Pharmacology
Summary
First-generation antipsychotics (FGAs) are a class of drugs often utilized for the management of schizophrenia, bipolar manic episodes, agitation, and various forms of acute psychosis. Their therapeutic activity primarily stems from antagonizing the dopamine D2 receptors in the central nervous system. While they serve as crucial agents in alleviating debilitating symptoms, FGAs are associated with several adverse effects. These include extrapyramidal symptoms such as dystonia, akathisia, and parkinsonism, tardive dyskinesia, and QT prolongation, with metabolic syndrome being a concern during prolonged treatment.
High and low-potency FGAs are distinct in their receptor blockade strength and side effect profiles. High-potency FGAs, exemplified by agents like haloperidol, fluphenazine, and loxapine, exhibit a pronounced D2 blocking activity. This strong receptor affinity increases the risk extrapyramidal symptoms and other conditions such as hyperprolactinemia and neuroleptic malignant syndrome. In contrast, low-potency FGAs, such as thioridazine and chlorpromazine, present a milder D2 blockade and hence fewer extrapyramidal effects. However, they are notable for side effects like retinal deposits (thioridazine) and corneal deposits (chlorpromazine). Low-potency FGAs also antagonize H1 histamine receptors, which can cause sedation. They also exhibit anticholinergic properties, resulting in side effects such as dry mouth, urinary retention, constipation, and blurred vision.
Lesson Outline
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FAQs
First-generation antipsychotics (FGAs) are principally recommended for treating conditions like schizophrenia, bipolar manic episodes, various forms of psychosis, and agitation.
FGAs achieve their therapeutic actions primarily by antagonizing dopamine D2 receptors in the brain, reducing the dopaminergic neurotransmission associated with the symptoms of these disorders.
FGAs can induce a series of side effects, most notably extrapyramidal symptoms such as dystonia, akathisia, and parkinsonism. Another long-term adverse effect, tardive dyskinesia, is a potential concern. Additionally, FGAs can lead to QT interval prolongation, which can escalate to torsades de pointes and subsequent cardiac arrest. Metabolic disturbances, encompassing elevated BMI, weight gain, diabetes mellitus, and dyslipidemia, are also associated with FGA use.
High-potency FGAs, such as haloperidol, fluphenazine, and loxapine, exhibit a robust D2 receptor blockade. This pronounced blockade predisposes to a heightened risk of extrapyramidal symptoms. High-potency FGAs can also induce hyperprolactinemia and precipitate neuroleptic malignant syndrome. Conversely, low-potency FGAs manifest milder D2 receptor blockade, resulting in fewer extrapyramidal symptoms. Notably, thioridazine may lead to retinal deposits, and chlorpromazine can cause corneal deposits. These low-potency drugs also act as H1 histamine receptor antagonists, leading to sedative effects, and have antimuscarinic properties that can result in dry mouth, urinary retention, constipation, and pupil dilation.
