Antipsychotic Medications

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Intro & Classification - Mind Menders

Antipsychotics: Treat psychosis (e.g., schizophrenia, bipolar disorder).

  • Two Major Classes:
    • Typical (1st Gen / FGAs):
      • Mechanism: Primarily $D_2$ receptor blockade.
      • Higher risk: Extrapyramidal Symptoms (EPS).
    • Atypical (2nd Gen / SGAs):
      • Mechanism: $5HT_{2A}$ & $D_2$ receptor blockade.
      • Risk: Metabolic syndrome; lower EPS. Antipsychotic Drug Classification Diagram

⭐ Chlorpromazine, introduced in the 1950s, was the first antipsychotic medication, revolutionizing psychiatric care.

Mechanism of Action - Dopamine's Domain

  • Core: Dopamine D2 receptor antagonism.
  • Pathway-specific effects of D2 blockade:
    • Mesolimbic: ↓ Positive symptoms (therapeutic effect).
    • Mesocortical: Affects negative/cognitive symptoms (First-Generation Antipsychotics [FGAs] may worsen; Second-Generation Antipsychotics [SGAs] may improve, partly via 5HT2A antagonism).
    • Nigrostriatal: Risk of Extrapyramidal Symptoms (EPS).

      ⭐ Blockade of D2 receptors in the nigrostriatal pathway is primarily responsible for Extrapyramidal Symptoms (EPS).

    • Tuberoinfundibular: ↑ Prolactin (e.g., galactorrhea, amenorrhea).
  • FGAs (Typicals): Primarily potent D2 blockade.
  • SGAs (Atypicals): D2 blockade + Serotonin 5HT2A antagonism (key for ↓ EPS risk & potential negative symptom benefit).

Brain Dopamine Pathways and D2 Receptor Sites

Typical Antipsychotics - Old School Cool

  • Aka FGAs. Mechanism: Dopamine D2 receptor blockade.
  • Potency Classes:
    • High: Haloperidol, Fluphenazine, Trifluoperazine. (📌 Try To Fly High)
      • Predominant SE: ↑ EPS risk.
    • Low: Chlorpromazine, Thioridazine. (📌 Cheating Thieves are Low)
      • Predominant SE: ↑ anticholinergic, antihistaminic, α1-blockade effects.
  • Other Major SE: Tardive Dyskinesia (TD), NMS, hyperprolactinemia.

⭐ High-potency First-Generation Antipsychotics (FGAs) like Haloperidol are associated with a higher risk of EPS, while low-potency FGAs like Chlorpromazine have more anticholinergic, antihistaminic, and alpha-adrenergic blocking effects. Antipsychotic Medication Comparison Guide

Atypical Antipsychotics - Newer Notions

  • Mechanism: Act on multiple receptors, primarily $D_2$ (less affinity than typicals) & $5-HT_{2A}$ antagonism.
    • Serotonin ($5-HT_{2A}$) blockade is key: ↑ dopamine in nigrostriatal/mesocortical pathways, reducing EPS & improving negative/cognitive symptoms.
  • Advantages:
    • Lower risk of Extrapyramidal Symptoms (EPS).
    • Greater efficacy for negative symptoms & cognitive deficits.
  • Common Side Effects:
    • Metabolic Syndrome: Weight gain, dyslipidemia, hyperglycemia (monitor BMI, lipids, glucose).
    • Sedation, orthostatic hypotension.
    • Hyperprolactinemia (esp. Risperidone, Paliperidone).
  • Clozapine, though highly effective (especially for treatment-resistant schizophrenia), requires regular blood monitoring due to the risk of agranulocytosis. Atypical Antipsychotics: Common Side Effects Summary

Adverse Effects & Management - Safety First!

  • Common AEs:
    • EPS (Akathisia, Dystonia, Parkinsonism, TD): Manage: ↓dose, switch, adjunctive meds (anticholinergics for EPS).
    • Metabolic Syndrome (Wt ↑, Glucose ↑, Lipids ↑): Monitor BMI, waist, BP, HbA1c, lipids.
    • Anticholinergic (dry mouth, constipation), Sedation.
    • Cardiovascular: Orthostatic hypotension, QTc prolongation (⚠️ risk Torsades de Pointes - monitor ECG).
    • Hyperprolactinemia.
  • Serious AEs:
    • Clozapine: ⚠️ Agranulocytosis (strict WBC monitoring).
    • Neuroleptic Malignant Syndrome (NMS): Medical emergency!

⭐ Neuroleptic Malignant Syndrome (NMS) is a medical emergency characterized by Fever, Autonomic instability, Rigidity, and Mental status change (FARM); immediate drug cessation and supportive care are critical.

High‑Yield Points - ⚡ Biggest Takeaways

  • FGAs (e.g., Haloperidol) block D2 receptors, treat positive symptoms, high EPS risk.
  • SGAs (e.g., Olanzapine, Risperidone) block D2/5-HT2A, treat positive/negative symptoms, risk metabolic syndrome.
  • Clozapine: For treatment-resistant schizophrenia; risk of agranulocytosis (monitor WBC).
  • NMS: Life-threatening; fever, rigidity, AMS, autonomic instability. Treat with Dantrolene/Bromocriptine.
  • Tardive Dyskinesia: Irreversible involuntary movements from chronic use, esp. FGAs.
  • EPS: Dystonia, akathisia, parkinsonism. Manage with anticholinergics (e.g., benztropine).

Practice Questions: Antipsychotic Medications

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Which of the following antipsychotics is a partial D2 agonist?

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Flashcards: Antipsychotic Medications

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The first-line treatment for antipsychotic-induced acute dystonia is _____

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The first-line treatment for antipsychotic-induced acute dystonia is _____

diphenhydramine

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