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PHRM 845 > 4.3 Pharmacotherapy of schizophrenia > Flashcards

4.3 Pharmacotherapy of schizophrenia Flashcards

1
Q

What are the key features that define psychotic disorders?

A
  • Delusions
  • Hallucinations: usually auditory
  • Disorganized thinking and speech
  • Disorganized or abnormal motor behavior
  • Negative sxs
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2
Q

What is the avg diagnosis age by sex and disease course progression in schizophrenia?

A
  • Onset late adolescence to early adulthood
  • Late teens/early 20’s for men
  • Late 20’s, early 30’s for women
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3
Q

Why is it thought that women have a later age of schizophrenia onset?

A

Estrogen might be protective against schizophrenia

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4
Q

What is the link between smoking and schizophrenia?

A
  • Smoking is associated w 1A2 induction due to the hydrocarbons
  • Hydrocarbons decreases serum conc. of 1A2 substrate antipsychotics (olanzapine, asenapine, clozapine, loxapine)
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5
Q

Which substances are linked to hastening the onset of schizophrenia, but not causing it?

A

Marijuana, cocaine, and amphetamine can hasten the onset, but not exacerbate sxs, and reduce time to relapse

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6
Q

How can substance abuse with schizophrenia be treated?

A
  • Substance use tx can be successfully achieved along w mental health tx in pts w schizophrenia
  • Should be undertaken at the same time
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7
Q

What must be considered during antipsychotic drug therapy?

A
  • Doses per day
  • SEs
  • Previous drug therapy
  • Cost of drug therapy
  • Concomitant drug therapy
  • Need for monitoring: labs, weight, ECG
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8
Q

Which therapy is considered 1st line?

A

Oral antipsychotic drug therapy is generally considered 1st line, unless the pt presents w reasons to consider IM depot drug therapy first

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9
Q

What are typical antipsychotics?

A

Older agents: primarily D2 receptor antagonists

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10
Q

What is the efficacy of typical antipsychotics?

A

Efficacy for positive sxs, similar to atypical antipsychotics

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11
Q

What drugs are typical antipsychotics?

A
  • Haloperidol
  • Fluphenazine, chlorpromazine, perphenazine, thioridazine
  • Loxapine (atypical in practice)
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12
Q

What is the most commonly used typical antipsychotic?

A

Haloperidol, routine and PRN

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13
Q

What do higher potency typicals have?

A

EPS (extrapyramidal SEs) w higher potency typicals

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14
Q

What are typical antipsychotics effective for?

A

Very effective for treating the positive sxs, but are likely to worsen negative and cognitive sxs

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15
Q

What drugs are partial agonists (atypical)?

A

Aripiprazole, Brexpiprazole, Cariprazine

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16
Q

How do partial agonists (atypical) work?

A

“Stabilize” dopamine transmission

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17
Q

What are partial agonists (atypical) associated more with?

A

Associated with more akathisia than other antipsychotics

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18
Q

What are partial agonists (atypical) approved for?

A

Approved for adjunct tx in depression so all have boxed warning for suicidal thoughts/behavior

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19
Q

Aripiprazole drug info.

A
  • 2D6 and 3A4 substrate
  • Moderate akathisia
  • Low weight gain
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20
Q

Brexpiprazole drug info.

A
  • 2D6 and 3A4 substrate
  • Moderate akathisia
  • Low-moderate weight gain
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21
Q

Cariprazine drug info.

A
  • 3A4 substrate
  • Moderate akathisia
  • Low-moderate weight gain
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22
Q

Which drugs are the “pines” atypicals?

A
  • Asenapine
  • Clozapine
  • Olazapine
  • Quetiapine
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23
Q

Asenapine drug info.

A
  • Sublingual and patch formulations
  • UGT and 1A2 substrate
  • QTc prolongation
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24
Q

Clozapine drug info.

A
  • 1A2 substrate
  • Boxed warnings: neutropenia, orthostasis, bradycardia, syncope, seizures, myocarditis, cardiomyopathy
  • SEs: sedation, weight gain, constipation, hypersalivation, dry mouth, GI hypomotility w obstruction risk
  • QTc prolongation
  • Most weight gain
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25
Q

Olanzapine drug info.

A
  • 1A2 substrate
  • Significant weight gain and sedation
  • High risk metabolic syndrome
  • DRESS warning
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26
Q

Quetiapine drug info.

A
  • 3A4 substrate
  • QTc prolongation
  • Weight gain and sedation
  • Boxed warning for suicidal ideation
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27
Q

What are application directions for asenapine transdermal patch (secuado)?

A

Apply one patch q24h, rotate patch site to minimize application site rxns

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28
Q

Asenapine transdermal patch (secuado) is a UGT and 1A2 substrate. What must be done if given w strong 1A2 inhibitors?

A

Reduce dose of patch if given w strong 1A2 inhibitors (e.g. fluvoxamine)

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29
Q

What is required for a clozapine prescription?

A

Absolute neutrophil count (ANC) monitoring; within last 7 days

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30
Q

What is the required ANC count for clozapine and what are the monitoring timelines?

A
  • ANC to 1500 uL or higher to initiate therapy
  • Monitoring weekly x6 months, biweekly x6 months, then q4 weeks
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31
Q

Lybalvi is the brand product of olanzapine/samidorphan. Why is samidorphan in the mix?

A

Samidorphan added to mitigate weight gain

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32
Q

What is samidorphan?

A

An opioid antagonist w preferential activity at the mu opioid receptor

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33
Q

When is samidorphan CI?

A

CI in pts currently taking opioids or in opioid withdrawal

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34
Q

What drugs are the “dones” atypicals?

A

Iloperidone, lurasidone, ziprasidone, risperidone, paliperidone

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35
Q

Iloperidone drug info.

A
  • Highest risk for orthostasis
  • QTc prolongation
  • 2D6 substrate
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36
Q

Lurasidone drug info.

A
  • 3A4 substrate
  • Higher risk for akathisia
  • Warning for suicidal thoughts, adjunct for bipolar depression
  • Take w food (350 calories) to increase bioavailability
37
Q

Ziprasidone drug info.

A
  • QTc prolongation (CI)
  • DRESS warning
  • Take w food to increase absorption and bioavailability
  • 3A4 substrate (1/3) and aldehyde oxidase (2/3) (less worry for P450 interactions)
38
Q

Risperidone drug info.

A
  • 2D6 substrate (minor 3A4 substrate)
  • EPS, hyperprolactinemia, weight gain, sedation, orthostasis, gynecomastia
39
Q

Paliperidone drug info.

A
  • Renally eliminated: dose adjustments in renal impairment
  • Similar SEs w risperidone
  • QTc prolongation
40
Q

Lumateperone (Caplyta) drug info.

A
  • Low risk for weight gain or metabolic side effects
  • Low risk for EPS or akathisia
  • 3A4 substrate
41
Q

What is pimavanserin (Nuplazid) indicated for?

A

FDA approved for tx of hallucinations or delusions in a pt w Parkinson’s disease

42
Q

What is pimavanserin’s MOA?

A

Inverse agonist and antagonist at 5HT2A and 2C receptors

43
Q

What is pimavanserin a substrate for?

A

3A4 substrate

44
Q

What are the warnings for all antipsychotics?

A
  • Boxed warnings: increased risk of death in elderly pts treated w antipsychotics for dementia w related behaviors
  • Metabolic AEs
  • EPS
  • Risk of somnolence, postural hypotension, and motor and/or sensory instability increases the risk for falls/fractures
  • Fall risk assessment should be done
45
Q

Haloperidol decanoate drug info.

A
  • Given q4 weeks
  • Load: 20x oral dose
  • Maintenance: 10x oral dose, if only used for maintenance may need oral overlap, oil based is Z track
46
Q

What must be supplemented with risperdal consta (risperidone)?

A

MUST supplement w oral risperidone (or another oral antipsychotic) for first few weeks of tx

47
Q

What is the dosage form of Perseris (risperidone)?

A

Abdominal subq injection

48
Q

What should the dose of Perseris (risperidone) be if given w 3A4 inducers?

A

120 mg or may need oral supplementation

49
Q

Rykindo (risperidone) drug info.

A
  • Every 2 week IM injection
  • Oral dose overlap is shorter than risperdal consta (7 days v 21 days)
50
Q

Uzedy (risperidone) drug info.

A
  • Abdominal or upper arm subq injection
  • Given once monthly or every 2 months
51
Q

What is the administration timeline for invega sustenna (paliperidone)?

A

Loading dose, then booster, then every 4 weeks (starting 5 weeks after loading injection)

52
Q

Where must initial loading and booster doses be given for invega sustenna (paliperidone) and why?

A

Initial loading and booster doses must be given in deltoid to improve absorption consistency

53
Q

For invega sustenna (paliperidone), if the loading strategy is followed, is oral overlap required?

A

No need for oral overlap antipsychotic tx

54
Q

When could dose adjustments be required for invega sustenna (paliperidone)?

A

May require dose adjustments in moderate to severe renal impairment

55
Q

When can invega trinza (paliperidone q3m) be initiated?

A

May be initiated for a pt who has been on a stable monthly IM invega sustenna injection, at least 4 stable invega sustenna doses

56
Q

Where can invega trinza (paliperidone q3m) be given?

A

Recommended to be given deltoid

57
Q

Gluteal admin of invega trinza (paliperidone q3m) results in what?

A

Gluteal admin results in a lower Cmax

58
Q

When is invega trinza (paliperidone q3m) not recommended?

A

If CrCl <50 ml/min

59
Q

When can invega hafyera (paliperidone q6m) be initiated?

A

May be initiated after stable invega sustenna for 4 months or stable invega trinza after one 3 month dose

60
Q

What is only location for invega hafyera (paliperidone q6m) admin?

A

Gluteal injection only

61
Q

What is required for zyprexa relprevv (olanzapine)?

A

REMS (risk evaluation mitigation strategy)

62
Q

What can zyprexa relprevv (olanzapine) cause?

A

PDSS - post dose delirium sedation syndrome

63
Q

What is the oral and IM depot dosing of zyprexa relprevv (olanzapine)?

A
64
Q

What is required for abilify maintena (aripiprazole)?

A

MUST overlap w oral aripiprazole (or another oral antipsychotic) for at least 14 days after first injection

65
Q

Where is abilify maintena (aripiprazole) admin?

A

Deltoid or gluteal injection

66
Q

What is the abilify maintena (aripiprazole) dose adjustments for P450 interactions?

A

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

67
Q

What is the dosing schedule for abilify asimtufii (aripiprazole)?

A

Every 2 month dosing

68
Q

Where is abilify asimtufii (aripiprazole) administered?

A

Gluteal injection only

69
Q

What is required after the first injection of abilify asimtufii (aripiprazole)?

A

Continue oral aripiprazole for 2 weeks after first injection

70
Q

What must be overlapped w Aristada (aripiprazole lauroxil)?

A

Overlap w oral aripiprazole for 3 weeks after first injection

71
Q

Why was aristada initio developed?

A

Developed to avoid need for 21 day oral overlap of antipsychotic

72
Q

When should aristada initio (aripiprazole lauroxil) be avoided?

A

Avoid in pts who are 2D6 poor metabolizers or w strong 3A4 or 2D6 inhibitors

73
Q

Which immediate release antipsychotic injections are commonly used for psychiatric emergencies?

A
  • Haloperidol, chlorpromazine, fluphenazine are used
  • Haloperidol most commonly
74
Q

When can olanzapine immediate release IM NOT be used and why?

A

CANNOT be given at the same time as a benzodiazepine immediate release injection - boxed warning for respiratory depression

75
Q

What inhalation dosage form med is available for psychiatric emergencies?

A

Loxapine for inhalation (Adasuve)

76
Q

What is the tx for acute dystonia of EPS?

A

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

77
Q

What is the tx for drug induced parkinson’s of EPS?

A

Oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine)

78
Q

What is the tx for akathisia of EPS?

A
  • BB (propranolol preferred 1st line)
  • Benzodiazepine (usually lorazepam)
79
Q

What is the tx for tardive dyskinesia of EPS?

A

VMAT inhibitors

80
Q

Which drugs are the VMAT inhibitors?

A

Tetrabenazine (Xenazine), Valbenazine (Ingrezza), Deutetrabenazine (Austedo)

81
Q

Valbenazine (Ingrezza) drug info.

A
  • 2D6/3A4 substrate
  • QTc prolongation
82
Q

Deutetrabenazine (Austedo) drug info.

A
  • 2D6 substrate
  • QTc prolongation
83
Q

What is the danger of neuroleptic malignant syndrome?

A

Life threatening - is a medical emergency

84
Q

What are characteristics of neuroleptic malignant syndrome?

A
  • Hyperpyrexia, tachycardia, labile BP
  • Muscle rigidity: elevated (significantly) CK, myoglobinuria
85
Q

What is not CI in tx of neuroleptic malignant syndrome?

A

Future antipsychotics

86
Q

What characterizes metabolic AEs?

A

Hyperglycemia, hyperlipidemia, HTN

87
Q

What are the atypical antipsychotic risk comparisons for metabolic AEs?

A
  • Clozapine, olanzapine >
  • Quetiapine, risperidone, paliperidone, asenapine, iloperidone, cariprazine, brexipiprazole >
  • Ziprasidone, lurasidone, aripiprazole
88
Q

What are the metabolic monitoring parameters during antipsychotics use?

A

PHRM 845 (48 decks)

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