Antipsychotics: Typical and Atypical

Introduction & Classification - Mind Menders

• Antipsychotics (neuroleptics): Key drugs for psychosis (e.g., schizophrenia, bipolar mania, acute agitation).
• Aim to reduce positive symptoms (hallucinations, delusions) & thought disorders.
• Broadly classified by receptor affinity & side effect profiles.

⭐ Atypical antipsychotics generally have lower D2 receptor affinity and faster dissociation than typicals, contributing to lower EPS risk.

Typical Antipsychotics (FGAs) - Dopamine Blockers

• Mechanism: Block Dopamine D2 receptors (D2 antagonists).
• Classification & Examples:
  • High Potency: More EPS, less sedation/anticholinergic.
    • Haloperidol, Fluphenazine, Trifluoperazine.
    • 📌 Hal FlT (High potency For Treatment)
  • Low Potency: Less EPS, more sedation/anticholinergic/orthostatic hypotension.
    • Chlorpromazine, Thioridazine.
• Adverse Effects (AEs):
  • Extrapyramidal Symptoms (EPS): Acute dystonia, akathisia, parkinsonism. Treat with anticholinergics (e.g., Benztropine).
  • Neuroleptic Malignant Syndrome (NMS): Fever, rigidity, autonomic instability, ↑CK. ⚠️ Life-threatening! Treat with Dantrolene/Bromocriptine.
  • Tardive Dyskinesia (TD): Chronic use; often irreversible choreoathetoid movements.
  • Hyperprolactinemia, Anticholinergic effects, Sedation, Orthostatic hypotension.
  • Thioridazine: Retinal pigmentation.
  • Chlorpromazine: Corneal deposits, Jaundice.
• Clinical Uses: Schizophrenia (positive symptoms), psychosis, acute mania, Tourette's syndrome.

⭐ Haloperidol is a high-potency FGA commonly used for acute agitation and has a high risk of EPS but low risk of sedation and hypotension compared to low-potency FGAs like Chlorpromazine.

Atypical Antipsychotics (SGAs) - Serotonin Savvy

• Mechanism: $D_2$ & $5-HT_{2A}$ antagonism. Aripiprazole: $D_2$ partial agonist.
• Advantages: Treat negative symptoms, ↓ EPS risk compared to typicals.
• Key Drugs & Unique Points:
  • Risperidone: ↑ Prolactin, highest SGA EPS risk at higher doses.
  • Olanzapine: Significant weight gain, sedation.
  • Quetiapine: Sedation, orthostatic hypotension; low EPS risk.
  • Clozapine: For treatment-resistant schizophrenia; risks: agranulocytosis, myocarditis, seizures.
  • Aripiprazole: Akathisia; $D_2$ partial agonism; less weight gain.
  • Ziprasidone: QTc prolongation risk; take with food.
• Class Adverse Effects:
  • Metabolic syndrome (↑ weight, dyslipidemia, diabetes). Monitor BMI, glucose, lipids.
  • QTc prolongation.
  • 📌 Old Clothes Quietly Rip (Olanzapine, Clozapine, Quetiapine, Risperidone - high metabolic risk).

⭐ Clozapine requires mandatory regular blood monitoring (CBC) due to agranulocytosis risk (1-2%).

FGA vs. SGA Comparison - The Great Debate

Key Antipsychotics & Pearls - Clinical Champs

• Clozapine: For treatment-resistant schizophrenia. Strict ANC monitoring (risk of agranulocytosis). 📌 ClozaPine Always Needs Counts.
• Risperidone: Highest ↑prolactin risk among atypicals (gynecomastia, galactorrhea).
• Olanzapine: Significant metabolic risk (weight gain, ↑glucose, ↑lipids).
• Aripiprazole: Partial D2 agonist; generally lower EPS & metabolic side effects.
• Haloperidol: Potent D2 antagonist (typical); high EPS, for acute psychosis/agitation.

⭐ Clozapine is the only antipsychotic proven effective for treatment-resistant schizophrenia and reducing suicide risk in schizophrenia.

High‑Yield Points - ⚡ Biggest Takeaways

• Typical antipsychotics (Haloperidol) block D2 receptors, causing significant EPS.
• Atypical antipsychotics (Olanzapine) block D2/5-HT2A receptors; lower EPS, higher metabolic syndrome risk.
• Clozapine: for treatment-resistant schizophrenia; risk of agranulocytosis (monitor WBC).
• Neuroleptic Malignant Syndrome (NMS): life-threatening; fever, rigidity, AMS, autonomic instability.
• Tardive Dyskinesia (TD): chronic use complication; irreversible involuntary movements.
• Hyperprolactinemia: common with typicals and risperidone due to D2 blockade.
• Risk of QTc prolongation with many antipsychotics; ECG monitoring advised.