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Which of these is not a disorder in which psychosis is defined?
Frage 2
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Schizophrenia:
~ [blank_start]1[blank_end] % of population, psychotic illness, mostly [blank_start]young[blank_end] people, [blank_start]chronic[blank_end] (regular/irregular psychotic episodes), lifelong and highly disabling.
Positive and negative symptoms:
- A positive symptom is one that [blank_start]adds[blank_end] a behavior, thought or feeling. Positive symptoms associated with schizophrenia also occur in other disorders such as [blank_start]bipolar[blank_end], psychotic depression, and [blank_start]Alzheimer[blank_end]'s. Positive symptoms are – [blank_start]delusions[blank_end] (paranoid), hallucinations, thought [blank_start]disordered[blank_end], other abnormal behaviors e.g. aggression.
- Negative symptoms [blank_start]take away[blank_end] a behavior, thought or feeling. Negative symptoms – flattened [blank_start]emotional[blank_end] response, social [blank_start]withdrawal[blank_end], apathy, anhedonia.
Cognitive symptoms:
- [blank_start]Executive dysfunction[blank_end] - poor methodical planning in brain makes basic tasks difficult
- Difficulty representing and maintaining [blank_start]goals[blank_end], allocating [blank_start]attention[blank_end], evaluating/monitoring performance
- Impaired [blank_start]verbal[blank_end] fluency
These are the best predictor of outcome.
Antworten
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1
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young
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chronic
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adds
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bipolar
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Alzheimer
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delusions
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disordered
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take away
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emotional
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withdrawal
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Executive dysfunction
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goals
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attention
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verbal
Frage 3
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Burden of illness
• 25-50% attempt suicide and [blank_start]10[blank_end]% eventually succeed
• Mortality rate 8 times higher than general population due to high rate of [blank_start]CV disease, suicide[blank_end] etc,
• Life expectancy [blank_start]25-30[blank_end] years shorter than the general population
• Patients - early onset, intellectual [blank_start]development[blank_end], relationships, risk of suicide, stigma, self treatment: [blank_start]drugs, alcohol and smoking[blank_end]
• Family/Care Giver - stressors, financial [blank_start]cost[blank_end], pressure on [blank_start]relationships[blank_end]
• Community – healthcare, economic, stigma
• Duration of [blank_start]untreated psychosis[blank_end] (DUP) has major impact on outcomes
Frage 4
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Early symptoms indicating the onset of schizophrenia:
• Worrisome drop in [blank_start]grades or job performance[blank_end]
• New trouble [blank_start]thinking clearly or concentrating[blank_end]
• Suspiciousness, [blank_start]paranoid[blank_end] ideas or uneasiness with others
• Withdrawing socially, spending a lot more time [blank_start]alone[blank_end] than usual
• Unusual, overly intense new [blank_start]ideas[blank_end], strange feelings or having [blank_start]no[blank_end] feelings at all
• Decline in [blank_start]self-care or personal hygiene[blank_end]
• Difficulty telling reality from fantasy
• Confused [blank_start]speech[blank_end] or trouble communicating
Antworten
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grades or job performance
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thinking clearly or concentrating
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paranoid
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alone
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no
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ideas
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self-care or personal hygiene
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speech
Frage 5
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Match the symptoms to the region:
Positive symptoms - [blank_start]mesolimbic pathway[blank_end]
Affective symptoms (anxiety, suicidality) - [blank_start]ventromedial prefrontal cortex[blank_end]
Aggressive symptoms - [blank_start]orbitofrontal cortex, amygdala[blank_end]
Cognitive symptoms - [blank_start]dorsolateral prefrontal cortex[blank_end]
Negative symptoms - [blank_start]mesocortical pathway, prefrontal cortex[blank_end]
Antworten
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mesolimbic pathway
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ventromedial prefrontal cortex
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orbitofrontal cortex, amygdala
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dorsolateral prefrontal cortex
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mesocortical pathway, prefrontal cortex
Frage 6
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Diagnosis
• Based on patient and often family [blank_start]interviews[blank_end] following presentation of first psychotic episode
• Clinical status/rating determined using psychiatric examination with [blank_start]Positive and Negative Symptom Score[blank_end] (PANSS) and Clinical Global Impression scales (CGI) - commonly use Diagnostics and Statistics Manual (DSM-V) or ICD-11
• Also use At Risk Mental State (ARMS) Brief Psychiatric Scale (BPS)
• [blank_start]Psychosis[blank_end] not otherwise specified often in patient notes due to [blank_start]stigma[blank_end] associated with the term schizophrenia
Frage 7
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Five dopaminergic pathways:
a) [blank_start]Nigrostriatal[blank_end] – controls motor function/movement
b) [blank_start]Mesolimbic[blank_end] - pleasurable sensations, euphoria & delusions/hallucinations (positive sypmtoms)
c) [blank_start]Mesocortical[blank_end] - mediates cognition and affect (and negative symptoms)
d) [blank_start]Tuberoinfundibular[blank_end] - prolactin secretion
e) there's another one he didn't tell us it's name i don't think it's important??
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Nigrostriatal
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Mesolimbic
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Mesocortical
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Tuberoinfundibular
Frage 8
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Schizophrenia - the [blank_start]Integrated[blank_end] Dopamine Hypothesis.
Majority of symptoms explained by dysregulation of dopaminergic pathways:
- [blank_start]High[blank_end] activity of mesolimbic pathway explains pos symptoms
- [blank_start]Low[blank_end] activity of mesocortical pathways explains cog, aff, neg symptoms
- [blank_start]Normal[blank_end] activity of nigrostriatal and tuberoinfundibular
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Integrated
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High
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Low
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Normal
Frage 9
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Order these drugs from lowest affinity for D2 Rs (low potency, to highest affinity for D2 Rs (high potency); low being 1 and high being 4.
1. [blank_start]Haloperidol[blank_end]
2. [blank_start]Prochlorperazine[blank_end]
3. [blank_start]Clozapine[blank_end]
4. [blank_start]Chlorpromazine[blank_end]
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Haloperidol
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Prochlorperazine
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Clozapine
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Chlorpromazine
Frage 10
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NMDA receptor hypofunction hypothesis:
There are NMDA receptors in the brain. NMDA receptors in the [blank_start]cortical brainstem[blank_end] have glutamate projections. A glutamate projection is a [blank_start]descending[blank_end] pathway that uses glutamate, an [blank_start]excitatory[blank_end] neurotransmitter. Schizophrenia may be caused by [blank_start]low[blank_end] activity in these glutamate projections.
When the glutamate projections are [blank_start]hypo[blank_end]-active, downstream [blank_start]inhibition[blank_end] of the mesolimbic DA pathway does [blank_start]not[blank_end] occur, meaning the [blank_start]mesolimbic[blank_end] DA pathway is [blank_start]hyperactive[blank_end]. This causes positive symptoms.
Also low [blank_start]activity[blank_end] of the excitatory NT glutamate means [blank_start]tonic excitation is lost[blank_end], and [blank_start]mesocortical[blank_end] DA pathways become [blank_start]hypoactive[blank_end]. This may cause the cognitive, negative, and affective symptoms.
TLDR; Low activity of [blank_start]NMDR receptors[blank_end] in the [blank_start]brainstem[blank_end] causes low activity of [blank_start]glutamate[blank_end] in connected pathways, causing high activity in the [blank_start]mesolimbic pathway[blank_end] and low activity in the [blank_start]mesocortical pathways[blank_end].
Antworten
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cortical brainstem
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descending
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excitatory
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low
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hypo
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inhibition
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not
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mesolimbic
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hyperactive
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activity
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tonic excitation is lost
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mesocortical
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hypoactive
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NMDR receptors
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brainstem
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glutamate
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mesolimbic pathway
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mesocortical pathways
Frage 11
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Therapy - Antipsychotics
• Note that DA [blank_start]agonists[blank_end] (e.g. methamphetamine) can produce behavioural phenomenon indistinguishable from acute schizophrenia, so this supports the dopamine [blank_start]overactivity[blank_end] hypothesis
• Nearly all antipsychotics are [blank_start]D2 antagonists[blank_end] but some also block [blank_start]5-HT2A[blank_end] to varying degrees
• Potency correlates with [blank_start]activity[blank_end] at D2 receptors - not but dose [blank_start]not[blank_end] correlate effectiveness.
• “Typicals” are [blank_start]less[blank_end] effective at treating [blank_start]negative[blank_end] symptoms vs “atypicals”
• Days/weeks/months to work suggests [blank_start]secondary[blank_end] effects e.g. [blank_start]↑ D2 receptors in limbic structures[blank_end]
Frage 12
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“Typical” antipsychotics – D2 antagonists - and how they affect the dopaminergic pathways:
1. Mesolimbic - reduces to [blank_start]normal[blank_end] activity, stopping positive symptoms and the [blank_start]pleasure/reward[blank_end] response.
2. Mesocortical - still low activity
3. Nigrostriatal - reduced to [blank_start]low[blank_end] activity, explains [blank_start]parkinsonian[blank_end] side effects
4. Tuberoinfundibular - [blank_start]reduced[blank_end] to low activity, explains elevated [blank_start]prolactin[blank_end]
Antworten
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normal
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pleasure/reward
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low
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parkinsonian
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reduced
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prolactin
Frage 13
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‘Typicals’ aka ‘First generation antipsychotic’ side effects:
- Extrapyramidal side effects – direct block of nigrostriatal DA receptors
• [blank_start]Dystonia[blank_end] - Muscle spasm within hours, can be fatal
• [blank_start]Akathisia[blank_end] - subjective tension & need to move, objective restlessness, distress
• Pseudo-Parkinsonism - [blank_start]rigidity, tremor, bradykinesia,[blank_end] gait disturbance
• Tardive Dyskinesia - [blank_start]abnormal involuntary[blank_end] movements, reversible?
- Dry [blank_start]mouth[blank_end], blurred [blank_start]vision[blank_end], constipation, weight [blank_start]gain[blank_end], sedative, [blank_start]QT[blank_end]-prolongation, dyscrasia’s, postural [blank_start]hypotension[blank_end], elevated prolactin
- Sexual [blank_start]dysfunction[blank_end] common with both typical and ‘atypicals’
Role in current treatment - history of [blank_start]good[blank_end] response, [blank_start]range[blank_end] of depots, good for [blank_start]acute[blank_end] management e.g. chlorpromazine, haloperidol, zuclopenthixol, fluphenazine.
Frage 14
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“Atypical” antipsychotics
• D2 antagonists AND [blank_start]5-HT2A antagonism[blank_end] - defining property of ‘atypicals’
• Critically, [blank_start]less[blank_end] likely to induce dystonia/akathisia/[blank_start]Parkinsonism[blank_end] in the antipsychotic naïve
• Reduced [blank_start]negative[blank_end] symptoms in contrast to the ‘typicals’- debatable?
• Perceived side effects [blank_start]less common[blank_end] with atypicals? e.g. olanzapine, risperidone etc.
• Metabolic syndrome - weight [blank_start]gain[blank_end], elevated [blank_start]lipids[blank_end], insulin [blank_start]resistance[blank_end], diabetes
• Less effect on prolactin - except [blank_start]risperidone[blank_end]
• ~ 30-50% of all patients are treatment-resistant to varying degrees and need [blank_start]clozapine[blank_end]
Antworten
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5-HT2A antagonism
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less
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Parkinsonism
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negative
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less common
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gain
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lipids
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resistance
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risperidone
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clozapine
Frage 15
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Antipsychotic antagonism of WHICH RECEPTORS is associated with weight gain?
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5-HT2c & H1
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5-HT2c & H2
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5-HT1a & H1
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5-HT1a & H2
Frage 16
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Antipsychotic M3 antagonism impairs:
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insulin regulation
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prolactin regulation
Frage 17
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Which of these drugs is MOST likely to cause hypotension?
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Chlorpromazine
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Haloperidol
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Quetiapine
Frage 18
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Which 2 drugs are the most sedating?
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Chlorpromazine, Clozapine
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Clozapine, Olanzapine
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Olanzapine, Zuclopenthixol
Frage 19
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Which 3 drugs are most likely to cause extra-pyrimidal SEs?
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Zuclopenthixol, Haloperidol, Chlorpromazine
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Chlorpromazine, Risperidone, Aripiprazole
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Aripiprazole, Zuclopenthixol, Haloperidol
Frage 20
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Treatment resistant schizophrenia
• Defined by - treatment with a minimum of [blank_start]2[blank_end] antipsychotics for at least [blank_start]6[blank_end] weeks at maximum [blank_start]tolerated[blank_end] dose
• Occurs in ~[blank_start]30[blank_end]% of patients with schizophrenia
• Clozapine induces remission in ~[blank_start]30-50[blank_end]% of patients with TRS, and is the only antipsychotic shown to decrease [blank_start]suicide & re-hospitalization[blank_end] rates, and increase rate of [blank_start]independent[blank_end] living
• Takes about 9 [blank_start]years[blank_end] on average post-first-psychotic-episode before used in NZ due to significant side effects - during this time patients typically have very poor quality of life
Frage 21
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Which of these is NOT a side effect of clozapine?
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Tachycardia
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Hypotension
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Seizures
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Constipation
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Weight gain
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Hypersalivation
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Nausea and vomiting
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Sedation
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Diarrhoea
Frage 22
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Clozapine monitoring:
- Verbal for [blank_start]constipation[blank_end] - toxic megacolon risk
- Blood monitoring for [blank_start]agranulocytosis[blank_end] (0.8% of patients, during the first year peaks at 8-10 weeks of Tx) and [blank_start]neutropenia[blank_end] (3-4%)
• Monitor [blank_start]weekly[blank_end] for the first 18 weeks, then every 2 weeks for the remainder of the year, then [blank_start]monthly[blank_end]
• 2.4 fold higher incidence in [blank_start]Asians[blank_end] versus caucasians with a 5% increase in risk/decade
• [blank_start]38[blank_end]% experience a further issue following re-challenge after neutropenia...
• NO re-challenge following [blank_start]agranulocytosis or myocarditis[blank_end]
Frage 23
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Clozapine Interactions
• Metabolised by CYP450 1A2 and less so by 2D6)
– levels decreased by high levels of [blank_start]caffeine, valproate, carbamazepine[blank_end], cigarette smoking
- levels increased by [blank_start]clarithromycin, rifampicin, erythromycin[blank_end], [blank_start]fluoxetine, paroxetine[blank_end]
• [blank_start]Benzodiazepines[blank_end] may increase sedation and respiratory depression
• [blank_start]Anticholinergics[blank_end] may increase constipation risk, pyrexia
• Evening [blank_start]primrose[blank_end] oil and [blank_start]tramadol[blank_end] may increase seizures
• [blank_start]Lithium[blank_end] may exacerbate ADRs
Antworten
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caffeine, valproate, carbamazepine
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clarithromycin, rifampicin, erythromycin
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fluoxetine, paroxetine
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Benzodiazepines
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Anticholinergics
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primrose
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tramadol
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Lithium