What are the first and second generation antipsychotics (atypical and typical antipsychotics)?

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Last updated: May 11, 2025View editorial policy

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From the Guidelines

First-generation antipsychotics include chlorpromazine, haloperidol, fluphenazine, perphenazine, thioridazine, and trifluoperazine, while second-generation antipsychotics include clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, and lurasidone. The main difference between these two generations is their mechanism of action, with FGAs primarily blocking dopamine D2 receptors and SGAs blocking both dopamine and serotonin receptors, particularly 5-HT2A receptors 1. This dual mechanism of SGAs helps treat both positive and negative symptoms of schizophrenia, such as hallucinations, delusions, social withdrawal, and flat affect, while causing fewer extrapyramidal side effects than FGAs 1. However, SGAs generally carry a higher risk of metabolic side effects, including weight gain, diabetes, and dyslipidemia.

Some key points to consider when choosing between FGAs and SGAs include:

  • Efficacy: SGAs have been shown to be at least as effective as FGAs for positive symptoms, and possibly more effective for negative symptoms 1.
  • Side effects: FGAs are more likely to cause extrapyramidal side effects, while SGAs are more likely to cause metabolic side effects 1.
  • Individual patient factors: The choice between FGAs and SGAs depends on individual patient factors, including symptom profile, side effect sensitivity, and medical comorbidities.

It's worth noting that clozapine, a SGA, has been shown to be effective for treatment-resistant schizophrenia, but its use is limited due to the risk of serious side effects, including neutropenia and seizures 1. Other SGAs, such as risperidone, olanzapine, and quetiapine, have also been shown to be effective for schizophrenia, but more research is needed to establish their long-term safety and efficacy in juveniles 1.

From the Research

Cephalosporin Generations

  • First-generation cephalosporins have a narrow gram-negative spectrum but are most active against gram-positive bacteria, particularly Staphylococcus aureus 2
  • Second-generation cephalosporins, also known as cephamycins, include cefoxitin, cefotetan, and cefmetazole, and have the best activity against anaerobes 2

Characteristics of Each Generation

  • First-generation: narrow gram-negative spectrum, active against gram-positive bacteria 2
  • Second-generation: best activity against anaerobes, includes cefoxitin, cefotetan, and cefmetazole 2

Note: The provided evidence does not contain information about the second generation of cephalosporins beyond the cephamycins subgroup. Therefore, the information provided is limited to the available data 2. The study 3 does not provide relevant information on this topic.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cephalosporins: rationale for clinical use.

American family physician, 1991

Research

Consequences of ileal dysfunction: an approach to management.

The Medical journal of Australia, 1978

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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