First-generation antipsychotic

First-generation antipsychotics (FGAs), also known as typical antipsychotics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, or disordered thought), particularly in schizophrenia and bipolar disorder. First introduced in the 1950s, these medications marked a significant advancement in the treatment of psychiatric disorders.

History

The discovery of the first antipsychotic drug, chlorpromazine, in the 1950s revolutionized the treatment of schizophrenia and other psychotic disorders. Before the advent of antipsychotic medications, treatments for psychotic conditions were largely ineffective and often inhumane. Chlorpromazine's introduction led to the development of more first-generation antipsychotics, such as haloperidol, fluphenazine, and thioridazine, among others.

Mechanism of Action

First-generation antipsychotics primarily exert their effects by blocking dopamine D2 receptors in the brain. Dopamine is a neurotransmitter involved in many functions, including motivation, pleasure, cognition, memory, learning, and fine motor control. The blockade of dopamine receptors is thought to reduce the psychotic symptoms, particularly the positive symptoms of schizophrenia like hallucinations and delusions. However, this dopamine blockade is also responsible for many of the side effects associated with FGAs.

Uses

FGAs are used in the management of:

• Schizophrenia - particularly for controlling positive symptoms.
• Acute mania - as part of bipolar disorder treatment.
• Severe agitation and psychotic depression.
• Tourette syndrome and other severe behavioral disorders.

Side Effects

The use of first-generation antipsychotics is often limited by their side effects, which can include:

• Extrapyramidal symptoms (EPS) - such as parkinsonism, akathisia, dystonia, and tardive dyskinesia.
• Neuroleptic malignant syndrome (NMS) - a rare but potentially fatal condition.
• Sedation and drowsiness.
• Anticholinergic effects - such as dry mouth, blurred vision, constipation, and urinary retention.
• Weight gain and metabolic changes.

Comparison with Second-Generation Antipsychotics

Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, were developed to offer effective treatment with fewer side effects. SGAs tend to have a broader mechanism of action, including effects on serotonin receptors, which may contribute to their lower risk of extrapyramidal side effects and potentially better efficacy in treating the negative symptoms of schizophrenia.

Conclusion

First-generation antipsychotics have played a pivotal role in the treatment of psychosis and continue to be used today, particularly in cases where cost or the specific side effect profile of SGAs is a concern. Despite their limitations, FGAs remain an important tool in the management of severe psychiatric disorders.

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