Chapter 39
Neurodegenerative Diseases
Jinsy A. Andrews and Paul H. Gordon
Questions
1.
Which one of these medications for Alzheimer's disease is NOT a cholinesterase inhibitor?
a. galantamine
b. rivastigmine
c. tacrine
d. memantine
2.
What are the side effects that limit the prolonged usefulness of levodopa therapy in Parkinson disease?
a. muscle fasciculation
b. motor fluctuations and dyskinesias
c. postural instability
d. bradykinesia
3.
Major side effects of levodopa therapy include which of the following?
a. nausea, vomiting, anorexia and orthostatic hypotension
b. abnormal liver function tests
c. bradykinesia and tremor
d. dry eyes and dry mouth
4.
Which class of medications is associated with compulsive behavior?
a. COMT (catechol-o-methyltransferase) inhibitors
b. memantine
c. dopamine agonists
d. MAO (monoamine oxidase) inhibitor
5.
Amantadine is a useful medication in the treatment of dyskinesias in Parkinson Disease. What side effect
limits its use in the elderly?
a. diarrhea
b. sialorrhea
c. dyskinesias
d. neuropsychiatric and cognitive effects
6.
Which is the only FDA approved medication for amyotrophic lateral sclerosis?
a. memantine
b. lamotrigine
c. riluzole
d. coenzyme Q10
7.
What are the major factors that influence patients in their decision to take riluzole in the United States?
a. cost of the medication and opinion of the physician
b. medication interaction and dosing regimen
c. side effects
d. size of the tablet
8.
Memantine and riluzole exert their neuroprotective effects by what proposed mechanism?
a. inhibiting superoxide dismutase
b. inhibiting glutamatergic excitotoxicity
c. inhibiting caspase activity
d. inhibiting mitochondrial injury
39.
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Neurodegenerative Diseases
Jinsy A. Andrews and Paul H. Gordon
2
Memantine is approved for use in which disease?
a. moderate to severe Huntington disease
b. early stages of Huntington disease
c. moderate to severe Alzheimer disease
d. early stages of Alzheimer disease
10. In a patient with Alzheimer disease, what is the ideal class of medication for the treatment of depression?
a. tricyclics
b. selective serotonin reuptake inhibitors
c. anticholinergics
d. neuroleptics
11. Hallucinations in Parkinson disease would ideally be treated with which of the following medications?
a. haloperidol
b. thorazine
c. nortriptyline
d. clozaril
12. Which medication is currently FDA approved for the treatment of pseudobulbar affect in ALS?
a. dextromethorphan/quinidine
b. SSRI antidepressants
c. tricyclic antidepressants
d. none of the above
13. In ALS patients, sialorrhea can be a major symptom as bulbar weakness worsens. Which of these
medications is ideal for a patient with swallowing difficulty?
a. amitriptyline
b. scopolamine
c. diphenyhydramine
d. glycopyrrolate
14. Which one of these medications is used to treat chorea in Huntington disease?
a. risperidone
b. levodopa
c. fluoxetine
d. bupropion
15. Sildenafil citrate is effective in treating erectile dysfunction in several neurodegenerative diseases. What
side effect can this medication cause in Parkinson disease?
a. bradykinesia
b. tremor
c. orthostatic hypotension
d. chorea
16. Proposed mechanisms in neurodegenerative diseases include all of the following EXCEPT:
a. oxidative stress
b. apoptosis
c. inflammation
d. excess GABA
17. Which of the FDA approved therapy for Multiple Sclerosis is currently being studied in ALS?
a. alpha- interferon
b. beta-interferon
c. glatiramer acetate
d. corticosteroids
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Neurodegenerative Diseases
Jinsy A. Andrews and Paul H. Gordon
3
18. Phase II clinical trials of beta amyloid immunization in Alzheimer disease were interrupted because:
a. patients vaccinated with the immunization developed aseptic meningitis
b. immunization supplies were not sufficient
c. the trial was not randomized and blinded
d. patients developed reaction at the site they received the immunization
19. Which of these medications investigated in neurodegenerative diseases are/is no longer recommended
for?
a. remacemide
b. minocycline
c. insulin growth factor
d. ceftriaxone
20. Which of the following antioxidants have been shown in randomized, placebo controlled trials to be
beneficial in any of the neurodegenerative diseases is no longer recommended for treatment?
a. vitamin E
b. n-acetylcycteine
c. selegeline
d. none of the above
39.
Neurodegenerative Diseases
Jinsy A. Andrews and Paul H. Gordon
4
Answers
1.
Which one of these medications for Alzheimer's disease is NOT a cholinesterase inhibitor?
a. galantamine
b. rivastigmine
c. tacrine
d. memantine
Memantine is an NMDA receptor antagonist.
2.
What are the side effects that limit the prolonged usefulness of levodopa therapy in Parkinson disease?
a. muscle fasciculation
b. motor fluctuations and dyskinesias
c. postural instability
d. bradykinesia
Motor fluctuations and dyskinesias. Levodopa usually produces an excellent initial response for motor
symptoms of Parkinson disease, especially bradykinesia and tremor. However, its prolonged use can cause
motor fluctuations and dyskinesias.
3.
Major side effects of levodopa therapy include which of the following?
a. nausea, vomiting, anorexia and orthostatic hypotension
b. abnormal liver function tests
c. bradykinesia and tremor
d. dry eyes and dry mouth
Nausea, vomiting, anorexia and orthostatic hypotension. The co-administration of carbidopa, a dopa
decarboxylase inhibitor, insures that the majority of levodopa is converted to dopamine in the brain, reducing
these side effects
4.
Which class of medications is associated with compulsive behavior?
a. COMT (catechol-o-methyltransferase) inhibitors
b. memantine
c. dopamine agonists
d. MAO (monoamine oxidase) inhibitor
Dopamine agonists medications have been reported to be associated with pathological gambling and
compulsive behavior
5.
Amantadine is a useful medication in the treatment of dyskinesias in Parkinson Disease. What side effect
limits its use in the elderly?
a. diarrhea
b. sialorrhea
c. dyskinesias
d. neuropsychiatric and cognitive effects
Neuropsychiatric and cognitive effects: amantadine has both anticholinergic and NMDA antagonist properties.
Common side effects include insomnia and levido reticlaris. In the elderly, it can cause neuropsychiatric and
cognitive adverse events.
6.
Which is the only FDA approved medication for amyotrophic lateral sclerosis?
a. memantine
b. lamotrigine
c. riluzole
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Neurodegenerative Diseases
Jinsy A. Andrews and Paul H. Gordon
d.
5
coenzyme Q10
Despite many trials of potential therapeutic agents screened in animal models, riluzole remains the only FDA
approved medication for ALS.
7.
What are the major factors that influence patients in their decision to take riluzole in the United States?
a. cost of the medication and opinion of the physician
b. medication interaction and dosing regimen
c. side effects
d. size of the tablet
Cost of the medication and the opinion of the physician: In the United States not all insurance plans cover the
cost of the medication, a major reason why patients decide whether they take riluzole or not. In Europe, where
the health systems covers the cost, the use of riluzole is nearly 100% compared to 60% in the United States.
8.
Memantine and riluzole exert their neuroprotective effects by what proposed mechanism?
a. inhibiting superoxide dismutase
b. inhibiting glutamatergic excitotoxicity
c. inhibiting caspase activity
d. inhibiting mitochondrial injury
Inhibiting glutamatergic excitotoxicity: Memantine is an NMDA receptor antagonist and riluzole blocks the
presynaptic release of glutamate.
9.
Memantine is approved for use in which disease?
a. moderate to severe Huntington disease
b. early stages of Huntington disease
c. moderate to severe Alzheimer disease
d. early stages of Alzheimer disease
Moderate to severe Alzheimer disease: Additional studies are needed to determine whether memantine can be
used as monotherapy or part of a combination therapy in early Alzheimer disease.
10. In a patient with Alzheimer disease, what is the ideal class of medication for the treatment of depression?
a. tricyclics
b. selective serotonin reuptake inhibitors
c. anticholinergics
d. neuroleptics
Selective serotonin reuptake inhibitors: Tricyclic antidepressants and anticholinergic medications can cause
adverse cognitive effects. Neuroleptics are not indicated for depression.
11. Hallucinations in Parkinson disease would ideally be treated with which of the following medications?
a. haloperidol
b. thorazine
c. nortriptyline
d. clozaril
Clozaril: Atypical antipsychotics are the treatment of choice for psychoses in Parkinson disease because they
have less extra-pyramidal side effects than standard antipsychotic medications. Clozaril may also help to reduce
motor symptoms of Parkinson disease. However, rare cases of agranulocytosis necessitate weekly blood counts.
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Neurodegenerative Diseases
Jinsy A. Andrews and Paul H. Gordon
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12. Which medication is currently FDA approved for the treatment of pseudobulbar affect in ALS?
a. dextromethorphan/quinidine
b. SSRI antidepressants
c. tricyclic antidepressants
d. none of the above
None of the above: There is currently no FDA approved therapy for pseudobulbar affect.
Dextromethorphan/quinidine has undergone phase III clinical trials, which showed that it reduced emotional
lability.
13. In ALS patients, sialorrhea can be a major symptom as bulbar weakness worsens. Which of these
medications is ideal for a patient with swallowing difficulty?
a. amitriptyline
b. scopolamine
c. diphenyhydramine
d. glycopyrrolate
Scopolamine: All of the other medication can be used for sialorrhea; however, they require oral administration.
For a patient with significant dysphagia, scopolamine can be adminstered via transdermal patch.
14. Which one of these medications are used to treat chorea in Huntington disease?
a. risperidone
b. levodopa
c. fluoxetine
d. bupropion
Risperidone: Atypical antipsychotics help reduce chorea and some behavior symptoms. Typical neuroloeptics
are generally not tolerated well. Other medications that have been used to treat chorea include benzodiazepines
and amantidine.
15. Sildenafil citrate is effective in treating erectile dysfunction in several neurodegenerative diseases. What
side effect can this medication cause in Parkinson disease?
a. bradykinesia
b. tremor
c. orthostatic hypotension
d. chorea
Orthostatic Hypotension: The use of sildenafil citrate can unmask orthostatic hypotension in Parkinson disease.
It should also be used with caution in patients with risk of vascular events.
16. Proposed mechanisms in neurodegenerative diseases include all of the following EXCEPT:
a. oxidative stress
b. apoptosis
c. inflammation
d. excess GABA
Excess GABA: Proposed mechanisms involved in neurodegeneration include oxidative stress, excitotoxic injury
due to excess glutamate, altered metal homeostasis, aberrant protein aggregation, mitochondrial injury,
apoptosis and inflammation.
17. Which of the FDA approved therapy for Multiple Sclerosis is currently being studied in ALS?
a. alpha- interferon
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Neurodegenerative Diseases
Jinsy A. Andrews and Paul H. Gordon
b.
c.
d.
7
beta-Interferon
glatiramer acetate
corticosteroids
Glatiramer acetate: Glatiramer acetate (Copaxone) has been shown to prolong survival in mouse models of ALS
and initial human trials have shown that the therapy is safe and well tolerated by ALS patients.
18. Phase II clinical trials of beta amyloid immunization in Alzheimer disease were interrupted because:
a. patients vaccinated with the immunization developed aseptic meningitis
b. immunization supplies were not sufficient
c. the trial was not randomized and blinded
d. patients developed reaction at the site they received the immunization
Patients vaccinated with the immunization developed aseptic meningitis: Approximately 6% of patients
vaccinated developed ascetic meningitis and the trials were interrupted.
19. Which medication(s), investigated in neurodegenerative diseases, are/is no longer recommended?
a. remacemide
b. minocycline
c. insulin growth factor
d. ceftriaxone
Minocycline is a tetracycline antibiotic. Although it was shown to inhibit caspase-3 and caspase-1 activation
(pathways for apoptosis) in relevant animal models of ALS, it was shown to accelerate disease progression in
humans and therefore, is no longer recommended.
20. Which of the following antioxidants have been shown in randomized, placebo controlled trials to be
beneficial in any of the neurodegenerative diseases?
a. vitamin E
b. n-acetylcycteine
c. selegeline
d. none of the above
None of the above: More research is needed to determine whether selegeline has neuroprotective effects in
addition to symptomatic benefits in Parkinson disease.