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Antipsychotics: Typical and Atypical

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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.

Antipsychotic Receptor Binding 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.

Typical Neuroleptics: D2 Receptor Blockade

⭐ 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%).

Typical vs Atypical Antipsychotics Comparison

FGA vs. SGA Comparison - The Great Debate

FeatureFGA (Typical)SGA (Atypical)
Receptor ActionPrimarily D2 antagonistsD2 & 5-HT2A antagonists (broader)
Positive SymptomsGood efficacyGood efficacy
Negative/CognitiveLimited efficacyOften better efficacy (varies by agent)
EPS RiskHigh (parkinsonism, dystonia)Lower (📌 "Atypical" for lower EPS)
Metabolic RiskLowHigh (weight gain, diabetes, dyslipidemia)
Prolactin ↑Common & often significantLess common (except risperidone/paliperidone)

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.

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Sedation as an adverse effect is most commonly associated with which of the following atypical antipsychotics?

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_____ is a D2 and D3 receptor antagonist used as an antiemetic and antipsychotic.

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_____ is a D2 and D3 receptor antagonist used as an antiemetic and antipsychotic.

Amisulpride

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