Antipsychotics

most 1st gen antipsychotic agents MOA

high selective D2 blockade in mesolimbic/mesocortical dopaminergic system

what are agents that can aggravate psychosis by enhancing DA activity in schizophrenia pts (according to the dopamine hypothesis?

levodopa, bromocriptine, amphetamines

hypotheses on schizophrenia pathophysiology

dopamine, serotonin, glutamate hypotheses

serotonin hypothesis

excess serotonin activity in specific brain area that contribute to schizophrenia pathology

hallucinogens

potent serotonin receptor agonists

glutamate hypothesis

PCP and ketamine both worsen cognitive impairment and psychosis in schizophrenics

which types of schizophrenia sx are easier to treat?

positive sx

which class of antipsychotics has a higher rate of EPS?

1st gen

formulations that help with adherence of schizophrenia meds

long-acting injections (IM), oral solutions, oral disintegrating tablets

1st gen antipsychotics MOA

block D2 in mesolimbic pathway (ass. with positive schizophrenia sx)

low potency

chlorpromazine, thioridazine

mid potency

loxapine, perphenazine

high potency

haloperidol (can come in IV form), fluphenazine

offered as long-acting injections

BOX warnings for FGAs

elderly pts with dementia-related psychosis - death

thioridazine - QT prolongation

FGAs with a risk of prolonged QT interval

thioridazine, haloperidol, chlorpromazine

hyperprolactinemia

warning for use of FGAs, infertility, amenorrhea, galactorrhea, ED, decreased libido

neuroleptic malignant syndrome (NMS)

occurs within 2 wks of starting therapy

warning for FGAs, hyperthermia, autonomic instability (tachycardia, BP), muscle rigidity, mental status change

how to treat NMS

stop the antipsychotic, supportive care, control pt’s temp, use Benzos to relax muscles

ADEs for FGAs

sedation, dizziness, wt gain, anticholinergic effects

anticholinergic effects

tachycardia, dry mouth, blurred vision

extrapyrimidal side effects (EPS)

dystonias, akathisia, Parkinsonism, TD

dystonia

prolonged contraction of muscles, painful spasms

akathisia

restlessness, repetitive movements

Parkinsonism

similar appearance to Parkinson’s disease - tremors, stiffness, slowed movement

tardive dyskinesia (TD)

abnormal facial movements, usually tongue/mouth

can be irreversible

2nd gen antipsychotics (SGAs)

aripiprazole, brexpiprazole, cariprazine

olanzapine, lurasidone, paliperidone, quetiapine, risperidone

SGA MOA

block D2 in mesolimbic pathway to decrease +sx, block 5-HT2A receptors (inverse agonists) in mesocortical pathway to decrease -sx

why do SGAs have a lower risk than FGAs of causing EPS?

SGAs have lower D2 receptor affinity

lurasidone contraindications

strong CYP3A4 inducer and inhibitor, take with meal

olanzapine contraindications

high risk for metabolic syndrome (wt gain, increased blood glucose/lipids)

*smoking reduces levels of this drug - pts who snoke need a higher dose

aripiprazole formulations

oral, long-acting IM injection

paliperidone formulations and SEs

oral, long-acting IM injection

increases prolactin levels → sexual dysfunction, galactorrhea, irregular/missed periods

quetiapine

taken at HS (drowsy effect), low EPS risk, high metabolic syndrome risk

risperidone formulations and SEs

high risk of metabolic syndrome (wt gain, increased blood glucose and lipids)

increases prolactin → sexual dysfunction, galactorrhea, amenorrhea

EPS at higher doses

which SGAs have a risk of cause wt gain?

olanzapine, clozapine, quetiapine, risperidone

clozapine BOX warning

neutropenia, agranulocytosis

effects of clozapine

reducing suicide attempts, lower risk of EPS

what is the program that one needs to be enrolled in to receive clozapine?

REMS

what needs to be checked prior to initiating clozapine treatment?

ANC levels

clozapine warnings

seizures, metabolic syndrome (wt gain, increased blood glucose and lipids), myocarditis, cardiomyopathy

what meds have a risk of wt gain, metabolic risk, and DM?

olanzapine, quetiapine

what is an option for pts who experience nonadherence?

long-acting IM injection

why are 2nd gen antipsychotics thought to produce lower EPS?

they block D2 receptors but dissociate quickly from the receptors

what is another word for antipsychotics?

neuroleptics