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Psychopharmacology > Psychosis/Psychotic Disorders > Flashcards

Psychosis/Psychotic Disorders Flashcards

1
Q

Disorders requiring psychosis as defining feature

A

Schizophrenia, substance-induced psychotic disorder, schizophreniform dis., schizoaffective dis., delusional dis., brief psychotic dis., psychotic disorder due to medical condition.

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2
Q

Disorders in which psychosis is associated feature but not required for diagnosis

A

Mania, depression, cognitive disorders including Alzheimer’s.

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3
Q

Perceptual distortions

A

Hallucinations (distressing) - threatening voices, disturbing visions, hallucinations of touch/taste/smell, changes in familiar people or things.

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4
Q

Motor disturbances

A

Peculiar/rigid postures, overt tension, inappropriate expressions, repetitive gestures, talking/muttering to self, glancing around (hearing voices).

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5
Q

Paranoid psychosis

A

Paranoid projections, hostile belligerence and grandiose expansiveness.

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6
Q

Paranoid projection

A

Preoccupation with delusions, belief that others are talking about oneself, belief that one is being persecuted or conspired against and believing external forces control actions.

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7
Q

Hostile belligerence

A

Verbal expression of feelings of hostility, expressions of disdain, hostile/sullen attitude, irritability/grouchiness, tendency to blame others, feelings of resentment, complaining and being suspicious of others.

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8
Q

Grandiose expansiveness

A

Exhibiting an attitude of superiority, hearing voices that praise/extol, belief in unusual powers or fame, or belief in divine mission.

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9
Q

Disorganized/excited psychosis

A

Conceptual disorganization, disorientation, and excitement.

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10
Q

Conceptual disorganization

A

Giving answers that are irrelevant or incoherent, drifting off subject, using neologisms or repeating words/phrases.

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11
Q

Disorientation

A

Not knowing where one is, season/year/age/etc.

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12
Q

Excitement

A

Expressing feelings without restraint, hurried speech, elevated mood, attitude of superiority, dramatizing oneself or one’s symptoms, manifesting boisterous speech, overactivity/restlessness, and excess of speech.

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13
Q

Depressive psychosis

A

Psychomotor retardation, apathy, and anxious self-punishment/blame.

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14
Q

Psychomotor retardation and apathy

A

Slowed speech, indifference to one’s future, fixed facial expression, slowed movements, deficiencies in recent memory, blocking in speech, apathy toward self, slovenly appearance, low/whispered speech, and failure to answer questions.

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15
Q

Anxious self-punishment and blame

A

Tendency to blame self, anxiety/apprehensiveness about vague future events, self-deprecation, depressed mood, feelings of guilt/remorse, preoccupation with suicidal thoughts, unwanted ideas, specific fears, and feeling unworthy.

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16
Q

Schizophrenia development/duration for diagnostic criteria

A

Disturbance must last for six months or longer including at least one month of delusions, hallucinations, disorganized speech, grossly catatonic or disorganized behavior, or negative symptoms.

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17
Q

Positive symptoms

A

Primary target of antipsychotic medications. Delusions, hallucinations, distortions or exaggerations in language and communication, disorganized speech, disorganized behavior, catatonic behavior, agitation

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18
Q

Negative symptoms

A

Alogia, affective blunting or flattening, asociality, anhedonia, avolition

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19
Q

Delusions

A

A misinterpretation of perception or experiences. Most common is persecutory but may be referential (erroneously thinking something refers to self), somatic, religious, or grandiose.

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20
Q

Hallucinations

A

Auditory are most common but may occur in any sensory modality.

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21
Q

Alogia

A

Poverty of speech. Dysfunction of communication; restrictions in the fluency and productivity of thought and speech.

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22
Q

Affective blunting or flattening

A

Restrictions in the range and intensity of emotional expression.

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23
Q

Asociality

A

Reduced social drive and interaction.

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24
Q

Anhedonia

A

Reduced ability to experience pleasure.

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25
Q

Avolition

A

Reduced desire, motivation or persistence; restrictions in the initiation of goal-directed behavior.

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26
Q

Cognitive symptoms of schizophrenia

A

Impaired attention and information processing, impaired verbal fluency, problems with serial learning, and impaired executive functioning (i.e. problems sustaining attention, concentrating, prioritizing, and modulating behavior based on social cues).

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27
Q

Brain region most associated with positive symptoms of schizophrenia

A

Mesolimbic

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28
Q

Brain region most associated with negative symptoms of schizophrenia

A

Mesocortical/prefrontal cortex and nucleus accumbens/reward circuits

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29
Q

Brain region most associated with affective symptoms of schizophrenia

A

Ventromedial prefrontal cortex

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30
Q

Brain region most associated with aggressive symptoms in schizophrenia

A

Orbitofrontal cortex and amygdala

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31
Q

Brain region most associated with cognitive symptoms of schizophrenia

A

Dorsolateral prefrontal cortex

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32
Q

Dopamine precurser

A

Tyrosine

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33
Q

Primary binding site for almost all antipsychotic agents and dopamine agonists used for Parkinson’s disease.

A

D2 receptor

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34
Q

Nigrostriatal dopamine pathway

A

Deficit of dopamine in this area related to movement disorders including Parkinson’s. Part of the extrapyramidal nervous system and controls motor function and movement.

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35
Q

Mesolimbic dopamine pathway

A

Hyperactivity associated with positive symptoms of schizophrenia. Part of the limbic system thought to be involved in behaviors such as pleasurable sensations (motivation, pleasure, reward), euphoria of drugs, and delusions and hallucinations of psychosis.

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36
Q

Mesocortical dopamine pathway

A

Deficit of dopamine in this region associated with negative symptoms of schizophrenia. Sends axons to areas of prefrontal cortex where they have a role in mediating cognitive symptoms (dorsolateral prefrontal cortex, DLPFC), and affective symptoms (ventromedial prefrontal cortex, VMPFC).

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37
Q

Tuberoinfundibular dopamine pathway

A

Projects from hypothalamus to anterior pituitary and controls prolactin.

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38
Q

Mesolimbic dopamine pathway location

A

From dopaminergic cell bodies in ventral tegmental area of brainstem to axon terminals in limbic area of brain (nucleus accumbens in ventral striatum).

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39
Q

Symptoms produced by drugs that increase/enhance dopamine like amphetamines and cocaine.

A

Positive symptoms result.

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40
Q

Glutamate

A

Major excitatory neurotransmitter in CNS which can turn on almost all CNS neurons in the brain. Abundance of this is thought to lead to downstream dysfunction of dopamine release in mesolimbic and mesocortical pathways.

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41
Q

NMDA receptors

A

Neurodevelopmental dysfunction in formation of this receptor is thought to contribute to excess glutamate release causing downstream effects on dopamine release.

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42
Q

Conventional antipsychotics

A

Primary pharmacological property of D2 antagonism. Narrow therapeutic threshold between antipsychotic efficacy and side effects for D2 binding.

43
Q

Tardive dyskinesia

A

Hyperkinetic motor condition due to long-term blockade of D2 receptors in nigrostriatal dopamine pathway causing upregulation of receptors to overcompensate.

44
Q

Tardive dyskinesia s/s

A

Tongue protrusions, facial grimaces, chewing, jerky limb movements.

45
Q

Gynecomastia, galactorrhea (breast secretions) and amenorrhea cause

A

D2 antagonism in tuberoinfundibular dopamine pathway leading to upregulation.

46
Q

Negative consequences of D2 antagonism in mesolimbic dopamine pathway

A

Drug side effect of blocking reward pathway leading to increase in anhedonia, lack of motivation, lack of interest, and potentially increase in smoking and drug abuse.

47
Q

Neuroleptic-induced deficit syndrome

A

Increase in negative and cognitive symptoms of schizophrenia due to D2 antagonism (blockade) in mesocortical DA pathway.

48
Q

Extrapyramidal symptoms (EPS) or drug-induced Parkinsonism

A

Physical symptoms related to acute or chronic D2 antagonism (blockade) and acetylcholine excess in nigrostriatal DA pathway. May include tremor, slurred speech, akathesia, dystonia, anxiety, distress, paranoia, and slowed thinking (bradyphrenia).

49
Q

Neuroleptic malignant syndrome

A

Extreme muscular rigidity, high fevers, coma, and potentially death related to D2 blockade in nigrostriatal DA pathway.

50
Q

Anticholinergic side effects of medications

A

Undesirable side effects of dry mouth, blurred vision, constipation, and cognitive blunting due to muscarinic cholinergic blockade from reduced acetylcholine release.

51
Q

Conventional antipsychotic blockade of histamine H1 receptors

A

Side effects of weight gain and drowsiness.

52
Q

Conventional antipsychotic blockade of alpha1-adrenergic receptors

A

Side effects of cardiovascular dysfunction such as hypotension and drowsiness.

53
Q

Haloperidol

A

Conventional high-potency antipsychotic with relatively low anticholinergic or antihistminic binding activity but higher risk of EPS than chlorpromazine.

54
Q

Chlorpromazine

A

Conventional low-potency antipsychotic with high anticholinergic and antihistamine binding, and higher risk of hypotension than Haldol.

55
Q

Atypical antipsychotics

A

D2 receptor antagonists and 5HT2A receptor antagonists - block dopamine release where needed (limbic) but permit enough dopamine release in striatum and pituitary to prevent EPS and hyperprolactinemia (80% D2 occupancy reduced to 60%).

56
Q

Clozapine, olanzapine, quetiapine (“pines”)

A

Atypical antipsychotics with higher binding affinity for 5HT2A than D2. Binding to 5HT2A is more potent than D2.

57
Q

Risperidone, paliperidone, ziprasidone, iloperidone, lurasidone (“dones”)

A

Antipsychotics with middle-range or greater binding affinity for 5HT2A over D2, but less than the pines.

58
Q

Aripiprazole, brexpiprazole (Rexulti), cariprazine (Vraylar) (“two pips and a rip”)

A

Antipsychotics with less binding affinity for 5HT2A receptors over D2. Binding to 5HT2A is less potent than D2. Binding to 5HT1A (partial agonist) is as potent or more potent than D2 (serotonin modulation).

59
Q

Lumateperone (Caplyta)

A

Antipsychotic with higher binding affinity for 5HT2A than D2 but also may modulate presynaptic D2 activity without full antagonism.

60
Q

Aripiprazole, brexpiprazole, cariprazine, clozapine, quetiapine, lurasidone, iloperidone, ziprasidone

A

Antipsychotics with 5HT1A partial agonist actions (stronger than 5HT2A antagonist actions and comparable to D2 in “pips” and “rip”), elevating mood component of drug effects, decreasing risk of EPS, and boosting antimanic actions.

61
Q

Quetiapine and aripiprazole

A

Antipsychotics proven to work for antidepressent augemtation due to 5HT1A partial agonism action.

62
Q

5HT2C agonism

A

Postsynaptic receptor stimulation that suppresses dopamine release in mesolimbic more than nigrostriatal and suppresses norepinephrine release leading to antipsychotic effects with minimal EPS and may help lose weight.

63
Q

5HT2C antagonism

A

Stimulates dopamine and norepinephrine release in prefrontal cortex for pro-cognitive and antidepressant actions. May contribute to weight gain. (quetiapine, olanzapine)

64
Q

5HT6 antagonism

A

Blockade improves learning and memory and improves cognitive symptoms of schizophrenia (clozapine, olanzapine, asenapine - potent relative to D2 binding).

65
Q

5HT7 antagonism

A

Blockade increases serotonin release and may help regulate circadian rhythms, sleep, and mood (quetiapine and aripiprazole - especially in combination with SSRIs and SNRIs).

66
Q

Aripiprazole, brexpiprazole and cariprazine

A

D2 partial agonists that work on positive symptoms without activating negative symptoms of schizophrenia and mania at higher doses and work as antidepressants at lower doses. Has side effect profile with increased akathisia (aripiprazole).

67
Q

Potent antihistamine and anticholinergic actions

A

Leads to sedation and may decrease cognitive arousal - clozapine, quetiapine, olanzapine. May increase time needed to taper and switch drugs.

68
Q

High metabolic risk profile (drugs)

A

clozapine and olanzapine

69
Q

Moderate metabolic risk profile (drugs)

A

risperidone, paliperidone, quetiapine, iloperidone (weight only)

70
Q

Low metabolic risk (drugs)

A

ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine, brexpiprazole/cariprazine

71
Q

Clozapine

A

“Gold standard” atypical for positive symptoms in schizophrenia when other atypicals fail and lacks significant EPS and reduce TD severity. May create rare occurrence of “awakening” in use and documented to reduce risk of suicide in schizophrenia.

72
Q

Clozapine

A

Increased risk of agranulocytosis and cardiometabolic risk mandating increased frequency in lab testing. Increased risk of seizures, sedating, constipation (even paralytic ileus) and increased salivation at high doses - due in part to muscarinic, histaminic, and adrenergic antagonism.

73
Q

Clozapine

A

Monitoring parameters: CBC w/diff at baseline, ANC q week x6 months, then q 4 weeks for duration of treatment. Additional ANC monitoring following treatment cessation. Recommend CMP, lipid panel, PE, bowel fxn, LFTs, weight, fasting glucose at baseline and then periodically. Consider ECG at baseline.

74
Q

Olanzapine

A

Generally less EPS even at higher doses, can be sedating, does not often raise prolactin levels, but one of two atypicals with higher weight gain due to antihistaminic and 5HT2C antagonism and highest known cardiometabolic risk for increased fasting triglyceride and insulin resistance.

75
Q

Olanzapine

A

Often used in higher doses than clinically approved (40mg/day) and improves mood in both schizophrenia and bipolar disorder with tx-resistant depression.

76
Q

Olanzapine

A

Available in combination with fluoxetine (Symbyax) for tx-resistant depression and BP depression. Second-line tx in patients with significant weight gain or significant cardiometabolic risks/diabetes. Available in oral disintegrating tablet, acute IM injection, and long-acting IM depot.

77
Q

Quetiapine

A

Active metabolite with NET reuptake inhibition, 5HT7, 5HT2C, and adrenergic antagonism. Also has 5HT1A partial agonist action. Strong antidepressant profile.

78
Q

Quetiapine

A

Prominent H1 antagonism contributes to improved sleep but may cause daytime sedation and weight gain. Anticholinergic side effects.

79
Q

Quetiapine

A

Comes in IR and XR formulation. IR has rapid onset but short duration of action. 300mg/day considered lowest effective antipsychotic dose but may wear off too quickly and XR formulation hits peak more slowly (6 hours) but with rapid onset and without same amount of sedation. Declines to therapeutic over 18 hours. 800mg highest dose (antipsychotic dose).

80
Q

Quetiapine

A

At sedative-hypnotic doses (50mg/day, not approved as hypnotic), most prominent pharmacological property is histamine 1 antagonism.

81
Q

Quetiapine and clozapine

A

Preferred for psychosis treatment for patients with Parkinson’s due to little to no risk for EPS or prolactin increase.

82
Q

Quetiapine

A

Approved for bipoalr depression and augmentation of SSRIs/SNRIs in tx-resistant depression. Has monoamine action of increasing serotonin, dopamine, and norepinephrine via metabolite antagonism of 5HT2C plus prefrontal cortex NET blockade while simultaneously treating insomnia and anxiety via antihistaminic action.

83
Q

Asenapine (Saphris)

A

Antipsychotic with chemical structure similar to mirtazapine approved for mania and several serotonergic and dopaminergic receptor binding actions greater than D2 but does not perform as well for depression.

84
Q

Asenapine (Saphris)

A

Comes in SL formulation because active drug is poorly bioavailable if swallowed due to extensive first-pass metabolism. Generally taken twice daily due to limited surface area of oral cavity for absorption at high doses in spite of long half-life.

85
Q

Asenapine (Saphris)

A

Rapidly absorbed sublingually with rapid peak drug levels and may be effective as oral PRN for psychosis. Patients cannot eat or drink 10 min following administration and drug can be sedating but does not have high risk of weight gain/dyslipidemia due to weaker antihistaminic properties.

86
Q

Asenapine (Saphris)

A

Theoretically structurally effective for depression due to 5HT2C receptor antagonism, actions linked to elevating norepinephrine, serotonin, and dopamine via adrenergic antagonism and also theoretically linked to improvement in negative symptoms of schizophrenia but this has yet to be proven.

87
Q

Risperidone

A

EPS can occur at high doses but effective antipsychotic for schizophrenia and mania at moderate doses. Approved for tx of irritability associated with autism in children ages 5-16. Approved for symptoms of aggression, self-injury, tantrums and mood swings in ages 10-17. Approved for early-onset schizophrenia in ages 13-17.

88
Q

Risperidone

A

Available in long-acting depot injection (2 weeks), oral disintegrating tablet and liquid formula. Does raise prolactin levels even at low doses and has a moderate risk for weight gain and dyslipidemia, even in children.

89
Q

Paliperidone (Invega)

A

Active metabolite of risperidone and not hepatically metabolized, eliminated via urinary excretion with few drug interactions. Similar side effect profile to risperidone. Available in ER and only needs once daily dosing. Also available in long-term administration (4 weeks) injectable depot (sustenna) with less risk of side effects and sedation as with other depots and no need to begin with oral tx. Option to transition from monthly IM to q3 month IM (Trinza).

90
Q

Ziprasidone (Geodon)

A

Less risk for weight gain, lower cardiometabolic risk profile, and less sedation. Must be dosed twice daily with at least 500 cal meal or will result in lower oral absorption and inconsistent efficacy. Has IM formula for acute agitation in psychosis.

91
Q

Iloperidone (Fanapt)

A

Newer antipsychotic with low risk of EPS and dyslipidemia. Potent adrenergic antagonism causing risk for orthostatic hypotension and sedation. Has a long half-life but is still dosed twice daily and titrated over several days to avoid sedation and orthostasis which can delay onset of effects.

92
Q

Lurasidone (Latuda)

A

5HT2A-D2 antagonist with high affinity for 5HT7 and D4 (antagonism) and moderate affinity for 5HT1A and alpha 2 receptors. Minimal histamine and cholinergic affinity. Dosed at night to reduce risk of EPS and taken with 500 cal meal for absorption and efficacy. Strong efficacy for depression and mixed mood episodes - approved for BP depression.

93
Q

Aripiprazole

A

D2 partial agonist with reduced EPS and hyperprolactinemia. 5HT1A partial agonist and less affinity for 5HT2A antagonism than other atypicals. Less risk of sedation and lower cardiometabolic risk and risk of weight gain. Approved for treatment in children including acute mania/mixed mania (ages 10 and older), and autism-related irritability (ages 6-17).

94
Q

Aripiprazole

A

Approved for antipsychotic and approved as antidepressant augmentation at lower doses. May act as dopamine agonist at D2 (partial agonist) and D3 (partial agonist) at lower doses and can be activating/agitating in psychosis, even at high doses. Available in long-acting depot formulations and requires overlap dosing with PO.

95
Q

Brexpiprazole (Rexulti)

A

More of a D2 antagonist with more potent 5HT2A antagonism, 5HT1A partial agonism, and alpha 1 antagonism relative to D2 partial agonism. Approved for schizophrenia and antidepressant adjunct. Lower side effects profile.

96
Q

Cariprazine (Vraylar)

A

D2 partial agonist approved for schizophrenia and bipolar depression/mania/mixed. Higher doses appropriate for psychotic symptoms and lower doses appropriate for depressive symptoms due to D3 partial agonist actions relative to D2 partial agonism. Long-acting metabolites so may be doses less than daily PO as needed. Lower side effect profile.

97
Q

D3 partial agonism

A

May account for positive atypical effects on cognition, mood, emotions, and reward/substance abuse, especially in drugs with D2 and D3 partial agonism (Abilify, Rexulti, and Vraylar).

98
Q

Switching from a pine to pine or a done to done

A

Titrate from one drug to another over one week.

99
Q

Switching from a pine (except clozapine) to a done

A

Titrate from the first drug to the second over two weeks to allow patient to adapt to cholinergic, histaminic, and alpha 1 blockade and reduce risk of anticholinergic rebound, agitation, and insomnia.

100
Q

Stopping clozapine

A

Reduce med over 4 or more weeks due to risk of rebound psychosis and anticholinergic rebound. Take at least 4 weeks of down-titration before starting another antipsychotic.

101
Q

Switching from a done to a pine

A

Titrate new med up over two weeks but old drug can be titrated down over one week.

102
Q

Switching to a pip or a rip

A

When switching from a pine or done, may need to start new drug at middle dose and build rapidly over 3-7 days due to immediate replacement of old drug with new drug at D2 receptors. While taking 2 weeks to taper the pine and 1 week for a done.

103
Q

Stopping a pip or rip

A

May need to abruptly stop this drug when switching to a pine or done and start new drug at middle dose and rapidly taper up ( pine over 2 weeks, done over 1 week).

Psychopharmacology (6 decks)

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