Unit 3- Schizophrenia

Etiology of psychosis

Medical conditions including HIV, syphilis, Alzheimer’s, Parkinson’s, Schizophrenia, Bipolar, severe depression, anxiety; drugs such as alcohol, cannabis, cocaine, LSD, steroids

What neurochemical alterations are associated with schizophrenia?

hyperactivity of mesolimbic DA leads to positive symptoms, hypoactivity of mesocortical DA leads to negative symptoms, decreased function of NMDA receptors leads to impaired signaling causing positive/negative symptoms

Diagnoses where psychosis is a symptom

Parkinson’s, dementia, HIV, epilepsy, Schizophrenia, Bipolar, MDD, postpartum psychosis, alcohol withdrawal, drug abuse

Proposed etiology of Schizophrenia

Genetic heritability, viral infections in utero, maternal stress, OB complications, winter/spring births, drug induced by cannabis, LSD, cocaine, altered glutamate/DA signaling and brain structure changes

Risk factors for Schizophrenia

FH/genetics, in utero viral infections, birth trauma/hypoxia, substance use, urban living, high stress, seasonality

DSM-5 diagnosis criteria for Schizophrenia

two or more of delusions, hallucinations, disorganized speech and/or behavior, negative symptoms for 1 month or more, social/occupational decline, continuous signs for 6 months

Exclusions for DSM-5 diagnosis of schizophrenia

Symptoms not due to other medical condition or substance, not better explained by schizoaffective or mood disorder

Positive symptoms of schizophrenia

hallucinations, delusions, disorganized speech, catatonia

Negative symptoms of schizophrenia

flat affect, alogia, avolition, social withdrawal

Cognitive symptoms of schizophrenia

poor concentration, memory issues, impaired executive functioning

Affective symptoms of schizophrenia

inappropriate affect, depression, anxiety, hostility

Drug classes used to treat schizophrenia

first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs)

FGAs MOA

D2 receptor antagonists reducing hyperactivity and suppressing positive symptoms

SGAs MOA

D2 and 5-HT antagonists reducing positive and negative symptoms

FGAs drug examples

chlorpromazine, haloperidol, fluphenazine, thioridazine

SGAs drug examples

clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole

D2 blockade effect on mesolimbic pathway

decreases positive Schizophrenia symptoms

D2 blockade effect on nigrostiatal pathway

can lead to extrapyramidal syndrome (rigidity, tremors, bradykinesia)

D2 blockade effect on tuberoinfundibular pathway

hyperprolactinemia

D2 blockade effect on mesocortical pathway

worsens negative/congnitive symptoms

5-HT2A blockade effect on nigrostriatal pathway

enhanced DA release, lowering EPS risk

Off-target ADRs of APs

sedation, weight gain, dry mouth, constipation, cognitive impairment, orthostatic hypertension, QTc prolongation

Drug metabolism interactions for APs

Metabolism by CYP 1A2, 3A4, 2D6

Other Drug interactions for APs

DA agonists oppose AP effects, additive CNS depression with alcohol, benzos, opioids, additive hypotension with antihypertensives

Common ADRs of APs

EPs, tardive dyskinesia, hyperprolactinemia, weight gain, hyperglycemia, dyslipidemia, anticholinergic effects, sedation, agranulocytosis (clozapine mainly), seizure risk (clozapine)

Treatment to fix EPS

benztropine, diphenhydramine

Treatment to fix Akathisia

propranolol, benzos

treatment to fix NMS

stop AP, supportive care, amantadine

treatment to fix tardive dyskinesia

VMAT2 inhibitors