ATYPICAL ANTI-PSYCHOTICS
ATYPICAL ANTI-PSYCHOTICS
- A subdivision of anti-psychotic group of drugs.
- Mainly useful for schizophrenia.
Classification:
- Atypical antipsychotics (acting via other mechanisms – Low D2/5HT2A affinity).
- Note: Another drug group – Typical (D2-blockers).
MOA:
- Acts by antagonistic to 5-HT2 & alpha receptors.
Drugs included:
- Clozapine, Olanzapine, Quetiapine, Risperidone, Iloperidone, Paliperidone, Ziprasidone, Aripiprazole, Asenapine, Sertindole & Zotepine.
General adverse effects:
- Most drugs cause extrapyramidal symptoms.
- Weight gain.
- Hyperlipidemia.
- New-onset diabetes mellitus.
- Last 3 effects not seen with ziprasidone & aripiprazole.
Individual drugs:
1. Clozapine:
- Atypical antipsychotic drug with weak D2 blocking action.
MOA:
- Mainly acts by blocking 5-HT2, alpha-adrenergic & D4 receptors.
- Powerful anticholinergic effects (equivalent to chlorpromazine & thioridazine).
Uses:
- 1st FDA approved drug for antisuicide indication of schizophrenia.
- Suppresses both positive & negative symptoms.
Adverse effects:
- Convulsions – Dose-dependent, only in high doses.
- Only as a reserve drug.
- Due to seizures precipitation risk, even in non-epileptics.
- Agranulocytosis – Dose- independent.
- Myocarditis – Hence, contra-indicated cardiac patients.
- Specific risk of intestinal dysfunction – Potentially severe ileus & sialorrhea.
- Least risk of extrapyramidal symptoms.
2. Risperidone:
- Active metabolite – Paliperidone.
- Paliperidone – Has lesser risk of causing metabolic adverse effects.
- MOA:
- Acts by blocking 5-HT2, alpha adrenergic & D2 receptors.
- More potent D2 blocker than clozapine.
- Risk of seizures precipitation is less than clozapine.
- Adverse effects:
- Hyperprolactinemia (more commonly)
- Cause extrapyramidal symptoms at high dose.
3. Olanzapine:
- Similar MOA as risperidone.
- Potent anticholinergic drug.
- Adverse effects:
- Stroke & death in elderly patients (Significantly higher risk).
- Dry mouth.
- Constipation.
- Seizures.
- Weight gain.
- Uses:
- Schizophrenia.
- Acute Mania.
- Bipolar disorder.
4. Ziprasidone:
- Causes QT prolongation.
- Risk of arrhythmias.
- Not associated with weight gain, hyperlipidemia or diabetes (Unlike other atypical antipsychotics)
5. Quetiapine:
- Shortest half-life.
- Cause cataract formation.
6. Aripiprazole:
- Acts as partial agonist at 5-HT1A & D2 receptors and antagonist at 5-HT2A receptor.
- Also known as “Dopamine- serotonin stabilizer”.
- Longer half-life.
- Uses: Approved for treatment of irritability associated with autistic disorders in children.
7. Asenapine:
- Used sublingually for schizophrenia & acute mania.
8. Iloperidone:
- Cause orthostatic hypotension.
- QT interval prolongation.
- Less risk of extrapyramidal effects.
Exam Important
- Atypical antipsychotics act via other mechanisms due to their low D2/5HT2A affinity.
- Clozapine, Olanzapine, Quetiapine, Risperidone, Iloperidone, Paliperidone, Ziprasidone, Aripiprazole, Asenapine, Sertindole & Zotepine are all atypical antipsychotics.
- All atypical antipsychotics cause extrapyramidal symptoms, weight gain & hyperlipidemia, except ziprasidone & aripiprazole.
- Clozapine is an atypical antipsychotic drug with weak D2 blocking action.
- Clozapine mainly acts by blocking 5-HT2, alpha-adrenergic & D4 receptors.
- Clozapine has powerful anticholinergic effects equivalent to chlorpromazine & thioridazine.
- Clozapine is the 1st FDA approved drug for antisuicide indication of schizophrenia, suppressing both positive & negative symptoms.
- Clozapine is used as a reserve drug due to risk of seizures precipitation even in non-epileptics.
- Convulsions are dose-dependent adverse effect of clozapine, only in high doses.
- Agranulocytosis is a dose-independent clozapine.
- Specific risk of intestinal dysfunction severe ileus & sialorrhea is adverse effect of clozapine.
- Active metabolite of risperidone is Paliperidone.
- Paliperidone has lesser risk of causing metabolic adverse effects.
- Risperidone acts by blocking 5-HT2, alpha adrenergic & D2 receptors.
- Risperidone is more potent D2 blocker than clozapine.
- For Risperidone risk of seizures precipitation is less than clozapine.
- Risperidone more commonly causes hyperprolactinemia.
- Risperidone causes extrapyramidal symptoms at high dose.
- Olanzapine is a potent anticholinergic drug.
- Olanzapine has significantly higher risk of stroke & death in elderly patients.
- Ziprasidone causes QT prolongation & arrhythmia risk.
- Quetiapine has shortest half-life & cause cataract formation.
- partial agonist at 5-HT1A & D2 receptors and antagonist at 5-HT2A receptor, hence known as “Dopamine- serotonin stabilizer”.
- Aripiprazole is approved for treatment of irritability associated with autistic disorders in children.
- Asenapine is used sublingually for schizophrenia & acute mania.
- Iloperidone cause orthostatic hypotension & QT interval prolongation.
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