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PHAR 358 > Psychosis > Flashcards

Psychosis Flashcards

1
Q

Schzophrenia DSM-5 Definition

A

DSM-5: ≥6 months + ≥ 1 month of ≥ 2 sxs.

One must be: delusions, hallucinations, disorganized speech.

Other: disorganized/catatonic behavior, negative symptoms (blunted affect, alogia, avolition, anhedonia, amotivation). ↓ social/occupational function

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2
Q

Define Psychosis

A

Presence of gross impairment of reality testing (e.g. lose touch with reality) as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behavior without apparent awareness on the part of the patient of the incomprehensibility of their behavior

Schizophrenia is one of MANY causes of psychosis

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3
Q

Define treatment reistant schizophrenia

A

No significant improvement in sxs despite tx with ≥ 2 APs from 2 different AP classes at optimal dose for 6-8w

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4
Q

Define schizophreniform Disorder

A

1-6 months, same sxs as schizophrenia, social/occupation functional impairment not required

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5
Q

Define schizoaffective disorder

A

≥2 wks of delusions or hallucinations without mood sxs + uninterrupted period of illness containing either major depressive or manic episode with concurrent sxs diagnostic of schizophrenia. Social/occupation functional impairment not required.

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6
Q

Define brief psychotic disorder

A

1 day to 1 month of ≥ 1 of delusions, hallucinations, disorganized speech. Return to premorbid function.

Medication induced, acute stressor event, post-partum –> If return back to normal levels, classified as brief  If dysfunction and longer than 1 month  Schizoaffective

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7
Q

Define Delusional Disorder

A

1 month of delusions. Hallucinations not prominent. Function only mildly impaired, behavior not blatantly bizarre.

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8
Q

Define Substance Induced Psychosis

A

Hallucinations or delusions development during or within 1 month of substance use/withdrawal.

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9
Q

Substance with highest risk of substance induced psychosis

A

Crystal Methamphetamine

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10
Q

Define the duration of untreated psychosis

A

Time from the manifestation of the first psychotic symptom to initiation of adequate treatment

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11
Q

Schizophrenia Prevalence. Onset and differences between sexes?

A

Schizophrenia prevalence: 1% in Canada. Usual onset at age 16-30 yrs (men earlier 15-24 yr vs. women 25-34). Equal distribution between sexes.

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12
Q

Risk factors for Scizophrenia

A

immigrant ethnic groups
perinatal/early childhood (hypoxia, maternal infection/stress/malnutrition)
urban upbringing
cannabis use
life stress

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13
Q

Does a genetic link exist in schizophrenia?

A

Genetic heritability 80%. ↑risk 15-20x if parent has schizophrenia.

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14
Q

Describe some commorbidities with Schizophrenia

A

Patients with schizophrenia die 10-20 yrs earlier than avg. population:

↓ access to care, poor diet
↓ exercise
↑ obesity/diabetes (irrespective of meds)
↑ smoking 60-90% (tobacco is a high risk substance; most od use some form of tobacco)
Substance use disorders 45%
↑ CVD ~doubles in first year (not just due to antipsychotics)
Suicide 4.5%

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15
Q

What is one reason for which tx with AP is crucial?

A

Risk of death ~doubles if never treated with AP

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16
Q

What is a major issue pertaining to treatment of schizophrenia?

A

Medication nonadherence rates ~50-60%

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17
Q

Describe the pathophysiology of Schizophrenia

A

Dopamine dysregulation is the key theory underlying the pathophysiology of the disease

Serotonin dysregulation also contributes
Modulates dopamine

Glutamate and GABA also have a role
Less clearly understood

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18
Q

Describe the dopaminergic pathways of the brain

A
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19
Q

What are some prodromal features of schizophrenia?

A

often recognized retrospectively after the diagnosis has been made

reclusive adolescence without close friends (e.g. not involved in school activities or teams)

not functioning well in occupational, social and personal activities

markedly peculiar behavior, abnormal affects, unusual speech, bizarre ideas and strange
–> perceptual experiences
preoccupation with religion; magical thinking; excessive writing without meaning; sensitivity and irritability when touched by others; unusual sensitivity to stimuli

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20
Q

Describe the over-arching experience of schizophrenia sx

A

Complex, heterogenous disorder

No sign or symptoms is specific of schizophrenia

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21
Q

Describe the 4 clusters of sx in Schizophrenia

A

Psotive Sx (psychosis)
Negative Sx
Cognitive Sx
Mood Sx

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22
Q

Describe Positive Sx

A
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23
Q

Describe Negative Sx

A
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24
Q

Describe cognitive sx

A
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25
Q

describe mood sx

A

Dysphoria, Depression
Excitement, mania

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26
Q

What are some common positive Sx of Schizophrenia? Examples?

A

Delusions
Hallcuinations
Disorganized Thinking
Grossly Disorganized/Abnormal Motor Behaviour
Catatonia

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27
Q

Define Delusions

A

Fixed beliefs that are not amenable to change in light of conflicting evidence
Common themes: persecutory, referential, somatic, religious, grandiose

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28
Q

Define Hallucinations

A

Perception-like experiences that occur without an external stimuli

Vivid and clear with the full force and impact of normal perceptions and not under voluntary control

May occur in any sensory modality but auditory are most common in schizophrenia

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29
Q

Most common type of hallucination

A

Auditory

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30
Q

Describe disorganized thinking

A

Usually inferred from the individual’s speech
Loose associations (talk about one thing; goes all over no idea where conversation is going)

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31
Q

Describe grossly disorganized/abnormal behaviour

A

May manifest in a variety of ways, ranging from childlike “silliness” to unpredictable agitation

Problems may be noted in any form of goal-directed behavior, leading to difficulties in performing activities of daily living

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32
Q

Describe Catatonia

A

Marked decrease in reactivity to the environment

Ranges from resistance to instructions (negativism); to maintaining a rigid, inappropriate or bizarre posture; to a complete lack of verbal and motor responses (mutismandstupor)

Can also include purposeless and excessive motor activity without obvious cause (catatonic excitement)

Other features are repeated stereotyped movements, staring, grimacing, mutism, and the echoing of speech

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33
Q

Describe some negative sx of schizophrenia? Define the term?

A
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34
Q

What are some associated clinical features of schizophrenia?

A

Substance USe
Smoking
Sucidiality

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35
Q

Describe substance use in Schizophrenia

A

Comorbid SUD very common (~45% of patients)

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36
Q

Describe smoking in Schizophrenia. Effect?

A

More than 50-75% are smokers (vs. 25-30% gen pop.)
Smoking induces CYP1A2 which affects metabolism of olanzapine and clozapine
Smoking may decrease some ADEs of AP through nicotine-dept activation of DA neurons

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37
Q

Describe suicidality in Schizophrenia?

A

Suicide is the leading cause of premature death in patients with schizophrenia
40-50% of all patients with schizophrenia attempt suicide at least 1/lifetime
10-15% of patients with schizophrenia die by suicide

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38
Q

What are some risk factors for suicide in schizophrenia?

A

Risk factors: depressive sxs, young age, male, high socioeconomic status, high premorbid functioning, early onset and a chronic deteriorating course

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39
Q

How is schizophrenia diagnosed?

A

clinical psychiatric history
mental status exam
family/social history
medical history
physical exam

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40
Q

What are some lab and diagnostic work ups for Schizophrenia

A
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41
Q

What are some causes of Drug Induced Psychosis?

A

AMphetamine and coacine use and withdrawal
Bupropion
Caffeine
Cannabis
Steroids

Increase dopamine in mesolimbic pathway –> too mcuh dopamine, leads to positive sx (psychosis)

Chloroquine, efavirenz, ketamine –different mechanism but still dopamine mechanisms

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42
Q

Describe substance induced psychosis. WHich agents are most likely to cause psychosis in withdrawal states ?

A

Most likely where withdrawal can be lead to psychotics is alcohol, benzodiazepines

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43
Q

What scales can be used for assesing Schizophrenia?

A
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44
Q

Non-pharm TX Schizophrenia

A

Exercise, healthy diet, adequate sleep
Decrease substance use
Decrease caffeine/nicotine/alcohol
Support service interventions to ↑ medication adherence individualize based on patients’ needs
Establish trusting therapeutic relationship; include patient in treatment decisions (shared decision making) when possible
Community-case management (multidisciplinary team), vocational and occupational rehabilitation techniques, cognitive behavioural therapy (↑ coping and decraesed distress and negative affect)

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45
Q

What are the main receptor targets in schizophrenia?

A
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46
Q

describe Anti-psychotics and the receptors they work on

A
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47
Q

Describe the A/E associated with the different generations of AP

A
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48
Q

Describe the unique profiles of anti-psychotics

A

Despite groupings, antipsychotics are very different from each other
Overall efficacy is similar (except clozapine)
Receptor profiles & rate of dissociation from receptors relates to tolerability
Differences in metabolic pathways is important for drug interactions

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49
Q

Describe the effect of D2 Antagonism

A
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50
Q

Describe the effect of 5HT for anti-psychottic function

A
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51
Q

Where does D2 blockage and 5HT antagonism fit into doapminergic pathways?

A
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52
Q

D2 Blockade A/E

A
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53
Q

Alpha Antgonism S/E

A
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54
Q

Muscarinic Antgonism S/E

A
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55
Q

H1 Antagonism A/E

A
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56
Q

Hallmark of 1st Gen AP

A

Strong D2 Blockers

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57
Q

FGA’s High Potency

A

High Potency FGAs = Higher risk of movement disorders

Weaker anticholinergic effect

Common meds:

Haloperidol
Fluphenazine
Perphenazine
Flupenthixol

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58
Q

Low potency FGA

A

Low Potency FGAs = Lower risk of movement disorders

Stronger anticholinergic effects

Highly sedating

Most common agents
Chlorpromazine
Methotrimeprazine

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59
Q

Comparison of FGA’s

A

Methotrimeprazine - Most Sedating
Haloperidol - Most risk of EPS

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60
Q

2nd Gen AP’s

A
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61
Q

Second GeneratioN ANtipsychotics Receptors

A

Developed based on different receptor activity (esp. 5HT2A/2c) in addition to D2 blockade

↓ risk of movement disorders but ↑ metabolic adverse drug effects

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62
Q

Risperidone Receptors

A

High affinity for dopamine (D2), serotonin (5-HT2) and alpha-adrenergic receptors

Also binds, with lower affinity, to alpha-2 and H1 receptors – not very sedating

NO affinity for muscarinic receptors
No anticholinergic side effects!

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63
Q

Risperidone Dosing Main Concept

A

> 8 mg OD - Behaving like FGA –> EPS s/e

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64
Q

Risperidone Formulations

A

oral solution, oral tablets, orally disintegrating tablets (M-tabs), and LAI

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65
Q

A/E Unique Risperidone

A

Increased prolactin/sexual dysfunction (more vs other SGAs) –> Highest risk of Galactorhhea

EPS (more vs SGAs; less vs haloperidol)

Possible risk of QT prolongation

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66
Q

DI Risperidone

A

Pharmacodynamic interactions (e.g., CNS depressants) and 3A4/2D6 interactions

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67
Q

Paliperidone MOA

A

Primary active metabolite of risperidone (9-hydroxyrisperidone)

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68
Q

Formulation Paliperidone

A

Oral: OROS technology (like Concerta)

Delivers sustained level over 24 hours
Shell will pass in the stool

Tablets
Long acting injectable
Invega Sustenna (once monthly), Invega Trinza (every 3 months)

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69
Q

Paliperidone A/E

A

Headache
Orthostatic hypotension (less vs risperidone)
EPS
Insomnia (more vs risperidone) or somnolence
Weight gain (less vs risperidone)
Increased prolactin/sexual dysfunction (similar to risperidone)
Anxiety
Rhinitis
Possible risk of QT prolongation

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70
Q

Drug Interactions Paliperidone

A

Minimal risk of drug interactions

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71
Q

Olanazpine USe

A

Metabolic ADEs limit initial use.

Histamine and Muscarinic Effects

72
Q

Olanzapine Formulations

A

Short-acting injectable available (for inpatient use for acute agitation)
Tablets
Orally disintegrating tablets (Zydis)
Long-acting injectable available US only*

73
Q

Olanzapine A/E

A

WEIGHT GAIN (>10lbs or >7% of baseline weight)
Dizziness
Sedation
Anticholinergic effects
Increased liver enzymes
Orthostatic hypotension
Increased risk of T2DM, dyslipidemia (more vs. others)
EPS (especially akathisia); dose-dependent
Possible risk of QT prolongation

74
Q

Olanzapine D.I.

A

Smoking! (CYP1A2)
Pharmacodynamic interactions with drugs of similar actions, 1A2 inhibitors/inducers

75
Q

Quetiapine Formulations

A

XR - OD
IR - BID

76
Q

Quetiapine Dosing

A

Lower doses used for insomnia, bipolar, depression, anxiety

77
Q

Quetiapine A/E

A

Headache, dizziness
Sedation / somnolence
Orthostatic hypotension
Conditional risk of QT prolongation
Weight gain
Increased liver enzymes
Increased risk of T2DM and dyslipidemia
May reduce thyroid hormone levels

78
Q

Quetiapine D.I>

A

PD interactions and 3A4 interactions

79
Q

Ziprasidone Dosing

A

Rapidly titrate in the first week up to 120-160mg/day in bipolar disorder or agitated/irritable patients

To avoid ziprasidone-induced “activation” syndrome
Anxiety, restlessness, insomnia, increased energy, and hypomanic-like symptoms, which develop soon after treatment initiation and occur at the lower end of the dosage range (20-40mg PO BID). Over comes these effects at higher doses due to

80
Q

Ziprasisone Administration

A

Administer WITH FOOD

Meals with >500 kcal to maximize absorption & therapeutic effect

81
Q

Ziprasidone Unique A/E

A

Considered to be weight neutral
Some will experience weight gain due need to take with food

Less hyperglycemia/ hyperlipidemia vs. other SGA

Dyspepsia, nausea, constipation

Conditional risk of QT prolongation
?higher risk versus other agents
Contraindicated in patients with QT prolongation, recent MI, uncompensated heart failure, or with concurrent QT prolonging drug

82
Q

Ziprasidone D.I.

A

Pharmacodynamic interactions and 3A4 inducers/inhibitors

83
Q

Asenapine Dosing

A

SL tablets
Initial = 5mg BID
Max= 10mg BID

84
Q

Asenapine Coverage

A

EDS (for bipolar disorder)
Failed/intolerance to less costly SGA options (e.g., quetiapine and/or risperidone)

Not covered for use in schizophrenia
Because superiority vs placebo not clearly demonstrated
Not clinically used for schizophrenia

85
Q

Asenapine A/E

A

Headache, dizziness
Drowsiness or insomnia
EPS
Akathisia (restless, agitation)
Suicidal ideation
Mouth numbness x 1 hr post dose (oral hypoesthesia)
Orthostatic hypotension
Minimal effect on weight, glucose, lipids
Increased prolactin
Possible risk for QT prolongation

86
Q

Asenapine DI

A

PK DIs with 1A2 inhibitors/inducers; PD interactions with CNS depressants, QTc prolonging agents, etc

87
Q

Lurasidone Benefit

A

Little to no metabolic concerns

88
Q

Lurasidone Effoicacy

A

Efficacy established in studies up to 6-weeks
Rarely used for schizophrenia in clinical practice
Still some EPS, sedation, etc.

89
Q

Lurasidone Metabolism

A

Metabolized by 3A4
Thus influenced by inhibitors/inducers of 3A4

90
Q

Lurasidone Dose

A

Dose = 40mg PO daily WITH food
Titrate as needed to 120-160mg PO daily
WITH food – to increase bioavailability (350kcal)

91
Q

3rd Generaton AP

A
92
Q

Third Gen AP EFfects

A

↓ risk of metabolic & movement ADEs

High rates of akathisia
Aripiprazole&raquo_space; brexpiprazole

93
Q

Describe the MOA of Ariprazole

A
94
Q

What is a key feature of 3rd generations AP compared to otehr regarding dosing?

A

All have long half-lives

95
Q

Dosing of ARiprazole and Formulations. Half-life and titration?

A
96
Q

Adeverse EFfecrs of Ariprazole

A

Headache
GI complaints (e.g., nausea)
Insomnia or sedation (more often activating vs. sedating)
Akathisia
Some anxiety
Minimal weight gain
EPS
Orthostatic hypotension
Suicidal behaviour
Possible risk of QT prolongation

97
Q

Drug Interactions of ARiprazole

A

Monitor for PK interactions (2D6, 3A4)

98
Q

Brexiprazole Indication and MOA

A

Indication: schizophrenia, MDD add-on therapy

Acts as a partial agonist at the 5HT1A and D2 and antagonist at 5HT2A (+ additional receptor effects)

99
Q

Brexiprazole HAlf-Life

A

Half-life = 91 hours

100
Q

A/E of Brexiprazole

A

similar to aripiprazole but less akathisia

101
Q

Carprazine limittaions

A

Just introduced to the Canadian market in 2022

Limited clinical experience

Not covered by SK drug plan

+++ expensive

102
Q

Cariprazine Receptor Action

A

High affinity partial agonist at D3 + D2 receptors

At low doses → higher affinity for D3 than D2

Lower affinity for D2 than aripiprazole and brexpiprazole

High affinity partial agonist at 5HT1A

Antagonist at 5HT2A, 5HT2B

D3 Receptor activity may theoretically improve negative sx and cognitive impairments

103
Q

CAriprazine PK

A
104
Q

CADTH Cariprazine Recccomendations

A

Unclear whether cariprazine offers clinical benefits over other treatments

Not enough evidence to show cariprazine filled a treatment gap

Additional therapy for non-responsive patients, provide greater range of dosages, lower frequency of administration, minimize adverse effects

105
Q

Cariprazine Uses

A
106
Q

Key Points for Selecting an AP

A
107
Q

What occurs in first episode psychocis relating to phsyiology?

A

First episode psychosis destroys 10-12 cc of brain tissue

Neurotoxicity of psychosis is mediated by neuro-inflammation and oxidative stress

Each subsequent psychotic episode will destroy more brain tissue  clinical deteroriation, treatment resistance, functional disability

108
Q

When/why should long-acting injectable antipsychotics be considered?

A

If oral medications are effective and tolerated, may continue with oral therapy or switch to long-acting injectable depot to improve adherence (given q2-4weeks)

May be considered if a patient relapses due to non-adherence or if patient prefers injection
Paradigm shift in practice to offer depots earlier (however must first confirm oral tolerability)

109
Q

Key Thing with LAIA

A

Would never start a depot without a trial of oral for a week or a few days – no way to remove depot agents – develop a/e are stuck with the agent in their system
- Before starting an agent, must always do an oral trial first

110
Q

Benefits of LAIA’s

A
111
Q

Key Critical Poinmts for initiation of LAIA

A

Establish tolerability with oral first!

Always double check how long to overlap with oral! (different periods of overlap)

May not show up on last 4 months of PIP but may still be pharmacologically active in the patient’s body. Always double check date of last dose! (given long half-life)

Consult the product monograph or SwitchRx for information on how to switch for one depot to another.
Still need to establish oral tolerability first! (of new agent prior to depot)

112
Q

Avilable LAIA’s

A

Ariprazole –> 3rd Gen –> Abilify Materna

PAliperidone –> Invega SUstenna and INvega Trinza

113
Q

ABlify MAterna

A

Long half-life – takes time for onset of action; needs two weeks of standard oral initiation
New initiation – two abilify injection (no way to know if oral is tolerated)  risk of akathisia

114
Q

Invega Sustenna

A

No oral overlap

Risperidone – can swict to Invega Sustenna

115
Q

Invega Trinza

A

Invega Trinza – Need to have been on Invega Sustenna for 4 months
Very long t1/2- if present with EPS – scary

116
Q

Anti-psychotic A/E Summary

A

Someone eats pussy and works avenues

117
Q

AP Monitoring

A
118
Q

Canadian Schizophrenia Guidelines

A

tress the importance of:
earlier treatment of symptoms
need for greater attention to the physical care of people with schizophrenia due to the reduced lifespan
greater emphasis on recovery and the need to provide personalized care rather than focusing primarily on symptomatic management

119
Q

What is important in first episode psychosis management?

A

Early treatment is critical

Early detection & tx can dcrease depression, ↑ mood/cognitive scores, ↑ overall function at 10yrs

First 2-5 years of illness are critical to offset future disability and improve outcomes;

longer duration of untreated psychosis results in dcreased response to treatment.

120
Q

TX of first Episode Psychosis

A

No particular AP or class found to be clinically superior in 1st episode population
usually SGA (compared to FGA: decraesed AE, decraesed discontinuation, & equal efficacy)

choose agent based on AE profile & use lowest effective dose

using a long-acting antipsychotic injection may decrease relapse vs oral therapy

121
Q

First Episode Psychosis Tx Duration. Risk of relapse?

A

controversial; minimum 18 months CDN’17
Indefinite therapy reasonable
risk of relapse after first episode 82%
5x higher if not on tx & relapses have decreased response to treatment

122
Q

First Episode PSychosis Adequate TRial

A

Adequate trial: 4-6 weeks @ optimally tolerated dose

123
Q

Acute Exacerbation Mangement

A
124
Q

Sx Treatment in Psychosis

A

Symptoms fluctuate over lifetime; target therapy to sxs
Non-psychotic symptoms such as mood changes may also be present and necessitate treatment with non-AP medications
mood stabilizers, anti-depressants

125
Q

Benefits of Maintenance TX

A

Maintenance treatment contributes to relapse prevention and  hospitalization rates but does not eliminate risk of relapse

Risk of re-hospitalization or death ↑ when the duration of AP tx prior to discontinuation gets longer; may relate to AP-induced neurologic changes

126
Q

Duration of Maintenance Tx

A

2017 Can. Schizophrenia Guidelines suggest maintenance AP therapy for 2 yr
Possibly up to 5 years longer

127
Q

Psychosis and SUD

A

SUDs are found in up to 45% of schizophrenia patients
Stimulant and cannabis use are associated with psychosis
Example: cannabis users develop psychosis 2.7 years before non-users
Substance use also results in worse outcomes
Treatment nonadherence, relapse, etc.
Often difficult to determine whether psychosis came first and substances are used for self-treatment, or whether substances have caused the psychosis
Screen all psychosis patients for SUD

128
Q

Psychosis and SUD: Indicative of underlying psychotic disorder

A

psychosis persists with abstinence;
symptoms do not align with type/amount of substance used;
family hx of psychosis;
typical positive symptoms of schizophrenia
e.g. auditory hallucinations
presence of negative/cognitive symptoms

129
Q

Psychosis and SUD: TX

A

No evidence of benefit for one AP over another for psychosis &
Clozapine preferred limited data.

130
Q

Define TRS/Psychosis. How many meet this criteria?

A
131
Q

First Line TX TRS

A

Clozapine; response rate of 30 but often underprescribed due to fear of ADE, lack of familiarity
Delaying clozapine initiation may decrease response

132
Q

Cloazapine MOA and receptors

A
133
Q

Cloazpine Efficacy. Other indications?

A

Most effective antipsychotic for treatment-resistant schizophrenia
30% response rate

Other uses:
Tardive dyskinesia (mixed evidence)
Bipolar disorder
Schizoaffective disorder
Psychosis in patients with Parkinson’s disease (lot less likely to cause movement effects)

134
Q

Common s/e Clozapine

A
135
Q

Serious S/E Cloazpine

A
136
Q

Cloazpine Induced Agranulocytosis

A

Clozapine-induced agranulocytosis 1-2%
Dangerously low neutrophil count (<0.5x109/L)
Neutropenia occurs at neutrophil count <1.5x109/L
↑ infection risk
Reversible upon discontinuation of clozapine
Health Canada mandates registration of each patient into a monitoring database to detect potentially reversible agranulocytosis (2%)
Requires monitoring of CBC with differential

137
Q

Clozapine Induced Myocarditis

A

Clozapine-induced myocarditis 0.06-3.88%
Mortality rate 10-23%
Inflammation of the heart muscle
Cardiomyopathy can also occur
Requires monitoring of CRP and troponin

138
Q

Clozapine Induced Constipation

A

Constipation 14%
Severe constipation can lead to adynamic ileus
Mortality rate 7.3%
Requires bowel function monitoring

139
Q

When does agranulocytosis occur?

A

Agranulocytosis most likely to occur in first 6 months of treatment

140
Q

When does myocarditis occur? Monitoring?

A

Myocarditis most likely to occur in first 4-8 wks of treatment
Monitoring Troponin and CRP weekly x 6 weeks is 99% sensitive to identify myocarditis

141
Q

When does cardiomyopathy occur?

A

Cardiomyopathy most likely to occur after months to years of treatment

142
Q

What should be noted about mserious a/e of clozapine?

A

However, agranulocytosis, myocarditis and cardiomyopathy can still occur at anytime during treatment
Literature demonstrates a clear need to implement close and structured monitoring of patients on clozapine to prevent development of agranulocytosis and myocarditis

143
Q

What is myocarditis?

A

Allergic-like reaction causing inflammation of the heart

144
Q

What is cardiomyopathy?

A

Disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body

145
Q

how can Cardiomyopathy and myocarditis be monitored?

A

High sensitivity troponin T

CRP

146
Q

What is agranulocytosis and reason for blood work?

A
147
Q

Is agranulocytosis reversible?

A

reversible upon clozapine discontinuation

148
Q

What is required by health canada regarding Clozapine?

A

Clozapine can only be used if hematological monitoring (CBC with diff - neutrophils) can be guaranteed AND patient is actively registered with a clozapine registry (has a clozapine “PIN #”)

Available through manufacturer-specific registries and distribution systems (e.g. CSAN – Clozaril Support and Assistance Network)

149
Q

Clozapine Registeries Avilable

A
150
Q

Monitroing of Clozapine

A

Weekly blood tests for the first 6 months
High risk period
Change to once every 2 weeks if “green light” has been maintained during the first 6 months of therapy and patient is clinically stable
Change to once every 4 weeks if “green light” for another 6 months
Monitoring MUST continue for as long as the patient is on clozapine and even for 4 weeks after stopping

151
Q

Clozapine Missed Doses

A

Monitoring frequency does not have to be modified if therapy is interrupted for 3 days or less but dosing needs to re-titrated if miss >48 hours

Hematological testing should be resumed weekly for an additional 6 weeks if therapy is disrupted for more than 3 days

So important to always assess adherence!

152
Q

Describe the zones of clozapine and what to do in each zone?

A
153
Q

Clozapine: If in red zone?

A

Non-rechallengeable =

Must stop and cannot ever restart therapy if total WBC <2.0 x 109 or ANC <1.5 x 109 from clozapine therapy

Must be communicated with clozapine registry

Will require weekly CBC x 4 weeks when stopped
Likely would be done more frequently than weekly when patient is neutropenic (patient would be hospitalized)

154
Q

Key Critical Point for dispensing of clozapine?

A

Also quantity of clozapine dispensed must be limited to the frequency of clozapine bloodwork
i.e. patient on q2weekly blood work can only have 2 weeks of clozapine dispensed from community pharmacy

155
Q

Can clozapine be switched to a generic?

A

Do NOT switch between brand/generics

paid by the government

156
Q

How does smoking interfere with clozapine?

A

Smooking reduces clozapine by 40%

1A2 Induction

Does not occur via nicotine rather aromatic hydrocarbons

157
Q

Clozapine Augmentation

A

Multiple clozapine augmentationstrategies but lim. consensus on best
Data for aripiprazole, fluoxetine, sodium valproate for total psychosis, memantine for negative symptoms

158
Q

Clozapine Resistant TRS and AP use

A

No consistent evidence to support use of high dose AP, switching APs, or AP polypharmacy

159
Q

Non-Pharm TRS

A

ECT if clozapine resistance; Trans Magnetic Stimulation less evidence but better tolerated than ECT; Cognitive Behavioural Therapy.

160
Q

Acute EPS Sx: How do they occur?

A

o Most are due to dopamine (D2) blockade
o Involuntary

161
Q

What dos tardive mean?

A

Appearing late; after 30 days

162
Q

WHy are tardive sx concerning?

A

Often permemenant

163
Q

When do acute EPS side effects occur?

A

Within 30 days

164
Q

TX of Acute EPS

A

Respond to antiparkinsonian drugs (except akathisia which may be mediated by alternate mechanism and thus responds to other treatments)

165
Q

Tardive Syndrome TX

A

Valbenazine and deutetrabenazine are FDA-approved drugs for treating tardive dyskinesia (TD). No other medication or strategy have proven efficacy in clinical trials.
PREVENTION is key!

166
Q

Tardive Sx TX Facts

A

Early recognition and discontinuation of offending antipsychotic are recommended to improve chance of remission but stopping antipsychotic is not always an option

Dosage reduction or use of lowest effective dose is an another alternative but the success of dosage reduction or cessation has not been proven and must be weighed against the risk of relapse

If medication is stopped or dose reduced, a slow taper is recommended to avoid worsening TD due to withdrawal emergent syndromes

Switching to atypical antipsychotics such as clozapine/quetiapine has been recommended but high doses of atypical may also cause TDs
Anticholinergic agents: No benefit and may worsen TDs (may benefit tardive dystonia)

167
Q

Acute Dystonias Summary

A

 Head and neck torsions and spasms
 Occurs within 24-48 hours of the first dose. Can be tardive.
 May be life-threatening if laryngeal/pharyngeal involvement
 1st line: benztropine. Can also use IM diphenhydramine

168
Q

Acute dystonia Scale

A

Extrapyramidal Symptom Rating Scale (ESRS)
Simpson Angus EPS SCALE (SAS)

169
Q

Akathesia, Tx and Rating Scale

A

 Restless symptoms, can cause violent outbursts
 Can be tardive
 Contributes to suicide and violence
 Treament: reduce dose or change AP, benzodiazepines, beta-blockers, mirtazapine
 Use the BARS scale to monitor

170
Q

Acute pseudoparkinism

A

 Tremors, rigidity, brady kinesia
 Biggest risk if high potency FGA
 Treatment: reduce dose/change AP, antiparkinsonian drugs

Same rating scales as acute dystonias

171
Q

Pisa Syndrome

A

 Leaning to one side
 Treat with antiparkinsonian drugs
Antiparkinsonian drugs (benztropine, procyclidine, trihexyphenidyl)

172
Q

Rabbit Syndrome

A

 Fine tremor of lower lip
 Treat with antiparkinsonian drugs

Antiparkinsonian drugs (benztropine, procyclidine, trihexyphenidyl)

173
Q

Tardive Dyskinesia

A

Involunary abnormal movements of the face, lips, jaw, tongue, eyelids, limbs, trunk, neck, or respiratory
 Onset after 3 or more months of therapy
 Persistent, does not go away when you stop the AP
 Treatment: switch to SGA or TGA?
Valbenazine and deutetrabenazine
 Use AIMS scale to monitor

174
Q

What is neuroleptic malignant syndrome? Sx, Time it occurs, TREATMENT?

A
175
Q

Drug Interactions Chart

A

PHAR 358 (4 decks)

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