Pharmacology
Summary
Second-generation antipsychotics, often termed atypical antipsychotics, emerged during the 1990s and marked a shift from their first-generation counterparts. SGAs are known for having fewer neurological side effects while manifesting more metabolic effects. Their antipsychotic effects are mainly due to the inhibition of D2 receptors, but the blockage of 5HT-2A serotonin receptors might also contribute to their effectiveness.
Second-generation antipsychotics are primarily employed to treat both positive and negative symptoms of schizophrenia. Their utility extends to adjunctive treatments for treatment-resistant depression, OCD, and Tourette syndrome. Second-generation antipsychotics are associated with metabolic syndrome - characterized by weight gain, dyslipidemia, and hyperglycemia. Clozapine and olanzapine are particularly notorious for their pronounced metabolic effects. Clozapine, specifically, poses risks such as neutropenia, agranulocytosis, myocarditis, cardiomyopathy, and a decreased seizure threshold. A significant advantage of second-generation antipsychotics is their reduced likelihood of causing extrapyramidal symptoms, hyperprolactinemia, and neuroleptic malignant syndrome when compared to first-generation antipsychotics.
Lesson Outline
Don't stop here!
Get access to 133 more Pharmacology lessons & 13 more medical school learning courses with one subscription!
FAQs
Second-generation antipsychotics primarily exert their therapeutic effects by blocking D2 dopamine receptors and serotonin receptors (5-HT 2A) in the CNS, which contributes to their antipsychotic properties.
Second-generation antipsychotics are primarily utilized to treat the positive and negative symptoms of schizophrenia. managing treatment-resistant depression. Additionally, certain second-generation antipsychotics like risperidone can be used adjunctively with SSRIs for managing obsessive-compulsive disorder (OCD) and separately for Tourette syndrome.
Common side effects of second-generation antipsychotics include sedation due to H1 histamine receptor blockade and orthostatic hypotension from alpha-1 receptor blockade. Some SGAs, notably olanzapine and clozapine, can lead to weight gain, dyslipidemia, and hyperglycemia. Second-generation antipsychotics, though less than FGAs, can cause antimuscarinic effects such as dry mouth, constipation, blurred vision, and urinary retention, especially with clozapine. Notably, clozapine can cause agranulocytosis, myocarditis, cardiomyopathy, and reduced seizure threshold. Extrapyramidal symptoms (EPS), although less common than with first-generation antipsychotics, can still manifest, especially with risperidone, which poses the highest risk among second-generation antipsychotics.
Second-generation antipsychotics generally have a lower incidence of extrapyramidal symptoms (such as acute dystonia, akathisia, and parkinsonism) and hyperprolactinemia, both consequences of D2 blockade, compared to first-generation antipsychotics. However, the risk of neuroleptic malignant syndrome (e.g. mental status changes, rigidity, autonomic instability, fever) exists for both second-generation and first-generation antipsychotics, a complication that may lead to rhabdomyolysis.
