Psych Neuro Exam 3 : Lasilla Schizophrenia/Psychosis DRUGS (p69-153)

_____ gen antipsychotics

-clozapine

-olanzapine

-quetiapine

-risperidone

-paliperidone

-iloperidone

-asenapine

-ziprasidone

2nd

Clozapine = the ___ atypical

first

Clozapine

-___ (IR)

-___ (ODT)

Clozaril, Fazaclo

Clozapine

-place in therapy is for patients who are considered "treatment ___," also those who present with persistent ___ attempts, persistent aggression, or history of TD

resistant, suicidal

"treatment resistant" = patient has failed __ other antipsychotics

2

Clozapine

-dosing is gradual increase by 25mg/day over ___ days to target dose of 300mg to reduce risk of ____

-once at 300mg/day, may titrate up to 900mg/day no faster than twice a week

12, orthostasis

clinical pearl: ___ is approved for augmentation of treatment resistant patients taking clozapine

lamotrigine

Clozapine side effects

1. sedation

2. blood pressure dueing dose escalation (___ hypotension)

3. _____ (T2D)

orthostatic, hyperglycemia

Clozapine side effects

4. severe weight __ (40-50lb)

5. hyperlipidemia

6. ____ occurs in initial phase of treatment

gain, hypersalivation

Clozapine side effects

7. urinary retention + constipation at high doses

8. can elevate ____ levels

9. monitor QTc at baseline and yearly

10. monitor for ____

prolactin, neutropenia

increased prolactin levels = increased ___ risk

seizure

Clozapine Drug Interactions

-Strong CYP1A2 inducers can decrease clozapine SDL (eg ___ or ___ ___)

-also interacts with CYP1A2 inhibitors (fluvoxamine) and CYP3A4 inducers (carbamazepine)

cigarettes, cannabis smoke

clinical pearl = for hypersalivation, may use ___ 1% opthalmic solution as oral mouth rinse

atropine

Clozapine SDL Monitoring

-optimal levels are between __-___mcg/mL

200-600

Clozapine SDL Monitoring

-norclozapine metabolite, at steady state and with patient adherence, should be approximately __% of clozapine level

50

Clozapine SDL Monitoring

-clozapine:norclozapine ratio of __:___ shows patient is adherent

2:1

Clozapine SDL Monitoring

-remember ___ may decrease SDL by 50%

smoking

Clozapine SDL Monitoring

-added levels above ___ greatly increase seizure risk!

1000

ANC ( ___ ___ ___)

-nuetrophil % x WBC

absolute neutrophil count

Clozapine ANC Monitoring

-minimum ANC of ___/ul (or 1000/ul for patients with benign ethnic neutropenia)

1500

Clozapine ANC Monitoring

-monitor ___ for first ___ months of therapy

weekly, 6, other

Clozapine ANC Monitoring

-if levels are consistently >1500/ul for first 6 months, then every ____ week

other

Clozapine (Patient Counseling)

-____ and ___ during titration

sedation, orthostasis

Clozapine (Patient Counseling)

-___ throat and ___ may be sign of low ANC

sore, fever

Clozapine (Patient Counseling)

-monitor blood pressure, cholesterol, and blood glucose for ___ syndrome

metabolic

Clozapine (Patient Counseling)

-monitor serum drug levels (cloz:norcloz) to monitor for ___:___

-monitor ___ for ANC

adherence:toxicity, CBC

Clozapine (Patient Counseling)

-nonadherence with medication may require re-initiation and upward ___

titration

Clozapine (Patient Counseling)

-___ cessation

-excessive ___ possible

smoking, salivation

Olanzapine

-___ (IR, ODT, IM, LAI)

Zyprexa

Olanzapine

-moderate affinity for D2, so lower rate of ___

-high degree of anticholinergic binding, so weight ___ (35-40lb)

EPS, gain

Olanzapine

-low ___ prolongation

QTc

Olanzapine Side Effects

-sedation and ___ hypotension (especially if given with BZD)

-constipation, urinary retention

-___ may decrease levels by 30%

orthostatic, smoking

Olanzapine

-Safety Warning for ___ reactions (drug reaction with eosinophilia and systemic symptoms) (appears with general rash, 10% mortality)

DRESS

Quetiapine

-___ (IR, ER)

Seroquel

Quetiapine Dosing

-Multiple daily dosing may be required with __ formulation (XR formulation available for QD)

-but recent studies show IR and ER very similar

IR

Quetiapine

-high degree of ___ effect (sedation)

antihistaminic

Quetiapine Side Effects

-drowsiness

-___ weight gain

-anticholinergic (constipation, dry mouth, orthostatic hypotension)

moderate

Quetiapine

-lower incidence of __

EPS

Quetiapine

-also approved for ___ augmentation/combination and bipolar depression

-off label use for GAD

-we like to use this in substance use disorder patients

MDD

Risperidone

-_____ (IR, liquid, tabs, ODT, LAI)

-____ (LA SC injection)

risperdal, perseris

Risperidone

-useful in the ___ due to very low anticholinergic effects BUT higher risk of ___

elderly, EPS

Risperidone Side Effects

-orthostatic hypotension (so titrate upward slowy)

-_____ weight gain (15-20lb)

-sedation

moderate

Risperidone Side Effects

-high risk of ___ increase! (drug likes TIF pathway)

prolactin

Risperidone

-can induce Tardive dyskinesia if dosage range exceeds ___mg per day

6

Paliperidone

-____ (IR, LAI)

Invega

Paliperidone

-9-OH risperidone (this drug is active metabolite of risperidone with much longer half life of __ hours)

24

Paliperidone

-Only antipsychotic that requires dose adjustment based on ___ function

renal

Paliperidone

-do not use if CrCl < ___

80

Paliperidone Side Effects

-moderate weight gain (20lb)

-highest ___ stimulation!!

prolactin

Paliperidone

-only agent approved for ___ disorder (bipolar+schizoprenia)

schizoaffective

Iloperidone- not a mainstream drug

-___ (IR, titration pack)

Fanapt

Iloperidone Therapeutic Issues

-high incidence of severe ____ (requires slow titration)

orthostasis

Iloperidone Therapeutic Issues

-potential for concern at high doses of Wolff-Parkinson-White ____ (fatal)

arrhythmia

Iloperidone Therapeutic Issues

-___ and ___ substrate, so potential for rapid SDL increases with concomitant inhibitors

3A4, 2D6

Clincal Pearl: Iloperidone is a 3A4 and 2D6 substrate, so potential for rapid SDL increases with concomitant inhibitors, like ___, ____, or ___ (which may be used to treat mood/negative symptoms)

fluoxetine, paroxetine, bupropion

Iloperidone Side Effects

-___ weight gain (15lb) and moderate sedation

moderate

Asenapine

-____ (SL)

-____ (Transdermal)

Saphris, Secuado

Asenapine

-dosed is 5mg to 10mg tabs given SL BID

-given in SL dosage form only due to significant __ pass metabolism

first

Asenapine

-offers slight improvement over other AAPs for negative symptoms due to ___ ___

5HT1A agonism

Asenapine Side Effects

-___ mouth

-sedation

-constipation

-weight ___

dry, neutral

Asenapine Therapeutic Issues

-route and ___ (pt must keep in mouth for 5-8 min, and it tastes RLLY BAD)

adherence

Asenapine

-now available as ___ patch, but might not be the best idea because people with schizophrenia experience delusions, paranoia, etc and probably won't be compliant

transdermal

Ziprasidone

-____ (IR, IM)

Geodon

Ziprasidone

-similar to 3rd gen agents, partial agonist at ___ receptors

-weight ___

-BID dosing due to short half life

5HT1A, neutral

Ziprasidone Side Effects

-rash

-sedation

-____ (EPS due to too much NE)

-prolongation of ___ interval

akasthisia, QTc

Ziprasidone

-must take with ___ cal to improve absorption

500

Ziprasidone

-product warning = ___ prolongation!!

-so need baseline EKG

-avoid in patient with ___ issues

QTc, cardiac

_____ gen antipsychotics

-aripiprazole

-brexpiprazole

-lurasidone

-cariprazine

-lumateperone

3rd

Aripiprazole

-____ (IR, MyCite, IM, Liquid)

-____ (LAI)

Abilify, Aristada

MyCite:

-Uses a wearable patch + ___ to track adherence

-not a good idea bc patient may be paranoid/dysregulated

Bluetooth

Aripiprazole MOA

-___ ___ of D2

-___ ___ of 5HT1A

-____ of 5HT2A

partial agonist, partial agonist, antagonist

Aripiprazole Side Effects

-____

-restlesseness

-agitation

-somnolence

-very __ weight gain

-low QTc prolongation

akathisia, low

Aripiprazole

-add-on for treatment ___ depression

resistant

Aripiprazole

-FDA warning for increased ___ (gambling, shopping, binge eating, promiscuity)

impulsivity

Aripiprazole Drug Interactions

-mild/moderate 3A4 and 2D6 inhibitors increase aripiprazole (eg ___ and ___)

paroxetine, fluoxetine

Test Question

Best agents for low/no QT prolongation = ____ or any __ gen agent

olanzapine, 3rd

Test Question

Worst agent for QT prolongation risk = ____ and IV _____

ziprasidone, haloperidol

Brexpiprazole

-___ (IR)

Rexulti

Brexpiprazole

-FDA approved for ___ or add-on for ___

schizophrenia, MDD

Brexpiprazole MOA

-___ ___ of D2

-___ ___ of 5HT1A

-____ of 5HT2A

partial agonist, partial agonist, antagonist

Brexpiprazole Side Effects

-____

-_____

-somnolence

-very low weight gain

-low QTc prolongation

akathisia, headache

Lurasidone

-____ (IR)

Latuda

Lurasidone MOA

-___ of D2 and 5HT2A

-___ ___ of 5HT1A

-____ at α₂C receptor and 5HT7 receptor (to improve cognition)

antagonist, partial agonist, antagonist

Lurasidone

-approved for __ AND __ ___

schizophrenia, bipolar depression

Lurasidone Side Effects

-low incidence of QTc

-high incidence of ___

-weight ___

akathisia, neutral

Lurasidone

-weight neutral, but must administer with ≥___ calories to improve absorption

350

Lurasidone

-Contraindicated with potent 3A4 inhibitors (___, ___, ___) and potent 3A4 inducer (___ and ___)

clarithromycin, ritonavir, voriconazole, carbamazepine, phenytoin

Cariprazine

-____ (IR)

Vraylar

Cariprazine

-FDA approved for ___, manic/mixed ___, and __ ___

schizophrenia, BPD, bipolar depression

Cariprazine MOA

-__ partial agonism > > D2 partial agonism

-5HT1A partial agonist

-5HT2A antagonism

D3

Cariprazine

-first agent to show statistically significant improvements in ___ symptoms

negative

Cariprazine Side Effects

-___

-headache

-insomnia

-weight __

-___ on QTc

akathisia, neutral, neutral

Cariprazine

-substrate for CYP3A4 inducers (__, ___, ___)

carbamazepine, rifampin, phenytoin)

Lumateperone- never seen in practice

-____ (IR)

Caplyta

Lumateperone MOA

-___ receptor modulation

-5HT2A antagonist

-D2 partial agonist

-D2 antagonist

-SERT inhibition

NMDA

Lumateperone Drug Interactions

-avoid ___ inhibitors (quinidine, atazanavir, diclofenac, VPA, probenecid)

-avoid with strong CYP3A4 inducers and inhibitors

UGT

Overall Therapeutic Algorithm

-1st line = ___ ___

atypical antipsychotic

Overall Therapeutic Algorithm

-if patient fails after upward dose adjustment on atypical antipsychotic:

-TMAP guidelines say ___ to a different agent

-APA guidelines say augment with ___ agent OR switch to ___

switch, typical, clozapine

Managing Adverse Effects

-to manage mood lability/schizoaffective disorder, add ___ ____ to atypical antipsychotic

mood stabilizer

Managing Adverse Effects

-to manage affective blunting/negative symptoms, add ___

SSRI