CLOZAPINE

CLOZAPINE

Q. 1

Drug of choice for schizophrenic patient with poor oral absorption is:

 A Haloperidol
 B Fluphenazine
 C Clozapine
 D Olanzapirte
Q. 1

Drug of choice for schizophrenic patient with poor oral absorption is:

 A Haloperidol
 B Fluphenazine
 C Clozapine
 D Olanzapirte
Ans. C

Explanation:

Clozapine


Q. 2

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. 3 A 26-year-old man with schizophrenia and tardive dyskinesia. Which is the most appropriate pharmacotherapeutic agent?

 A

Clozapine

 B

Valproic acid

 C

Haloperidol

 D

Paroxetine

Ans. A

Explanation:

Valproic acid is an anticonvulsant used as a mood stabilizer. It is found useful in the treatment of mania in a bipolar disorder.

It has also been valuable in the treatment of rapid cycling bipolar patients.

Paroxetine is an example of a selective serotonin reuptake inhibitor (SSRI), which is a newer form of antidepressant.

The SSRis are being found to be as effective as the tricyclic antidepressants.

Haloperidol is an example of a neuroleptic or antipsychotic medication useful in the management of acute psychosis, as well as long-term care. Clozapine is a newer atypical antipsychotic medication.

It is not associated with tardive dyskinesia as are the older neuroleptics.

This makes it a drug of choice for individuals who have developed signs of tardive dyskinesia after using other neuroleptics.

Problems with agranulocytosis prevent clozapine from being used as a “first line” neuroleptic.  

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. 4

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


Q. 5

A patient of depression is getting chlorpromazine, but his auditory hallucination are not controlled. The next drug is given

 A

Haloperidol

 B

Clozapine

 C

Suipride

 D

Tianeptin

Ans. B

Explanation:

Ans:B-Clozapine

  • Clozapine is an antipsychotic drug with least extrapyramidal side effects, i.e. it has least chances of producing muscular dystonia, akathisia, malignant neuroleptic syndrome, & tardive dyskinesia.
  • The patient who has depression & auditory hallucinations & is being treated with CPZ i.e. the patient is a case of schizophrenia.
  • The patient is a case of resistant schizophrenia as the auditory hallucinations are not responding to treatment.
  • As you must know – Auditory hallucinations are first symptom to go with treatment & also 1st symptom to reappear after drug resistance.

Q. 6 Tardive dyskinesia is produced by following except:

 A

Fluphenazine

 B

Haloperidol

 C

Chlorpromazine

 D

Clozapine

Ans. D

Explanation:

Ans:D-Clozapine

  • Side effects of clozapine include agranulocytosis, myocarditis, seizures, increased mortality in elderly patients with dementia related psychosis (mostly because cardiovascular or infectious cause), severe cardiovascular and respiratory events (eg severe episodes of orthostatic hypotension, syncope, cardiac or respiratory arrest; more likely to occur early in treatment when the dose is being increased especially when combined with benzodiazepines). 
  • Other adverse events include sialorrhea (hypersalivation; b/o decrease swallowing in night), anticholinergic S/E (dry mouth, blurred vision, constipation, urinary retention, and constipation), weight again, type 2 diabetes mellitus, liver function disturbance and very low incidence of extrapyramidal side effects & neuroleptic malignant syndrome.
  • Clozapine has strong potency (affinity) for 5H2TA and weak potency (affinity) for D2 receptors.
  • It should not be combined with carbamazepine b/o combined bone marrow suppression (Vt agranulocytosis) and carbamazepine induced metabolism of clozapine (resulting in decreased plasma concentration).
  • Therapeutic range of plasma concentration is 200-400 ng/mL; however, the correlation between plasma concentration & clinical improvement or side effects are week, but studis indicate patients are more likely to respond when their clozapine concentrations are > 350 ng/mL. WBC count 23500 cellVmm3 and absolute neutrophil count (ANC) or granulocyte count 22000 cells/mm3 is required for initiating and continuing clozapine therapy.

Q. 7 An elderly woman suffering from schizophrenia is on antipsychotic medication. She developed purposeless involuntary facial and limb movements, constant chewing and puffing of cheeks. Which of the following drugs is least likely to be involved in this side effect:

 A

Halperidol

 B

Clozapine

 C

Fluphenazine

 D

Loxapine

Ans. B

Explanation:

Ans:B-Clozapine

Common side effects of clozapine include:

  1. Sedation
  2. Hypersalivation
  3. Tachycardia
  4. Hypotension
  5. Hypertension
  6. Weight gain
  7. Constipation 
  8. Hepatic effects
  9. Urinary incontinence
  10. Fever

Serious side effects include:

  1. Agranulocytosis
  2. Cardiovascular/respiratory arrest
  3. Seizures

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

Ans. D

Explanation:

Ans. is ‘d’ i.e., Weight loss

Clozapine causes weight gain.


Q. 10

Drug of choice for the treatment of negative symptoms of schizophrenia is –

 A

Chlorpromazine

 B

Haloperidol

 C

Clozapine

 D

Doxepin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Clozapine

o Drugs for negative symptoms

  • Clozapine 
  • Olanzapine 
  • Risperidone 
  • Aripiprazole 
  • Ziprazidone

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

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.

Q. 13 A young patient of schizophrenia is intolerant to antipsychotic medications. Which drug is most preferred for such a patient?

 A

Clozapine

 B

Olanzapine

 C

Risperidone

 D

Haloperidol

Ans. A

Explanation:

Ans: A i.e. Clozapine

About 30% of patients do not respond to antipsychotics or are intolerant to them, usually because of extrapyramidal side effects. The only proven drug intervention for this group is clozapine, which is effective in between a third and a half of such patients.

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

Which of the following drug(s) comes in risk category B of FDA teratogenic risk categories for pregnancy:

 A Phenytoin

 B Resperidone

 C

Olanazapine

 D

Clozapine

Ans. D

Explanation:

Ans. D. Clozapine

[Ref: KDT 7th/90; Katzung 13th/1018; Rang 6 Dale 8th/700; Pharmacology by Satoskar 24th/ 1 122; http://schizophrenia bulletin- oxford journal]

Category A:

  • No risk to fetus in human studies
  • Levothyroxine
  • Potassium
  • Supplementation
  • MgSO4

Category B

  • Animal studies show no risk
  • Human studies are lacking
  • Penicillins
  • Cephalosporins
  • Macrolides
  • Brimonidine
    • Clozapine is rated FDA Pregnancy Category B, despite paucity of data.
    • Reproductive studies performed in rats and rabbits at doses of approximately 2-4 times the human dose revealed no harm to the fetus.
    • 34In humans, information on the safety of clozapine in human pregnancies has been available since the early 1990s

Category C

  • Animal studies show Positive teratogenic risk
  • Human studies are not available
  • Albuterol
  • Zidovudine
  • CCB
  • Morphine
  • Atropine

Category D

  • Human and animal studies show positive teratogenic risk
  • Can be used in pregnancy because of benefits greater than risk might be acceptable.
  • Corticosteroids
  • Azathioprine
  • Carbamazepine
  • Valproate
  • Methotrexate
  • Lithium

Category X

  • Human and animal studies show positive teratogenic risk
  • Absolutely contraindicated in pregnancy because of risk greater than benefits.
  • Thalidomide
  • isotretinoin
  • Fluoroquinolones
  • Tetracyclines
  • Chloramphenicol
  • Warfarin
  • ACE inhibitors

Q. 16

Side effect of clozapine are ‑

 A

Sedation

 B

Seizures

 C

Urinary incontinence

 D

Decreased salivation

Ans. A:B:C

Explanation:

Ans. (A) Sedation (B) Seizures (C) Urinary incontinence

[Ref : KDT p.429;Katzang /ep- 497-498]

Side effects of clozapine

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

Q. 17 In comparison to haloperidol, clozapine causes:

 A Weight gain

 B

Agranulocytosis

 C

Sedation

 D

Severe extrapyramidal symptoms

Ans. A:B:C

Explanation:

Ans. (A) Weight gain (B) Agranulocytosis (C) Sedation

Haloperidol:

  • Produces fewer autonomic effects, is less epileptogenic, does not cause weight gain, jaundice is rare.
  • Severe extrapyramidal syndrome.
  • Preferred drug for acute schizophrenia.

Clozapine:

  • Produces few or no extrapyramidal symptoms; tardive dyskinesia is rare & prolactin level does not rise.
  • Quite sedative sedation.
  • Higher incidence of agranulocytosis.
  • Metabolic complications like weight gain, hyperlipidemia & precipitation of diabetes is another major limitation.
  • High doses can induce seizures even in non-epileptics.


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