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Chapter 20 Drugs for Degenerative Diseases of the Nervous System

Terms in this set (39)

Alzheimer's disease
Defintion
Progressive loss of brain function characterized by memory loss, confusion, and dementia
Multiple sclerosis
Definiton
Demyelination of neurons in the CNS, resulting in progressive weakness, visual disturbances, mood alterations, and cognitive deficits
Parkinson's disease
Definition
Progressive loss of dopamine in the CNS causing tremor, muscle rigidity, and abnormal movements and posture
Symptoms of Parkinson's Disease
Affects mainly men and women over the age of 50.

Tremors: Hands and head develop a palsy-like motion of shakiness when at rest; "pill rolling" is a common behavior in progressive states, in which patients rub the thumb and forefinger together as if a pill were between them.

Muscle Rigidity: Stiffness may resemble symptoms of arthritis; patients have difficulty bending over or moving limbs. Symptoms are less noticeable at first but progress to become more obvious in later years.

Bradykinesia: Most noticeable of all symptoms such as difficulty chewing, swallowing or speaking. Patients will have trouble initiating movement and controlling fine muscle movements. Walking becomes difficult and patients may shuffle their feet without taking normal strides.

Postural instability: Patients may be stooped over and easily lose their balance and results in frequent falls with associated injuries.

Affective flattening: Patients offend have a "masked face" where there is little facial expression or blinking of the eyes.
Health Problems in Parkinson's Patients
Primarily affects muscle movement

Patients often experience other health issues:
Anxiety, depression
Sleep disturbances
Dementia
Autonomic nervous system disturbances (difficulty urinating and performing sexually)
Cause of Symptoms of PD
Potential harmful agents include carbon monoxide, cyanide, manganese, chlorine, and pesticides, viral infections, head trauma, and stroke

Secondary Parkinsonism refers to slowness and mobility issues.

Symptoms of Parkinsonism develop because of the degeneration and destruction of dopamine-producing neurons
Found in the Substantia nigra portion of brain

Corpus striatum affected:

Normally controls unconscious muscle movement
Neurons in the substantia nigra supply dopamine to the corpus striatum
Nigrostriatal pathway
Neurotransmitters of PD
Proper balance of dopamine (inhibitory) and acetylcholine (stimulatory) in corpus striatum
Affect balance, posture
Affect muscle tone, involuntary movement

Absence of dopamine
Allows acetylcholine stimulation

PD focuses not only on restoring dopamine function but also on blocking the effect of acetylcholine within the corpus striatum.
Drug Therapy for PD
1)Restores dopamine function
2)Blocks acetylcholine
3)Avoid extrapyramidal side effects (EPS)

Treatment with certain antipsychotic drugs may induce EPS by interfering with the same neural pathway and functions affected by the lack of dopamine. EPS may include acute dystopias (muscle spasms), akathisia (restless movement), and tardive dyskinesia (involuntary face and jaw movements).
Antparkinsonism Agents
Restore balance of dopamine and acetylcholine in brain
Dopaminergic drugs
Dopaminergic adjunct agents
Anticholinergics (cholinergic blockers)
Dopamine agonists
Restore balance of dopamine and acetylcholine
Dopaminergic examples
Levodopa
1)Amantadine (Symmetrel)
2)Apomorphine (Apokyn)
3)Bromocriptine (Parlodel)
levodopa-carbidopa-entacapone (Stalevo)

General Aspects
Prototype drug: levodopa-carbidopa-entacapone (Stalevo)

Mechanism of action: increases biosynthesis of dopamine within nerve terminals

Primary use: to restore dopamine function or stimulate dopamine receptors within the brain

Adverse effects: uncontrolled and purposeless movements, involuntary movement, loss of appetite, nausea, vomiting

Contraindicated in narrow-angle glaucoma
levodopa-carbidopa-entacapone (Stalevo)

(More detailed)
Therapeutic Class: Antiparkinson drug

Pharmacologic Class: Dopamine precursor; dopamine-enhancing drug combination

Actions and Uses
Stalevo restores the neurotransmitter dopamine in extrapyramidal areas of the brain, thus relieving some Parkinson's symptoms, especially tremor, bradykinesia, gait, and muscle rigidity. To increase its effect, levodopa is combined with two other drugs, carbidopa and entacapone, which prevent its enzymatic breakdown. Several months may be needed to achieve maximum therapeutic effects.

Administration Alerts
The patient may be unable to self-administer medication and may need assistance.
Administer exactly as ordered.
Abrupt withdrawal of the drug can result in Parkinson'slike symptoms or neuroleptic malignant syndrome (NMS).
Pregnancy category C.

Adverse Effects :
Side effects of Stalevo include uncontrolled and purposeless movements such as extending the fingers and shrugging the shoulders, involuntary movements, loss of appetite, nausea, and vomiting. Muscle twitching and spasmodic winking are early signs of toxicity. Orthostatic hypotension is common in some patients. The drug should be discontinued gradually, because abrupt withdrawal can produce acute Parkinson'slike symptoms.

Contraindications:
Stalevo is contraindicated in the treatment of narrow-angle glaucoma. This drug is contraindicated in patients with suspicious pigmented lesions or a history of melanoma. This medication should be avoided in cases of acute psychoses and severe psychoneurosis within 2 weeks of therapy with monoamine oxidase inhibitors (M A O I s).

Interactions
Drug-Drug: Stalevo interacts with many drugs. Haloperidol taken concurrently may antagonize the therapeutic effects of Stalevo. Methyldopa may increase toxicity. Antihypertensives may cause increased hypotensive effects. Anticonvulsants may decrease the therapeutic effects of Stalevo. Antacids containing magnesium, calcium, or sodium bicarbonate may increase Stalevo absorption, which could lead to toxicity. Pyridoxine reverses the antiparkinson effects of Stalevo.

Lab Tests: Abnormalities in laboratory tests may include elevations of liver function tests such as alkaline phosphatase, aspartate aminotransferase (A S T), alanine aminotransferase (A L T), lactic dehydrogenase, and bilirubin. Abnormalities in blood urea nitrogen and positive Coombs' test have also been reported.

Herbal/Food: Kava may worsen the symptoms of Parkinson's.

Treatment of Overdose: General supportive measures should be taken along with immediate gastric lavage. Intravenous (I V) fluids should be administered judiciously, and an adequate airway should be maintained.
Dopaminergic Adjunct Agents
Inhibit enzymes that break down dopamine
Example: tolcapone (Tasmar)

Activate dopamine receptors (dopamine agonists)
Example: ropinirole (Requip)

Cause dopamine release from nerve terminals
Example: amantadine (Symmetrel)
Catechol-O-Methyl Transferase (COMT) Inhibitors
Reduce requirement for levodopa-carbidopa

Increase concentration of existing dopamine in nerve terminals; improve motor fluctuations

Entacapone in combination with carbidopa and levodopa is marketed as Stalevo

Side effects: mental confusion, nausea and vomiting, headache, diarrhea, possible liver damage
Anticholinergic Agents
Centrally acting

Block acetylcholine
Inhibit overactivity in brain

Not as effective as dopaminergics

Used in early stages of PD therapy

Examples:
Benztropine (Cogentin)
Biperiden (Akineton)
Trihexyphenidyl (Artane)
benztropine (Cogentin)

General Aspects
Prototype drug: benztropine (Cogentin)

Mechanism of action: block excess cholinergic stimulation of neurons in corpus striatum; inhibit overactivity in brain

Primary use: in early stages of disease

Adverse effects: dry mouth, blurred vision, photophobia, urinary retention, constipation, tachycardia, glaucoma
benztropine (Cogentin)

(more detailed)
Therapeutic Class: Antiparkinson drug

Pharmacologic Class: Centrally acting cholinergic receptor blocker
Actions and Uses Benztropine acts by blocking excess cholinergic stimulation of neurons in the corpus striatum. It is used for relief of Parkinson's-like symptoms and for the treatment of EPS brought on by antipsychotic pharmacotherapy. This medication suppresses tremors but is not effective at relieving tardive dyskinesia.

Administration Alerts
The patient may be unable to self-administer medication and may need assistance.
Benztropine may be taken in divided doses, two to four times a day, or the entire day's dose may be taken at bedtime.
If muscle weakness occurs, the dose should be reduced.
Pregnancy category C.

Adverse Effects
As expected from its autonomic action, benztropine can cause typical anticholinergic side effects such as dry mouth, constipation, and tachycardia. Adverse general effects include sedation, drowsiness, dizziness, restlessness, irritability, nervousness, and insomnia.

Contraindications:
Contraindications include narrowangle glaucoma, myasthenia gravis, blockage of the urinary tract, severe dry mouth, hiatal hernia, severe constipation, enlarged prostate, and liver disease.

Interactions
Drug-Drug: Benztropine interacts with many drugs. Common medications that should not be used in combination with benztropine are aripiprazole (Abilify), lorazepam (Ativan), docusate (Colace), divalproex sodium (Depakote), gabapentin, ziprasidone (Geodon), haloperidol (Haldol), clonazepam (Klonopin), lamotrigine (Lamictal), lisinopril, lithium, metformin, fluoxetine (Prozac), risperidone (Risperdal), quetiapine (Seroquel), levothyroxine (Synthroid), topiramate (Topamax), trazodone, bupropion (Wellbutrin), sertraline (Zoloft), and olanzapine (Zyprexa).

Over-the-counter (O T C) cold medicines should be avoided. Drugs that enhance dopamine release or activate dopamine receptors may produce additive effects. Haloperidol decreases the effectiveness of benzotropine. Benztropine should not be taken with alcohol because of combined sedative effects. Antihistamines, phenothiazines, tricyclic antidepressants, disopyramide, and quinidine may increase anticholinergic effects, and antidiarrheals may decrease absorption.

Lab Tests: Unknown.

Herbal/Food: Unknown.

Treatment of Overdose: Physostigmine 1 to 2 mg subcutaneously or I V, will reverse symptoms of anticholinergic intoxication. A second injection may be given after 2 hours, if required. Otherwise, treatment is symptomatic and supportive.
Role of the Nurse: Dopamine Agonist Drug Therapy
Know it is contraindicated in narrow-angle glaucoma

Monitor for hypotension and tachycardia

Look for symptoms of drug toxicity
Dopaminergics Patient Teaching
Increase fiber and fluids

Avoid food and drugs high in pyridoxine

May take several months for full effect

Abruptly stopping the drug may cause parkinsonism crisis
Anticholinergics Patient Teaching
Relieve dry mouth with frequent drinks or sugarless hard candy

Take with food or milk to prevent GI upset

Avoid alcohol

Wear dark glasses; avoid bright sunlight

Do not stop taking abruptly
Alzheimer's Disease (AD)

(more detail)
AD responsible for 70% of all dementia

Progressive loss of brain function
Memory loss, confusion, dementia
Affects memory, cognitive function, and behavior

Cause of most dementia unknown; associated with cerebral atrophy

Possible causes
Genetic factors (10% of cases)
Chronic inflammation, excess free radicals
Environmental factors
Immunologic factors
Nutritional factors
Viruses
Structural Damage in Brain
Consists of
Amyloid plaques
Neurofibrillary tangles

Changes found during autopsies

Structural changes cause loss in number and function of neurons

Symptoms result from progressive damage to neurons in hippocampus
Hippocampus - learning and memory
Requires acetylcholine as neurotransmitter
Symptoms of Alzheimer's Disease
Impaired memory and judgment
Confusion and disorientation
Inability to recognize family and friends
Aggressive behavior
Depression
Psychoses, including paranoia and delusions
Anxiety
Goals of Pharmacotherapy for Alzheimer's Disease
Slow memory loss
Slow dementia symptoms
Improve activities of daily living
Improve behavior
Improve cognition
Efficacy of Drug Therapy
No cure
Intensify effect of acetylcholine at cholinergic receptor
Drugs have modest efficacy
Ineffective in late stages
Cholinesterase Inhibitors
Prevent breakdown of acetylcholine
Enhance transmission in cholinergic neurons

Slow progression of A D

Examples
Donepezil (Aricept)
Galantamine (Razadyne, Reminyl)
Rivastigmine (Exelon)
Cholinesterase Inhibitor:
donepezil (Aricept)

General Aspects
Prototype drug: donepezil (Aricept)

Mechanism of action: to prevent breakdown of acetylcholine; enhance transmission in neurons

Primary use: slow progression of the disease

Adverse effects: nausea/vomiting; less commonly dizziness and headache, abnormal dreams, irritability, darkened urine
Prototype: Drug Donepezil (Aricept)

(more detailed)
Therapeutic Class: Alzheimer's disease drug

Pharmacologic Class: Cholinesterase inhibitor

Actions and Uses
Donepezil is an AchE inhibitor that improves memory in cases of mild to moderate Alzheimer's dementia by enhancing the effects of acetylcholine in neurons in the cerebral cortex that have not been damaged. Patients should receive pharmacotherapy for at least 6 months prior to assessing maximum benefits of drug therapy. Improvement in memory may be observed as early as 1 to 4 weeks following medication. The therapeutic effects of donepezil are often short lived, and the degree of improvement is modest, at best. An advantage of donepezil over other drugs in its class is that its long half-life permits it to be given once daily.

Administration Alerts
Give medication prior to bedtime.
Medication is most effective when given on a regular schedule.
Pregnancy category C.

Adverse Effects
Common side effects of donepezil are vomiting and diarrhea. Less common effects are abnormal dreams, fainting, and darkened urine. C N S side effects include insomnia, syncope, depression, headache, and irritability. Musculoskeletal side effects include muscle cramps, arthritis, and bone fractures. Generalized side effects include headache, fatigue, chest pain, increased libido, hot flashes, urinary incontinence, dehydration, and blurred vision. Hepatotoxicity has not been observed. Patients with bradycardia, hypotension, asthma, hyperthyroidism, or active peptic ulcer disease should be monitored carefully.

Contraindications: Donepezil is contraindicated in patients with G I bleeding and jaundice.

Interactions
Drug-Drug: Donepezil will cause anticholinergics to be less effective. Donepezil interacts with several other drugs. For example, bethanechol causes a synergistic effect. Phenobarbital, phenytoin, dexamethasone, and rifampin may speed the elimination of donepezil. Quinidine or ketoconazole may inhibit the metabolism of donepezil. Because donepezil acts by increasing cholinergic activity, two cholinergic drugs should not be administered concurrently.

Lab Tests: Unknown.

Herbal/Food: Unknown.

Treatment of Overdose: Anticholinergics such as atropine may be used as an antidote for donepezil overdosage. I V atropine sulfate titrated to effect is recommended: an initial dose of 1 to 2 mg I V with subsequent doses based on clinical response.
Memantine (Namenda)
Approved for treatment of moderate to severe A D
Reduces abnormally high levels of glutamate
May have a protective function in reducing neuronal calcium overload
Adjunct AD Medicines
Atypical antipsychotic agents
Anxiolytics
Mood stabilizers
Nursing Considerations with AChE Inhibitors
Assess baseline vitals
Monitor for hypotension
Monitor for change in mental status or mood
Monitor for dizziness, insomnia, anorexia
AChE Inhibitors Patient Teaching
Take with food or milk to avoid G I upset

Take as prescribed

Teach signs and symptoms of overdose:
Severe nausea/vomiting, sweating, salivation, hypotension
Bradycardia, convulsions, increased muscle weaknesses (including respiratory muscles)
Multiple Sclerosis
Etiology unknown and no cure exists
Possible causes
Genetic or microbial factors
Climate (colder regions)
Microscopic pathogens
Demyelination of neurons in C N S
Destruction of axons impairs ability of nerves to conduct electrical impulses
Inflammation; plaque (scleroses)
Signs and Symptoms of MS
Fatigue
Heat sensitivity
Neuropathic pain; spasticity
Impaired cognitive ability
Disruption of balance and coordination
Visual impairment; slurred speech
Sexual dysfunction
Bowel and bladder symptoms
Dizziness; vertigo
Immune-modulating Drugs
Disease-modifying drugs used for treatment of relapse-remitting M S and secondary-progressive M S
Two categories
Interferon beta (Avonex, Betaseron)
Glatiramer (Copaxone)
Synthetic protein that simulates myelin basic protein
Reduce symptoms and decrease lesions
Immunosuppressants
Used for progressive forms of M S
Mitoxantrone (Novantrone)
Primarily a chemotherapeutic drug; toxicity is a concern
Immunomodulators
Drugs
Interferon beta (Avonex, Rebif, Betaseron)
Glatiramer (Copaxone)

Primary use: reduce severity of symptoms; decrease lesions

Adverse effects: flushing, chest pain, weakness, infection, pain, nausea, joint pain, anxiety, muscle stiffness
Immunosuppressants
Drug: mitoxantrone (Novantrone)

Primary use: for MS patients who have not responded to immune-modulating therapy

Adverse effects: toxicity; hair loss; G I discomfort; allergic symptoms; blue-green tint to urine
Drugs for Degenerative Diseases of the Nervous System

Assessment
Nursing Diagnoses
Planning
Implementation
Evaluation
Assessment
Complete health and drug history
Assess severity of disease
Monitor vital signs and lab tests
Assess patient/family knowledge of disease

Nursing Diagnoses
Risk for Falls
Deficient Knowledge (related to drug therapy)
Deficient Knowledge (related to disease process)
Impaired Physical Mobility
Self-Care Deficit
Constipation

Planning
Goals
Increased ease of movement
Decrease in symptoms
Understanding of drug regimen/disease
Adherence to drug regimen
Reporting of side effects

Implementation
Monitor vital signs and lab tests
Ensure patient safety
Monitor behavior changes
Observe for symptoms of overdose
Monitor for improved functional status
Monitor for drug side effects

Evaluation
Effectiveness of drug therapy
Patient goals/outcomes met
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