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Pharmacotherapeutics > Antipsychotics - Schizophrenia > Flashcards

Antipsychotics - Schizophrenia Flashcards

1
Q

Clinical presentation of schizophrenia

A
  • A mix of positive symptoms, negative symptoms and functional impairment
  • Two or more of the following for at least 6 months (each symptom taking up a significant portion of at least a month)
    » Delusions
    » Hallucinations
    » Disorganized speech
    » Grossly disorganized or catatonic behavior
    » Negative symptoms
  • Socio-occupational dysfunction
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2
Q

Symptoms of schizophrenia are caused by medicines and substance abuse. T/F?

A

False.

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3
Q

Non-pharmacological treatments for schizophrenia and what are they used to treat

A
  • Individual Cognitive Behavioral Therapy (CBT)
    » Used in conjunction with all medications and family intervention.
    » Applicable for those with schizophrenia
  • Electroconvulsive therapy (ECT)
    » Used for treatment-resistant schizophrenia
  • Repetitive Transcranial Magnetic Stimulation (rTMS)
    » Effective for reducing auditory hallucinations amongst patients with schizophrenia
  • Psychosocial rehabilitation programs: improving patient’s adaptive functioning
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4
Q

Individual, group, cognitive behavioural non-pharmacological therapies

A

Individual - Counselling, social skills therapies, vocational rehab

Group - Interactive/social

Cognitive behavioural - CBT, Compliance therapy

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5
Q

What are the different phases of treatment and their goals?

A
  • Acute Stabilization
    » Goal: ↓ agitation, aggression, hostility; improve sleep
    » Minimize threat to self and others
    » Minimize acute symptoms
  • Stabilization
    » Minimise/prevent relapse
    » Promote medication adherence
    » Optimize dose vs. adverse effects
  • Stable/maintenance phase
    » Improve functioning and QoL
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6
Q

Antipsychotic medications treatment principles

A
  • In the short term, they are used to calm disturbed patients whatever the underlying psychopathology might be.
    » E.g. schizophrenia, mania, toxic delirium, agitated depression
  • Common indication: schizophrenia and other psychoses.
  • Relieve symptoms of psychosis such as thought disorder, hallucinations and delusions, and prevent relapse.
  • Long-term treatment is often necessary after first episode of psychosis, to prevent illness from becoming chronic.
  • Relapse often delayed for several weeks after cessation of treatment
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7
Q

Methods to overcome poor treatment adherence

A
  • IM long-acting injections
  • Community psychiatric nurse
  • Patient and Family (caregiver) education
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8
Q

MOA for antipsychotics (different nervous tracts)

A
  1. Mesolimbic tract
    - Blockade of dopamine receptors in the tract is the most common mechanism of action for all antipsychotic.
    - Overactivity in this region is responsible for the positive symptoms of schizophrenia.
  2. Blockade of the remaining 3 dopamine tracts will cause adverse effects:
    - Mesocortical tract: dopamine blockade results in negative symptoms.
    - Nigrostriatal tract: dopamine blockade results in EPSE.
    - Tuberoinfundibular tract: dopamine blockade results in hyperprolactinemia
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9
Q

Receptor affinities: Clinical implications

D2

A

Therapeutic effects:
improves positive symptoms

Side effects:
EPSE, hyperprolactinemia

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10
Q

Receptor affinities: Clinical implications

5-HT2A

A

Therapeutic effects:

Antidepressant effects, improve negative symptoms

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11
Q

Receptor affinities: Clinical implications

5-HT2c

A

Side effect:

Weight gain

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12
Q

Receptor affinities: Clinical implications

H1

A

Side effects:

Sedation, weight gain

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13
Q

Receptor affinities: Clinical implications

alpha-1

A

Side effects:

Orthostasis, sedation

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14
Q

Receptor affinities: Clinical implications

M1

A

Side effects:

Anticholinergic effects

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15
Q

Receptor affinities: Clinical implications

Ikr

A

Side effects:

QTc interval prolongation

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16
Q

Pharmacological treatment: algorithm for schizophrenia

A
  1. Use of FGA or SGA
  2. If it doesn’t work, swap out with another FGA or SGA
  3. If it still doesn’t work, administer clozapine
  4. Consider clozapine + augmenting agent (FGA or SGA or ECT) and combination therapy (FGA + FGA, FGA+SAG), antipsychotic + ECT or other agent (e.g. mood stabiliser)
17
Q

Key things to note for the regimen

A
  • Medication selection is individualized for a patient
  • Patients require compliance to an adequate trial of antipsychotics (at least 2-6 weeks at optimal therapeutic doses.
  • Manage any intolerable side effects.
  • Consider long-acting IM If inadequately compliant.
  • Consider Clozapine in those who are treatment-resistant (i.e. those who had failed ≥ 2 adequate trails of different antipsychotics (at least 1 should be a SGA).
  • Routine hematological monitoring is required for those on Clozapine.
18
Q

Adjunctive treatment for schizophrenia

A
  1. Acute agitation (psychiatric emergency)
    - If patient cooperates, consider oral medication:
    » Oral lorazepam, or oral risperidone (second-line)
    » Oral antipsychotic +/- benzodiazepine
  • If patient does not cooperate, consider fast-acting IM injection:
    » IM Lorazepam (2mg) + IM Haloperidol (5mg)
  1. Catatonia
    - Benzodiazepines, IM Lorazepam
19
Q

Pharmacokinetics of antipsychotics

A

Administer lurasidone and ziprasidone with food

20
Q

Side effects of medications, risks and management

  1. Dystonia
  2. Pseudo-parkinsonism
  3. Akathisia
  4. Tardive dyskinesia
  5. Hyperprolactinemia
  6. Metabolic
  7. Cardiovascular
  8. CNS
  9. Hematological
A
  1. Dystonia
    Risks:
    - High potency antipsychotics (haloperidol)
    Management:
    - IM anticholinergics (benzodiazepine, diphenhydramine)
    - Or switch to lower-potency antipsychotics (e.g. Quetiapine, Sulpiride)
  2. Pseudo-parkinsonism
    Management:
    - Decrease antipsychotic dose, or switch to SGA.
    - Anticholinergics PRN (benzodiazepines)
  3. Akathisia
    Management:
    - Decrease antipsychotic dose, or switch to SGA
    - Clonazepam (low dose) PRN
4. Tardive dyskinesia 
Risks: 
- Higher risk of getting it on FGA than on SGA 
- Can worsen with anticholinergic drugs 
Management: 
- Discontinue any anticholinergics 
- Decrease antipsychotic use, or switch to SGA 
- Administer valbenazine or clonazepam
  1. Hyperprolactinemia
    Management:
    - Switch to aripiprazole
  2. Metabolic
    Risks:
    - High: olanzapine, clozapine
    - Low: aripiprazole, lurasidone
    Management:
    - Maintain on current antipsychotic to prevent relapse, but treat the emergent diabetes (e.g. with metformin, hyperlipidemia)
    - Switch to lower-risk agents (aripiprazole, brexiprazole, lurasidone)
7. Cardiovascular 
Risks: 
- Focus on: VTE/PE: 
- SGA>FGA>Aripiprazole 
Management: 
- Manage emergent DVT
  1. CNS
    Risks:
    - Caused by: high potency antipsychotics (e.g. haloperidol)
    - Focus on: Neuroepileptic malignant syndrome (NMS):
    -Muscle rigidity, fever, autonomic dysfunction
    Management:
    - IV Dantrolene, oral dopamine
    - Switch to SGA
9. Hematological 
Risks: 
- Caused by: Clozapine ↓ WBC
- Agranulocytosis 
Management:
- Discontinue antipsychotics if severe
21
Q

Monitoring of the following side parameters and side effects:

A). General requirements

  1. BMI
  2. Fasting blood sugar
  3. Lipid panel (mmol/L)
  4. Blood pressure (mmHg)
  5. EPSE exam

B). Drug-specific requirements
1. WBC and ANC (Clozapine)

A

A). General requirements

  1. BMI
    - Side effect: weight gain
    - Periodical monitoring: Q3 months when dose stabilized
  2. Fasting blood sugar
    - Side effect: diabetes mellitus
    - Periodical monitoring: 3 months after initiating SGA, then annually
  3. Lipid panel (mmol/L)
    - Side effect: hyperlipidemia
    - Periodical monitoring:
    Low risk patients: q2-5 years
    High risk patients: 3 months after initiating SGA, q6 months
  4. Blood pressure (mmHg)
    - Side effect: increase or decrease BP
    - Periodical monitoring:
    3 months then annually
  5. EPSE exam
    - Side effect: EPSE
    - Periodical monitoring:
    Weekly for first 2 weeks after initiation of new antipsychotic or until dose stabilized
B). Drug-specific requirements 
1. WBC and ANC (Clozapine)
- Side effect: 
Leucopenia / Agranulocytosis 
Periodical monitoring: 
- Weekly for first 18 weeks, then monthly
22
Q

Treatment for special populations (elderly)

A
  • Avoid drugs with high propensity for α1-adrenergic blockade or anticholinergic side effects
  • Simplify regime
23
Q

Time course of treatment response

A
  • Early improvements
    » 1st week: reduced agitation
    » 2-4 weeks: reduced paranoia and hallucinations
  • Late improvements
    » 6-12 weeks: reduced delusions
    » 3-6 months: cognitive symptoms may improve (with SGAs)
24
Q

MOA of antipsychotics

A
  • FGA and SGA
    » D2 antagonism (on mesolimbic dopamine tract) improves positive symptoms
  • SGA only:
    » 5HT2A antagonism may improve mood symptoms and also negative symptoms
25
Q

Clinical differences between SGA and FGA

A
  1. Efficacy:
    - SGA is effective for both positive and mood symptoms
    - FGA effective for mainly positive symptoms
  2. Toxicity:
    - FGA generally has more “muscle side effects” (EPSE)
    - SGA: generally has more “metabolic sied effects” (except Aripiprazole, Brexipiprazole, Lurasidone etc.)
  3. SGAs
    - The “-Ines” (e.g. clozapine, olanzapine, quetiapine)
    » Relatively more sedating, more weight gain
    - The ‘-ones’ or ‘-piprazoles)
    » Relatively less sedating, less weight gain
26
Q

Pharmacotherapy management for the different schizophrenia phases

A
  1. Acute Stabilization Phase
    - Goal: reduce agitation, aggression, hostility, improve sleep
  • If acutely agitated/aggressive:
    » 1st: De-escalate
    » 2nd: Consider oral antipsychotic +/- benzodiazepine
    » 3rd: if refuse or not possible to administer oral medications
    »> Consider fast-acting IM alternatives with monitoring (IM haloperidol + IM Lorazepam)
  • Monitor for treatment-emergent adverse effects
    » E.g. dystonia, pseudo-parikinsonism side effects: treat accordingly (e.g. oral or IM benztropine 2mg)
  1. Stabilization and maintenance phase
    - If poor adherence to oral medication, or if patient prefers IM, consider:
    » IM long-acting antipsychotic, e.g. IM haloperidol decanoate
27
Q

Haloperidol dose

A

5-15mg/day

28
Q

Clozapine dose

A

900mg max

29
Q

Olanzapine dose

A

900mg max

30
Q

Quetiapine

A

800mg max

31
Q

Risperidone

A

2-6mg/day starting dose

32
Q

Haloperidol decanoate

A

max 300mg/4wk

33
Q

Risperidone long-acting

A

starting dose: 25-37.5mg/2weeks

max: 50mg/2 weeks

Pharmacotherapeutics (28 decks)

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