Pharm - CNS Degenerative Diseases
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Central nervous system disorders are a group of neurological disorders that affect the structure or function of the brain or spinal cord. Degenerative brain diseases have an enormous impact on our aging society. Take this pharmacology test on the CNS degenerative diseases and test your knowledge on the prescribed drugs for a patient.
Questions and Answers
- 1.
Which of the following statements correctly pair the drugs used in parkinsonism with their appropriate mechanism of action? (Check all that apply)
- A.
Levodopa - inhibits dopamine metabolism in the brain
- B.
Benztropine - blocks central Nn cholinergic receptors
- C.
Selegiline - selectively inhibits MAO B
- D.
Amantadine - selectively inhibits catechol-O-methyl-transferase
- E.
Bromocriptine - activates central dopaminergic receptors
- F.
Entacapone - blocks central muscarinic receptors
Correct Answer(s)
C. Selegiline - selectively inhibits MAO B
E. Bromocriptine - activates central dopaminergic receptorsExplanation
Answer: CE
(Katzung, pp 452,453 Brunton, pp 535, 537)
Selegiline is a selective inhibitor of MAO B (the enzyme that metabolize dopamine) so
preventing the oxidation of dopamine to DOPAC and hydrogen peroxide. Bromocriptine is a D2
receptor agonist.
A) Levodopa is biotransformed into dopamine by the enzyme DOPA decarboxylase. It does not
affect the metabolism of dopamine.
B) Actuallybenztropine blocks central muscarinic receptors. It has negligible blocking activity on
central Nn cholinergic receptors.
D) In fact the mechanism of action of amantadine is still unknown, but the drug is not an
inhibitor of catechol-O-methyl-transferase.
F) Entacapone is a selective inhibitor of catechol-O-methyl-transferaseRate this question:
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- 2.
Damage of basal ganglia can produce either hyperkinetic or hypokinetic disorders. Which of the following statements best describes the effects of cholinergic and dopaminergic agonists on these conditions?
- A.
Cholinergic agonists exacerbate hyperkinetic disorders and alleviate hypokinetic disorders
- B.
Cholinergic agonists alleviate both hyperkinetic and hypokinetic disorders
- C.
Dopaminergic agonists alleviate both hyperkinetic and hypokinetic disorders
- D.
Dopaminergic agonists exacerbate hyperkinetic disorders and alleviate hypokinetic disorders
- E.
Dopaminergic agonists alleviate hyperkinetic disorders and exacerbate hypokinetic disorders
Correct Answer
D. Dopaminergic agonists exacerbate hyperkinetic disorders and alleviate hypokinetic disordersExplanation
Answer: D
(Katzung, pp 457, Brunton, pp 540)
The main hypokinetic disorder related to damage of basal ganglia is parkinsonism, whereas the
main hyperkinetic disorder related to damage of the same area is Huntington disease.
Dopaminergic agonist and dopamine like-drugs tend to exacerbate Huntington disease, but they
are useful drugs for the therapy of parkinsonism.
A, B) Cholinergic agonists tend to exacerbate parkinsonism which is instead alleviated by
antimuscarinic drugs.
C, E) (see explanation above)Rate this question:
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- 3.
The following table shows the relative intensities of blockade of CNS receptors of five new drugs, each of which may have potential therapeutic value. Which of the drugs is most likely to be useful in treating Parkinson’s disease?
- A.
Drug 1
- B.
Drug 2
- C.
Drug 3
- D.
Drug 4
- E.
Drug 5
Correct Answer
E. Drug 5Explanation
Answer: E
(Katzung, pp 454, Brunton, pp 537)
Drugs that block muscarinic receptors may improve tremor and rigidity of parkinsonism. In this
disease the loss of dopaminergic neurons results in the loss of balance that normally exists
between acetylcholine and dopamine mediated neurotransmission. It seems likely that the
antimuscarinic agents work by blocking the transmission of cholinergic striatal neurons, thereby
minimizing the effect of the relative increase in cholinergic sensitivity.
A, B) Dopaminergic blockade would exacerbate, not improve, the symptoms of parkinsonism.
C, D) Adrenergic and GABAergic blockade would have negligible effect on parkinsonism.Rate this question:
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- 4.
Which of the following statements best explains the mechanism of action of levodopa in the treatment of Parkinson’s disease?
- A.
Increased sensitivity of dopaminergic receptors in the striatum
- B.
Increased sensitivity of dopamine receptors in the substantia nigra
- C.
Increased availability of dopamine in the striatum
- D.
Inhibition of DOPA decarboxylase in the striatum
- E.
Inhibition of dopamine reuptake in the substantia nigra
Correct Answer
C. Increased availability of dopamine in the striatumExplanation
Answer: C
(Katzung, pp 448, Brunton, pp 533)
Dopamine cannot cross the blood brain barrier an therefore has no therapeutic effects on
parkinsonism if given into the peripheral circulation. However levodopa, the immediate
precursor of dopamine, is readily carried across the blood brain barrier by the neutral amino
acid transported. In the brain levodopa is biotransformed into dopamine and therefore the
availability of dopamine in the striatum increases.
A, B) Neither levodopa, nor dopamine can cause an increased sensitivity of dopaminergic
receptors.
D, E) These action would decrease, not increase, the availability of dopamine in basal ganglia.Rate this question:
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- 5.
Carbidopa is currently used in combination with levodopa in the treatment of Parkinson’s disease because it inhibits which of the following actions?
- A.
Dopamine metabolism in the striatum
- B.
Active transport of levodopa outside the brain
- C.
Conversion of dopamine into norepinephrine in the striatum
- D.
Peripheral biotransformation of levodopa
- E.
Dopamine reuptake in the striatum
Correct Answer
D. PeripHeral biotransformation of levodopaExplanation
Answer: D
(Katzung, pp 449, Brunton, pp 534)
Carbidopa is a DOPA decarboxylase inhibitor that cannot cross the blood brain barrier. When
levodopa is given in combination with carbidopa the peripheral metabolism of levodopa is
reduced, plasma levels of levodopa are higher and more levodopa is available to enter the
brain. Indeed concomitant administration of levodopa and carbidopa may reduce the daily
requirement of levodopa by about 75%.
A, B, C, E) All these actions are not inhibited by carbidopaRate this question:
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- 6.
Co-administration of which of the following drugs with levodopa / carbidopa will increase the availability of levodopa in the brain?
- A.
Amantadine
- B.
Entacapone
- C.
Methyldopa
- D.
Benztropine
- E.
Bromocriptine
- F.
Haloperidol
Correct Answer
B. EntacaponeExplanation
Answer: B
(Katzung, pp 453, Brunton, pp 536)
Entacapone belongs to the class of COMT inhibitors, a new class of drugs for parkinsonism.
These drugs are selective inhibitors of catechol-O-methyl-transferase (COMT), the enzyme that
converts levodopa into 3-O-methyl-DOPA, a pharmacologically inactive compound. The main
therapeutic action of entacapone is to block the peripheral conversion of levodopa into 3-omethyl-
dopa, so increasing both the plasma half life of levodopa as well as the fraction of each
doses that reaches the CNS.
A, C, D, E, F) These drugs are not COMT inhibitors.Rate this question:
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- 7.
Which of the following drugs is a selective monoamine oxidase B inhibitor used to reduce dopamine metabolism in Parkinson's disease?
- A.
Levodopa
- B.
Benztropine
- C.
Selegiline
- D.
Phenelzine
- E.
Bromocriptine
- F.
Entacapone
Correct Answer
C. SelegilineExplanation
Answer: C
(Katzung, pp 453, Brunton, pp 537)
Two isoenzymes of monoamine oxidase (MAO) metabolize monoamines. MAO A metabolizes
mainly norepinephrine and serotonin, MAO B metabolize mainly dopamine and is predominant
in the striatum. Selegiline is a selective inhibitor of MAO B leading to irreversible inhibition of
the enzyme, so retarding the breakdown of dopamine in the striatum. Since MAO B is mainly in
the brain selegiline does not inhibit the peripheral metabolism of dopamine and can be taken
safely with levodopa.
A, B, D, E, F) (see explanation above)Rate this question:
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- 8.
A 72-year-old man, who has been suffering from Parkinson’s disease for 4 years, complained of a purplish-red mottling of the skin which began on the thighs and spread to lower legs. The eruption appeared two weeks after a new drug was added to his therapeutic regimen. A diagnosis of livedo reticularis was made. Which of the following drugs could have caused this skin eruption?
- A.
Levodopa
- B.
Carbidopa
- C.
Selegiline
- D.
Amantadine
- E.
Bromocriptine
- F.
Benztropine
Correct Answer
D. AmantadineExplanation
Answer: D
(Katzung, pp 454, Koda-Kimble, pp 53-24)
Livedo reticularis can occur in up to 805 of patients taking amantadine and usually clears within
a month after drug withdrawal. The disorder is believe to be caused by local release of
catecholamines which causes vasoconstriction and alter the permeability of skin blood vessels.
A, B, C, E, F) These drugs do not cause livedo reticularis.Rate this question:
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- 9.
A 72-year-old man, suffering from Parkinson disease for 5 years, complains of a resting tremor, which at present is one of the most debilitating symptoms of his disease. He has gained improvement in rigidity, bradykinesia and posture as well as improvement in the ‘on-off’ effects with levodopa/carbidopa combination and benztropine, but he has experienced little if any improvement in tremor. Which of the following would be an appropriate therapeutic conduct for the reduction of the tremor in this patient?
- A.
To decrease the dose of carbidopa
- B.
To substitute levodopa/carbidopa with bromocriptine
- C.
To withdraw benztropine
- D.
To add propranolol to the present drug regimen
- E.
To start brief periods of ‘drug holidays‘ during therapy
Correct Answer
D. To add propranolol to the present drug regimenExplanation
Answer: D
(Katzung, pp 457, Koda-Kimble, pp 53-25)
Parkinsonian tremor is often less responsive to dopaminergic therapy than other symptoms.
Tremor can be worsened by peripheral factors such as catecholamine release often in
association with stress or anxiety. Propranolol improves parkinsonian tremor in about 50% of
patients and therefore a trial with propranolol can be appropriate for this patient.
A, B, C, E) All these procedures would not affect the tremor of the patient.Rate this question:
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- 10.
A 75-year-old diabetic man, suffering from Parkinson’s disease, complained of worsening of his tremor and rigidity in arms and legs. His Parkinson’s disease has been responding well to a treatment of levodopa/carbidopa and amantadine, and his diabetes has been controlled by chlorpropamide and metformin. Recently metoclopramide was prescribed to manage diabetic gastroparesis. Which of the following drugs could have triggered the worsening of the symptoms reported by the patient?
- A.
Chlorpropamide
- B.
Amantadine
- C.
Carbidopa
- D.
Metformin
- E.
Metoclopramide
Correct Answer
E. MetoclopramideExplanation
Answer: E
(Katzung, pp 1045, Koda-Kimble, pp 53-27)
The symptoms reported by the patient point out a worsening of his Parkinson’s disease
Metoclopramide, a prokinetic drug used to treat diabetic gastroparesis, can block D2 receptors
in the brain, so leading to a decreased levodopa effect.
A, B, C, D) (see explanation above)Rate this question:
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- 11.
A 66-year-old man with Parkinson’s disease has been taking levodopa/carbidopa but lately the therapy was sometimes ineffective in controlling his symptoms. His neurologist prescribed another drug, to take concurrently with levodopa/carbidopa, that should enhance and prolong the effects of levodopa. Which of the following drugs was most likely prescribed?
- A.
Propranolol
- B.
Selegiline
- C.
Benztropine
- D.
Haloperidol
- E.
Imipramine
- F.
Diazepam
Correct Answer
B. SelegilineExplanation
Answer: B
(Katzung, pp 453, Brunton, pp 537)
Selegiline is a selective inhibitor of MAO B that reduces the metabolism of dopamine. In this
way it enhances and prolongs the effects of levodopa and is therefore used as an adjunct to
levodopa in Parkinson’s disease.
A, C) These drugs are sometimes used in Parkinson’s disease, but they do not prolong
dopamine effects since they act on different receptors.
D, E, F) these drugs are not effective in Parkinson’s disease.Rate this question:
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- 12.
A 62-year-old woman with Parkinson’s disease complained of blurred vision, dry mouth, palpitations and constipation. She has been receiving a levodopa/carbidopa combination for 8 months but recently her neurologist added another drug to the therapeutic regimen. Which of the following drugs most likely caused the patient’s symptoms?
- A.
Benztropine
- B.
Selegiline
- C.
Bromocriptine
- D.
Amantadine
- E.
Pergolide
- F.
Entacapone
Correct Answer
A. BenztropineExplanation
Answer: A
(Katzung, pp 454, Brunton, pp 537)
The symptoms of the patient are typical adverse effects of antimuscarinic drugs. These drugs
(benztropine, trihexyphenidyl, etc.) are used adjunctively in parkinsonism since they may
improve tremor and rigidity.
B, C, D, E, F) All these drugs do not cause the set of symptoms reported by the patient.Rate this question:
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- 13.
A 77-year-old woman has been showing an increasing memory impairment and recognition deficits over the past 2 years. Recently she became disoriented and confused at night. Physical examination revealed an awake and oriented to place person with no focal neurological deficits. Her physician prescribed a drug which might help to slow the progression of her symptoms. Which of the following drugs was most likely prescribed?
- A.
Fluoxetine
- B.
Chlorpromazine
- C.
Donepezil
- D.
Amitriptyline
- E.
Trazodone
Correct Answer
C. DonepezilExplanation
Answer: C
(Katzung, pp 1011, Brunton, pp 539)
The woman is most likely in the early stages of Alzheimer’s disease. She displayed several
symptoms associated with dementia, including impaired reasoning (recognition deficits), loss of
memory, confusion and disorientation. A major approach to the treatment of Alzheimer’s
disease has involved the attempt to augment the cholinergic function in the brain, because a
loss of cholinergic neurons is prominent in this disease. Donepezil, tacrine, rivastigmine and
galantamine are cholinesterase inhibitors approved for treatment of AD. Donepezil selectively
inhibits cholinesterase in the CNS with less effect on cholinesterase in peripheral tissues.
A, B, D, E) (see explanation above)Rate this question:
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- 14.
A 65-year-old man presented to the hospital complaining of difficulty in writing, because of unsteadiness in his right hand, and tightness in his harms and legs. These symptoms started about one week ago. Physical examination showed a well-nourished, anxious male with a notable lack of normal changes in facial expression and with a soft, monotone voice. Tremor was present in his hands and a festinating gait was noted. A preliminary diagnosis was made and an appropriate treatment was prescribed. Which of the following drug was most likely prescribed?
- A.
Carbidopa
- B.
Entacapone
- C.
Benztropine
- D.
Pramipexole
- E.
Clonazepam
- F.
Propranolol
Correct Answer
D. PramipexoleExplanation
Answer: D
(Katzung, pp 452, Koda-kimble, pp 53-7)
The patients presents with symptoms and signs typical of Parkinson’s disease. The four classic
features of Parkinson’s disease, i.e tremor, rigidity (tightness in his harms and legs)
bradykinesia (lack of normal changes in facial expression) and postural instability (festinating
gait) are easily recognized. Pramipexole is a dopamine receptor agonist which is effective when
used as monotherapy for mild parkinsonism. Dopaminergic therapy of parkinsonism is usually
initiated with a dopamine agonist, since these drugs have a number of potential advantages
over levodopa, including a lower incidence of response fluctuations and dyskinesias.
A, B, C) These drugs are not currently used as monotherapy, but only in addition to levodopa
therapy.
E, F) These drugs are only used adjunctively to control symptoms that, in a particular patient,
are resistant to the conventional therapy, like tremor (propranolol) or myoclonus (clonazepam).Rate this question:
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- 15.
A 65-year-old man with Parkinson’s disease complained of periods of few minutes of complete immobility followed by a sudden switch to involuntary movements such as twitching, nodding, and jerking. The patient’s current medications included levodopacarbidopa. In order to reduce these rapid fluctuations the neurologist reduced the daily dose of levodopa-carbidopa and added another drug. Which of the following drugs was most likely prescribed?
- A.
Amantadine
- B.
Benztropine
- C.
Haloperidol
- D.
Bromocriptine
- E.
Fluoxetine
Correct Answer
D. BromocriptineExplanation
Answer: D
(Katzung, pp 452, Koda-Kimble, pp 53-16)
The patient is most likely suffering from the on-off phenomenon in which off periods of marked
akinesia alternate over the course of a few hours with on periods of improved mobility and
marked dyskinesia. These response fluctuations can be improved by adjunctive drugs which
include dopamine agonists like bromocriptine, COMT inhibitors and in some cases selegiline.
A, B, C, E ) These drugs are not useful to improve response fluctuations.Rate this question:
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- 16.
A 64-year-old woman with Parkinson’s disease complained that her tremor gradually worsened over the past two weeks. She has been receiving a levodopa-carbidopa combination for one years. The neurologist decided to add benztropine to the therapeutic regimen. Which of the following statement best explains why benztropine can alleviate the tremor of the patient?
- A.
The drug inhibits levodopa metabolism in the striatum
- B.
The drug inhibits the abnormally high cholinergic tone in the striatum
- C.
The drug activates dopaminergic receptors in the striatum
- D.
The drug blocks beta-2 receptors which mediate the tremor in the skeletal muscle
- E.
The drug activate a specific transport system that allows levodopa to enter the brain
Correct Answer
B. The drug inhibits the abnormally high cholinergic tone in the striatumExplanation
Answer: B
(Katzung, pp 454 , Brunton, pp 537)
In Parkinson’s disease the loss of dopaminergic neurons results in a loss of balance that
normally exists between acetylcholine and dopamine mediated neurotransmission
Antimuscarinic drugs, like benztropine, seem to act by blocking muscarinic receptors in the
striatum, so decreasing the abnormally high cholinergic tone, which results from lack of the
inhibitory activity of dopamine. These drugs may improve tremor and rigidity but have little
effect on bradykinesia.
A, C, D, E) Antimuscarinic drugs do not produce these effectsRate this question:
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- 17.
A 72-year-old man, recently diagnosed with Alzheimer’s disease, has been prescribed a drug which might help to slow the progression of her symptoms. Which of the following sets of adverse effects is most likely to occur from this treatment?
- A.
Hypertension, palpitations
- B.
Nausea, vomiting and diarrhea
- C.
Dry mouth, anhydrosis
- D.
Drowsiness, lethargy
- E.
Mydriasis, cycloplegia
Correct Answer
B. Nausea, vomiting and diarrheaExplanation
Answer: B
(Brunton, pp 539, Koda-Kimble pp.100-7)
The drugs most frequently used in Alzheimer’s disease are cholinesterase inhibitors like
donepezil, rivastigmine etc. Even if these drugs preferentially inhibit acetylcholinesterase in the
CNS, they can cause most of the adverse effects shared by all cholinergic drugs, which are due
to activation of cholinergic receptors. Effects affecting the gastrointestinal tract (nausea
vomiting and diarrhea) are the most common.
A, C, D, E) Actually these effects are caused by antimuscarinic drugs, not by cholinergic drugs.Rate this question:
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- 18.
A 57-year-old woman recently diagnosed with Parkinson’s disease has been receiving a levodopa- carbidopa combination for three weeks. Which of the following adverse effects is most likely to occur from this treatment?
- A.
Blurred vision
- B.
Diarrhea
- C.
Postural hypotension
- D.
Bradycardia
- E.
Bradykinesia
Correct Answer
C. Postural hypotensionExplanation
Answer: C
(Katzung, pp 241, Brunton, pp 169, 534)
Postural hypotension is the most common cardiovascular adverse effect of levodopa, especially
in the early stage of treatment. Levodopa is a prodrug and all its effects are due to dopamine.
Postural hypotension is most likely due both to the activation of e vasodilation D1 receptors in
the renal and mesenteric vascular bed, which leads to vasodilation and to the activation of D1
receptors in the proximal tubule which causes inhibition of tubular sodium reabsorption, so
increasing the diuresis.
A) Dopamine has negligible effects on accommodation, so blurred vision is unlikely.
B) Dopamine can activate alpha-1 receptors in the gastrointestinal system. Activation of these
receptors in the gastrointestinal smooth muscle cause hyperpolarization and relaxation, so
diarrhea is unlikely.
D) Dopamine can activate beta receptor in the heart, so causing tachycardia, not bradycardia.
E) Dopamine can cause dyskinesias, but bradykinesia is a classic symptoms of parkinsonism,
which is in fact alleviated, not caused by levodopa.Rate this question:
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- 19.
A 51-year-old woman presented to her doctor complaining of a unilateral rhythmic tremor, and slowing down of all movements. Her medical history was significant for two schizophrenic episodes in her late forties which had been treated with phenothiazines. On examination she showed cog wheel rigidity. A presumptive diagnosis of parkinsonism was made. Which one of the following drugs would be relatively contraindicated at the start of her therapy?
- A.
Amantadine
- B.
Benztropine
- C.
Bromocriptine
- D.
Entacapone
- E.
Entacapone
Correct Answer
C. BromocriptineExplanation
Answer: C
(Katzung, pp 453, Koda-Kimble, pp 78-3)
Dopaminergic drugs, like bromocriptine, levodopa, amphetamines, etc., are contraindicated, or
should be used with caution, in patients with a history of psychosis, since they constantly
exacerbate the symptoms of schizophrenic disorders.
A, B, D, E) These drugs are not contraindicated in patients with a history of psychosis.Rate this question:
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- 20.
A 67-year-old man with Parkinson’s disease complained that recently he felt increasingly confused at times, often had vivid dreams and on occasion experienced visual hallucinations. He has been receiving a levodopa-carbidopa combination for 1 years and his disease was well controlled. Which of the following actions could be implemented to reduce the occurrence of these adverse effect?
- A.
To substitute levodopa with selegiline
- B.
To substitute levodopa with bromocriptine
- C.
To add benztropine to the present regimen
- D.
To add amantadine to the present regimen
- E.
To add clozapine to the present regimen
Correct Answer
E. To add clozapine to the present regimenExplanation
Answer: E
(Katzung, pp 451, Koda-Kimble pp 53-18)
The symptoms of the patients are typical mental disturbances caused by levodopa and are
more common in patients taking the drug in combination with carbidopa, presumably because
higher levels are reached in the brain. Psychotic symptoms often respond to neuroleptic
treatment, but classical neuroleptics are not indicated since they may cause marked worsening
of parkinsonism, likely through the blockade of D2 receptors in the striatum. Atypical
neuroleptics like clozapine do not block D2 receptors, do not worsen parkinsonism and are
effective in the treatment of levodopa-induced Psychotic symptoms.
A) Selegiline has only a minor therapeutic effect on parkinsonism when given alone, and
therefore the substitution of levodopa with selegiline most likely would cause a worsening of the
disease.
B) Dopaminergic agonists like bromocriptine can cause mental disturbances very similar to
those caused by levodopa, likely because both adverse effects have the same underlaying
mechanism.
C, D) Actually mental disturbances can be exacerbated, not alleviated, by concurrent
anticholinergic or amantadine therapy.Rate this question:
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