1. 1OHN ONNSClozapine LoxapineCH3NNHS CH3NNClCH3NNNOClCH3HNNNNOlanzapine (Zyprexa) AtypicalOFCH3N ONNNHClONNNSNRisperidone (Risperdal) AtypicalQuetiapine (Seroquel) AtypicalZiprasidone (Geodon) Atyical

2. Other names 2nd generation Serotonin Dopamine AntagonistsFeatures Higher ratio of serotonin : dopamine receptorblockade Appear more specific for mesolimbic than striataldopamine system 3. Developments in Medical Treatmentsfor Psychotic Disorders30s 40s 50s 60s 70s 80s 90s 00 02ECTHaloperidolFluphenazineThioridazineChlorpromazineLoxapinePerphenazineClozapineRisperidoneOlanzapineQuetiapineZiprasidoneAripiprazoleNext-generationFirst-generationantipsychotics Second-generationantipsychoticsECT = electroconvulsive therapy.Kapur and Remington. Ann Rev Med. 2001;52:503.Worrel et al. Am J Health Syst Pharm. 2000;57:238. 4. MARTA (multi acting receptor targeted agents) clozapine, olanzapine, quetiapineSDA (serotonin-dopamine antagonists) risperidone, ziprasidone, sertindoleSelective D2/D3 antagonists sulpiride, amisulpiride 5. Atypical Antipsychotics In Vivo Binding AffinitiesLow D2 receptor blocking effectsReduced risk of extrapyramidal sideHealoffpeercidtsol. Clozapine Risperidone OlanzapineQuetiapine Ziprasidone5HT2A D2 D1 Alpha 1 Musc H1 5HT1A (agonist)Casey 1994 6. Schizophrenia and schizoaffective disorder acute and chronic psychoses Treatment of severe tardive dyskinesia (clozapine)Mood disorder acute mania OLANZAPINE bipolar disorder Augments anti depressants in acute managementof depression. 7. Other indications Exhibits outwardly aggressive and violent behaviour Autistic spectrum disorder Tourettes syndrome Huntingtons disease Lesch Nyhan Syndrome Along with methylphenidate/dextroamphetamine inchildren with ADHD. Psychosis secondary to head trauma, dementia,treatment resistant Decreases the risk of suicide and water intoxication inpatients with schizophrenia 8. Extra pyramidal side effects (EPS): Risperidone > Olanzapine = Ziprasidone >Quetiapine > Aripiprazole = ClozapineAnticholinergic: Clozapine > Olanzapine > othersHypotension: Clozapine > > Quetiapine, Risperidone >Ziprasidone, Olanzapine, Aripiprazole 9. Sedation Clozapine > > Olanzapine, Quetiapine >Risperidone, Ziprasidone, AripiprazoleProlactin elevation Risperidone > othersWeight gain Clozapine = Olanzapine > Quetiapine, Risperidone> Ziprasidone, AripiprazoleAgranulocytosis: Clozapine 10. Sexual dysfunction result from NE and SE blockade erectile dysfunction in 23-54% of men retrograde ejaculation loss of libido and anorgasmia in men and women Seizures -