SCHI

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3 diagnosis

At least 1 + symptom and 1 other symptoms
Over 6 months
No evidence of Drug induced or mood disorders

3 domains of major symptoms

Positive
Negative
Cognitive defects

4 positive symptoms

Hallucinations, Delusions
Disorganized speech/formal thought disorder
Disorganized/bizarre/tanatonic behavior

4 negative symptoms

Alogia
Affective blunting
Anhedonia
Avolition/amotivational

4 cognitive defects

Tangentiality
Incoherence
Looseness of Associations
Neologisms

4 theories of psychotic disorders

Dopamine hypothesis
Serotonin
Glutamate
Neurodevelopmental

What's glutamate hypothesis

NMDA antagonists cause negative symptoms and cognitive defects

What's Nigrostriatal pathway? What's DA do?

Motor control.
Increase in DA causes PA

2 endocrine pathways

Tuberoinfundibular
Tuberohypophyseal
DA decrease prolactin release

3 therapeutic indications for antipsychotic agents

Psychotic disorders
neurologic disease
Motion sickness

4 neurologic diseases

tourette's syndrome
Huntington's disease
Lesch-Nyhan
Dementia/alzheimer's

Parkinson disease caused by what receptor?

D2 antagonists

Drug treatment works best for acute episodes of?

+ symptoms

How long would it take to have full efficacy?
Acute episode responds faster or slower?

2-6 weeks
Faster

Slowly tapering the dose would increase or decrease relap?
Avoid what kind of SE?

decrease
Extrapyramidal 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
Antimuscarinic
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

Dizziness
Postural Hypotension
Reflex tachycardia

5 SE caused by antimuscarinic activities

Blurred vision, Dry mouth, Contipations
Relieves initial parkinsonism
Worsen TD

H1 receptor blockade causes? (2)

Sedation
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

D2
Musc
A1
H1
5HT

2 drugs with low potency

Chlorpromazine
Thioridazine

Potency for Chlorpromazine

+
++
+++
+++
+

Thioridazine has same potency as?
With higher affinity for

Chlorpromazine
Muscarinics

5 drugs with mid potency

Chlorprothixene
Perphenazine
Prochlorperazine
Triflupromazine
Acetophenazine

Affinity of chlorprothixene

2
2
2
3

Affinity of Perphenazine

2
2
1
2

Affinity of Prochlorperazine

2
1
1
1

TRiflupromazine has same affinity as?
Without affinity for?

as prochlorperazine
No H1 and 5HT

Affinity of Acetophenazine

2 for D2
+/- for A1
+ for H1

4 drugs with high potency for D2

Thiothixene
Trifluoperazine
Loxapine
Pimozide

2 drugs with very high potency for D2

Haloperidol
Fluphenazine

Affinity of Thiothixene

3
1
1
1
+/-

Affinity of Trifluoperazine

3
1
1
1

Affinity of Loxapine

3
1
2
2
2A

Affinity of Pimozide

3
0
+/-
1
1

Affinity of Haloperidol

4
+/-
+/-
+/-
2A

Affinity of fluphenazine

4
1
2
1

4 extrapyramidal SE

parkinson like
Dystonia
Akathisia
Tardive Dyskinesia

5 symptomos of parkinson-like

catatonia
Motor rigidity
Tremor
Bradykinesia

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
D2 blockade

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?

anticholinergics
L dopa

4 symptoms of signs and symptoms of TD

Chewing licking movements
Tongue protrusions
Limb movements

4 pathogenesis of TD

D2 receptor hypersensitivity
D2 subtype theory
GABA hypothesis
ABnormal D2/D1 ratio

D2 receptor hypersensitivity theory

Continuous exposure to DA antagonists causes increased receptor number or increased sensitivity to DA

GABA hypothesis

Decreased striatal GABA activity

Abnormal D2/D1 ratio theory

D1 agonists cause more TD if D2 receptors blocked

3 treatment options for TD

Drug holidays
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
Striatum
NAC

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

55-65%

How much D2 receptor occupancy causes EPS

80%

how much D2 occupancy is required for a typical drug to work?

70%

how much D2 occupancy does an atypical drug require?

20%

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

agranulocytosis

Blocks K channel- QT prolongation

Ziprasidone
sertindole
thioridazine

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

Less EPS
Effective for depression and anxiety

SE of aripiprazole

increase risk of stroke

First 6 Atypical drugs

Clozapine,
Risperidone, paliperidone, iliperidone,
Olanzapine
Quetiapine

last 6 atypical drugs

Ziprasidone, Lurasidone
Aripiprazole, Asenapine
Sertindole, Zotepine

Affinity for Clozapine

D2-4, 1
3
1
3
2A,C

Affinity for risperidone

D2-4
0
2
1
2A,C

Affinity for Olanzapine

D2-4
3
1
1
2A,C

Affinity for Quetiapine

D1,2
+/-
2
1
part 1A,2

Affinity for ziprasidone

D2,3
-
+
+
2A,C,1D part 1A

Affinity for Lurasidone

D2
-
-
-
7, 2A, 1A agonist

affinity for aripiprazole

Part D2
-
-
-
2, part 1A

Affinity for Asenapine

D3
-
+
+
2, part 1A

Affinity for Sertindole

D2-4
-
+
-
2, part 1A

Affinity for Zotepine

D1,2
-
NE-T
2
2A,C

2 atypical drugs with high antimuscarinic activity

clozapine
olanzapine

the only atypical drug with high sedation property

clozapine

atypical drug that binds to 5HT7

lurasidone

2 atypical drugs that bind to NE-T

ziprasidone
Zotepine

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