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pharm 2 > antipsychotics > Flashcards

antipsychotics Flashcards

1
Q

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~~~

DSM-5 Criteria for
Schizophrenia

A
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2
Q

positive Symptoms of Schizophrenia

A
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3
Q

negative Symptoms of Schizophrenia

A
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4
Q

cognitive symptoms of Schizophrenia

A
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5
Q

Proposed Pathophysiology of
Schizophrenia
*

A
  • dopamine theory
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6
Q

Dopaminergic Pathways

A

Nigrostriatal (A9)
Mesolimbic (A10)
Mesocortical (A10)
Tuberoinfundibular

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7
Q

Nigrostriatal (A9) function

A

EP system - movement

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8
Q

mesolimbic function

A

arousal, memory,
motivation

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9
Q

mesocortical function

A

cognition,
communication,
social function,
response to stress

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10
Q

tuberoinfundibular function

A

regulates prolactin
release

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11
Q

Uses for Antipsychotics
* FDA Approved Indications

A

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

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12
Q

off label Uses for Antipsychotics

A

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

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13
Q

FGA – Mechanism of Action

diagram

A

postsynaptic d2 antagonism

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14
Q

Effect of Nonselective Dopamine (D2) Antagonism of FGA

at dif D paths

A
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15
Q

Dopaminergic Pathways – Effect of FGA on pathways

A
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16
Q

FGA Efficacy and activity

A
  • limited spectrum of efficacy/ activity, only tx’s psychosis
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17
Q

Relative Potencies of FGA

A

halo= high and chlorpro=low

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18
Q

what other receptors afre affects by FGAs

A

a1, M1, H1

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19
Q

Adverse Effects by Receptor
Blockade at H1 due to FGA

A

dry mouth, drowsy

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20
Q

Adverse Effects by Receptor
Blockade at M1 due to FGA

A
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21
Q

Adverse Effects by Receptor
Blockade at alpha due to FGA

A
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22
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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23
Q

Side Effect Profile - FGA: haloperidol

A
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24
Q

Side Effect Profile - FGA: Chlopromazine

A
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25
Q

which FGA is more likely to have side effect associated with H, M and a receptors?

A

Chlopromazine

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26
Q

Extrapyramidal Side Effects (EPS) of antipsychotics

A
  • acute dystonia
  • pseudoparkinsonism
  • akathasia
  • tarditive dyskenisia
    *
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27
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

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28
Q

incidence acute dystonia

A

2-64%

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29
Q

acute dystonia pathophys

A

mbalance between DA and ACh

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30
Q

acute dystonia onset

A

usually occurs during first 5 days of treatment or after a dosage increase

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31
Q

acute dystonia risk factors:

A

high potency AP, large doses, IM administration, young males

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32
Q

acute dystonia tx:
– acute treatment
– chronic treatment

A

– acute treatment - AC agent [ex. benztropine, diphenhydramine or a benzodiazepine
– chronic treatment - decrease dose, change AP agent, AC agent

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33
Q

Drugs to Treat Dystonia

dental implication?

A
  • Benztropine- IM
  • Trihexyphenidyl-IM
  • Diphenhydramine
    Oral side effect – dry mouth

Anticholinergic agenst target M1

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34
Q

Pseudoparkinsonism
signs

A
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35
Q

what aspects of pseudopark may influence dentistry

A

excessive drooling and rigidity/trembling of head

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36
Q

four cardinal symptoms of pseudoparkinsonism
– motor?
– tremor?
– rigidity?
– posture?

A

four cardinal symptoms
– akinesia, bradykinesia or decreased motor activity
– tremor
– cogwheel rigidity
– postural abnormalities

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37
Q

Pseudoparkinsonism incidence

A

15-36%

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38
Q

pseudopark pathophysiology:

A

decrease in DA activity

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39
Q

pseudopark onset

A

1-2 weeks after AP initiation or increase in dose

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40
Q

pseudopark risk factors

A

high potency AP, increased AP doses, age >40, female

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41
Q

tx pseudopark

A

treatment: decrease dose, change AP agent, AC agents [benztropine/Trihexyphenidyl], DA agonist [amantadine]

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42
Q

Drugs to Treat
Pseudoparkinsonism

dental implications?

A
  • Benztropine
  • Trihexyphenidyl
    Oral side effect – dry mouth

M1 antagonists

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43
Q

Akathisia

A
  • extreme motor restlessness/inability to sit still
    – patient can not typically control akathisia for even a short time period
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44
Q

akathsia incidence

A

incidence: 25-36%

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45
Q

akathasia pathophys

A

pathophysiology: unknown

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46
Q

akathasia onset

A

onset: 2-4 weeks

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47
Q

Akathisia dif to distinguish from?

A

difficult to distinguish from anxiety/agitation/psychosis
– akathisia made worse with increased AP doses

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48
Q

akathasia risk factors

A

high potency AP, large AP dose

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49
Q

akathasia tx

A

treatment: decrease dose, change AP agent, beta blocker
propranolol , or a benzodiazepine

50
Q

how can propranolol be useful for akathasia tx from a dental view

A

no oral side effect

51
Q

Propranolol (Inderal)
* MOA

A

Propranolol (Inderal)
* MOA - nonselective
beta-adrenergic
receptor blocking
agen

used for akathaisa

52
Q

Propranolol:
* Common Side Effects
* life-threatening?
* oral side effects?
* Overdose?
* ddi?

A
  • Common Side Effects
    – Dizziness, weakness and fatigue
  • No life-threatening side effects
  • No oral side effects
  • Overdose – hypotension and bradycardia
  • High risk for drug interactions
53
Q

Tardive Dyskinesia

A
  • syndrome characterized by involuntary movements
  • – buccal-lingual-masticatory syndrome (BLM)- makes dental tx hard
    – orofacial movements
    – writhing movements of face, neck, back, trunk and extremities
54
Q

incidence tarditive dyskenesia

55
Q

tarditive dyskenesia pathophysiology

A

(1) increase in DA receptor sensitivity
(2) neuronal degeneration

56
Q

tarditive dykenesia onset

57
Q

tarditive dyskenesia risk factors

A

increased age, female, concurrent diagnosis of mood d/o, long duration of AP use

58
Q

Tardive Dyskinesia Treatments:
* first step?
* dosages?
* AP agent?
* Rx’s used?

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
59
Q

Oral Side Effects
* FGA’s

60
Q

Oral side effects of Medications to treat
side effects of FGA

61
Q

CV Side Effects of FGA

62
Q

Weight Gain and FGA

63
Q

FGA advantages

A

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

64
Q
  • FGA Disadvantages
A

– 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

65
Q

SGA – Mechanism of Action

A

Selective Dopamine (D2) Antagonism and Serotonin Antagonsim (5 -HT2A) of SGA

66
Q

Advantages of SGA different moa

A

Advantages of Selective Dopamine (D2) Antagonism and Serotonin Antagonsim (5-HT2A) of SGA
block of 5ht works to increase DA in non-mesolimbic paths to prevent ADRs

67
Q

Dopaminergic Pathways – Effect of SGA’s at the pathways

68
Q

clozapine:

69
Q

Risperidone

70
Q

Olanzapine (OLZ)

71
Q

Quetiapine (QUE)

72
Q

Aripiprazole (ARI)

73
Q

Lurasidone (LUR)

74
Q

SGA and side effect burden

75
Q

clozapine receptors acted on

76
Q

clozapine indications

A

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

77
Q

which SGA has the greatest potential for binding other receptors?

(not D2/5HT)

A

clozapine

olanzapine high as well but a little less with a/M

78
Q

clozpaine
– CBC?
– dose related risk of?
– cv
– oral effects?

A

– agranulocytosis, must be monitored
– dose related seizure risk
– myocarditis
– oral side effects
» dry mouth, sialorrhea, hypersalivation; could cause either

79
Q

Receptor Binding Affinities
Reflecting Side Effect Profiles of clozapine

A

high action at all 3

80
Q

metabolic effects of clozapine

A

highest, these are MC of mortality

81
Q

Risperidone receptors acted on

82
Q

Risperidone (Risperdal)
* Indications

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

83
Q

Risperidone
* Additional information
– doses > 6 mg/day = ?
– prolactin?
– oral?

A

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

84
Q

Receptor Binding Affinities
Reflecting Side Effect Profiles of risperidone

A

only action at a= hypo

85
Q

Metabolic Side Effects of risperidone

A

moderate risk

86
Q

Olanzapine receptors affected

87
Q

Olanzapine (Zyprexa)
* Indications

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)

– 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

88
Q

Olanzapine oral effects?

89
Q

Receptor Binding Affinities
Reflecting Side Effect Profiles of olazapine

A

high actions at all three

90
Q

Metabolic Side Effects of olazapine

91
Q

Quetiapine receptors affected

92
Q

Quetiapine (Seroquel and Seroquel XR)
* Indications

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

93
Q

Quetiapine
Oral effect?
– off label uses?

A

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

94
Q

Receptor Binding Affinities
Reflecting Side Effect Profiles of quetapine

A

high effects at h1: WG and xero
moderate at a1: hypotension

95
Q

Metabolic Side Effects of quetiapine

96
Q

Aripiprazole targeted receptors

97
Q

Aripiprazole (Abilify)
* Mechanism of action

A

– D2 partial agonist; can increase DA in def paths and decrease in path with too much
– 5HT2a antagonist

98
Q

Aripiprazole indications

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

99
Q

Aripiprazole
– mc EPS?
– oral?

A

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

100
Q

Receptor Binding Affinities
Reflecting Side Effect Profiles of aripriprazole

A

well tolerated

101
Q

Metabolic Side Effects of aripiprazole

102
Q

Lurasidone (Latuda) indications

A

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

103
Q

Lurasidone
– Must be taken with?
– oral?

A

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

104
Q

Receptor Binding Affinities
Reflecting Side Effect Profiles of Lurasidone

A

well tolerated

105
Q

Metabolic Side Effects of Lurasidone

106
Q

Oral Side Effects of SGA’s
* Sialorrhea, Hypersalivation?
* Dry Mouth?

which agents can cause these? why?

A
  • Sialorrhea, Hypersalivation
    – Clozapine (Clozaril)
  • Dry Mouth
    – Clozapine (Clozaril)
    – Olanzapine (Zyprexa)
    – Quetiapine (Seroquel

due to blocking action at h1or m1 (xero)

107
Q

CV Side Effects of SGA’s scale

108
Q

SGA advantages
– effective for?
– may be effective for?
– clozapine effective in treatment of?
– side effect profile?
» decreased risk of?
» decreased incidence of ?
» prolactin? exception>/

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

109
Q

SGA disadvantage

A

risk of metabolic side
effects

110
Q

Selection of Antipsychotic Therapy

what is first line for schizophrenia?

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.
111
Q

Maintenance Antipsychotic Therapy
* Relapse rates

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 therap
112
Q

Treatment duration antipsychotics:
1st episode -
2nd episode -
> 2 episodes -

A

1st episode - treat x 1 year
2nd episode - treat x 5 years
> 2 episodes - treat for lifetime

113
Q

initial response to AP and maximal response timeframes

A

Expect to see initial improvement in symptoms within 2 weeks of starting antipsychotic therapy.
Maximum response make take up to 6-8 weeks.

114
Q

which SGA have the greatest chances of metabolic ADR

Weight Gain, Risk for Diabetes, Worsening of lipid profiles

A

clozapine/olanzapine

115
Q

which SGA are least likely to interact with extra receptors

A

Aripiprazole
Lurasidone

116
Q

which SGA are least likely to cause metabolic disturbances

A

Aripiprazole
Lurasidone

117
Q

which SGA may only affect a receptors additionally?

A

risperidone

118
Q

which SGA have moderate effects on metabolic state

A

risperidone
quetiapine

119
Q

which SGA do not affect M receptors

A

Risperidone
Quetiapine
Aripiprazole
Lurasidone

120
Q

which SGA do not affect H receptors

A

Risperidone
Aripiprazole
Lurasidone

121
Q

VMAT 2 inhibitors used for? ADE?

A

velbenzamine and debueterbenzamine
used for tarditive dyskensia
can cause xerostomia

122
Q

which SGA may not prevent prolactin increase?

A

risperidone

pharm 2 (20 decks)

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