Snapshot A 19-year-old male is brought into the ED by his parents. The patient recently started college and was living in the dorms. He struggled with school and friends and had some issues with his roommate so he moved back home. His parents have noticed that he has become more reclusive and often stays in his room alone. He no longer cares for himself, and has not showered in over a month. The patient is often seen talking to himself, and when his parents ask him what he is doing he says, "It's classified information." 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 Antipsychotics High Potency Antipsychotics (in Descending Order) Advantages Disadvantages Unique Features Haloperidol Fluphenazine Perphenazine 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 situations Chlorpromazine Lower frequency of extrapyramidal side effects Greater incidence of anticholinergic side-effects, hypotension, sedation Corneal deposits Thioridazine Lower frequency of extrapyramidal side effects Greater incidence of anticholinergic side-effects, hypotension, sedation Retinal deposits QT prolongation Typical Antipsychotics Overview AKA neuroleptics two types high potency low potency highly fat soluble → stored for long time in body fat Drugs ("haloperidol + -azines") high potency - low dose needed (more movement side-effects) haloperidol trifluoperazine fluphenazine low potency - high dose needed (more anti-cholinergic side-effects) thioridazine chlorpromazine Clinical use schizophrenia primarily positive symptoms psychosis acute mania temporary treatment because lithium has slow onset Tourette's syndrome Toxicity high potency ↑ extrapyramidal system (EPS) side effects login to view 17 more bullets ↓ non-specific side effects (SE) low potency ↓ EPS SEs ↑ non-specific SEs login to view 11 more bullets endocrine side effects dopamine normally inhibits prolactin secretion login to view 1 more bullet neuroleptic malignant syndrome (NMS) Extrapyramidal Side Effects of High Potency D2 Blockers (Haloperidol, Fluphenazine, Perphenazine) 3 Hours: Acute Dystonia 3 Days - Weeks: Bradykinesia (Pseudo-Parkinsonism) 3 Months: Akathisia 3 Years: Tardive Dyskinesia Emergency: 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's NOTE: 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. Treatment of Side Effects 3 Hours: Acute Dystonia 3 Days - Weeks: Bradykinesia (Pseudo-Parkinsonism) 3 Months: Akathisia 3 Years: Tardive Dyskinesia Emergency: Neuroleptic Malignant Syndrome Anticholinergic medications:(benztropine, diphenhydramine, trihexyphenidyl) Anticholinergic medications:(benztropine, diphenhydramine, trihexyphenidyl) β-blockers Benzodiazepines Stop high potency D2 blockers Switch to atypicals Stop antipsychotic IV fluids Cooling Dantrolene Atypical Antipsychotics - Overview Atypical Antipsychotics Medication Unique features and side effects Risperidone High potency Usually first line Hyperprolactinemia Weight gain Olanzapine Severe weight gain Very sedating Ziprasidone Minimal to no weight gain Increased QTc Quetiapine Low potency Sedating Weight gain Useful in bipolar depression and augmentation of major depression therapy Lurasidone Minimal weight gain Useful in biploar depression Clozapine Weight gain Most effective anti-psychotic Decreased suicide risk Agranulocytosis Myocarditis Sialorrhea Orthostatic hypotension Increased seizures Aripiprazole D2 partial agonist Augmentation of major depression therapy Atypical Antipsychotics 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 olanzapine weight gain/metabolic syndrome clozapine agranulocytosis login to view 1 more bullet weight gain/metabolic syndrome ziprasidone prolonged QT and possible resultant torsades risperidone may result in hyperprolactinemia→ galactorrhea EPS