Schizophrenia and Antipsychotics Flashcards
Types of Schizophrenia
Paranoid, Disorganized, Catatonic, Undifferentiated, and Residual
- Schizophreniform disorder: early disease/first break
- Schizoaffective disorder: combined with bipolar
- Psychotic disorder due to general medical condition or substance abuse
DSM-IV Criteria for Schizophrenia
- Two or more of the following in a one month period: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, or negative symptoms
- Social/occupational dysfunction from above symptoms
- Continuous signs of the disorder for 6 months
- Exclude mood disorders with psychotic symptoms
- Not due to medical disorder or substance abuse
- If a history of pervasive developmental disorder is present (PDD), must have hallucinations/delusions for one month
Positive vs Negative symptoms
Positive: hallucinations, delusions, disorganized speech, bizarre behaviors, psychomotor agitation
Negative: alogia, flattened affect, avolition, anhedonia, poverty of speech, psychomotor retardation
Types of Schizophrenia symptoms
positive negative cognitive mood symptoms social and occupational dysfunction
Pathophysiology of schizophrenia
Excess of dopamine leads to psychotic s/sx DA hyperactivity in limbic system DA hypofunctioning in prefrontal cortex Decreased glutamate NMDA receptor dysfunction
Typical Antipsychotics (Neuroleptics/Conventional Antipsychotics)
High potency (eg Haldol), mid potency, and low potency (eg thorazine)
All of the above lower DA at all pathways
Four DA Pathways
Mesolimbic- lower DA here, decrease positive symptoms :)
Nigrostriatal- lower DA here, create EPS :(
Mesocortical- lower DA here, increase negative symptoms :(
Turberoinfundibular- lower DA here = gynecomastia issues :(
Typical Antipsychotic SE
sedation anticholinergic cardiac (QTc prolongation) EPS neuroleptic malignant syndrome tardive dyskinesia
Tardive Dyskinesia
post-synaptic DA blockade leads to hypersensitivity to DA
neuronal degeneration
20% of all patients per year with conventionals
risk factors: typical agents, elderly, women
presentation: irreversible involuntary movements, blinking, lip smacking, movements of the face, neck, back, trunk, and extremities
Neuroleptic Malignant syndrome
0.2% of patients on conventionals
mortality is high, up to 20%
at risk: mood disorders, catatonia, lithium
about 1/3 of NMS cases develop again if re-challenged
diagnosis: treatment with APs within 7 days of onset (2-4 weeks for depots), hyperthermia, muscle rigidity, exclusion of other causes, and five of the following- change in mental status, tremor, tachycardia, labile BP, tachypnea or hypoxia, diaphoresis, incontinence, CPK elevation or myoglobinuria, metabolic acidosis
treat: manage with supportive care, remove DA blocking agent
atypical antipsychotics: MOA
D2 and 5HT antagonists (block DA and 5HT)
mesolimbic selectivity for D2 antagonism (decrease SE)
5HT blocking works to decrease EPS and benefits negative s/sx
each drug works on many receptors and works differently
Antipsychotic Receptor Activity
D1-5: relief of psychosis, EPS
5HT2: help suppress DA activity, protect from EPS, +weight gain
Alpha 1: orthostatic hypoTN, dizziness
M1: anticholinergic effects, protect against EP (drowsy, dizzy, dry mouth, blurred vision, constipation)
H1: +weight gain, drowsiness
Olanzapine (Zyprexa)
DDI: CYP 1A2 substrate (cigarette smoking can decrease efficacy)
Risperidone (Risperdal)
doses above 6mg/day begins to clinically look more like typical AP
DDI: CYP 2D6 major substrate, 34A minor substrate
Quetiapine (Seroquel)
DDI: CYP 34A major, 2D6 minor
risk of lenticular formations (cataracts)
commonly used for sleep, anxiety, agitation, depression
Ziprasidone (Geodon)
must take with food (affects absorption)
DDI: minimal CYP activity
monitor closely with other QTc prolongers (worse than other atypical APs, but better than even low potency typicals)
Clozapine (Clozaril)
must start slowly, titrate over 2-3 weeks minimum
NOT a first-line agent due to multiple SE
DDI: CYP 1A major substrate, multiple other CYP interactions
cigarette smoking may decrease drug effect
some antidepressants may increase drug effect
use caution in seizure disorder
use with caution in combo with benzos due to respiratory depression
1% risk of agranulocytosis (must monitor WBC and ANC weekly for first six months of therapy, then continue less frequent monitoring; don’t initiate tx if WBC <2000)
Aripiprazole (Abilify)
dopamine modulator (controls receptors to antagonize receptors when DA is increased and agonize receptors when DA is decreased) antagonist at 5HT2A partial agonist at 5HT1A long half-life, good for non compliance DDI: CYP 2D6 and 34A major substrates
Paliperidone (Invega)
- newest availble, active metabolite of risperidone
- once daily dosing due to osmotic pump delivery system
- proposed to have less risk of EPS and prolactin elevation than risperidone, but need more data
Atypical AP side effects
anticholinergic, orthostasis, sedation, weight gain, diabetes/metabolic syndrome, lipid abnormalities
clozapine (Clozaril) – olanzapine (Zyprexa) – risperidone (Risperdal) – quetiapine (Seroquel) – ziprasidone (Geodon) – aripiprazole (Abilify)
Metabolic syndrome
any three of the following: abdominal obesity hypertension impaired fasting glucose decreased HDL elevated triglycerides
baseline screening and regular monitoring: personal/family hx, weight/BMI, waist circumference, blood pressure, fasting plasma glucose, FLP
Depot APs
long acting injection, every few weeks suspended in sesame oil to limit absorption Haloperidol & fluphenazine (lower rate of EPS/TD than oral) risperdal consta (new)
Schizophrenia treatment guidelines
monotherapy of atypical antipsychotic
if fail, switch to another atypical or conventional
if fail, use clozapine
combo therapy as last resort
common to go through all atypicals before switching to typical AP or clozaril
