Antipsychoses Flashcards
Etiology: of schizophrenia
Stress diathesis
Biological (transmethylation,serotonin,da, hypothesis)
Psychological
serotonin hypothesis
Blockade of the 5HT2A-receptor
( clozapine, quetiapine)
> release da, ne, gluatamate, GABA, Ach
Dopamine hypothesis
Blockade d2 cns receptor (mesolimbic-mesocortical pathway)
Mesolimbic pathway
Positive symptoms
Mesocortical pathway
Negative and cognitive symptoms
Glutamate hypothesis
Decrease glutamate transmission
Fewer receptor in the prefrontal cortex and hippocampus
INHIBITS NMDA GLUTAMATE RECEPTORS
+ - high doses symptoms
ABUSE OF PHENCYCLIDINE (ANGEL DUST)
Glycine modulatory site on NMDA RECEPTOR
reduction in negative symptoms cognitive and positive in glutamate hypo. (CLOZAPINE)
Type 1 -acute schizo
Positive symptoms (hallucination, delusions) good prognosis..
Type 2-chronic schizo
Negative symptoms .. less prognosis
Phenothiazines derivatives:
Aliphatic- clorpromazine(prototypye)
Piperadine-(thioridazine)
Piperazine-(fluphenazine)
Aliphatic and piperadine less potent(sedation &weightgain)
Piperazine more potent(effective lower dose)
Haloperidol
Butyrophenone(fewer autonomic) greater extrapyramidial effect.
Typical antipsycho drugs
Miscalleanous: PIMOZIDE AND MOLINDONE
2nd gen antipsycho
CLOZAPINE- PROTOTYPE
Glutamatergic antipsycho
BITOPERTIN AND SARCOSERINE
(Grreater 5-HT2A RECEPTOR) Than with D2
Class of atypical potent in D2 and D3 but also 5HT7 Antagonist
SULPRIDE AND SULPIRIDE
(Increase SERUM PROLACTIN) tardive dyskinesia
Clozapine
Rapid and severe relapse should never abruptly withdrawn
(EFFECT: myocarditis and agranulocytosis)
Metabolized: CYP450, 2D6, 1A2, 3A4
Drug intx: ketoconazole- inhibitor of 450
5 impt dopaminergic pathways in brain:
- Mesolimbic-mesocortical (first pathway) related behavior
- Nigrostriatal -substantia nigra >caudate/putamen: coordination of voluntary movt
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