Tag: Atypical Anti-Psychotics

Atypical Anti-Psychotics

ATYPICAL ANTI-PSYCHOTICS

Q. 1 Atypical antipsychotics are all, except:
 A Olanzapine
 B Clozapine
 C Risperidone
 D Thioridazine
Q. 1 Atypical antipsychotics are all, except:
 A Olanzapine
 B Clozapine
 C Risperidone
 D Thioridazine
Ans. D

Explanation:

Thioridazine


Q. 2

Which of the following neuroleptics is not an atypical antipsychotic?

 A

Clozapine

 B

Ziprazidone

 C

Zuclopenthixol

 D

Quetiapine

Q. 2

Which of the following neuroleptics is not an atypical antipsychotic?

 A

Clozapine

 B

Ziprazidone

 C

Zuclopenthixol

 D

Quetiapine

Ans. C

Explanation:

Atypical antipsychotics are new generation anti-psychotics which are called serotonin-dopamine antagonists (SDA).

These drugs include Olanzapine, Risperidone, Quetiapine, Clozapine and Ziprazidone.

They have higher ratio of serotonin (5-HT2) receptor blockade compated to the higher dopamine receptor blockade in the old generation anti-psychotics like Haloperidol, Chlorpromazine, Zuclopenthixol etc. 

Atypical antipsychotics are a reduced risk for extra-pyramidal side effects (EPSEs) including tardive dyskinesia.

Efficasy of the atypicals are proved in Schizophrenia and acute mania. 

Ref: Kaplan & Sadock’s Synopsis of Psychiatry, By Benjamin J Sadock, M.D., Harold I. Kaplan, Virginia A Sadock, M.D, 10th Edition, Page : 1091


Q. 3

Which of the following properties distingiush Aripiprazole from atypical antipsychotics?

 A

It is a potent 5-HT2A receptor antagonist

 B

Reduced risk of extrapyramidal side effects

 C

It can be used in Schizophrenia

 D

It is not a D2 receptor antagonist

Q. 3

Which of the following properties distingiush Aripiprazole from atypical antipsychotics?

 A

It is a potent 5-HT2A receptor antagonist

 B

Reduced risk of extrapyramidal side effects

 C

It can be used in Schizophrenia

 D

It is not a D2 receptor antagonist

Ans. D

Explanation:

Aripiprazole is a potent 5-HT2A receptor antagonist like atypical antipsychotics.

It is one of the newer drugs which belongs to a class of patial D2 receptor agonists.

It is not D2 antagonists like other antipsychotics, which makes them an entirely different class.

They are used in Schizophrenia and Acute mania.

They have very low risk of extrapyramidal side effects, weight gain and diabetis.


This are also a distinguishing factors from other Atypical Antipsychotics. 

Atypical antipsychotics are new generation anti-psychotics which are called serotonin-dopamine antagonists (SDA).
These drugs include Olanzapine, Risperidone, Quetiapine, Clozapine and Ziprazidone.
They have higher ratio of serotonin (5-HT2) receptor blockade compared to the higher dopamine receptor blockade in the old generation anti-psychotics like Haloperidol, Chlorpromazine, Zuclopenthixol etc.  
Atypical antipsychotics are a reduced risk for extra-pyramidal side effects (EPSEs) including tardive dyskinesia. Efficacy of the atypicals are proved in Schizophrenia and acute mania. 
 
Ref: Kaplan & Sadock’s Synopsis of Psychiatry, By Benjamin J Sadock, M.D., Harold I. Kaplan, Virginia A Sadock, M.D, 10th Edition, Page : 1091

Quiz In Between


Q. 4

Clozapine was the first antipsychotic drug. Which of the following is an indication for the use of Clozapine?

 A

Resistant schizophrenia

 B

Akathesia

 C

First drug to be used for schizpophrenia

 D

Used for schizophrenia with depression

Q. 4

Clozapine was the first antipsychotic drug. Which of the following is an indication for the use of Clozapine?

 A

Resistant schizophrenia

 B

Akathesia

 C

First drug to be used for schizpophrenia

 D

Used for schizophrenia with depression

Ans. A

Explanation:

Clozapine has been approved for,

  • Patients with schizophrenia who have failed to respond adequately to typical neuroleptic drugs (treatment-resistant schizophrenia)
  • Patients who are intolerant of typical neuroleptic drugs because of EPS or tardive dyskinesia
  • Patients who are at high risk for suicide
Ref: Meltzer H.Y., Bobo W.V., Heckers S.H., Fatemi H.S. (2008). Chapter 16. Schizophrenia. In M.H. Ebert, P.T. Loosen, B. Nurcombe, J.F. Leckman (Eds),CURRENT Diagnosis & Treatment: Psychiatry, 2e.

Q. 5

A 9 year old child with a history of ADHD diagnosed at 5 years of age has presented to you with multiple tics in different parts of the body. The child had also developed vocal tics including barking sounds and coprolalic. There is history of similar illness in the family. Note that the child has never had any pharmacotherapeutic agents for ADHD. Which of the following drugs will you consider in the treatment of the child initially?

 A

Risperidone

 B

Baclofen

 C

Methylphenidate

 D

Levetiracetam

Q. 5

A 9 year old child with a history of ADHD diagnosed at 5 years of age has presented to you with multiple tics in different parts of the body. The child had also developed vocal tics including barking sounds and coprolalic. There is history of similar illness in the family. Note that the child has never had any pharmacotherapeutic agents for ADHD. Which of the following drugs will you consider in the treatment of the child initially?

 A

Risperidone

 B

Baclofen

 C

Methylphenidate

 D

Levetiracetam

Ans. A

Explanation:

This is a case of Gilles de la Tourette syndrome that has an onset at 2 – 21 years of age.

Obsessive compulsive disorders and ADHD are also frequently associated with it.

It is inherited in most cases as an autosomal dominant disease and the gene responsible has been mapped to chromosome 18.


In this case it is also important to know that Methylphenidate given for ADHD may unmask Tourette syndrome. Here initially Haloperidol or Risperidone may be given at a dose of 0.25mg/24 hours and later increased to a dose of 2 – 6 mg/24 hours. It is effective in 50% of children.

Ref: Nelson, 17th Edition, Page  2023

Q. 6

A patient of schizophrenia on CPZ (chlorpromazine) develops auditory hallucination again. The next drug to  be given is

 A

Haloperidol

 B

Clozapine

 C

Suipride

 D

Tianeptin

Q. 6

A patient of schizophrenia on CPZ (chlorpromazine) develops auditory hallucination again. The next drug to  be given is

 A

Haloperidol

 B

Clozapine

 C

Suipride

 D

Tianeptin

Ans. B

Explanation:

B i.e. Clozapine

Quiz In Between


Q. 7

The major difference between typical and atypical antipsychotics is that –

 A

The latter cause minimal or no increase in prolactin

 B

The former cause tardive dyskinesia

 C

The former are available as parenteral preparations

 D

a and b

Q. 7

The major difference between typical and atypical antipsychotics is that –

 A

The latter cause minimal or no increase in prolactin

 B

The former cause tardive dyskinesia

 C

The former are available as parenteral preparations

 D

a and b

Ans. D

Explanation:

Ans. is ‘a’ i.e., The latter cause minimal or no increase in prolactin; ‘b’ i.e., The former cause tardive dyskinesia

“Aripiprazole, clozapine, olanzapine, quentiapine and ziprasidone (all are atypical antipsychotics) are exceptional in having minimal or transient effect on prolactin” – Goodman & Gilman 116/e p. 473. “Atypical antipsychotics less likely induce extrapyramidal side effects and hyperpralactinemia.” – Laurence 9th/e p. 388.

o So option a & b both are correct i.e.,

  1. Typical antipsychotics have more extrapyramidal effects including tardive dyskinasia.
  2. Atypical antipsychotics have minimal effect on prolactin secretion.



Q. 8

Extrapyramidal side-effect least seen with ‑

 A

Clozapine

 B

Haloperidol

 C

Thioridazine

 D

Fluphenozine

Q. 8

Extrapyramidal side-effect least seen with ‑

 A

Clozapine

 B

Haloperidol

 C

Thioridazine

 D

Fluphenozine

Ans. A

Explanation:

Ans. is ‘a’ i.e., Clozapine

o Antipsychotics with no extrapyramidal effects.

1. Clozapine                  2. Aripiprazole                      3. Quetiapine

o Amongst typical antipsychotics, thioridazone has least extrapyramidal effects.


Q. 9

Which of the following is not a side effect of clozapine –

 A

Agranulocytosis

 B

Seizure

 C

Sialosis

 D

Weight loss

Q. 9

Which of the following is not a side effect of clozapine –

 A

Agranulocytosis

 B

Seizure

 C

Sialosis

 D

Weight loss

Ans. D

Explanation:

Ans. is ‘d’ i.e., Weight loss

Clozapine causes weight gain.

Quiz In Between


Q. 10

Antipsychotic with less extra pyramidal side effects –

 A

Loxapine

 B

Pimozide

 C

Quetiapine

 D

Resperidone

Q. 10

Antipsychotic with less extra pyramidal side effects –

 A

Loxapine

 B

Pimozide

 C

Quetiapine

 D

Resperidone

Ans. C

Explanation:

Ans. is ‘c’ i.e., Quetiapine

o Quetiapine, clozapine, aripiprazole have no (o) extrapyramidal symptoms.

o Risperidone may or may not (o/+) have extrapyramidal effect.


Q. 11

Refractory schizophrenia – What is the treatment of choice

 A

Haloperidol

 B

Flupenthixol

 C

Trifluoperazine

 D

Clozapine

Q. 11

Refractory schizophrenia – What is the treatment of choice

 A

Haloperidol

 B

Flupenthixol

 C

Trifluoperazine

 D

Clozapine

Ans. D

Explanation:

Ans. is ‘d’ i.e., Clozapine

o Clozapine (but not the newer atypicals) is more effective than classical agents for resistant schizophrenia.


Q. 12

Which of the following has highest potential to cause metabolic syndrome?

 A

Clozapine

 B

Risperidone

 C

Quetiapine

 D

Aripiprazole

Q. 12

Which of the following has highest potential to cause metabolic syndrome?

 A

Clozapine

 B

Risperidone

 C

Quetiapine

 D

Aripiprazole

Ans. A

Explanation:

Ans. is ‘a’ i.e. Clozapine

Potential of antipsychotic drugs to cause metabolic syndrome

  • High Potential: Clozapine, Olanzapine, Chlorpromazine, thioridazine
  • Intermediate potential: Quetiapine
  • Low potential: Risperidone, Paliperidone
  • Least potential: Iloperidone, aripiprazole, asenapine, ziprasidone.

Quiz In Between


Q. 13

Which of the following is the drug of choice for medication-resistant schizophrenia:       

September 2009

 A

Haloperidol

 B

Chlorpromazine

 C

Clozapine

 D

Flupentixol

Q. 13

Which of the following is the drug of choice for medication-resistant schizophrenia:       

September 2009

 A

Haloperidol

 B

Chlorpromazine

 C

Clozapine

 D

Flupentixol

Ans. C

Explanation:

Ans. C: Clozapine

Clozapine

  • It may inhibit serotonin, muscarinic, and dopamine effects.
  • Revolutionized treatment of medication-resistant schizophrenia.
  • Effective in 30% of patients in whom other medications have failed.
  • May improve tardive dyskinesia resulting from long-term use of traditional antipsychotics.
  • Major drawback of reversible agranulocytosis occurs in 1-2%
  • Interactions-Epinephrine and phenytoin may decrease effects; tricyclic antidepressants, neuroleptics, CNS depressants, guanabenz, and anticholinergics may increase effects
  • Contraindications-Documented hypersensitivity; WBC (less than 3500 cells per millimeter cube) before or during therapy.
  • Precautions-Pregnancy, Do not abruptly stop the medication; to minimize risk of agranulocytosis.

Q. 14

Drug causing agranulocytosis ‑

 A

Pimozide

 B

Clozapine

 C

Risperidone

 D

Olanzapine

Q. 14

Drug causing agranulocytosis ‑

 A

Pimozide

 B

Clozapine

 C

Risperidone

 D

Olanzapine

Ans. B

Explanation:

Ans. is ‘b’ i.e., Clozapine

Agranulocytosis is a known side effect of clozapine

“Because of the risk of agranulocytosis, patients, recieving clozapine must have weekly blood counts for the first 6 months and every 3 weeks thereafter”

Side effects of clozapine

  • Agranulocytosis
  • Unstable BP & Tachycardia 
  • Worsening of diabetes
  • Seisures
  • Urinary incontinence
  • Hypersalivation (sialorrhoea) 
  • Weight gain
  • Sedation

Q. 15

Following is false about aripiprazole except ‑

 A

Only antipsychotic with D1 agonistic activity

 B

It has 5HT1A antagonistic action

 C

It has maximum sedating potential

 D

It is the drug of choice in treatment of acute mania

Q. 15

Following is false about aripiprazole except ‑

 A

Only antipsychotic with D1 agonistic activity

 B

It has 5HT1A antagonistic action

 C

It has maximum sedating potential

 D

It is the drug of choice in treatment of acute mania

Ans. D

Explanation:

Ans. is `d’ i.e., It is the drug of choice in treatment of acute mania

Atypical antipsychotics —> Olanzapine, risperidone, aripiprazole or quetiapine with or without benzodiazepine is the treatment of choice for acute mania.

Aripiprazole

Only antipsychotic with D2 agonistic activity. (all others are D2 antagonists).

Longest acting

It also has 5HT,A agonistic and 5HT2 antagonistic activity – Also known as dopamine-serotinine stabilizer.

It is least sedating antipsychotic → can cause insomnia.


Q. 16

All are side effects of Clozapine, except ‑

 A

Granulocytopenia

 B

Seizures

 C

Sedation

 D

Extrapyramidal side effects

Q. 16

All are side effects of Clozapine, except ‑

 A

Granulocytopenia

 B

Seizures

 C

Sedation

 D

Extrapyramidal side effects

Ans. D

Explanation:

Ans. is ‘d’ i.e., Extrapyramidal side effects

Side effects of clozapine

  • Agranulocytosis        
  • Unstable BP & Tachycardia  
  • Worsening of diabetes 
  • Seisures
  • Urinary incontinence  
  • Hypersalivation (sialorrhoea)
  • Weight gain            
  • Sedation

Quiz In Between



Atypical Anti-Psychotics

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.
  • AgranulocytosisDose- independent.
  • Myocarditis – Hence, contra-indicated cardiac patients.
  • Specific risk of intestinal dysfunctionPotentially 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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