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Author: Second Generation (Atypical) Anti-Psychotics: Mechanisms and Side Effects Sara Meunier Reviewers: Note: Receptor binding affinities are highly variable within the class making Yan Yu Second Generation Anti-Psychotics for unique therapeutic and side effect profiles. Clozapine is considered to Aaron Mackie* (Atypical Anti-Psychotics): be the most efficacious, but also has the most side effects including * MD at time of publication agranulocytosis (0.5-2%). As such, it is considered 2nd line treatment and Examples: Clozapine, Olanzapine, Quetiapine, the patient's complete blood count must be monitored closely. Risperidone, Zotepine, Paliperidone, etc. Abbreviations: 5-HT Serotonin Hallucinations Dopamine D2 Receptor Antagonism DA Dopamine Mesolimbic Pathway Positive Symptoms Block action of DA on D2 receptors NE Norepinephrine DA blockade > 5-HT blockade Therapeutic Effect Delusions ACh Acetylcholine throughout the brain Nigrostriatal Pathway Blocking 5-HT leads to Extrapyramidal Serotonin 2A Receptor Antagonism 5-HT blockade > DA blockade DA release in striatum Symptoms (EPS)* Block action of 5-HT on 5-HT 2A receptors throughout the brain *Relative to 1st Tuberoinfundibular Blocking 5-HT inhibits Hyperprolactinemia* generation anti- Pathway pituitary prolactin release psychotics, see relevant slide Blocking 5-HT 2C receptors Serotonin 2C Receptor Antagonism Pro-cognitive and Mesocortical Pathway stimulates DA and NE Clozapine, Olanzapine, Quetiapine Antidepressant actions release in prefrontal cortex Acetylcholine M1 Antagonism Cognitive Symptoms* Dry Mouth Blurred Vision Block ACh action throughout body and (ex. Gut, mouth, eyes, brain) Constipation Cognitive Slowing Negative Symptoms* Antagonism in Vasculature Ability to maintain Orthostatic Arteriolar smooth muscle dilation blood pressure Hypotension High Metabolic Risk: Clozapine, Olanzapine Drowsiness Moderate Metabolic Risk: Risperidone, Quetiapine Low Metabolic Risk: 3rd generation anti-psychotics Histamine H1 Receptor Antagonism Appetite Block Histamine action throughout body Obesity Risk Risk Diabetic Ketoacidosis in high risk patients Weight Gain Risk Cardiovascular Events Cardio-metabolic effects Fasting Triglycerides Mechanism unknown Insulin Resistance Risk Premature Death Type 2 Diabetes Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published March 17, 2014 on cc