biperiden (Akineton)biperiden (Akineton) procyclidine (Kemadrin)procyclidine (Kemadrin)


Anticholinergic Therapy:Anticholinergic Therapy:IndicationsIndications

Used in the treatment of PD to cause smooth Used in the treatment of PD to cause smooth muscle to relax, resulting in reduced muscle muscle to relax, resulting in reduced muscle rigidity and akinesiarigidity and akinesia

Also used to treat drug-induced Also used to treat drug-induced extrapyramidal reactions to certain extrapyramidal reactions to certain antipsychotic drugsantipsychotic drugs


Anticholinergic Therapy:Anticholinergic Therapy:Adverse EffectsAdverse Effects

Drowsiness, confusion, disorientationDrowsiness, confusion, disorientation Constipation, nausea, vomitingConstipation, nausea, vomiting Urinary retention, pain on urinationUrinary retention, pain on urination Blurred vision, dilated pupils, photophobia, Blurred vision, dilated pupils, photophobia,

dry skindry skin Decreased salivation, dry mouthDecreased salivation, dry mouth


Nursing ImplicationsNursing Implications

Perform a thorough assessment, nursing Perform a thorough assessment, nursing history, and medication historyhistory, and medication history

Include questions about the patient’s:Include questions about the patient’s: CNSCNS GI and GU tractsGI and GU tracts Psychologic and emotional statusPsychologic and emotional status


Nursing Implications (cont’d)Nursing Implications (cont’d)

Assess for signs and symptoms of PDAssess for signs and symptoms of PD Mask-like expressionMask-like expression Speech problemsSpeech problems DysphagiaDysphagia Rigidity of arms, legs, and neckRigidity of arms, legs, and neck

Assess for conditions that may be Assess for conditions that may be contraindicationscontraindications



Administer drugs as directed by manufacturerAdminister drugs as directed by manufacturer Provide patient education regarding PD and Provide patient education regarding PD and

the medication therapythe medication therapy Inform patient not to take other medications Inform patient not to take other medications

with PD drugs unless he or she checks with with PD drugs unless he or she checks with physicianphysician



When starting dopaminergic drugs, assist When starting dopaminergic drugs, assist patient with walking because dizziness may patient with walking because dizziness may occuroccur

Oral doses should be given to minimize GI Oral doses should be given to minimize GI upsetupset

Encourage patient to force fluids to at least Encourage patient to force fluids to at least 2000 mL/day (unless contraindicated)2000 mL/day (unless contraindicated)



Pyridoxine (vitamin BPyridoxine (vitamin B66) in doses greater than ) in doses greater than 10 mg will reverse the effects of levodopa10 mg will reverse the effects of levodopa

Teach patient to avoid foods high in vitamin Teach patient to avoid foods high in vitamin BB66

Taking levodopa with MAOIs may result in Taking levodopa with MAOIs may result in hypertensive crisishypertensive crisis



Patients should be told not to discontinue Patients should be told not to discontinue antiparkinsonian drugs suddenlyantiparkinsonian drugs suddenly

Teach patients about what therapeutic and Teach patients about what therapeutic and adverse effects to expect with adverse effects to expect with antiparkinsonian drug therapyantiparkinsonian drug therapy



Levodopa preparations may darken the Levodopa preparations may darken the patient’s urine and sweatpatient’s urine and sweat

Therapeutic effects of COMT inhibitors may Therapeutic effects of COMT inhibitors may be noticed within a few days; it may take be noticed within a few days; it may take weeks with other drugsweeks with other drugs

““Drug holidays”Drug holidays”



Monitor for response to drug therapyMonitor for response to drug therapy Improved sense of well-being and mental statusImproved sense of well-being and mental status Increased appetiteIncreased appetite Increased ability to perform ADLs, to concentrate, Increased ability to perform ADLs, to concentrate,

and to think clearlyand to think clearly Less intense parkinsonian manifestations, such as Less intense parkinsonian manifestations, such as

less tremor, shuffling gait, muscle rigidity, and less tremor, shuffling gait, muscle rigidity, and involuntary movementsinvoluntary movements

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