1. Drugs Used to Treat Schizophrenia
Chapter 17

2. Positive symptoms of schizophrenia
Delusions
Hallucinations
Bizarre behaviors
Dissociated or fragmented thoughts
Incoherence
illogicality

3. Negative symptoms of schizophrenia
Blunted affect
Impaired emotional responsiveness
Apathy
Loss of motivation & interest
Social withdrawal

4. Why are these symptoms important in drug therapy?
Classic agents affect primarily positive symptoms, while the atypical antipsychotics relieve both positive and negative symptoms

5. Neurotransmitters involved in the pathogenesis of schizophrenia
Dopamine: antipsychotics work by being antagonists of dopamine
Glutamate: a glutamate-NMDA receptor deficiency may explain negative symptoms & cognitive dysfunction
Serotonin: serotoninergic activity may be a complementary action to dopaminergic blockade; also may be a serotonin-glutamate interaction—drug-induced serotonin blockade functions to limit glutamate release

6. Are all antipsychotics neuroleptics?
Neuroleptic means “to take control of the neuron”.
Traditional antipsychotics were previously viewed to be inseparable from extrapyramidal side effects. The neuroleptic dose was gradually increased to the level that produced these effects—a neuroleptic state.
Atypical antipsychotics can produce effects at doses that do not produce motor side effects and do not produce a neuroleptic state.

7. Primary clinical differences between traditional and atypical antipsychotics
Separation of side effects and antipsychotic effects
Traditional block dopamine—effective for positive symptoms; Atypical block dopamine plus action on serotonin & glutamate—effective for negative and symptoms and cognitive deficits as well

8. What is a tranquilizer?
Tranquilizers are typically thought of as agents that induce a peaceful, tranquil, calm, or pleasant state
It is important to distinguish between two types
Minor: (benzodiazapines) reduce anxiety, produce calm, pleasant state
Major: (antipsychotics) psychological effects produced are seldom pleasant or euphoric; especially unpleasant & dysphoric with nonpsychotic persons

9. Mechanisms of action of traditional antipsychotics
Block dopamine D2 receptors

10. Mechanisms of Atypical Antipsychotics
Clozapine: blocks serotonin 5-HT2 receptors; weak blocker of dopamine
Olanzapine: blocks dopamine D2 and serotonin 5-HT receptors
Sertindole: effects a variety of dopamine and serotonin receptors
Quetiapine & ziprasidone: antagonists at neurotransmitter receptors including 5-HT1A, 5-HT2, D1, D2, histamine, and adrenergic

11. Side Effects of Phenothiazines
Altered pigmentation of the skin
Pigment deposits in the retina
Permanently impaired vision
Decreased pituitary function
Menstrual dysfunction
Allergic reactions, which include liver dysfunction and blood disorders

12. Clozapine
It is the only antipsychotic drug that is effective in treating treatment-resistant schizophrenics.
It is clinically superior to traditional antipsychotics
It relieves many of the negative symptomatology of schizophrenia, and lacks many of the extrapyramidal side effects of standard neuroleptics

13. Chlorpromazine
Chlorpromazine was first used to allay fears and anxieties in surgery patients the night before surgery.
It was found to be remarkably effective in alleviating the clinical manifestations of the psychotic process.

14. Olanzapine
Olanzapine has been shown to be produce improvements in positive and negative symptoms of schizophrenia.
Extrapyramidal side effects are only rarely observed.
Results suggest olanzapine may be more effective and better tolerated than traditional antipsychotics in less severely impaired patients.

15. Atypical Antipsychotic Drugs
Molindone, loxapine, clozapine, risperidone, pimozide, olanzapine, sertindole, quetiapine, and ziprazadone
They are all alternatives to phenothiazines, and the all are unique in action.

16. Amisulpride
This drug has a unique neurochemical and psychopharmacological profile: it has high selectivity for blocking dopamine D2 & D3 receptor subtypes in the limbic system, but not the basal ganglia, and it blocks functional responses mediated by those receptors.

17. Amisulpride
As a dopamine blocker, one would predict that it would exert actions similar to those of the traditional antipsychotics, however, amisulpride is twice as selective for D3 receptors than for D2 receptors; at low doses it blocks presynaptic dopamine autoreceptors while postsynaptic dopamine receptor D2 antagonism becomes apparent at higher doses.

18. Amisulpride
This dual action results in increased dopamine activity in the mesolimbic system at low doses and an antipsychotic action at higher doses, with a low incidence of extrapyramidal side effects.