54 - Pharmacotherapy of schizophrenia and psychotic disorders (Ott) Flashcards
Key features that define psychotic disorders
- ___ - fixed false beliefs that are not amenable to change even with conflicting evidence
- ___ - perception-like experiences that occur without an external stimulus (usually ___ , but can be visual, tactile, or olfactory)
- disorganized thinking and speech
- disorganized or abnormal motor behavior
- negative symptoms
- delusions
- hallucinations, auditory
Disease Course in Schizophrenia
onset late adolescence to early adulthood
men - late ___, early ___
women - late ___ , early ___
teens, 20s
20s, 30s
Link to Substance Use
- more than 75% of people with schizophrenia use tobacco
smoking is associated with induction of CYP ___ due to hydrocarbons inhaled.
- decreases serum concentrations of ___ substrate antipsychotics (olanzapine, asenapine, clozapine, loxapine)
1A2
1A2
Link to Substance Use
- longer illness goes untreated, more likely it is that the patient will missuse a substance
- marijuana, cocaine, and amphetamine use can hasten ___ of schizoprenia, reduce time to ___, and exacerbate symtoms
- substance use treatment and mental health treatment should be undertaken at the same time
onset, relapse
T or F: all antipsychotics are considered to be equally effective in clinical trials and in generally equivalent doses in a large population . (Except clozapine - most effective)
True
antipsychotic drug selection
1st line) ___ antipsychotic drug therapy
- unless patient presents with reasons to consider IM depot drug therapy first
oral
changing injection perception to convienence and not punishment
typical antipsychotics
older agents - primarily ___ receptor antagonists
efficacy for positive symptoms similar to ___ antipsychotics (except ___)
examples: (6)
D2
atypical, clozapine
- haloperidol
- chlorpromazine
- fluphenazine
- perphenazine
- loxapine
- thioridazine
typical antipsychotics clinical pearls
- ___ - most commonly used (routine and prn)
- ___ is rarely used due to a black box warning for QTc prolongation
- more ___ with higher potency typicals - and atypical antipsychotics risperidone and paliperidone
- are very effective for treating ___ symptoms, but are likely to worsen ___ and cognitive symptoms
- haloperidol
- thioridazine
- EPS
- positive, negative
atypical antipsychotics
- ___ and ___ antagonism
- less ___ than typicals; more ___ side effects
(13)
- D2, 5HT2A
- EPS, metabolic
partial agonists
- stabilized ___ transmission - not too much, not too little
- associated with more ___ than other antipsychotics
- approved for adjunct treatment in depression so all have boxed warnign for ___ thoughts/behavior
- dopamine
- akathisia
- suicidal
partial agonists
aripiprazole
- D2 partial agonist and 5HT2A antagonist
- ___ and ___ substrate
- moderate ___
- ___ weight gain
- 2D6, 3A4
- akathisia
- low
partial agonists
brexpiprazole
- D2 partial agonist and 5HT2A antagonist
- ___ and ___ substrate
- moderate ___
- ___ weight gain
- 2D6, 3A4
- akathisia
- low-moderate
partial agonist
cariprazine
- ___ / ___ partial agonist and 5HT2A antagonist
- ___ substrate
- moderate ___
- ___ weight gain
- D2/D3
- 3A4
- akathisia
- low-moderate
the “pines”
- less ___ antagonism, more ___ antagonism
- significantly less ___
- ___ weight gain than other agents
- D2, 5HT2A
- EPS
- higher
the “pines”
asenapine
- ___ and ___ formulations
- metalic taste
- ___ substrate
- ___ prolongation
- sublingual, patch
- 1A2
- QTc
the “pines”
clozapine
- most effective
- ___ substrate
boxed warnings
- ___ , orthostasis, bradycardia, syncope, ___ , myocarditis, cardiomypathy
SE
- ___ , weight ___ , constipation, hypersalivation, dry mouth, GI ___ with obstruction risk, ___ prolongation
- 1A2
- neutropenia, seizures
- sedation, gain, hypomotility, QTc
the “pines”
olanzapine
- may be more effective
- ___ substrate
- significant weight ___ and ___
- high risk ___ syndrome
- ___ warning
- anticholinergic
- 1A2
- gain, sedation
- metabolic
- DRESS
the “pines”
quetiapine
- dibenzodiazepine - some misuse potential
- ___ substrate
- ___ prolongations, weight ___ , and ___
- boxed warning for ___ ideation
- 3A4
- QTc, gain, sedation
- suicidal
asenapine transdermal patch (Secuado)
- apply one patch every ___ hours
- rotate sites
- warnings for ___ prolongation, increased effectiveness of antihypertensives (orthostatic hypotension SE)
- ___ and ___ substate - reduce dose of patch if give with strong ___ inhibitors like ___
- 24
- QTc
- UGT, 1A2, 1A2, fluvoxamine
Clozapine REMS
- pharmacy cannot dispense without an absolute neutrophil count (ANC) lab report within the past 7 days
- online system streamlines reporting and reduces ANC to 1500/µL to intiate therapy
- monitoring timelines weekly for ___ months, biweekly x ___ months, then every ___ weeks
6, 6, 4
Olanzapine/Samidorphan (Lybalvi)
- samidorphan added to mitigate weight ___ and ___ syndrome
- samidorphan is an ___ antagonist with preferential activity at the mu receptor
- CI in patients currently taking opioids or in withdrawal
- gain, metabolic
- opioid
the “dones”
- ___ and ___ antagonists
- variable EPS and metabolic SE
D2, 5HT2A
the “dones”
iloperidone
- high risk for ___ and ___
- ___ prologation
- ___ substrate
- orthostasis, syncope
- QTc
- 2D6
the “dones”
lurasidone
- ___ substrate
- higher risk for ___
- warning for ___ thoughts - adjunct for bipolar depression
- take with ____ (350 calories) to increase bioavailability
- 3A4
- akathisia
- suicidal
- food
the “dones”
ziprasidone
- ___ prolongation (CI)
- ___ warning
- take with ___ to increase absorption and bioavailability
- ___ substrate (1/3) and aldehyde oxidase (2/3) (less worry for CYP interactions)
- QTc
- DRESS
- food
- 3A4
more “dones”
- highest ___ blockade for atypical antipsychotics
- high risk ___ , moderate risk metabolite side effects
D2
EPS
more “dones”
risperidone
- ___ substrate (minor ___ substrate)
- ___ , ___ , weight ___, sedation, ___
- 2D6, 3A4
- EPS, hyperprolactinemia, gain, orthostasis
more “dones”
paliperidone
- ___ eliminated - dose adjustments if impairment
- similar SE to ___
- ___ prolongation
- renally
- risperidone
- QTc
Lumateperone (Caplyta)
- primarily ___ antagonism with postsynaptic D2 blockade and presynaptic ___ partial agonist
- ___ risk for weight gain or metabolic side effects
- ___ risk for EPS or akathisia
- ___ substrate
- 5HT2A, D2
- low
- low
- 3A4
pimavanserin (Nuplazid)
- antipsychotic medication that is FDA-approved for the treatment of hallucinations or delusions in a patient with ___
- MOA: ___ agonist and antagonists at the serotonin (5HT2A and 2C)
- ___ substrate; dose adjustment needed if given with strong 3A4 inhibitors
- some preliminary studies in schizophrenia
- SE: peripheral edema, confusional states, nausea
- Parkinson’s
- inverse
- 3A4
