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PHRM 845 Exam 4 > Pharmacotherapy of Schizophrenia > Flashcards

Pharmacotherapy of Schizophrenia Flashcards

1
Q

Key features that define psychotic disorders

A
  1. Delusions: fixed false beliefs that are not amenable to change even with conflicting evidence
  2. Hallucinations-perception-like experiences that occur without external stimulus
  3. Disorganized thinking and speech-switching from one topic to another, unrelated answers to questions
  4. Disorganized or abnormal motor behavior
  5. Negative symptoms
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2
Q

Disease course in Schizophrenia

A

Onset late adolescence to early adult

Men-late teens, early 20s

Women–late 20s, early 30s

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3
Q

Link to Substance Use

A

Smoking is associated with 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)

Marijuana, cocaine, and amphetamine use can hasten the onset of schizophrenia, exacerbate symptoms, adn reduce time to relapse

Substance use treatment can be successfully achieved along with mental health treatment with schizophrenia, should be undertaken at the same time

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4
Q

Antipsychotic Drug Therapy overview

A

Doses per day

Side effects: what will patients tolerate? What are their other disease states?

Previous drug therapy: success or failure? Do family members have this disease?

Cost of drug therapy

Concomitant drug therapy

Need for monitoring: labs? weight? ECG?

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5
Q

Antipsychotic Drug Selection

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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6
Q

Typical antipsychotics

A

Older agents–primarily D2 receptor antagonists

Efficacy for positive symptoms is similar to atypical antipsychotics

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7
Q

Typical antipsychotics clinical pearls

A

Haloperidol is most commonly used–routine PRN

More EPS with high potency typical–and atypical antipsychotics risperidone and paliperidone

Are very effective for treating the positive symptoms, but are likely to worsen negative and cognitive symptoms

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8
Q

Partial agonists

A

“stabilize” dopamine transmission–not too much, not too little

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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9
Q

Aripiprazole

A

Partial Agonist

2D6 and 3A4 substrate

Moderate akathisia

Low weight gain

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10
Q

Brexpiprazole

A

Partial agonist

2D6 and 3A4 substrate

Moderate akathisia

Low-moderate weight gain

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11
Q

Cariprazine

A

Partial agonist

3A4 substrate

Moderate akathisia

Low-moderate weight gain

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12
Q

Asenapine

A

Sublingual and patch formulations

1A2 substrate

QTc prolongation

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13
Q

Clozapine

A

1A2 substrate

Boxed warnings: neutropenia, orthostasis, bradycardia, syncope, seizures, myocarditis, cardiomyopathy

Side effects: sedation, weight gain, constipation, hypersalivation, dry mouth, GI hypomotility with obstruction risk

QTc prolongation

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

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14
Q

Olanzapine

A

1A2 substrate

Significant weight gain and sedation

High risk metabolic syndrome

DRESS warning

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15
Q

Quetiapine

A

3A4 substrate

QTc prolongation

Weight gain and sedation

Boxed warning for suicidal ideation

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16
Q

Asenapine Transdermal Patch

A

Secuado

Apply 1 patch q24hrs, rotate patch site to minimize application site reactions

Warning for QTc prolongation

UGT and 1A2 substrate–reduce dose of patch if given with strong 1A2 inhibitors

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17
Q

Olanzapine/Samidorphan

A

Lybalvi

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

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18
Q

Iloperidone

A

High risk for orthostasis and syncope

QTc prolongation

2D6 substrate

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19
Q

Lurasidone

A

3A4 substrate

Higher risk for akathisia

Warning for suicidal thoughts

Adjunct for bipolar depression

Taken with food (350 calories) to increase bioavailability

20
Q

Ziprasidone

A

QTc prolongation

DRESS warning

Take with food to increase absorption

3A4 substrate (1/3) and aldehyde oxidase (2/3) (less worry for P450 interactions)

21
Q

Risperidone

A

2D6 substrate

EPS, hyperprolactinemia, weight gain, sedation, orthostasis

22
Q

Paliperidone

A

Renally-eliminated–dose adjustments in renal impairment

Similar side effects with risperidone

QTc prolongation

23
Q

Lumateperone

A

Low risk for weight gain or metabolic side effects

Low risk for EPS or akathisia

3A4 substrate

24
Q

Pimavanserin

A

Approved for the treatment of hallucinations or delusions in a patient with PD

Inverse agonist and antagonist at the serotonin (5HT) 2A

3A4 substrate

25
Q

Warnings for all antipsychotics

A

Boxed warning: Increased risk of death in elderly patients treated with antipsychotics for dementia with related behaviors

Metabolic adverse effects

EPS

Risk of somnolence, postural hypotension, and motor and/or sensory instability increases the risk for falls

Fall risk assessment should be performed for patients taking other medications or having other disease states that also have a fall/fracture or hypotension risk

26
Q

Haloperidol Injection

A

Given every 4 weeks

Load: 20 times oral dose

Maintenance: 10 times oral dose

If only use maintenance may need oral overlap

Oil-based–Z-track

27
Q

Risperdal Consta

A

risperidone

Must supplement with oral risperidone (or another antipsychotic) for the first few weeks of treatment (week 4)

28
Q

Perseris

A

risperidone

Abdominal subcutaneous injection

3A4 inducers: use 120 mg dose or may need oral supplementation

29
Q

Rykindo

A

risperidone

Every 2 week IM injection

Oral overlap is shorter than Risperdal Consta (7 days vs. 21 days)

Gluteal injection only

30
Q

Uzedy

A

Abdominal or upper arm subcutaneous injection

Given once monthly for every 2 months

31
Q

Invega Sustenna

A

paliperidone

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

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

If loading dose strategy followed, no need for oral overlap antipsychotic treatment

May require dose adjustment in moderate to severe renal impairment

32
Q

Invega Trinza

A

May be initiated for a patient who has been on a stable monthly IM injection of Invega Sustenna, at least 4 stable Invega Sustenna doses

Recommended to be given deltoid; gluteal administration results in a lower Cmax

Not recommended if CrCl < 50 mL/min

33
Q

Invega Hafyera

A

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

Gluteal injection only

34
Q

Zyprexa Relprevv

A

olanzapine

PDSS-post-dose delirium sedation syndrome

35
Q

Abilify Maintena

A

aripiprazole

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

Deltoid or gluteal injection

36
Q

Abilify Maintena Dose adjustments for P450 interactions

A

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

37
Q

Abilify Asimtufii

A

Every-2-month dosing

Gluteal injection only

continue oral aripiprazole for 2 weeks after first injection

38
Q

Aristada

A

aripiprazole lauroxil

overlap with oral aripiprazole for 3 weeks after the first injection

39
Q

Aristada Initio

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

40
Q

Immediate release Antipsychotic Injections/Psychiatric Emergencies

A

Haloperidol, chlorpromazine, fluphenazine are used, haloperidol most commonly

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

Loxapine for inhalation (Adasuve)

41
Q

Clinical treatment Strategies for EPS

A

Acute Dystonia: IM anticholinergic NOW dose (benztropine 2 mg, diphenhydramine)

Drug-induced Parkinson’s: Oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine)

Akathisia: Beta blocker (propranolol 1st line), Benzodiazepine– usually lorazepam

Tardive Dyskinesia: VMAT inhibitors

42
Q

VMAT inhibitors

A

50% reduction in AIMS score for tardive dyskinesia

43
Q

Valbenazine

A

2D6/3A4 substrate

QTc prolongation

44
Q

Deutetrabenazine

A

2D6 substrate

QTc prolongation

45
Q

Neurologic Malignant Syndrome

A

Life-threatening–IS a medical emergency

Hyperpyrexia, tachycardia, labile blood pressure

Muscle rigidity–elevated (significantly) CK, myoglobinuria

Treatment is supportive

Future antipsychotic use is NOT contraindicated

46
Q

Metabolic Averse Effects

A

Hyperglycemia, hyperlipidemia, hypertension

clozapine=olanzapine >

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

ziprasidone=lurasidone=aripiprazole

47
Q

Metabolic monitoring

A

Personal/family hx

Weight

Waist circumference

BP

FPG/A1c

Fasting lipids

PHRM 845 Exam 4 (10 decks)

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