Snapshot A 23-year-old male is brought into the inpatient psychiatric hospital after a suicide attempt. When talking with the patient he seemed to be responding to internal stimuli at times. He states that he heard voices telling him to kill himself. He said he has heard these voices for over a year now but within the past month they have become louder, more persistent and convincing. Overview 2 classes typical older stronger D2 receptor antagonism login to view 1 more bullet atypical newer weaker D2 receptor antagonism and stronger 5-HT2, α, and H1 antagonism Targets dopaminergic neurons specific pathways affected include: login to view 3 more bullets Typical Antipsychotics Overview Typical AntipsychoticsHigh Potency Antipsychotics (in Descending Order)AdvantagesDisadvantagesUnique FeaturesHaloperidol •Fewer side effects of sedation and hypotension •High association with extrapyramidal symptoms •Able to use as long-acting depot injections •Can be given IM in acute situationsFluphenazinePerphenazineChlorpromazine •Lower frequency of extrapyramidal side effects •Greater incidence of anticholinergic side-effects, hypotension, sedation •Corneal depositsThioridazine •Retinal depositsQT prolongation Introduction Overview also known as neuroleptics highly fat soluble results in storage for long time in body fat Drugs ("haloperidol + -azines") high potency - low dose needed haloperidol trifluoperazine fluphenazine low potency - high dose needed login to view 2 more bullets Clinical uses schizophrenia primarily positive symptoms acute mania psychosis temporary treatment because lithium has slow onset Tourette syndrome hiccups (persistent > 48 hours and intractable > 1 month) haloperidol chlorpromazine Toxicity high potency ↑ extrapyramidal system (EPS) side effects login to view 17 more bullets ↓ non-specific side effects fluphenazine has been implicated in causing hypothermia in select cases low potency ↓ EPS side effects ↑ non-specific side effects login to view 11 more bullets endocrine side effects dopamine normally inhibits prolactin secretion login to view 1 more bullet neuroleptic malignant syndrome (NMS) presentation login to view 1 more bullet treatment login to view 2 more bullets Side Effects of High Potency Antipsychotics Extrapyramidal Side Effects of High Potency D2 Blockers (Haloperidol, Fluphenazine, Perphenazine)3 Hours: Acute Dystonia3 Days - Weeks: Bradykinesia (Pseudo-Parkinsonism)3 Months: Akathisia3 Years: Tardive DyskinesiaEmergency: Neuroleptic Malignant Syndrome •Muscle spams (neck, eye, diffuse) •Trouble swallowing •Symptoms of Parkinson's disease: tremors, bradykinesia, rigidity •Sustained feeling of motion/restlessness •Uncontrollable repetitive, stereotypical writhing movements, usually of the tongue •High fever •Muscle rigidity •Unstable vitals •Increased CK, K+, and WBC'sTreatment of Side Effects •Anticholinergic medications:(benztropine, diphenhydramine, trihexyphenidyl) •β-blockers •Benzodiazepines •Stop high potency D2 blockers and switch to atypicals (clozapine preferred) •Can be treated with valbenazine •Stop antipsychotic •IV fluids •Cooling •DantroleneNOTE: You can always decrease the dose or switch to a different antipsychotic – choose the drug with the side-effect profile that the patient can tolerate. Atypical Antipsychotics Overview Atypical AntipsychoticsMedicationUnique features and side effectsRisperidone •High potency •Usually first line •Hyperprolactinemia •Weight gainOlanzapine •Severe weight gain •Very sedatingZiprasidone •Minimal to no weight gain •Increased QTcQuetiapine •Low potency •Sedating •Weight gain •Useful in bipolar depression and augmentation of major depression therapyLurasidone •Minimal weight gain •Useful in biploar depressionClozapine •Weight gain •Most effective anti-psychotic •Decreased suicide risk •Agranulocytosis •Myocarditis •Sialorrhea •Orthostatic hypotension •Increased seizuresAripiprazole •D2 partial agonist •Augmentation of major depression therapy Introduction Drugs olanzapine clozapine quetiapine risperidone aripiprazole ziprasidone Mechanism antagonist at 5-HT2, α, H1, and dopamine receptors Clinical use schizophrenia both positive and negative symptoms olanzapine OCD anxiety disorder depression mania Tourette's syndrome Toxicity less EPS and anticholinergic side effects as compared to traditional antipsychotics olanzipine weight gain login to view 1 more bullet clozapine agranulocytosis login to view 2 more bullets weight gain ziprasidone prolonged QT and possible resultant torsades risperidone EPS tardive dyskinesia