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UIC PCOL 425 - Antipsychotics and Mood Stabilizers

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Antipsychotics and Mood Stabilizers: Pharmacokinetics Adverse Effects Drug InteractionsGoalsAntipsychotics: Diagnostic IndicationsImpact of Schizophrenic Symptoms on Overall FunctioningPharmacokinetics of AntipsychoticsAntipsychotic AgentsAntipsychotic Agents (con’t)Slide 8Acute EPSDementia PatientsWeight Gain: OverviewThe Metabolic SyndromeSGAs and Metabolic AbnormalitiesBaseline MonitoringAnticholinergic EffectsHematologicalCardiovascularPotential Consequences of QTc Interval ProlongationQT intervalAntipsychotics: Drug InteractionsBipolar Disorder: Symptom DomainsMood Disorders: Therapeutic OptionsMood Stabilizer PharmacokineticsLITHIUMFactors Affecting Lithium CpLithium: Adverse EffectsAnticonvulsants for Mood DisordersVALPROATEValproic Acid PharmacokineticsCBZ PharmacokineticsCarbamazepine MetabolismLAMOTRIGINESlide 331Antipsychotics andAntipsychotics andMood Stabilizers:Mood Stabilizers:PharmacokineticsPharmacokineticsAdverse EffectsAdverse EffectsDrug InteractionsDrug InteractionsPhilip G. Janicak, MDPhilip G. Janicak, MDProfessor of PsychiatryProfessor of PsychiatryRush University Medical CenterRush University Medical Center2GoalsGoalsAntipsychoticsAntipsychoticsDiagnostic indicationsDiagnostic indicationsClassification Classification Relevant PharmacokineticsRelevant PharmacokineticsSerious Adverse EffectsSerious Adverse EffectsDrug InteractionsDrug InteractionsMood StabilizersMood StabilizersDiagnostic indicationsDiagnostic indicationsClassification Classification Relevant PharmacokineticsRelevant PharmacokineticsSerious Adverse EffectsSerious Adverse EffectsDrug InteractionsDrug Interactions23Antipsychotics:Antipsychotics:Diagnostic IndicationsDiagnostic IndicationsPsychiatricPsychiatricSchizophreniaSchizophreniaSchizoaffective disorderSchizoaffective disorderMood disorders with psychosisMood disorders with psychosisDelusional disorderDelusional disorderNonpsychiatricNonpsychiatricDementia/DeliriumDementia/DeliriumPsychosis secondary to a non-psychiatric medical disorder Psychosis secondary to a non-psychiatric medical disorder Developmental disability with psychosis and/or aggressionDevelopmental disability with psychosis and/or aggressionTourette’s disorderTourette’s disorderNausea, vomitingNausea, vomiting34Positive symptoms:Delusions*Hallucinations*Disorganized speechCatatonia Cognitive symptoms:AttentionMemoryExecutive functionsMoodsymptoms:DysphoriaSuicidalityHelplessnessNegativesymptoms:Affective flatteningAlogiaAvolitionAnhedoniaSocial inattentivenessOccupationalInterpersonalSelf- careSocialWorkImpact of Schizophrenic Impact of Schizophrenic Symptoms on Overall Symptoms on Overall FunctioningFunctioning*Schneiderian First Rank Symptoms45Pharmacokinetics of Pharmacokinetics of AntipsychoticsAntipsychoticsADME profilesADME profiles-All are readily absorbedAll are readily absorbed-All are metabolized by the hepatic cytochrome All are metabolized by the hepatic cytochrome P450 systemP450 system-prone to drug interactionsprone to drug interactions-TT1/21/2 is generally 20 hours except: is generally 20 hours except:-ziprasidone, quetiapine, aripiprazole ziprasidone, quetiapine, aripiprazole -Dosing adjustment in elderly renal and/or Dosing adjustment in elderly renal and/or hepatic impairmenthepatic impairment56Antipsychotic AgentsAntipsychotic Agents© JanicakClass/Trade Name Generic Name Dosage (average range; PO, qd) PhenothiazinesAliphaticsThorazine Chlorpromazine 100-1000 mgSparine Promazine 25-1000 mgVesprin Triflupromazine 20-150 mgPiperidinesMellaril Thioridazine 30-800 mgSerentil Mesoridazine 20-200 mgQuide Piperacetazine 20-160 mgPiperazinesStelazine Trifluoperazine 2-60 mgProlixin Fluphenzine 5-40 mgTrilafon Perphenazine 2-60 mgTindal Acetophenazine 40-80 mgCompazine Prochlorperazine 15-125 mgThioxanthenes Navane Thiothixene 6-60 mg Taractan Chlorprothixene 10-600 mgDibenzoxapines Loxitane Loxapine 20-250 mgButyrophenones Haldol Haloperidol 3-50 mg Inapsine Droperidol 2.5-10 mg (IM)Dihydroindolones Moban Molindone 15-225 mg67Antipsychotic Agents (con’t)Antipsychotic Agents (con’t)Class/Trade Name Generic Name Dosage (average range; PO, qd)DibenzodiazepinesClozaril Clozapine 100-900 mgBenzisoxazoleRisperdal InvegaRisperidonePaliperidone2-10 mg3-12 mgThienobenzodiazepinesZyprexa Olanzapine 5-20 mgDibenzothiazepinesSeroquel Quetiapine 75-750 mgBenzisothiazolylsGeodon Ziprasidone 40-160 mgQuinolinonesAbilify Aripiprazole 10-30 mgDiphenytbutyrylpiperidinesSemap Penfluridol 100 mg/wkOrap Pimozide 1-10 mg© Janicak78EPS*EPS*HPDLHPDLCLOZCLOZRISPRISPOLZOLZQTPQTPZIPZIPARIPARIPNeurologicalNeurological++++++00++0/+0/+000/+0/+0/+0/+Weight gain/ Weight gain/ EndocrineEndocrine++++++++++++++++++++++0/+0/+0/+0/+AnticholinergicAnticholinergic00++++++0/+0/++/+++/++0/+0/+0/+0/+00HematologicalHematological00++++++0000000000CardiovascularCardiovascular++0/+0/+++++++++++00ProlactinProlactin++++0/+0/+++++++0/+0/+0/+0/+0/+0/+00SedationSedation+++++++++++/+++/++++++++++++PALIPALI++++++0/+0/+00++++++++++Adapted from Masand PS et al. Handbook of Psychiatry in Primary Care. 1998.Antipsychotics:Antipsychotics:Adverse Effect ProfilesAdverse Effect Profiles*At appropriate doses; 0 = none; + = mild; ++ = moderate; +++ = substantial*At appropriate doses; 0 = none; + = mild; ++ = moderate; +++ = substantial9Maximum MinimumHIGH POTENCY RISPERIDONE OLANZAPINE CLOZAPINEFGAs PALIPERIDONE ZIPRASIDONE (DOSE-RELATED) QUETIAPINE ARIPIPRAZOLE*ADVERSE EFFECTS OF ANTIPSYCHOTICSADVERSE EFFECTS OF ANTIPSYCHOTICSAcute EPSAcute EPS*Based on clinical trial data• Psuedoparkinsonism• Dystonia• Akathisia• Tardive Dyskinesia910Dementia PatientsDementia PatientsRisksRisksMortality rateMortality rateCVA in 4% vs 2%CVA in 4% vs 2%Risks may be Risks may be higher for all APshigher for all APsRecommendationsRecommendationsAvoid in those with Avoid in those with vascular dementiavascular dementiaAvoid with TIA, Avoid with TIA, hypertension, Afibhypertension, AfibUse low doses Use low doses Monitor for Monitor for hypotension, hypotension, sedation, EPSsedation, EPS1011Weight Gain: OverviewWeight Gain: OverviewGeneral populationGeneral populationIncreased morbidity and mortalityIncreased morbidity and mortalityStigmatizationStigmatizationMajor mental disordersMajor


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