Schizophrenia Therapeutics Flashcards by amanda kastel

before diagnosing schizophrenia, it’s important to rule out what?

drug-induced psychosis

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7 drugs that can cause drug-induced psychosis

stimulants
PCP
marijuana
anticholinergics
MDMA
ketamine
dopamine agonists

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general distinction between the typical (1st gen) and atypical (2nd gen) antipsychotics

1st gen - D2 antagonism. improve positive symptoms and not negative

2nd gen - Serotonin 2a antagonism/ D2, 5HT1A partial agonists. possibly good for the negative symptoms
-allow for serotonin mediated dopamine inhibition

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true or false

in schizophrenia, the goal is to increase dopamine

false - decrease

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differentiate between the common AE of typicals vs atypicals

typicals - EPS, hyperprolactinemia. anticholinergic, sedation, orthostasis (in low potency)

atypicals - metabolic syndrome (hyperlipidemia, hyperglycemia, weight gain) hypertension, sedation, orthostasis

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true or false

the atypicals do NOT modulate dopamine in the nigrostriatal pathway

true

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which has less instances of EPS - the typicals or atypicals

atypicals

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true or false

ALL antipsychotics are considered equal in efficacy

false

all EXCEPT CLOZAPINE

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6 1st gen antipsych (all others are atypicals)

haloperidol
chlorpromazine
fluphenazine
loxapine
thiothixene
perphenazine

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akathesia and dystonias are more common in 1st gen or 2nd gen

1st gen

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hyperprolactinemia is more common in 1st gen or 2nd gen

1st gen

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black box warning for ALL antipsychotics

-increased risk of death in elderly patients with dementia-related psychosis (lewy body dementia, alzheimers)

-cardiac-related death. minimal benefit in treating this type of psychosis!

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true or false

the BBW for increased risk of death in elderly patients with dementia-related psychosis only applies to the atypicals

FALSE - all the antipsychotics

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contraindications/DDI concern with chlorpromazine

contraindicated with large amt of CNS depressants

also interacts with anticholinergics - too much!

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true or false

chlorpromazine has a lower risk of EPS than the other 1st gen antipsychotics

true

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perphenazine specific DDI concern

CYP2D6 inhibitors like fluoxetine and paroxetine

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loxapine unique attribute

has an active metabolite called amoxapine that is a TCA

also comes in inhalation form - but has REMS program

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what is generally considered the “first choice” if we use a 1st gen antipsychotic

haloperidol

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true or false

haloperidol is not selective for the D2 receptor

FALSE - very selective

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haloperidol is often administered with what? why?

a regularly-dosed anticholinergic

to lessen EPS effects

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true or fakse

the PO to IM conversion of fluphenazine is NOT 1:1

true

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true or false

compared to other 2nd gen antipsychotics, risperidone has a low affinity for D2 receptors

FALSE - high affinity

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does risperidone have an active metabolite?

YES - paliperidone
also marketed as an antipsychotic (LAI)

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risperidone and the other 2nd gen antipsychotics typically dont have much of an issue with hyperprolactinemia and EPS

when would we start to see these more?

at high doses

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black box warning ziprasidone

QT prolongation

2 antipsychotics that are HIGH RISK for metabolic syndrome and weight gain

olanzapine and quetiapine

how must lurasidone be taken

WITH FOODi

which antipsychotic is sometimes used to help reverse hyperprolactinemia

aripiprazole

FDA warning aripiprazole

increased gambling/impulsive behavior

differentiate between the side effects of aripiprazole vs brexpiprazole

aripiprazole - more akathesia/impulse behavior, but less weight gain than brexpiprazole brexpiprazole has more serotonergic binding affinity - so has antidepressant/anxiolytic properties

ONLY agent approved for treatment resistant schizophrenia

clozapine

THE MOST EFFECTIVE ANTIPSYCHOTIC

clozapine

only agent shown to reduce suicidality in schizophrenia

clozapine

M1 and M4 agonist with NO D2 affinity

cobenfy (xanomeline/trospium)

for 1st-break patients, consider starting what? why?

second gen antipsychotics EPS sparing, more LAI options, improved adherence

how is "treatment-refractory schizophrenia" defined? (this is when clozapine can be used)

when at least 2 trials of other meds (for 6 weeks, 80% adherence) has failed at a therapeutic dose

3 dividers in the treatment timeline of schizophrenia

acute stabilization inpatient treatment maintenance

considerations for acute stabilization

may need an IM injection admit to inpatient unit prolly. patient is agitated and aggressive

in managing agitation what formulations should be offered 1st?

oral 1st IM and oral are equal in efficacy tho

in managing agitation, what MUST the regimen include

an antipsychotic

true or false in managing agitation, a benzo alone may be sufficient

FALSE - REGIMEN MUST INCLUDE AN ANTIPSYCHOTIC

if, after giving the regimen with an antipsychotic, the patient's agitation is getting worse, what must be done

IM agitation meds

name the specific medication options for agitation in schizophrenia

B-52 (typicals) benadryl, haloperidol (5mg IM), lorazepam (2mg IM) (instead of haloperidol can use chlorpromazine, loxapine, fluphenazine) atypicals: olanzapine, ziprasidone ORAL SHOULD TYPICALLY BE OFFERED 1ST!

in managing agitation, why are benadril, haloperidol, and lorazepam all given?

benadryl decreases any EPS caused by haloperidol lorazepam gives sedation - bc haloperidol does not

true or false if we are giving olanzapine as part of the agitation regimen, we do NOT need to give an anticholinergic like benadryl

true olanzapine acts on these receptors already

true or false IM olanzapine CANNOT be given with IM benzos

true too sedating

if ziprasidone is given as part of the agitation regimen, can we also give a benzo?

yes, and we should

what is considered an adequate medication trial

6 weeks with 80% medication adherence

true or false many times, 2 antipsychotics have to be used at once

FALSE - minimal benefit (if any) not recommended by any set of guidelines

true or false ziprasidone must be taken with a meal

true

WHY does clozapine need to be started so low and titrated

seizure and orthostasis risk

baseline labs to obtain for clozapine

absolute neutrophil count WBC

true or false small bowel obstruction is a BBW for clozapine

false - not a BBW just a concern bc of anticholinergic properties patient should be on a bowel regimen to avoid!

which 2 BBW of clozapine are dose dependent

seizures and orthostatic hypotension

the previous REMS program for clozapine monitored what

ANC for agranulocytosis

2 AE of clozapine

sialorrhea (drooling) GI hypomotility

how to treat clozapine-induced sialorrhea (drooling)

typically TOPICAL anticholinergics (atropine/ipratropium) want to avoid systemic anticholinergics like glycopyyrolate bc synergistic effects, but used occassionally

true or false glycopyrrolate crosses the BBB

false - does not no CNS anticholinergic effects

how to treat/prevent GI hypomotility

osmotic laxatives (PEG 3350/lactulose)

smoking and clozapine

reductions in clozapine levels (as few as 6-7 a day) NRT does not cause the metabolism induction tho (combustible marijuana also interacts)

****which 3 antipsychotics have the highest risk of metabolic syndrome

clozapine (highest) olanzapine then quetiapine

metabolis syndrome is more often caused by the typicals or atypicals

atypicals

cut off QT point to stop the antipsychotic

over 500ms

2 antipsych that are HIGHEST RISK for prolonged QT. which is lowest risk

highest risk - haloperidol (IV) and ziprasidone lowest risk - abilify

high prolactin is due to what

D2 antagonism in the tuberofundibular pathway

which antipsych are more likely to cause increased prolactin

high potency first gens (typicals), risperidone, and paliperidone

how to manage drug-induced high prolactin

lower the dose d/c and switch to another (preferably dopamine partial agonist) potentially can add on low dose abilify (but not preferred due to minimal benefit)

earliest onset of all EPS

dystonia

true or false dystonia is usually pretty well managed

true - with anticholinergics

akatheisia

restlessness moving around and can't still still. numerous neurotransmitters involved - hard to treat!

explain waht tardive dyskinesia is

abnormal involuntary movements due to accumulation of antipsychotic in the cell membrane. hypersensitive to dopamine starts over 3 months-1-2 years after antipsycs start. can be irreversible!

which 2 antipsych have the lowest risk of EPS

clozapine and quetipaine

which 2 EPS use anticholinergics to manage

parkinsonism and acute dystonia

akathisia management

propranolol preferred benzos potentially - but dependence risk (clonazepam preferred bc long acting)

true or false anticholinergics are first line for akathisia

FALSE

3 treatment for tardive dyskinesia

valbenazine deutetrabenazine tetrabenazine valbenazine and deutetrabenazine are VMAT-2 inhibitors reduce dopamine and improve the dopamine hypersensitivity

AE of the VMAT-2 inhibitors for tardive dyskinesia

somnolence anticholinergic properties

deutetrabenazine BBW and CI

BBW - depression/suicide CI for suicidality and hepatic disease

neuroleptic malignant syndrome symptoms

"lead pipe" rigidity autonomic instability

what causes neuroleptic malignant syndrome

excessive dopamine blockade (usually due to overdose. very rare)

for which antipsych are you gonna monitor hemoglobin A1C and lipid levels

second gen (atypicals)

important thing that must be done before giving LAI

tolerance must be established on an oral dose 1st!

true or false oral risperidone can be substituted with paliperidone LAI

true

which LAI has REMS program and it thus isn't seen too much (post-injection delirium and sedation)

olanzaoine needs 3 hr monitoring after every injection

things to consider when switching antipsychotics

not recommended to abruptly discontinue! cross taper/titrate rebound psychosis and rebound histaminergic/cholinergic action IF switching abruptly - start the new one at equivalent dose. rarely done outpatient due to risk of decompensation

most important monitoring parameter for a patient on risperidone

weight and waist size

patient is on a long acting injectable. is having more breakthrough symptoms what should be done

increase dose

Schizophrenia Therapeutics Flashcards

(88 cards)