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Pharm 2 > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

DSM-5 Criteria for
Schizophrenia
* > 2 of following symptoms
present for 1 month period:
(5)

A
  • delusions
  • hallucinations
  • disorganized speech
  • grossly disorganized or
    catatonic behavior
  • negative symptoms
    (affective blunting, alogia
    or avolition)
  • significant effect
    major areas of
    functioning
  • continuous signs of
    disturbance persist for
    at least 6 months
  • symptoms are not due to a
    another psychiatric illness,
    medical disorder or
    substance induced
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2
Q

Schizophrenia
(3)

A

Primary Negative
Symptoms
Psychotic or
Positive
Symptoms
Primary
Cognitive
Symptoms

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3
Q

Proposed Pathophysiology of
Schizophrenia

A
  • dopamine theory
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4
Q

Uses for Antipsychotics
* FDA Approved Indications
(4)
* Off-Label Uses
(5)

A

– Schizophrenia
– Bipolar Disorder
– Adjunctive Therapy in Major
Depressive Disorder
– Autism Spectrum Disorder

– Anxiety Disorders
– PTSD
– OCD
– Psychosis (other than
schizophrenia)
– Acute treatment of
aggression and agitation

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5
Q

Adverse Effects by Receptor
Blockade
* Dopamine antagonism

A

– Extrapyramidal Side Effects (EPS) – “movement
disorders”
» Dystonic reaction
» Pseudoparkinsonism
» Akathisia
» Tardive dyskinesia
– Hyperprolactinemia –
» galactorrhea, menstrual irregularities /
amenorrhea, gynecomastia, sexual dysfunction

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6
Q

Extrapyramidal Side Effects (EPS)
Acute Dystonia

A
  • acute dystonic reaction - “severe muscle spasm”
    eye-oculogyric crisis neck-torticollis
    back-retrocollis tongue-glossospams
    pharyngeal-laryngeal dystonia
  • incidence: 2-64%
  • pathophysiology: imbalance between DA and ACh
  • onset: usually occurs during first 5 days of treatment or
    after a dosage increase
  • risk factors: high potency AP, large doses, IM
    administration, young males
  • treatment
    – acute treatment - AC agent [ex. benztropine (Cogentin)], diphenhydramine
    (Benadryl) or a benzodiazepine
    – chronic treatment - decrease dose, change AP agent, AC agent
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7
Q

Anticholinergic Drugs to Treat Dystonia
(3)

A
  • Benztropine
    (Cogentin)
  • Trihexyphenidyl
    (Artane)
  • Diphenhydramine
    (Benadryl)
    Oral side effect – dry mouth
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8
Q

EPS - Pseudoparkinsonism

A
  • four cardinal symptoms
    – akinesia, bradykinesia or decreased motor activity
    – tremor
    – cogwheel rigidity
    – postural abnormalities
  • incidence: 15-36%
  • pathophysiology: decrease in DA activity
  • onset: 1-2 weeks after AP initiation or increase in dose
  • risk factors: high potency AP, increased AP doses, age > 40,
    female
  • treatment: decrease dose, change AP agent, AC agents
    [benztropine (Cogentin)], DA agonist [amantadine
    (Symmetrel)]
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9
Q

Anticholinergic Drugs to Treat
Pseudoparkinsonism
(2)

A
  • Benztropine
    (Cogentin)
  • Trihexyphenidyl
    (Artane)
    Oral side effect – dry mouth
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10
Q

EPS - Akathisia

A
  • extreme motor restlessness/inability to sit still
    – patient can not typically control akathisia for even a short time period
  • incidence: 25-36%
  • pathophysiology: unknown
  • onset: 2-4 weeks
  • difficult to distinguish from anxiety/agitation/psychosis
    – akathisia made worse with increased AP doses
  • risk factors: high potency AP, large AP dose
  • treatment: decrease dose, change AP agent, beta blocker
    [propranolol (Inderal)] , or a benzodiazepine
    – No oral side effects associated with propranolol
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11
Q

Propranolol (Inderal)
* MOA -
* Common Side Effects
(5)

A

nonselective
beta-adrenergic
receptor blocking
agent

– Dizziness, weakness
and fatigue
* No life-threatening side
effects
* No oral side effects
* Overdose –
hypotension and
bradycardia
* High risk for drug
interactions

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12
Q

EPS - Tardive Dyskinesia

A
  • syndrome characterized by involuntary movements
    – buccal-lingual-masticatory syndrome (BLM)
    – orofacial movements
    – writhing movements of face, neck, back, trunk and extremities
  • incidence: 20%
  • pathophysiology: (1) increase in DA receptor sensitivity (2)
    neuronal degeneration
  • onset: usually late (years)
  • risk factors: increased age, female, concurrent diagnosis of
    mood d/o, long duration of AP use
  • AIMS (Abnormal Involuntary Movement Scale)
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13
Q

EPS - Tardive Dyskinesia
Treatment

A
  • prevention
  • reduce dose of AP – always use lowest effective
    dose
  • change AP to second generation antipsychotic (SGA)
    – clozapine – treatment option
  • 2 drugs recently FDA approved for TD
    – MOA – vesicular monoamine transporter 2 inhibitor
    (VMAT2)
    » Valbenazine (Ingrezza)
  • Oral side effect – dry mouth
    » Deutetrabenazine (Austedo)
  • Oral side effect – dry mouth
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14
Q

Oral Side Effects
* FGA
(7)
* Medications to treat
side effects of FGA
– Dry Mouth
(5)

A

– Chlorpromazine
(Thorazine)
» Dry mouth
» Hypersalivation (EPS)
» Sialorrhea (EPS)
– Haloperidol (Haldol)
» Hypersalivation (EPS)
» Sialorrhea (EPS)

» Benztropine (Cogentin)
» Trihexyphenidyl
(Artane)
» Diphenhydramine
(Benadryl)
» Valbenazine (Ingrezza)
» Deutetrabenazine
(Austedo)

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15
Q

Summary – First Generation
Antipsychotics
* Advantages
(3)
* Disadvantages
(6)

A

– effective for positive
symptoms
– multiple dosage
formulations available
– decreased cost

– not effective in 30% of
patients
– minimal efficacy for negative
symptoms
– minimal efficacy for cognitive
symptoms
– high side effect burden
(EPS)
– risk of tardive dyskinesia
– nonadherence

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16
Q

Clozapine (Clozaril or Fazaclo)
* Indications
(2)
* Additional Information
(5)

A

– Treatment refractory schizophrenia
» Lack of efficacy
» Intolerable side effects (i.e. TD)
– ↓ risk of recurrent suicidal behavior in schizophrenia and schizoaffective
disorder

– agranulocytosis
– dose related seizure risk
– myocarditis
– oral side effects
» dry mouth, sialorrhea, hypersalivation

17
Q

Risperidone (Risperdal)
* Indications
(3)

A

– Schizophrenia
» Acute treatment
* Adults + adolescents 13-17 years
» Maintenance treatment
– Bipolar I Disorder
» Acute Manic or Mixed Episodes – monotherapy or in combination with
lithium or VPA
* Adults + children and adolescents 10-17 years
– Autism
» Treatment of irritability associated with autistic disorder in children and
adolescents (ages 5-16 years)
» Symptoms of aggression towards others, deliberate self-injuriousness,
temper tantrums, and quickly changing moods

18
Q

Risperidone
* Additional information
(3)

A

– doses > 6 mg/day = increase risk of EPS
– ↑ prolactin - not dose related
– no oral side effects

19
Q

Olanzapine (Zyprexa)
* Indications
(2)

A

– Schizophrenia
» Acute treatment
* Adults and adolescents 13-17 years
» Maintenance treatment
– Bipolar I Disorder
» Acute Manic or Mixed Episode – monotherapy or combination with
lithium or VPA
* Adults and adolescents 13-17 years
» Maintenance treatment – monotherapy
» Depressed Episodes - combination product only (Symbyax - olanzapine
+ fluoxetine)

20
Q

Olanzapine
* Indications
(2)

A

– Treatment Resistant Major Depressive Disorder –
combination product only (Symbyax – olanzapine + fluoxetine)
» Defined as nonresponse to 2 separate trials of different
antidepressants of adequate dose and duration in the
current episode
– Acute agitation associated with schizophrenia or Bipolar I
mania (IM formulation only)

  • Other Information
    – oral side effect – dry mouth
21
Q

Quetiapine (Seroquel and Seroquel XR)
* Indications
(3)
* Additional Information
(2)

A

– Schizophrenia
» Acute treatment
» Maintenance Treatment
– Bipolar I Disorder
» Acute Manic of Mixed Episodes – monotherapy or in combination with
lithium or VPA
» Depression (Bipolar I and II disorder)
» Maintenance
– Adjunctive Treatment of Major Depressive Disorder (inadequate response to
antidepressant monotherapy)

– Oral side effect – dry mouth
– Commonly used off-label as a sedative hypnotic and anxiolytic

22
Q

Aripiprazole (Abilify)
* Mechanism of
action
(2)

A

– D2 partial agonist
– 5HT2a antagonist

23
Q

Aripiprazole
* Indications
(4)

A

– Schizophrenia (Adults + adolescents 13-17 years)
» Acute treatment
» Maintenance treatment
– Bipolar Disorder I (Adults + children/adolescents 10-17 years)
» Acute Manic or Mixed Episodes – monotherapy or in combination with
VPA or lithium
» Maintenance treatment
– Adjunctive treatment of Major Depressive Disorder (inadequate
response to antidepressant monotherapy)
– Autism
» Treatment of irritability associated with autistic disorder in children and
adolescents (ages 5-16 years)
» Symptoms of aggression towards others, deliberate self-injuriousness,
temper tantrums, and quickly changing moods

24
Q

Aripiprazole
* Other Information
(2)

A

– akathisia is more common than other types of EPS
– no oral side effects

25
Q

Lurasidone (Latuda)
* Indications
(3)
* Additional Information
(2)

A

– Schizophrenia
» Acute treatment
– Depressive episodes associated with Bipolar I disorder

– Must be taken with food (at least 350 kcal)
– No oral side effects

26
Q

Oral Side Effects
of SGA
* Sialorrhea,
Hypersalivation
(1)
* Dry Mouth
(3)

A

– Clozapine (Clozaril)

– Clozapine (Clozaril)
– Olanzapine (Zyprexa)
– Quetiapine (Seroquel)

27
Q

Summary – SGA
* Advantages
(4)
* Disadvantages
(1)

A

– effective for positive symptoms
– may be effective for negative
symptoms
– clozapine effective in treatment
refractory schizophrenia
– improved side effect profile as
compared with FGA
» decreased risk of TD
» decreased incidence of EPS
» minimal to no prolactin elevation
(except RIS)

– risk of metabolic side
effects

28
Q

Selection of Antipsychotic Therapy

A
  • Second Generation Antipsychotics (with the
    exception of clozapine, olanzapine, and iloperidone)
    have become the agents of first choice for the
    treatment of schizophrenia.
    – Practice guidelines and consensus statements support this
    recommendation.
29
Q

Maintenance Antipsychotic Therapy

A
  • Relapse rates are extremely high
    – 60-80% relapse rate within 1 year with no antipsychotic therapy
    – 20% relapse rate within 1 year with continued antipsychotic therapy
30
Q
  • Treatment duration:
    1st episode - treat x – year
    2nd episode - treat x – years
    > 2 episodes - treat for —
A

1
5
lifetime

30
Q

Response to
Antipsychotic Therapy

A

*decreased: agitation/
hostility/aggression/
combativeness/anxiety
*normalization of sleep
and eating patterns
*improvement in
socialization/
self-care habits/
mood
*improvement in
thought disorder/
mood
*decrease in
delusions/
hallucinations
*appropriate
conversation
potentially
persistent symptoms
*impaired insight/
judgment
*inappropriate affect
*fixed delusions/
hallucinations
Expect to see initial improvement
in symptoms within 2 weeks of
starting antipsychotic therapy.
Maximum response make take up
to 6-8 weeks.

30
Q
A
31
Q
A

Pharm 2 (13 decks)

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