At least 1 + symptom and 1 other symptoms
Over 6 months
No evidence of Drug induced or mood disorders
3 domains of major symptoms
4 positive symptoms
Disorganized speech/formal thought disorder
4 negative symptoms
4 cognitive defects
Looseness of Associations
4 theories of psychotic disorders
What's glutamate hypothesis
NMDA antagonists cause negative symptoms and cognitive defects
What's Nigrostriatal pathway? What's DA do?
Increase in DA causes PA
2 endocrine pathways
DA decrease prolactin release
3 therapeutic indications for antipsychotic agents
4 neurologic diseases
Parkinson disease caused by what receptor?
Drug treatment works best for acute episodes of?
How long would it take to have full efficacy?
Acute episode responds faster or slower?
Slowly tapering the dose would increase or decrease relap?
Avoid what kind of SE?
What do D2 like receptor subtype antagonism do to + symptoms?
Decrease + symptoms via decreasing NAC DA signaling
What do D2 like receptor subtype antagonism do to - symptoms?
Worsen - symptoms due to decrease PFC signaling
4 MOA of SE
D2 like antagonism
A 1 antagonists
H1 receptor blockade
3 SE D2 like antagonism causes?
Parkinson like symptoms initially
TD with prolong treatment
Gynecomastia: increase prolactin
3 SE caused by A 1 antagonists
5 SE caused by antimuscarinic activities
Blurred vision, Dry mouth, Contipations
Relieves initial parkinsonism
H1 receptor blockade causes? (2)
Weight gain due to 5 HT2C
High potency drugs cause more or less Parkinsonian SE?
More SE vs other SE's
order of 5 receptors
2 drugs with low potency
Potency for Chlorpromazine
Thioridazine has same potency as?
With higher affinity for
5 drugs with mid potency
Affinity of chlorprothixene
Affinity of Perphenazine
Affinity of Prochlorperazine
TRiflupromazine has same affinity as?
Without affinity for?
No H1 and 5HT
Affinity of Acetophenazine
2 for D2
+/- for A1
+ for H1
4 drugs with high potency for D2
2 drugs with very high potency for D2
Affinity of Thiothixene
Affinity of Trifluoperazine
Affinity of Loxapine
Affinity of Pimozide
Affinity of Haloperidol
Affinity of fluphenazine
4 extrapyramidal SE
5 symptomos of parkinson-like
Parkinson like caused by? what med could help to decrease this SE
caused by D2 blockade
L-dopa decreases SE but also decreases therapeutic effects
What's dystonia? caused by?
Involuntary muscle contractions that cause bizarre and uncontrolled movements of face, neck and tongue
What's Akathisia? caused by?
severe restlessness and agitation
NOT caused by D2 blockade
What's Tardive dyskinesia/ related by?
Movements are continuous during walking
Related to increased dose and increased duration of treatment
What 2 drugs could increase TD severity?
4 symptoms of signs and symptoms of TD
Chewing licking movements
4 pathogenesis of TD
D2 receptor hypersensitivity
D2 subtype theory
ABnormal D2/D1 ratio
D2 receptor hypersensitivity theory
Continuous exposure to DA antagonists causes increased receptor number or increased sensitivity to DA
Decreased striatal GABA activity
Abnormal D2/D1 ratio theory
D1 agonists cause more TD if D2 receptors blocked
3 treatment options for TD
discontinue antipsychotic treatment
Switch to atypical antipsychotic
What's the drawback of drug holidays
Decrease dose until symptoms decrease may return more severe even at lower dose
Characteristics of atypical antipsychotics
less potent for extrapyramidal and prolactin SE
More efficacy, less sedation, cognitive impairment, catalepsy, less TD with prolonged use
2 proposed mechanisms of atypical antipsychotics
Subregional selectivity of receptor subtype population
Dose response separation between therapeutic and motor effects
receptors in the Frontal cortex
FCTX: 90% D3/4
Striatum 90% D2
NAC 70% D2 30% D3
Blockade of frontal cortex 5HT-2 receptors stops
serotonin inhibition of mesocortical dopamine
How much D2 receptor occupancy causes Akathisia
How much D2 receptor occupancy causes EPS
how much D2 occupancy is required for a typical drug to work?
how much D2 occupancy does an atypical drug require?
8 agent non specific SE
Weight gain, impaired glucose tolerance, hyperlipidemia, Stroke, Seizure, HTN, increased mortality in elderly with dementia, EPS, malignant syndrome
5 Symptoms of malignant syndrome
Catatonia, stupor, fever, unstable BP, myoglobinemia
MOA of malignant syndrome
unknown but related to DA receptor antagonism
How to treat malignant syndrome
stop therapy and give dantrolene or bromocriptine
SE of clozapine
Blocks K channel- QT prolongation
2 SE of risperidone and paliperidone
Increased risk of stroke
Worst EPS and gynecomastia of atypical class
SE of olanzapine
Risk of stroke
Worst weight gain
SE of Lurasidone
Effective for depression and anxiety
SE of aripiprazole
increase risk of stroke
First 6 Atypical drugs
Risperidone, paliperidone, iliperidone,
last 6 atypical drugs
Affinity for Clozapine
Affinity for risperidone
Affinity for Olanzapine
Affinity for Quetiapine
Affinity for ziprasidone
2A,C,1D part 1A
Affinity for Lurasidone
7, 2A, 1A agonist
affinity for aripiprazole
2, part 1A
Affinity for Asenapine
2, part 1A
Affinity for Sertindole
2, part 1A
Affinity for Zotepine
2 atypical drugs with high antimuscarinic activity
the only atypical drug with high sedation property
atypical drug that binds to 5HT7
2 atypical drugs that bind to NE-T
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