Second Generation Antipsychotics: Mechanisms and Side Effects
(Atypical Anti-Psychotics) - Examples: Clozapine, Olanzapine, Quetiapine, Risperidone, Zotepine, Paliperidone, etc.
Note: Receptor binding affinities are highly variable within the class making for unique therapeutic and side effect profiles. Clozapine is considered to be the most efficacious, but also has the most side effects including agranulocytosis (0.5-2%). As such, it is considered 2nd line treatment and the patient's complete blood count must be monitored closely.
• Dopamine D2 Receptor Antagonism - Block action of DA on D2 receptors throughout the brain
• Serotonin 2A Receptor Antagonism - Block action of 5-HT on 5-HT 2A receptors throughout the brain
• Serotonin 2C Receptor Antagonism - Clozapine, Olanzapine, Quetiapine
• Acetylcholine MI Antagonism - Block ACh action throughout body (ex. Gut, mouth, eyes, brain)
• alpha1-Adrenergic Antagonism in Vasculature - Arteriolar smooth muscle dilation
• Histamine H1 Receptor Antagonism - Block Histamine action throughout body
• Cardio-metabolic effects - Mechanism unknown
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