Term
Describe the typical brain imaging in schizophrenia |
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Definition
Shows cerebral atrophy/elarged fluid filled ventricles/shrinkag of prefrontal cortex, temporal, basal ganglia and limbic regions like the hippocammpus. |
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Term
Describe the typical brain imaging in schizophrenia |
|
Definition
Shows cerebral atrophy/elarged fluid filled ventricles/shrinkag of prefrontal cortex, temporal, basal ganglia and limbic regions like the hippocammpus. |
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Term
Hyperactivity of the D2 receptor in the subcortical and limbic regions of the brain contributes to what phenomenon related to schizophrenia? |
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Definition
Hallucinations and delusions |
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Term
What is the major excitatory neurotransmitter in the CNS? |
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Definition
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Term
Schizophrenia typically begins with an excess, then ultimately a deficit in activity of this neurotransmitter: |
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Definition
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Term
Hypofunction of which receptor can lead to psychotic symptoms? |
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Definition
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Term
Which neurotransmitter is most associated with forming memories and helping us learn new things |
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Definition
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Term
What is typically the finding with regards to serotonin in schizophrenic patients? |
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Definition
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Term
In schizophrenic patients treaing the deregulation of 5-HT2 receptors can |
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Definition
improve the negative symptoms |
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Term
Describe "negative features" of schizophrenia |
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Definition
lack of pleasure, trouble with speech flattening of expressions |
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Term
Identify potential medical emergencies associated with antipsychotic medications and how to manage these emergencies. |
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Definition
Anticholinergic toxicity
Neuroleptic malignant syndrome
Seizrures
Sudden cardiac death
QRS prolongation |
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Term
What are the side effects of zyprexa? |
|
Definition
Dizziness, restlessness, depression, unusual behavior, depression, difficulty staying asleep or falling asleep, weakness, difficulty walking, constipation, weight gain, dry mouth, pain in arms, legs, back or joints, breast enlargement or discharge, late or missed periods, decreased sexual ability |
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Term
List medications with which olanzapine has serious interactions |
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Definition
apomorphine bomocriptine cabergoline dopamine fluvoxamine levodopa lisuride mefloquine methyldopa ondansetron pefloxacin pramipexole ropinirole sodium oxybate umeclidinium bromide/vilanterol vilanterol/fluticasone furoate |
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Term
Is olanzapine approved for the treatment of behavior disorders in older adults with dementia? why or why not? |
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Definition
No. It increases the risk of death during treatment as well as the chances of stroke and mini stroke. |
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Term
What labwork would you obtain before starting zyprexa? |
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Definition
Fasting plasma glucose, Hgb aqc, fasting lipid panel monthly for the 1st 3 months of taking medication then every 3 months thereafter unless otherwise indicated. |
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Term
What effect might paliperidone have on blood pressure? |
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Definition
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Term
What medication might increase a patient's risk of falling while on paliperidone? |
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Definition
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Term
What migh paliperidone do to medications used to treat parkinsons disease? |
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Definition
It can block the effects of medications such as levodopa, bromocriptine, pramipexole, ropinirole and others. |
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Term
Taking antipsychotics like chlorpromazine (thorazine), thioridizine, iloperidone, asenapine, quetiapine and ziprasidone with paliperidone may increase the risk of what? |
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Definition
May increase the risk of heart problems |
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Term
Taking depakote with paliperidon may: |
|
Definition
increase the levels and effects of paliperidone |
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Term
Which pathway projects from the substantia nigra to the basal ganglia or striatum? |
|
Definition
The nigrostriatal dopamine pathway |
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Term
What part of the nervous system is the nigrostriatal dopamine pathway and what does it control? |
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Definition
It's part of the etrapyramidal nervous system and controls motor function and movement. This is one reason when dopamine is deficient, it can cause parkinsonism like tremor, rigidity, and akinesia/bradykenisias. In untreated schizophrenia, activation of this pathway is considered to be "normal". |
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Term
Which dopamine pathway projects from the midbrain ventral tegmental area to the nucleus accumbens? |
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Definition
The mesolimbic dopamine pathway. |
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Term
What major part of the nervous system of the brain is the mesolimbic dopamine pathway a part of and what does it do? |
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Definition
Believed to be involved in many behaviors such as pleasurable sensations the powerful euphoria of drugs of abuse, as well as delusions and hallucinations of psychosis. |
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Term
Hyperactivity of dopamine neurons in the mesolimbic dopamine pathway theoretically: |
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Definition
mediates the positive symptoms of psychosis such as delusions and hallucinations. This pathway is also involved in pleasure, reward, and reinforcing behavior, and many drugs of abuse interact here. |
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Term
projects from the midbrain ventral tegmental area and sends axons to the prefrontal cortex, where they may have a |
|
Definition
role inmediating cognitive symptoms (dorsolateral prefrontal cortex, DLPFC) and affectivesymptoms (ventromedial prefrontal cortex, VMPFC) of schizophrenia |
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Term
Expression of cognitive symptoms (dorsolateral prefrontal cortex, DLPFC) and affectivesymptoms (ventromedial prefrontal cortex, VMPFC) of schizophrenia are thought to originate in this dopamine pathway: |
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Definition
The mesocortical dopamine pathway |
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Term
projects from the hypothalamus to theanterior pituitary gland and controls prolactin secretion into the circulation |
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Definition
The tuberoinfundibular dopamine pathway |
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Term
arises from multiple sites, including theperiaqueductal gray, ventral mesencephalon, hypothalamic nuclei, and lateralparabrachial nucleus, and it projects to the thalamus |
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Definition
he thalamic dopamine pathway |
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Term
Its function is not currently wellknown but may be involved in sleep and arousal mechanisms by gating information 2passing through the thalamus to the cortex and other brain areas. There is no evidence atthis point for abnormal functioning of this dopamine pathway in schizophrenia. |
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Definition
thalamic dopamine pathway |
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Term
NMDA, AMPA and kainite are all receptors for ______. They are ______ receoptos. |
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Definition
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Term
what happens after glutamate is released and attaches to receptor? |
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Definition
sodium channels open and depolarize the cell, glutamate flows in, then Gaba is released. |
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Term
Cortico-brainstem-descending projects from |
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Definition
cortical pyramidal neurons to brainstem NT centers including raphe for serotonin, VTA and substantia nigra for dopamine, ad locus coeruleus for NE. |
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Term
These excitatory cortico brainstem neurons stimulate NT release. |
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Definition
raphe for serotonin, VTA and substantia nigra for dopamine, ad locus coeruleus for NE |
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Term
raphe for serotonin, VTA and substantia nigra for dopamine, ad locus coeruleus for NE are: |
|
Definition
excitatory cortico brainstem neurons that stimulate NT release |
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Term
These neurons terminate on GABA neurons. |
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Definition
Corticostriatal-descending from cortical pyramidal neurons to striatal complex. |
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Term
Hippocampal accumbens-projects from |
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Definition
hippocampus to NA - This path is linked to schizophrenia |
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Term
brings info from thalamus back to cortex to process sensory info. |
|
Definition
Thalamo-cortical pathways |
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Term
This glutamate pathway projects back to the thalamus |
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Definition
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Term
one neuron inhibit another neuron via interneurons that release GABA. This is known as: |
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Definition
Indirect cortico-cortico pathway |
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Term
ortico-cortical-glutamate pathways are where? |
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Definition
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|
Term
People with these types of schizophrenic symptoms may lose touch with some aspects of reality. Symptoms: delusions, hallucinations, thought disorders (unusual or dysfunctional ways of thinking), movement disorder (agitated body movements) (Arising from the mesolimbic dopamine pathway) |
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Definition
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|
Term
Positive symptoms arise from which pathway? |
|
Definition
Mesolimbic dopamine pathway |
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Term
Positive symptoms of schizophrenia are hypothetically modulated by |
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Definition
malfunctioning mesolimbic circuits |
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Term
Delusions, Hallucinations, Distortions or exaggerations in language and communication, Disorganized speech, Disorganized behavior, Catatonic behavior, and Agitation commonly describe what? |
|
Definition
positive schizophrenia symptoms |
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Term
disruptions to normal emotions and behaviors. Characterized by: flat affect, reduced feelings of pleasure in everyday life, difficulty beginning and sustaining activities, decreased communication. (Arising from the mesocortical dopamine pathway) What does this describe? |
|
Definition
Negative schizophrenia symptoms |
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|
Term
Poverty of speech; e.g., talks little, uses few words |
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Definition
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|
Term
Reduced range of emotions (perception, experience and expression); e.g., feels numb or empty inside, recalls few emotional experiences, good or bad |
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Definition
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|
Term
Reduced social drive and interaction; e.g., little sexual interest, few friends, little interest in spending time with (or little time spent with) friends |
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Definition
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|
Term
Reduced ability to experience pleasure; e.g., finds previous hobbies or interests unpleasurable |
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Definition
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|
Term
Reduced desire, motivation, persistence; e.g., reduced ability to undertake and complete everyday tasks; may have poor personal hygiene |
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Definition
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|
Term
are associated with the ventromedial prefrontal cortex. |
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Definition
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Term
Depressed mood, Anxious mood, Guilt, Tension, Irritability, and Worry |
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Definition
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|
Term
_______ are associated with problematic information processing in the dorsolateral prefrontal cortex. |
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Definition
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|
Term
Problems representing and maintaining goals, Problems allocating attentional resources, Problems focusing and sustaining attention , Problems evaluating functions , Problems modulating behavior based upon social cues, Problems monitoring performance , Problems prioritizing , Problems with serial learning, Impaired verbal fluency, and Difficulty with problem solving |
|
Definition
Cognitive symptoms of schizophrenia |
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|
Term
list the DSM 5 criteria for schizophrenia |
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Definition
DSM five: two of the following during one month (one must be 1-3) delusions hallucinations disorganized speech grossly disorganized or catatonic behavior negative symptoms |
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|
Term
cognitive symptoms of schizophrenia originate from: |
|
Definition
Dorsolateral prefrontal cortex |
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|
Term
negative symptoms/reward circuits of schizophrenia originate from: |
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Definition
|
|
Term
aggressive symptoms of schizophrenia originate from: |
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Definition
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|
Term
motor function and movement symptoms of schizophrenia originate from: |
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Definition
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|
Term
positive symptoms of schizophrenia originate from ____ |
|
Definition
Mesolimbic region of the brain |
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|
Term
affective symptoms of schizophrenia originate from: |
|
Definition
Ventromedial prefrontal cortex |
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|
Term
Suicidal ideation of schizophrenia originates from: |
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Definition
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|
Term
________ can also be linked to mesolimbic system which involves the nucleus accumbens which is part of the brain's reward circuitry and plays a role in motivation |
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Definition
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|
Term
________ area of the brain may also be involved in substance abuse (negative symptoms/reward circuits) |
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Definition
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|
Term
projects from dopaminergic cell bodies in the ventral tegmental area of the brainstem to axon terminals in one of the limbic areas of the brain, mainly the nucleus accumbens located in the ventral striatum. |
|
Definition
The mesolimbic dopamine pathway |
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|
Term
This pathway is said to have an important functional role in many emotional behaviors (positive symptoms of psychosis - delusions & hallucinations). |
|
Definition
The mesolimbic dopamine pathway |
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|
Term
This pathway also plays a role in motivation, pleasure, and reward. |
|
Definition
The mesolimbic dopamine pathway |
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Term
Drugs that ________ dopamine will increase or produce positive symptoms of psychosis. |
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Definition
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|
Term
drugs that decrease dopamine -________ or _____ positive symptoms |
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Definition
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Term
All antipsychotics that treat ________ symptoms of schizophrenia are blockers of the dopamine D2 receptor |
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Definition
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Term
stimulants such as cocaine/amphetamines: release _______, if taken repeatedly, can cause _________ that is hard to differentiate from ________ symptoms of schizophrenia. |
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Definition
dopamine; paranoid psychosis; positive |
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Term
it is believed that hyperactivity in the ________, mediates _____ symptoms of psychosis |
|
Definition
mesolimbic pathway; positive |
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Term
IT IS NOT KNOWN what causes dopamine hyperactivity, but they think its consequence of dysfunction in ________ and hippocampal __________ |
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Definition
prefrontal cortex; glutamate |
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Term
________ is the main neurotransmitter in schizophrenia |
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Definition
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|
Term
There are four main dopamine receptors and all are ________ by some atypical antipsychotics |
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Definition
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Term
The cortico-striatal glutamate pathway projects to the ______ terminate on GABA neurons |
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Definition
|
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Term
________ is the name for Gradually reducing the dose of the first drug (antipsychotic or antidepressant) while starting the second antipsychotic/antidepressant at a low dose and then increasing this dose as the first drug is withdrawn |
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Definition
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Term
________in general have more anticholinergic, antihistaminic, a1 blockade actions and are more sedating than the ______, which are less potent binding at these sites. |
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Definition
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Term
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Definition
Stop the -pine slowly, over two weeks allowing the patient to readapt to withdrawal of blocking cholinergic, histaminic, alpha 1 receptors |
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Term
|
Definition
titrate the -pine up over two weeks or more, the -done can usually be stopped as quickly as over 1 week. This allows the patient to become tolerant to sedating effects of the -pines. |
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Term
To and from aripiprazole - arip has a higher affinity/potency for _______. Its administration causes immediate withdraw of the first drug from the _______ |
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Definition
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|
Term
Switching TO arip- from -pine |
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Definition
start a middle dose building up rapidly over 3-7 days while taper the pine over two weeks. Fast titration because arip- replace the first drug at D2 receptors immediately. |
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Term
Slower titration of the -pine allows ________ of _____ and _____ receptors. |
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Definition
readaptation; cholinergic; histaminergic |
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Term
Switching TO arip- from -done |
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Definition
start middle dose, build rapidly over 3-7 days. Taper done over 1 week since -dones are less likely to be associated with anticholinergic and antihistamine withdrawal |
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Term
|
Definition
stop immediately, due to long half life and strong affinity of D2. Starting a middle, not low doses, of -pines/-dones tapering up 2/1 week respectively. |
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Term
This drug is considered the most effective antipsychotic. However, it is never a first line choice because it can cause the fatal side-effect of agranulocytosis |
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Definition
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|
Term
Clozapine, a serotonin 5HT2A–dopamine D2 __________ or serotonin-dopamine _________ is considered to be the “prototypical” ________, and has one of the most complex pharmacologic profiles of any of the atypical antipsychotics. |
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Definition
antagonist; antagonist; atypical antipsychotics |
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Term
_______was the first antipsychotic to be recognized as “atypical” and thus to cause few if any extrapyramidal side effects, not to cause tardive dyskinesia, and not to elevate _____. |
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Definition
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Term
atypical properties of clozapine were linked particularly to the presence of serotonin 5HT2A _______ added to the dopamine D2 ________ of conventional antipsychotics, and this has become the prototypical binding characteristic of the entire class of atypical antipsychotics. |
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Definition
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Term
Clozapine may have a particular niche in treating _____ and ______ in psychotic patients. |
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Definition
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Term
Clozapine is also the antipsychotic associated with the greatest risk of developing a life-threatening and occasionally fatal complication called _________ |
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Definition
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Term
Clozapine also has an increased risk of _______, especially at high doses. It can be very ________, can cause excessive salivation, has an increased risk of ______ and is associated with the greatest degree of weight gain and possibly the greatest _______risk among the antipsychotics. |
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Definition
seizures; sedating; myocarditis; cardiometabolic |
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Term
Thus, clozapine may have the greatest efficacy but also the most side effects among the atypical antipsychotics. Because of these side-effect risks, clozapine is not considered to be the first-line treatment but is used when other antipsychotics fail. |
|
Definition
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|
Term
starting dose and duration for clozapine? |
|
Definition
Initial 25 mg at night; increase by 25–50 mg/day every 48–72 hours as tolerated |
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Term
Obtain trough plasma level when first initiating clozapine? |
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Definition
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|
Term
The threshold for response is what for clozapine? |
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Definition
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|
Term
Levels greater than _____ of clozapine are often not well tolerated |
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Definition
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Term
No evidence to support dosing of clozapine that results in plasma levels greater than _____ |
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Definition
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|
Term
Doses greater than ______ of clozapine per day may require a split dose |
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Definition
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|
Term
When switching from one antipsychotic to another, it is frequently prudent to __________ |
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Definition
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|
Term
What does it mean to cross titrate? |
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Definition
to build down the dose of the first drug while building up the dose of the other over a few days to a few weeks. This leads to transient administration of two drugs but is justified in order to reduce side effects and the risk of rebound symptoms and to accelerate the successful transition to the new medication. |
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Term
Switching from Oral Antipsychotics to Clozapine • With aripiprazole, amisulpride, and paliperidone ER,: |
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Definition
immediate stop is possible; begin clozapine at middle dose |
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Term
Switching from Oral Antipsychotics to Clozapine • With risperidone, ziprasidone, iloperidone, and lurasidone: |
|
Definition
begin clozapine gradually, titrating over at least 2 weeks to allow patients to become tolerant to the sedating effect |
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Term
Switching from Oral Antipsychotics to Clozapine -Benzodiazepine or anticholinergic medication can be administered during cross-titration to help alleviate side effects such as _____ _____ and/or _____ . However, use with caution in combination with clozapine |
|
Definition
insomnia, agitation, and/or psychosis |
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Term
Neuroscience-based Nomenclature: dopamine, serotonin, norepinephrine receptor antagonist (DSN-RAn). Atypical antipsychotic (serotonin- dopamine antagonist; second generation antipsychotic; also a mood stabilizer) |
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Definition
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|
Term
serotonin- dopamine antagonist; second generation antipsychotic; also a mood stabilizer |
|
Definition
Atypical antipsychotic risperidone |
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|
Term
Major s/e of risperidone: |
|
Definition
✽May increase risk for diabetes and dyslipidemia Dose-dependent extrapyramidal symptoms ✽ Dose-related hyperprolactinemia 10 ✽ Dose-dependent dizziness, insomnia, anxiety, sedation Nausea, constipation, abdominal pain, weight gain Tachycardia, dose-dependent sexual dysfunction Rare tardive dyskinesia (much-reduced risk compared to conventional antipsychotics) Rare orthostatic hypotension, usually during initial dose titration |
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Term
|
Definition
Fasting triglycerides, plasma glucose, lipids and LFT for patients with liver disease and CBC for patients with h/o drug-induced neutropenia. |
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Term
Starting dose for olanzapine |
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Definition
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|
Term
Labs for all antipsychotic starts: |
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Definition
Baseline and monitor weight gain, monitor and baseline for diabetes, dyslipidemia, BP in elderly, monitor prolactin levels, CBC to monitor WBC in patients with low WBC count or hx of drug induced leukopenia/neutropenia. BMI monthly for 3 months then quarterly; BP, fasting plasma glucose, and fasting lipids in first 3 months then annually, but earlier and more frequently for patients with diabetes and who have gained >5% of initial weight. |
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Term
for which antipsychotic should you Add baseline and periodic EKG. Baseline serum K+ and magnesium levels. |
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Definition
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|
Term
for which antipsychotic should you patients with liver disease should have blood tests done a few times a year |
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Definition
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|
Term
Lower ANC threshold for starting clozapine: normal pop. >______/ul, _________ (BEN): >_____/ul. |
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Definition
1500; benign ethnic neutropenia; 1000 |
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Term
________ is a type of restlessness due to dopamine deficiency in the ______ basal ganglia |
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Definition
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|
Term
________ is a feeling of muscle quivering, restlessness, and inability to sit still, sometimes a side effect of antipsychotic or antidepressant medications |
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Definition
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|
Term
______ ________ refers to late-appearing motor restlessness. Manifestations may include repeated leg-crossing, weight-shifting, or stepping in place (Up to date) |
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Definition
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Term
For akathisia, we suggest treatment with a ______ or a _____ _____ . |
|
Definition
benzodiazepine; beta blocker |
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Term
Long-term ______ of D2 receptors in the _______ dopamine pathway can cause _______ of those receptors, which may lead to a hyperkinetic motor condition known as _______ _______. |
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Definition
Blockade; nigrostriatal ;up-regulation; tardive dyskinesia |
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Term
Chronic receptor activation leads to _______ and a given amount of drug will have _____ receptors to act on and therefore will produce _____ biological effect. |
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Definition
down-regulation; fewer; less |
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|
Term
increased receptor activation is chronically reduced |
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Definition
Compensatory up-regulation |
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Term
Dopamine is a _______ which is more broadly a ________. |
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Definition
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Term
Atypical antipsychotic blocks ____ and ______ receptors which then _______ dopamine release in the striatum therefore resulting in the elimination of EPS |
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Definition
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|
Term
5HT2A receptor antagonism theoretically makes an antipsychotic _______ |
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Definition
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|
Term
_______ and dopamine have reciprocal roles in the regulation of _____ secretion from the pituitary lactotroph cells |
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Definition
Serotonin; prolactin; pituitary lactotroph |
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Term
Dopamine ________ prolactin release via _______ D2 receptors |
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Definition
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|
Term
Serotonin ________ prolactin release via _______ 5HT2A receptors – so serotonin can no longer stimulate prolactin release |
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Definition
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|
Term
This ______ the _____ of d2 receptor blockade |
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Definition
mitigates; hyperprolactinemia |
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Term
_____ receptor antagonism theoretically makes an antipsychotic atypical |
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Definition
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|
Term
Conventional antipsychotics only _______ dopamine at D2 receptors throughout the brain while atypical with their additional 5HT2A ______ properties have much more complicated net actions on dopamine activity |
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Definition
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|
Term
______ receptors are postsynaptic and regulate both dopamine and _______release |
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Definition
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Term
Fluoxetine is not only a well-known SSRI, but also has potent 5HT2C antagonist properties that may not only contribute to its antidepressant effects as monotherapy, but also add to the 5HT2C ______actions of olanzapine when given together |
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Definition
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Term
________ are postsynaptic and regulate both dopamine and norepinephrine release. |
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Definition
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Term
Stimulation of ________receptors suppresses more dopamine from the mesolimbic than nigrostriatal pathways. |
|
Definition
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|
Term
______ receptors are one of the glutamate receptor subtypes coupled to ion channels that modulate _____ ________ by gating the flow of calcium and sodium ions into the cell |
|
Definition
AMPA receptors are one of the glutamate receptor subtypes coupled to ion channels that modulate cell excitability by gating the flow of calcium and sodium ions into the cell |
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Term
Regulate ion flow and neuronal depolarization that can lead to NMDA receptor activation |
|
Definition
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|
Term
Many modulators of AMPA are under development including those that do not act directly at the ______ site of the AMPA receptor |
|
Definition
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|
Term
Members of the ligand-gated ion channel family of receptors\Mediate fast, excitatory neurotransmission, allowing Na to enter neuron to depolarize it |
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Definition
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|
Term
Metabotropic glutamate receptors (linked to G proteins) can occur either ____ OR ________ |
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Definition
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Term
____ and _____ receptors may mediate fast, excitatory neurotransmission, allowing sodium to enter the neuron to depolarize it. |
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Definition
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|
Term
NMDA receptors in the resting state are normally blocked by ______, which plugs a _____ ______. |
|
Definition
magnesium; calcium channel |
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Term
AMPA and kainate receptors require only ______ to bind in order for the channel to open. This leads to fast excitatory neurotransmission and membrane depolarization. |
|
Definition
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|
Term
Sustained binding of the agonist glutamate will lead to receptor desensitization, causing the channel to close and be transiently unresponsive to _______. |
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Definition
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|
Term
AMPA receptor with its sodium channel in the resting state, allowing minimal ________ to enter the cell in exchange for ______. |
|
Definition
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Term
Depolarization of the membrane removes _______ from the calcium ion channel. This, coupled with _______ binding to the NMDA receptor in the presence of _______, causes the NMDA receptor to open and allow ________ influx. This influx through NMDA receptors contributes to long-term potentiation, a phenomenon that may be involved in long-term learning, synaptogenes, and other neuronal functions. |
|
Definition
magnesium; glutamate; glycine; calcium |
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Term
Intersept study suggests that patients with schizophrenia be treated with clozapine for _____ behavior |
|
Definition
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