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Exam 1 Nurs 660
Maryville University Aaron Langford Psychopharmacology
146
Medical
Post-Graduate
06/07/2022

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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.
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.
Term
Hyperactivity of the D2 receptor in the subcortical and limbic regions of the brain contributes to what phenomenon related to schizophrenia?
Definition
Hallucinations and delusions
Term
What is the major excitatory neurotransmitter in the CNS?
Definition
Glutamate
Term
Schizophrenia typically begins with an excess, then ultimately a deficit in activity of this neurotransmitter:
Definition
Glutamate
Term
Hypofunction of which receptor can lead to psychotic symptoms?
Definition
NDMA N-methyl-D-asparte
Term
Which neurotransmitter is most associated with forming memories and helping us learn new things
Definition
?
Term
What is typically the finding with regards to serotonin in schizophrenic patients?
Definition
It's high
Term
In schizophrenic patients treaing the deregulation of 5-HT2 receptors can
Definition
improve the negative symptoms
Term
Describe "negative features" of schizophrenia
Definition
lack of pleasure, trouble with speech flattening of expressions
Term
Identify potential medical emergencies associated with antipsychotic medications and how to manage these emergencies.
Definition
Anticholinergic toxicity

Neuroleptic malignant syndrome

Seizrures

Sudden cardiac death

QRS prolongation
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
Term
List medications with which olanzapine has serious interactions
Definition
apomorphine
bomocriptine
cabergoline
dopamine
fluvoxamine
levodopa
lisuride
mefloquine
methyldopa
ondansetron
pefloxacin
pramipexole
ropinirole
sodium oxybate
umeclidinium bromide/vilanterol
vilanterol/fluticasone furoate
Term
Is olanzapine approved for the treatment of behavior disorders in older adults with dementia? why or why not?
Definition
No. It increases the risk of death during treatment as well as the chances of stroke and mini stroke.
Term
What labwork would you obtain before starting zyprexa?
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.
Term
What effect might paliperidone have on blood pressure?
Definition
It may lower it.
Term
What medication might increase a patient's risk of falling while on paliperidone?
Definition
Propranolol
Term
What migh paliperidone do to medications used to treat parkinsons disease?
Definition
It can block the effects of medications such as levodopa, bromocriptine, pramipexole, ropinirole and others.
Term
Taking antipsychotics like chlorpromazine (thorazine), thioridizine, iloperidone, asenapine, quetiapine and ziprasidone with paliperidone may increase the risk of what?
Definition
May increase the risk of heart problems
Term
Taking depakote with paliperidon may:
Definition
increase the levels and effects of paliperidone
Term
Which pathway projects from the substantia nigra to the basal ganglia or striatum?
Definition
The nigrostriatal dopamine pathway
Term
What part of the nervous system is the nigrostriatal dopamine pathway and what does it control?
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".
Term
Which dopamine pathway projects from the midbrain ventral tegmental area to the nucleus accumbens?
Definition
The mesolimbic dopamine pathway.
Term
What major part of the nervous system of the brain is the mesolimbic dopamine pathway a part of and what does it do?
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.
Term
Hyperactivity of dopamine neurons in the mesolimbic dopamine pathway theoretically:
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.
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
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:
Definition
The mesocortical dopamine pathway
Term
projects from the hypothalamus to theanterior pituitary gland and controls prolactin secretion into the circulation
Definition
The tuberoinfundibular dopamine pathway
Term
arises from multiple sites, including theperiaqueductal gray, ventral mesencephalon, hypothalamic nuclei, and lateralparabrachial nucleus, and it projects to the thalamus
Definition
he thalamic dopamine pathway
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.
Definition
thalamic dopamine pathway
Term
NMDA, AMPA and kainite are all receptors for ______. They are ______ receoptos.
Definition
Glutamate; ionotropic
Term
what happens after glutamate is released and attaches to receptor?
Definition
sodium channels open and depolarize the cell, glutamate flows in, then Gaba is released.
Term
Cortico-brainstem-descending projects from
Definition
cortical pyramidal neurons to brainstem NT centers including raphe for serotonin, VTA and substantia nigra for dopamine, ad locus coeruleus for NE.
Term
These excitatory cortico brainstem neurons stimulate NT release.
Definition
raphe for serotonin, VTA and substantia nigra for dopamine, ad locus coeruleus for NE
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
Term
These neurons terminate on GABA neurons.
Definition
Corticostriatal-descending from cortical pyramidal neurons to striatal complex.
Term
Hippocampal accumbens-projects from
Definition
hippocampus to NA - This path is linked to schizophrenia
Term
brings info from thalamus back to cortex to process sensory
info.
Definition
Thalamo-cortical pathways
Term
This glutamate pathway projects back to the thalamus
Definition
Corticothalamic
Term
one neuron inhibit another neuron via interneurons that release
GABA. This is known as:
Definition
Indirect cortico-cortico pathway
Term
ortico-cortical-glutamate pathways are where?
Definition
cortex
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)
Definition
Positive symptoms
Term
Positive symptoms arise from which pathway?
Definition
Mesolimbic dopamine pathway
Term
Positive symptoms of schizophrenia are hypothetically modulated by
Definition
malfunctioning mesolimbic circuits
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
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
Term
Poverty of speech; e.g., talks little, uses few words
Definition
Alogia
Term
Reduced range of emotions (perception,
experience and expression); e.g., feels numb or empty inside,
recalls few emotional experiences, good or bad
Definition
Affective blunting
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
Definition
Asociality
Term
Reduced ability to experience pleasure; e.g., finds
previous hobbies or interests unpleasurable
Definition
Anhedonia
Term
Reduced desire, motivation, persistence; e.g., reduced
ability to undertake and complete everyday tasks; may have poor
personal hygiene
Definition
Avolition
Term
are associated with the ventromedial prefrontal cortex.
Definition
Affective symptoms
Term
Depressed mood, Anxious mood, Guilt, Tension, Irritability, and Worry
Definition
Affective symptoms
Term
_______ are associated with problematic information
processing in the dorsolateral prefrontal cortex.
Definition
Cognitive symptoms
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
Term
list the DSM 5 criteria for schizophrenia
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
Term
cognitive symptoms of schizophrenia originate from:
Definition
Dorsolateral prefrontal cortex
Term
negative symptoms/reward circuits of schizophrenia originate from:
Definition
Nucleus accumbens
Term
aggressive symptoms of schizophrenia originate from:
Definition
Orbital frontal cortex
Term
motor function and movement symptoms of schizophrenia originate from:
Definition
Substantia nigra
Term
positive symptoms of schizophrenia originate from ____
Definition
Mesolimbic region of the brain
Term
affective symptoms of schizophrenia originate from:
Definition
Ventromedial prefrontal cortex
Term
Suicidal ideation of schizophrenia originates from:
Definition
VMPFC, amygdala
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
Definition
Negative symptoms
Term
________ area of the brain may also be involved in substance abuse (negative symptoms/reward circuits)
Definition
Nucleus accumbent
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
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
Term
This pathway also plays a role in motivation, pleasure, and reward.
Definition
The mesolimbic dopamine pathway
Term
Drugs that ________ dopamine will increase or produce positive symptoms of psychosis.
Definition
increase
Term
drugs that decrease dopamine -________ or _____ positive symptoms
Definition
Term
All antipsychotics that treat ________ symptoms of schizophrenia are blockers of the dopamine D2 receptor
Definition
positive
Term
stimulants such as cocaine/amphetamines: release _______, if taken repeatedly, can cause _________ that is hard to differentiate from ________ symptoms of schizophrenia.
Definition
dopamine; paranoid psychosis; positive
Term
it is believed that hyperactivity in the ________, mediates _____ symptoms of psychosis
Definition
mesolimbic pathway; positive
Term
IT IS NOT KNOWN what causes dopamine hyperactivity, but they think its consequence of dysfunction in ________ and hippocampal __________
Definition
prefrontal cortex; glutamate
Term
________ is the main neurotransmitter in schizophrenia
Definition
Dopamine
Term
There are four main dopamine receptors and all are ________ by some atypical antipsychotics
Definition
blocked
Term
The cortico-striatal glutamate pathway projects to the ______ terminate on GABA neurons
Definition
dorsal striatum
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
Definition
Cross-tapering
Term
________in general have more anticholinergic, antihistaminic, a1 blockade actions and are more sedating than the ______, which are less potent binding at these sites.
Definition
-Pines; -dones
Term
From -pine to -done -
Definition
Stop the -pine slowly, over two weeks allowing the patient to readapt to withdrawal of blocking cholinergic, histaminic, alpha 1 receptors
Term
From -done to -pine -
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.
Term
To and from aripiprazole - arip has a higher affinity/potency for _______. Its administration causes immediate withdraw of the first drug from the _______
Definition
D2 receptor;D2 receotor.
Term
Switching TO arip- from -pine
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.
Term
Slower titration of the -pine allows ________ of _____ and _____ receptors.
Definition
readaptation; cholinergic; histaminergic
Term
Switching TO arip- from -done
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
Term
Switching FROM arip-
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.
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
Definition
Clozapine
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.
Definition
antagonist; antagonist; atypical antipsychotics
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 _____.
Definition
Clozapine; prolactin
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.
Definition
antagonism; antagonism
Term
Clozapine may have a particular niche in treating _____ and ______ in psychotic patients.
Definition
aggression and violence
Term
Clozapine is also the antipsychotic associated with the greatest risk of developing a life-threatening and occasionally fatal complication called _________
Definition
agranulocytosis
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.
Definition
seizures; sedating; myocarditis; cardiometabolic
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
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
Term
Obtain trough plasma level when first initiating clozapine?
Definition
on 200 mg at bedtime
Term
The threshold for response is what for clozapine?
Definition
350 ng/mL
Term
Levels greater than _____ of clozapine are often not well tolerated
Definition
700 ng/mL
Term
No evidence to support dosing of clozapine that results in plasma levels greater than _____
Definition
1,000 ng/mL
Term
Doses greater than ______ of clozapine per day may require a split dose
Definition
500 mg
Term
When switching from one antipsychotic to another, it is frequently prudent to __________
Definition
cross-titrate
Term
What does it mean to cross titrate?
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.
Term
Switching from Oral Antipsychotics to Clozapine
• With aripiprazole, amisulpride, and paliperidone ER,:
Definition
immediate stop is possible; begin clozapine at middle dose
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
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
Term
Neuroscience-based Nomenclature: dopamine, serotonin, norepinephrine receptor antagonist (DSN-RAn). Atypical antipsychotic (serotonin- dopamine antagonist; second generation antipsychotic; also a mood stabilizer)
Definition
Risperidone
Term
serotonin- dopamine antagonist; second generation antipsychotic; also a mood stabilizer
Definition
Atypical antipsychotic risperidone
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
Term
Labs for olanzapie
Definition
Fasting triglycerides, plasma glucose, lipids and LFT for patients with liver
disease and CBC for patients with h/o drug-induced neutropenia.
Term
Starting dose for olanzapine
Definition
5-10mg PO daily
Term
Labs for all antipsychotic starts:
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.
Term
for which antipsychotic should you Add baseline and periodic EKG. Baseline serum K+ and magnesium levels.
Definition
Thioridazine
Term
for which antipsychotic should you patients with liver disease should have blood tests done a few times a
year
Definition
olanzapine
Term
Lower ANC threshold for starting clozapine: normal pop. >______/ul, _________ (BEN): >_____/ul.
Definition
1500; benign ethnic neutropenia; 1000
Term
________ is a type of restlessness due to dopamine deficiency in the ______ basal ganglia
Definition
Akathesia; basal ganglia
Term
________ is a feeling of muscle quivering, restlessness, and inability to sit still,
sometimes a side effect of antipsychotic or antidepressant medications
Definition
Akathesia
Term
______ ________ refers to late-appearing motor restlessness.
Manifestations may include repeated leg-crossing, weight-shifting, or stepping in
place (Up to date)
Definition
Tardive akathisia
Term
For akathisia, we suggest treatment with a ______ or a _____ _____ .
Definition
benzodiazepine; beta blocker
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 _______ _______.
Definition
Blockade; nigrostriatal ;up-regulation; tardive dyskinesia
Term
Chronic receptor activation leads to _______ and a given amount of drug will have _____ receptors to act on and therefore will produce _____ biological effect.
Definition
down-regulation; fewer; less
Term
increased receptor activation is chronically reduced
Definition
Compensatory up-regulation
Term
Dopamine is a _______ which is more broadly a ________.
Definition
catecholamine; monoamine
Term
Atypical antipsychotic blocks ____ and ______ receptors which then _______
dopamine release in the striatum therefore resulting in the elimination of EPS
Definition
D2; 5HT2A; INCREASES
Term
5HT2A receptor antagonism theoretically makes an antipsychotic _______
Definition
atypical
Term
_______ and dopamine have reciprocal roles in the regulation of _____ secretion
from the pituitary lactotroph cells
Definition
Serotonin; prolactin; pituitary lactotroph
Term
Dopamine ________ prolactin release via _______ D2 receptors
Definition
INHIBITS; stimulating
Term
Serotonin ________ prolactin release via _______ 5HT2A receptors – so serotonin
can no longer stimulate prolactin release
Definition
promotes; stimulating
Term
This ______ the _____ of d2 receptor blockade
Definition
mitigates; hyperprolactinemia
Term
_____ receptor antagonism theoretically makes an antipsychotic atypical
Definition
5HT2A
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
Definition
decrease
Term
______ receptors are postsynaptic and regulate both dopamine and _______release
Definition
5HT2C; norepinephrine
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
Definition
antagonist
Term
________ are postsynaptic and regulate both dopamine and norepinephrine release.
Definition
5HT2c
Term
Stimulation of ________receptors suppresses more dopamine from the mesolimbic than
nigrostriatal pathways.
Definition
5HT2C
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
Term
Regulate ion flow and neuronal depolarization that can lead to NMDA receptor activation
Definition
AMPA
Term
Many modulators of AMPA are under development including those that do not act
directly at the ______ site of the AMPA receptor
Definition
glutamate
Term
Members of the ligand-gated ion channel family of receptors\Mediate fast, excitatory neurotransmission, allowing Na to enter neuron to depolarize it
Definition
AMPA
Term
Metabotropic glutamate receptors (linked to G proteins) can occur either ____ OR ________
Definition
Pre- or post-synatically
Term
____ and _____ receptors may mediate fast, excitatory neurotransmission, allowing sodium to enter the neuron to depolarize it.
Definition
AMPA and kainate
Term
NMDA receptors in the resting state are normally blocked by ______, which plugs a _____ ______.
Definition
magnesium; calcium channel
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
glutamate
Term
Sustained binding of the agonist glutamate will lead to receptor desensitization, causing the channel to close and be transiently unresponsive to _______.
Definition
agonist
Term
AMPA receptor with its sodium channel in the resting state, allowing minimal ________ to enter the cell in exchange for ______.
Definition
sodium; potassium
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
Term
Intersept study suggests that patients with schizophrenia be treated with clozapine for _____ behavior
Definition
agressive
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