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Therapeutics III > Ott Pharmacotherapy of Schizo > Flashcards

Ott Pharmacotherapy of Schizo Flashcards

1
Q

Key features that define psychotic disorders

A

-Delusions
-Hallucinations
-Disorganized thinking and speech
-Disorganized or abnormal motor behavior
-Negative symptoms

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2
Q

What are delusions?

A

Fixed false beliefs that are not amenable to change even with conflicting evidence

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3
Q

What are hallucinations?

A

Perception-like experiences that occur without an external stimulus (usually auditory, but can also be visual, tactile, or olfactory)

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4
Q

What is disorganized thinking and speech?

A

Switching from one topic to another, unrelated answers to questions

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5
Q

When is the typical onset of schizophrenia for men?

A

Late teens, early 20s

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6
Q

When is the typical onset of schizophrenia for women?

A

Late 20s to early 30s

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7
Q

Which substances are linked to schizophrenia?

A

-Cigarette smoking
-Marijuana
-Cocaine
-Amphetamine

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7
Q

How does smoking cigarettes cause schizophrenia?

A

The induction of 1A2, not due to nicotine, but because of hydrocarbons produced and inhaled, which decreases the serum concentration of 1A2 substrate antipsychotics (olanzapine, asenapine, clozapine, loxapine)

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8
Q

How does marijuana, cocaine, and amphetamine use affect schizophrenia?

A

Can hasten the onset of schizophrenia, exacerbate symptoms, and reduce time to relapse

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9
Q

What must be considered in antipsychotic drug therapy?

A

-Dose per day
-Side effects
-Previous drug therapy
-Cost of drug therapy
-Concomitant drug therapy
-Need for monitoring

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10
Q

Which route of antipsychotic drug therapy is considered first-line?

A

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

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11
Q

What are the typical antipsychotics?

A

-Haloperidol
-Fluphenazine
-Loxapine
-Chlorpromazine
-Perphenazine
-Thioridazine

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12
Q

Typical antipsychotic clinical pearls

A

-Older agents - primarily D2 receptor antagonists
-Efficacy for positive symptoms is similar to atypical antipsychotics
-Haloperidol is most commonly used - routine and PRN
-More EPS with higher potency typicals
-Are very effective for treating the positive symptoms, but are likely to worsen negative and cognitive symptoms

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13
Q

What are the atypical antipsychotics?

A

-Aripiprazole
-Asenapine
-Brexpiprazole
-Cariprazine
-Clozapine
-Iloperidone
-Lumateperone
-Lurasidone
-Olanzipine
-Paliperidone
-Quetiapine
-Risperidone
-Ziprasidone

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14
Q

Which atypical antipsychotics are partial agonists?

A

-Aripiprazole
-Brexpiprazole
-Cariprazine

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15
Q

Partial agonist mechanism of action/CP

A

Stabilize dopamine transmission - not too much, not too little

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16
Q

Aripiprazole effects

A

-2D6 and 3A4 substrate
-Moderate akathisia
-Low weight gain

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17
Q

Brexpiprazole effects

A

-2D6 and 3A4 substrate
-Moderate akathisia
-Low-moderate weight gain

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18
Q

Cariprazine side effects

A

-3A4 substrate
-Moderate akathisia
-Low-moderate weight gain

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19
Q

Partial agonist clinical pearls

A

-Associated with more akathisia than other antipsychotics
-Approved for adjunct treatment in depression so all have boxed warning for suicidal thoughts/behavior

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20
Q

What are the “pines”

A

-Asenapine
-Clozapine
-Olanzapine
-Quetiapine

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21
Q

Asenapine clinical pearls

A

-Sublingual and patch formulations
-1A2 substrate
-QTc prolongation

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22
Q

Clozapine clinical pearls

A

-1A2 substrate
-QTc prolongation

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23
Q

Clozapine boxed warnings

A

-Neutropenia
-Orthostasis
-Bradycardia
-Syncope
-Seizures
-Myocarditis
-Cardiomyopathy

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24
Q

Clozapine side effects

A

-Sedation
-Weight gain
-Constipation
-Hypersalivation
-Dry mouth
-GI hypomotility with obstruction risk

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25
Q

Olanzapine clinical pearls

A

-1A2 substrate
-Significant weight gain and sedation
-High risk of metabolic syndrome
-DRESS warning

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26
Q

Quetiapine clinical pearls

A

-3A4 substrate
-QTc prolongation
-Weight gain and sedation
-Boxed warning for suicidal ideation

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27
Q

Pines clinical pearls

A

-Less D2 antagonism, more 5HT2A antagonist - significantly less EPS
-Higher weight gain than other agents

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28
Q

Asenapine patch clinical pearls

A

-Apply one patch every 24 hours, rotate patch site to minimize application site reactions
-Warnings for QTc prolongation
-UGT and 1A2 substrate - reduce dose of patch if given with strong 1A2 inhibitors

29
Q

How often do neutrophils have to be monitored with clozapine?

A

Monitor timelines weekly for 6 months, biweekly for 6 months then every 4 weeks

30
Q

What is samidorphan?

A

An opioid antagonist with preferred activity at the mu opioid receptor

31
Q

Why is samidorphan given in combination with olanzapine?

A

Clinical trials showed less weight gain with the combination vs monotherapy

32
Q

What are the dones?

A

-Iloperidone
-Lurasidone
-Ziprasidone

33
Q

Dones clinical pearls

A

-D2 and 5HT2A antagonists
-Variable EPS and metabolic side effects

34
Q

Iloperidone clinical pearls

A

-High risk for orthostasis and syncope
-QTc prolongation
-2D6 substrate

35
Q

Lurasidone clinical pearls

A

-3A4 substrate
-Higher risk for akathisia
-Warning for suicidal thoughts - adjunct to bipolar depression
-Take with food (350 calories) to increase bioavailability

36
Q

Ziprasidone clinical pearls

A

-QTc prolongation (contraindication)
-DRESS warning
-Take with food to increase absorption and bioavailability
-3A4 substrate (1/2) and aldehyde oxidase (2/3) (less worry for P450 interactions)

37
Q

More dones clinical pearls

A

-Highest D2 blockade for atypical antipsychotics
-High risk EPS, moderate risk metabolic side effects

38
Q

What are the more dones?

A

-Risperidone
-Paliperidone

39
Q

Risperidone clinical pearls

A

-2D6 substrate (minor 3A4 substrate)
-EPS, hyperprolactinemia, weight gain, sedation, orthostasis

40
Q

Paliperidone clinical pearls

A

-Renally eliminated - dose adjustments in renal impairment
-Similar side effects with risperidone
-QTc prolongation

41
Q

Lumateperone clinical pearls

A

-Low risk for weight gain or metabolic side effects
-low risk for EPS or akathisia
-3A4 substrate

42
Q

Primavanserin clinical pearls

A

-FDA approved for the treatment of hallucinations or delusions in patients with Parkinson’s disease
-Inverse agonist and antagonist at the serotonin 2A receptor
-3A4 substrate

43
Q

Warnings for all antipsychotics

A

-Boxed warning: increased risk of death in elderly patients treated with antipsychotics for dementia related behaviors
-Metabolic adverse effects
-EPS
-Risk of somnolence, postural hypotension, and motor and/or sensory instability increases the risk for falls/fractures
-Fall risk assessment should be preformed for patients taking other medications or having other disease states that also have fall/fracture or somnolence/hypotension risk; assess when initiating antipsychotic and repeat routinely if on continuous long-term treatment

44
Q

Haloperidol decanoate (IM) dosing

A

-Given every 4 weeks
-Load: 20 times the oral dose
-Maintenance: 10 times the oral dose
-If only using maintenance, may need oral overlap
-Oil-based - Z-track

45
Q

How do you start Risperdal Consta (IM risperidone)?

A

Supplement with oral risperidone (or another oral antipsychotic) for the first few weeks of treatment (third injection/week)

46
Q

Perseris (risperidone SC) clinical pearls

A

-Abdominal SC injection
-3A4 inducers - use 120 mg dose or may need oral supplementation

47
Q

Rykindo (risperidone IM) dosing

A

-Every 2 weeks IM injection
-Oral dose overlap is shorter than Risperdal Consta (7 days vs 21 days)

48
Q

Uzedy (risperidone SC) dosing

A

-Abdominal or upper arm SC injection
-Given once monthly or every 2 months

49
Q

Invega Sustenna (paliperidone IM) dosing

A

-Loading dose, then booster, then every 4 weeks (starting 5 weeks after loading dose injection)
-Initial loading dose and booster doses must be given in deltoid to improve absorption consistency
-If loading strategy followed, no need for oral overlap antipsychotic treatment
-May require dose adjustment in moderate to severe renal impairment

50
Q

Invega Trinza (paliperidone q3mo IM) clinical pearls

A

-May be initiated for a patient who has been on a stable monthly (every 4 week) IM injection of Invega Sustenna (only way that it should be used), at least FOUR stable Invega Sustenna doses
-Recommended to be given deltoid; gluteal administration results in lower Cmax
-Not recommended if CrCl is less than 50

51
Q

Invega Hafyera (paliperidone q6mo IM) clinical pearls

A

-May be initiated after stable Invega Sustenna for 4 months or stable Invega Trinza after 3-month dose
-Gluteal injection only

52
Q

Zyprexa Relprevv (olanzapine) clinical pearls

A

-REMS requires registration of patient, facility giving injection, prescriber, and pharmacy with Eli Lilly
-Can cause PDSS - post-dose delirium sedation syndrome

53
Q

Abilify Maintena (aripiprazole) clinical pearls

A

-MUST overlap with oral aripiprazole for at least 14 days after first injection
-Deltoid or gluteal injection

54
Q

Abilify Asimtulfi (aripiprazole) clinical pearls

A

-Every 2 month dosing
-Gluteal injection only
-Continue oral aripiprazole for 2 weeks after first injection

55
Q

How to start Aristada (aripiprazole lauroxil)

A

Overlap with oral aripiprazole for 3 weeks after first injection

56
Q

Aristada Initio clinical pearls

A

-Developed to avoid need for 21-day oral overlap of antipsychotic
-Avoid in patients who are 2D6 poor metabolizers or with strong 3A4 or 2D6 inhibitors

57
Q

Which medications are used for psychiatric emergencies?

A

Immediate release antipsychotics:
-Haloperidol (most common)
-Chlorpromazine
-Fluphenazine
-Olanzapine (cannot be given at the same time as immediate release injection benzodiazepines
-Loxapine for inhalation (not commonly used)

58
Q

EPS symptoms

A

-Acute dystonia
-Drug-induced Parkinson’s
-Akathisia
-Tardive dyskinesia

59
Q

How to treat acute dystonia

A

IM anticholinergic asap (benztropine 2mg, diphenhydramine 50mg)

60
Q

How to treat drug-induced Parkinson’s

A

Oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine)

61
Q

How to treat akathisia

A

-Beta-blocker - propranolol preferred first-line
-Benzodiazepine - usually lorazepam

62
Q

How to treat tardive dyskinesia

A

VMAT inhibitors

63
Q

VMAT inhibitor clinical pearls

A

-Inhibit the vesicular monoamine transporter to decrease storage/increase release of dopamine, serotonin, norepinephrine
-Efficacy expected to be around 50% reduction in AIMS score for tardive dyskinesia

64
Q

What are the VMAT inhibitors

A

-Tetrabenazine
-Valbenazine
-Deutetrabenazine

65
Q

Valbenazine clinical pearls

A

-2D6/3A4 substrate
-QTc prolongation

66
Q

Deutetrabenazine clinical pearls

A

-2D6 substrate
-QTc prolongation

67
Q

What is neuroleptic malignant syndrome

A

-Life-threatening - IS a medical emergency
-Hyperpyrexia, tachycardia, labile blood pressure
-Muscle rigidity - elevated (significantly) CK, myoglobinuria
-Treatment is supportive - discontinue antipsychotics, consider dopamine agonists
-Future antipsychotic use is NOT contraindicated

68
Q

Antipsychotic metabolic adverse effects

A

-Hyperglycemia
-Hyperlipidemia
-Hypertension

69
Q

Drug risk of metabolic adverse effects from highest to lowest risk

A

-Clozapine, olanzapine
-Quetiapine, risperidone, paliperidone, asenapine, iloperidone, cariprazine, brexpiprazole
-Ziprasidone, lurasidone, aripiprazole

Therapeutics III (42 decks)

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