Antipsychotic Medications

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.

⭐ 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).

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.

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.

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).