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PHRM 822 Medications List > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

Negative Symptoms

A

blunted emotion
poor self-care
social withdrawal
poverty in speech

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1
Q

Positive Symptoms

A

hallucinations
delusions
bizarre behavior
thought disorders

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2
Q

Cognitive Symptoms

A
  • decrease in cognitive function
  • involves D1 receptors and glutamate receptors
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3
Q

Serotonin Hypothesis of Schizophrenia

A
  • LSD and mescaline were identified as 5HT agonists
  • 5HT2A receptor as mediator of hallucinations
  • antagonism and inverse agonism linked to antipsychotic activity
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4
Q

Which receptors modulate dopamine release in cortex, limbic region, and striatum

A

5HT2A receptors

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5
Q

Which receptors modulate glutamate release and NMDA receptors

A

5HT2A receptors

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6
Q

Glutamate Hypothesis of Schizophrenia

A
  • glutamate is major excitatory neurotransmitter
  • phencyclidine and ketamine, noncompetitive inhibitors of NMDA receptors exacerbate psychosis and cognition deficits (increasing symptoms)
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7
Q

Dopamine Hypothesis of Schizophrenia

A
  • D2 receptor antagonists
  • dopaminergic agents exacerbate symptoms of schizophrenia
  • increased D2 receptor density in treated and untreated patients
    -D2 receptor antagonists initially increase metabolites in the CNS and later decrease metabolites in the CNS
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8
Q

Major Receptors Antagonized by Antipsychotics

A

Dopamine
D1 like = 1 and 5
D2 like = 2, 3, 4

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9
Q

5HT2A Receptor Antagonists

A

clozapine
olanzapine
risperidone

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10
Q

Older 5HT agents

A

chlorpromazine
haldol
thioridazine

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11
Q

Norepinephrine Alpha 1 Blockade Effects

A

hypotension, sedation

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12
Q

Norepinephrine Alpha 2 Blockade Effects

A

may be helpful in therapy

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13
Q

Acetylcholine Effects

A

anticholinergic effects
clozapine, thioridazine

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14
Q

Histamine Effects

A

H1 Receptor Antagonists

sedation, weight gain

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15
Q

Correlation between binding potency and clinical effectiveness for ________ receptors, therefore more _______ drug target

A

D2; effective

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16
Q

Most antipsychotics drugs are receptor _______

A

antagonists

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17
Q

D2 ____ D1 receptor binding

A

>

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18
Q

D2 Receptor Antagonist

A

blocks both pre and post-synaptic receptors

at first, Pre-synaptic blocked: increases the synthesis and release of dopamine

when dopamine diffuses back into the presynaptic receptor, it tells the receptor there is way too much dopamine, presynaptic receptor decreases synthesis

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19
Q

Dopamine Physiology and Function: Mesolimbic

A

primary therapeutic effects

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20
Q

D2 Receptor occupancy and rate of EPS as functions of plasma risperidone concentration

A

increased concentration of risperidone –> increased D2 occupancy –> increased EPS

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21
Q

EPS

A

extrapyramidal symptoms

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22
Q

Symptoms of EPS

A

dystonia (increased muscle tones)
pseudoparkinsonism (muscle rigidity)
tremor
akathisia (restlessness)

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23
Q

When does EPS occur?

A

early, days/weeks, reversible

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24
Q

Drug Therapy for EPS

A

benztropine, trihexyphenidyl, akineton (anticholinergic)

diphenhydramine (antihistamine)

amantadine (dopamine release agent)

propranolol (used for akathisia)

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25
Q

Tardive Dyskinesia

A

occurs late, months to a year
irreversible

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26
Q

Symptoms of Tardive Dyskinesia

A

rhythmic involuntary movements

choreiform: irregular purposelessness

athetoid: worm like

axial hyperkinesias: to and fro movements

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27
Q

MOA of Tardive Dyskinesia

A

unknown

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28
Q

Monitoring of Tardive Dyskinesia

A

AIMS (abnormal involuntary movement scale)

check q6months

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29
Q

Treatment of Tardive Dyskinesia

A

prevention
1. reduce dose of current agent
2. change to a different drug
3. eliminate anticholinergic drugs
4. VMAT inhibitors

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30
Q

VMAT2 Inhibitors use

A

newer drug therapies for tardive dyskinesia

prevent dopamine from being packaged, decreasing dopamine release

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31
Q

Tetrabenazine

A

VMAT2 for Huntington’s chorea

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32
Q

Valbenazine

A

VMAT2 for tardive diskinesia

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33
Q

Deutetrabenazine

A

for tardive diskinesia and huntington’s chorea

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34
Q

Neuroleptic Malignant Syndrome

A

serious and rapid; 10% fatility

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35
Q

Symptoms of neuroleptic malignant syndrome

A

EPS symptoms with fever
Impaired cognition (agitation, delirium, coma)
muscle rigidity

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36
Q

Treatment of neuroleptic malignant syndrome

A

Restore dopamine balance
d/c drug
use DA agonists, diazepam, or dantrolene

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37
Q

Intractable Hiccupts

A

chlorpromazine

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38
Q

Alcohol withdrawal (hallucinations)

A

haloperidol

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39
Q

nausea and vomiting

A

metoclopramide
promethazine

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40
Q

potentiation of opiates and sedatives

A

droperidol

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41
Q

Behavioral effects of antipsychotic drugs

A

unpleasant in normal subjects or reversal of signs and symptoms of psychosis in affected individuals

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42
Q

neuroleptic syndrome of antipsychotic drugs

A

suppress emotions
reduce initiative and interest
affect
may resemble negative syndromes

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43
Q

Loss of accomodation, dry mouth, difficulty urinating, constipation

A

muscarinic cholinoceptor blockade

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44
Q

orthostatic hypotension, impotence, failure to ejaculate

A

alpha adrenoceptor blockade

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45
Q

PD, akathasia, dystonias

A

dopamine receptor blockade

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46
Q

tardive dyskinesia cause

A

supersensitivity of dopamine receptors

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47
Q

toxic-confusal state

A

muscarinic blockade

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48
Q

sedation

A

histamine receptor blockade

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49
Q

amenorrhea-galactorrhea, infertility, impotence

A

dopamine receptor blockade resulting in hyperprolactinemia

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50
Q

weight gain

A

possibly combined H1 and 5HT2c blockade

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51
Q

precautions and contraindications of antipsychotics

A

CV
PD
epilepsy (clozapine will lower seizure threshold)
diabetes (for newer agents)

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52
Q

Aliphathic Phenothiazines

A

chlorpromazine (no longer 1st line therapy)

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53
Q

Chlorpromazine Structure

A

R2: important for potency

R10: requires 3 atom chain (allows nitrogen to bind receptor)

2 atom chain = antihistamine

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54
Q

Aliphatic Phenothiazines used for H1 antagonist properties

A

promethazine
(also for N/V)

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55
Q

piperidine phenothiazines

A

thioridazine (sedation, hypotension, anticholinergic, many SE)

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56
Q

piperazine phenothiazines

A

fluphenazine (EPS)
prochlorperazine (antiemetic)
perphenazine (CATIE studies: combo with anticholinergic)

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57
Q

Thioxanthines

A

thiothixene: modest EPS

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58
Q

Butyrophenones

A

haloperidol (EPS)
strong D2 block

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59
Q

molindone

A

moderate EPS

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60
Q

pimozide

A

tourette’s disease
tics, vocalizaitons

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61
Q

Atypical/Second Gen Antipsychotics overview

A

more metabolic problems
reduced EPS

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62
Q

Clozapine

A

1st atypical antipsychotic
very effective

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63
Q

Agranulocytosis in Clozapine

A

occurs in 1-2% within 6 months
(weekly blood monitoring)

2nd or 3rd line therapy

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64
Q

Side Effects of Clozapine

A

anticholinergic, antihistamine

reduced D2 potency = decreased movement disorders

risk of diabetes

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65
Q

Olanzapine

A
  • weight gain
  • less likely to cause N/V
  • less likely to cause movement disorders
  • risk of diabetes
66
Q

Loxapine

A
  • older agent
  • metabolite= amoxipine
  • inhibits NET –> antidepressant
67
Q

Quetiapine

A
  • metabolite w/ antidepressant activity
  • 5HT2a and D2
  • low EPS
  • low antimuscarinic
  • hypotension (alpha 1)
  • sedation (h2)
  • risk of diabetes
68
Q

Risperidone MOA

A

5HT2A and D3 receptor antagonist

69
Q

Risperidone Pearls

A

relatively low EPS < 8 mg/day
weight gain, sedation

70
Q

Paliperidone (Invega)

A

9-hydroxyrisperidone

71
Q

Iloperidone

A

structurally related to risperidone
very potent at alpha 1 receptors

72
Q

Ziprasidone MOA

A

5HT2A, D2, Alpha 1 affinity

73
Q

Ziprasidone Pearls

A

prolongs QT interval
long acting formulation under study

74
Q

Asenapine

A

5HT2A and D2

75
Q

Lurasidone MOA

A

5HT2A and D2

76
Q

Lurasidone Pearls

A
  • less weight gain and metabolic effects
  • fast onset (days without titration)
  • low doses similar effectiveness to high doses
77
Q

Pimavanserin

A

inverse agonist 5HT2A
PD psychosis

78
Q

Aripiprazole MOA

A

high affinity for 5HT2 and D2

partial agonist at 5HT1A receptors (used in depression)

moderate affinity for D4, alpha, and histamine

79
Q

Side Effects of Aripiprazole

A

weight gain
low risk for D2 effects

80
Q

When is aripiprazole lauroxil given

A

q4-8 weeks
prodrug

81
Q

Brexpiprazole MOA

A

D2/D3 partial agonist with less akathisia

82
Q

Cariprazine MOA

A

D2/D3 partial agonist with greater affinity for D3

weak partial agonist activity at 5-HT1A

akathisia is high

83
Q

Lumateperone MOA

A

partial D2 agonist presynaptic receptors/antagonists at postsynpatic receptors (5HT2A antagonist)

84
Q

Key features that define psychotic disorders

A

delusions: fixed false beliefs that are not amendable to change even with confliction evidence

hallucinations

disorganized thinking and speech

disorgaanized or abnormal motor behavior

negative symptoms

85
Q

Disease course in schizophrenia

A

onset late adolescence to early adulthood

men: late teens, early 20s

women: late 20s, early 30s

86
Q

Smoking and Antipsychotics

A

smoking is associated with induction of 1A2 due to hydrocarbons produced and inhaled

decreases the serum concentration of 1A2 substrate antipsychotics (olanzapine, asenapine, clozapine, loxapine)

87
Q

Which 3 medications can hasten the onset of schizophrenia, exacerbate symptoms, and reduce time to relapse

A

marijuana, cocaine, amphetamine

88
Q

Must consider when prescribing antipsychotics

A

doses per day
side effects
previous drug therapy
cost of drug therapy
concomitant drug therapy
need for monitoring

89
Q

First line for Schizophrenia

A

oral antipsychotic drug therapy is generally considered first-line, unless patient presents reasons to consider IM depot drug therapy first

90
Q

Typical Antipsychotics MOA

A

D2 receptor antagonist
efficacy for positive symptoms is similar to atypical antipsychotics

91
Q

Most commonly used typical antipsych

A

haloperidol: routine and prn

92
Q

EPS in typical antipsych

A

more eps with higher potency

93
Q

typical antipsych effect on positive, negative, cognitive symptoms

A

positive: effective
negative may worsen
cognitive: may worsen

94
Q

Atypical Antipsychotics MOA

A

D2 antagonism + 5HT2A antagonist

95
Q

Atypical EPS compared to Typical

A

less EPS, more metabolic side effects

96
Q

Partial Agonists

A

stabilize dopamine transmission (not too much, not too little)

associated with more akathisia than other antipsychotics

approved for adjunct treatment of depression (have boxed warning for suicidal thoughts/behavior)

97
Q

Aripiprazole MOA

A

partial agonist

98
Q

Aripiprazole CYP P450

A

2D6 and 3A4 substrate

99
Q

Aripiprazole akathisia

A

moderate

100
Q

Aripiprazole weight gain

A

low

101
Q

Brexpiprazole MOA

A

partial agonist

102
Q

Brexpiprazole CYP P450

A

2D6 and 3A4 substrate

103
Q

Brexpiprazole akathisia

A

moderate

104
Q

Brexpiprazole weight gain

A

low-moderate weight gain

105
Q

Cariprazine MOA

A

partial agonist

106
Q

Cariprazine CYP P450

A

3A4 substrate

107
Q

Cariprazine akathisia

A

moderate

108
Q

Cariprazine weight gain

A

low-moderate

109
Q

-Pines

A

less D2 antagonism, more 5HT2A antagonism

significantly less EPS

higher weight gain

110
Q

Asenapine

A

sublingual and patch
QTc prolongation

111
Q

Clozapine

A

boxed warnings for neutropenia, orthostaisis, bradycardia, syncope, seizures, myocarditis, cardiomyopathy

side effects: sedation, weight gain, constipation, hypersalivation, dry mouth, GI hypomotility with obstructive risk

QTc

112
Q

Olanzapine

A

signficant weight gain and sedation

high risk metabolic syndrome

DRESS warning

113
Q

1A2 Substrates

A

asenapine
clozapine
olanzapine

114
Q

Quetiapine

A

3A4 substrate
QTc prolongation
weight gaine an sedation
boxed warning for suicidal ideation

115
Q

Secuado (Asenapine) Patch Warning

A

QTc prolongation

116
Q

Secuado (Asenapine) Patch Interactions

A

UGT and 1A2 substrate

reduce dose of patch if given with strong 1A2 inhibitor (fluvoxamine)

117
Q

Clozapine REMS (ON EXAM)

A

monitoring timelines weekly x6months, biweekly x 6months, then every 4 weeks

118
Q

Olanzapine/Samidorphan (Lybalvi)

A

Samidorphan is an opioid antagonist with preferential activity at the mu opioid receptor

119
Q

the dones

A

D2 and 5HT2A antagonists

variable EPS and metabolic side effects

120
Q

Iloperidone warning

A

high risk for othostasis and syncope

QTc prolongation

121
Q

Iloperidone CYP interaction

A

2D6 substrate

122
Q

Lurasidone CYP interaction

A

3A4 substrate

123
Q

Lurasidone Warnings

A

suicidal thoughts
higher risk for akathisia
take with food to incrase bioavailability

124
Q

Ziprasidone warnings

A

QTc prolongation (contraindication)
DRESS warning
take with food to increase absorption and bioavailabiltiy

125
Q

Ziprasidone CYP interaction

A

3A4 and aldehyde oxidase

126
Q

Risperidone and Paliperidone

A

highest D2 blockade for atypicals

highest EPS, moderate metabolic side effects

127
Q

Risperidone CYP interaction

A

2D6 substrate (minor 3A4)

128
Q

Risperidone SEs

A

EPS
hyperprolactinemia
weight gain
sedation
orthostatis

129
Q

Paliperidone

A

renally eliminated
QTc prolongation

130
Q

Lumateperone

A

low risk for weight gain or metabolic side effects
low risk for eps or akathisia
3A4 substrate

131
Q

Pimavanserin

A

treatment of hallucinations or delusions in PD

inverse agonist and antagonist at the serotonin 5HT2A

3A4 inhibitor

132
Q

Warnings for all Antipsychotics

A
  • boxed warning for increased risk of death in elderly patients treated with antipsychotics for dementia with related behaviors
  • metabolic adverse effects
  • eps
  • risk of somnolence, hypotension, increases risk for falls and fractures
133
Q

Haloperidol Decanoate

A

given every 4 weeks

loading dose: 20x oral dose

maintenance: 10x oral dose

134
Q

Risperdal Consta

A

must supplement with oral risperidone (or another oral antipsychotic) for the first few weeks of treatment (until 3rd injection)

135
Q

Perseris (risperidone)

A

abdominal subq injection

34A inducers, use 120 mg dose or may need oral supplementation

136
Q

Rykindo (risperidone)

A

every 2 week IM injection

oral dose overlap is shorter than risperdal Consta ( 7 days vs 21 days)

137
Q

Uzedy (risperidone)

A

abdominal or upper arm subq injection

given once monthly or every 2 months

138
Q

Invega Sustenna (paliperidone)

A

loading dose, then booster q4 weeks starting 5 weeks after loading injection

inital loading and booster must be given in deltoid

if loading, no need for oral overlap

may require dose adjustment in moderate to severe renal impairment

139
Q

Invega Trinza (paliperidone)

A

may be initiated for a patient who has been on stable monthly (q4week) IM injection of Invega Sustenna at least four stable doses

recommended to be given in deltoid

not recommended if CrCl<50 mL/min

q3months

140
Q

Invega Hafyera (paliperidone)

A

may be initiated after stable invega sustenna for 4 months or stable invega trniza after one 3 month dose

gluteal injection only

q6month

141
Q

Zyprexa Relprevv (olanzapine)

A

PDSS - post dose delirium sedation syndrome

REMS

142
Q

Abilify Maintena

A

must overlap with oral aripiprazole for at least 14 days after first injection

deltoid or gluteal

143
Q

Dose Adjustments for P450 Interactiosn: Abilify Maintena

A

if taking 2D6 or 3A4 inhibitors or 3A4 inducers for more than 14 days as concomitant therapy

avoid 3A4 inducers use

144
Q

Abilify Asimtufii (aripiprazole)

A

every 2 month dosing

gluteal injection only

continue oral aripiprazole for 2 weeks after first injection

145
Q

Aristada (aripiprazole lauroxil)

A

overalap with oral aripiprazole for 3 weeks after first injection

146
Q

Aristada Initio (aripiprazole lauroxil)

A

developed to avoid 21 day oral overlap of antipsychotic

avoid in patients who are 2D6 poor metabolizers or with strong 3A4 or 2D6 inhibitors

147
Q

Commonly used immediate release antipsychotic injections

A

haloperidol, chlorpromazine, fluphenazine

148
Q

Olanzapine IM and benzodiazepine IM

A

cannot be given at the same time, boxed warning for respiratory depression

149
Q

Loxapine for inhalation

A

not commonly used for emergencies due to REMS

150
Q

Treatment of Acutre Dystonia

A

IM anticholinergic now dose (benztropine 2 mg, diphenhydramine 50 mg)

151
Q

Treatment of Drug Induced PD

A

oral anticholinergic
(trihexyphenidyl, diphenhydramien)

152
Q

Treatment of Akathisia

A

beta blocker (propranolol)
benzodiazepine (lorazepam)

153
Q

Treatment of Tardive Dyskinesia

A

VMAT inhibitors

154
Q

Valbenzine CYP interacgtion

A

2D6/3A4 substrate

QTc prolongation

155
Q

Duetetrabenazine CYP Interaction

A

2D6 substrate
QTc prolongation

156
Q

Neuroleptic Malignant Syndrome

A

life threatening, medical emergency

hyperpyrexia, tachycardia, labile bp

muscle rigidity

treatment is suspportive

future antipsychotic use is not contraindicated

157
Q

metabolic adverse effects

A

hyper glycemia, hyperlipidemia, hypertension

clozapine = olanzapine >

quetiapine = risperidone = paliperidone = asenapine = iloperidone = cariprazine = brexpiprazole >

ziprasidone = lurasidone = aripiprazone

158
Q

personal family hx monitoring

A

baseline
yearly

159
Q

weight (BMI) metabolic monitoring

A

baseline
4 weeks
8 weeks
12 weeks
every 3 months

160
Q

waist circumference monitoring

A

baseline
yearly

161
Q

BP/A1C monitoring

A

baseline
12 weeks
yearly

162
Q

fasting lipids monitoring

A

baseline
12 weeks
every 5 years

PHRM 822 Medications List (17 decks)

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