Mitotic Spindle Inhibitors

MITOTIC SPINDLE INHIBITORS

Q. 1 Microtubule formation is inhibited by:
 A Taxol
 B Vincristine
 C Etoposide
 D Irinotectan
Q. 1 Microtubule formation is inhibited by:
 A Taxol
 B Vincristine
 C Etoposide
 D Irinotectan
Ans. B

Explanation:

Vincristine


Q. 2

Which of the following chemotherapeutic agents is specific for the M phase of the cell cycle?

 A

Cytarabine

 B

Daunorubicin

 C

Hydroxyurea

 D

Vincristine

Q. 2

Which of the following chemotherapeutic agents is specific for the M phase of the cell cycle?

 A

Cytarabine

 B

Daunorubicin

 C

Hydroxyurea

 D

Vincristine

Ans. D

Explanation:

Vincristine (and vinblastine) are Vinca alkaloids that bind to tubulin, a component of cellular microtubules.
This leads to disruption of the mitotic spindle apparatus and results in metaphase arrest since the chromosomes are unable to segregate.
Since these drugs interfere with mitosis, they are considered cell-cycle specific for the M phase.
 
Cytarabine belongs to the class of antineoplastics that are antimetabolites.
This drug class interferes with normal metabolic pathways by competing for enzymatic sites.
Specifically, cytarabine (Ara-C) is a pyrimidine nucleoside analog.
It interrupts DNA synthesis and function by inhibiting DNA polymerase and incorporating into the DNA or RNA of the cell. As you would expect, this drug is cell-cycle specific for the S phase.
 
Daunorubicin is one of the antibiotic antineoplastic agents (others include dactinomycin, doxorubicin, bleomycin, plicamycin, and mitomycin). These agents work by disrupting DNA functioning.
Daunorubicin binds to DNA between base pairs on adjacent strands, resulting in uncoiling of the helix and destruction of the DNA template. While this drug has its maximum effect during the S phase, it is not cell-cycle specific. (Note: the only antibiotic that is cell-cycle specific is bleomycin.)
 
Hydroxyurea works by interfering with ribonucleoside diphosphate reductase, the enzyme responsible for generating the deoxyribonucleotides needed for DNA synthesis. It is S-phase specific.
 
Ref: Chu E., Sartorelli A.C. (2012). Chapter 54. Cancer Chemotherapy. In B.G. Katzung, S.B. Masters, A.J. Trevor (Eds), Basic & Clinical Pharmacology, 12e.

Q. 3

Which one of the following statements is false regarding vincristine –

 A

It is an alkaloid

 B

Its use is associated with neurotoxicity

 C

It does not cause alopecia

 D

It is a useful drug for induction of remission in acute lymphoblastic leukaemia

Q. 3

Which one of the following statements is false regarding vincristine –

 A

It is an alkaloid

 B

Its use is associated with neurotoxicity

 C

It does not cause alopecia

 D

It is a useful drug for induction of remission in acute lymphoblastic leukaemia

Ans. C

Explanation:

Ans. is ‘c’ i.e., It does not cause alopecia

o Vincristine belongs to the plant alkaloid group of anticancer.

o Useful for inducing remission in childhood ALL (not useful in maintenance therapy)

o It can also be used for pediatric solid tumors (Wilm’s tumor, neuroblastoma, rhabdomyosarcoma) and lymphomas.

o Prominent adverse effects‑

o Peripheral neuropathy            

Alopecia         

SIADH

Quiz In Between


Q. 4

Peripheral neuropathy as a side effect is caused by which of the following anti cancer drugs ‑

 A

Vincristine

 B

Cyclophosphamide

 C

Etoposide

 D

Irinotecan

Q. 4

Peripheral neuropathy as a side effect is caused by which of the following anti cancer drugs ‑

 A

Vincristine

 B

Cyclophosphamide

 C

Etoposide

 D

Irinotecan

Ans. A

Explanation:

Ans. is ‘a’ i.e., Vincristine


Q. 5

About vinca alkaloids true is

 A

Inhibits mitotic spindle

 B

Enhances polymerization of tubulin

 C

Inhibits topoisomerase I

 D

Inhibits topoisomerase II

Q. 5

About vinca alkaloids true is

 A

Inhibits mitotic spindle

 B

Enhances polymerization of tubulin

 C

Inhibits topoisomerase I

 D

Inhibits topoisomerase II

Ans. A

Explanation:

Ans. is ‘a’ i.e., Inhibits mitotic spindle

Vinca alkaloids (vincristine) inhibit mitotic spindles by preventing polymerization of tubulin


Q. 6

Antimitotic drugs of plant source is/are‑

 A

Vincristine

 B

Isotretinoin

 C

Bleomycine

 D

Methotraxate

Q. 6

Antimitotic drugs of plant source is/are‑

 A

Vincristine

 B

Isotretinoin

 C

Bleomycine

 D

Methotraxate

Ans. A

Explanation:

Ans. is ‘a’ i.e., Vincristine

Quiz In Between


Q. 7

SIADH is associated with the following drug :

 A

Vincristine

 B

Erythromycin

 C

5 – FU

 D

Methotrexate

Q. 7

SIADH is associated with the following drug :

 A

Vincristine

 B

Erythromycin

 C

5 – FU

 D

Methotrexate

Ans. A

Explanation:

Answer is A (Vincristine):

Vincristine is known to cause SIADH.

Drugs associated with SIADH : 

  • Vasopressin or desmopressin
  • Chlorpropamide
  • Oxytocin, high dose
  • Vincristine
  • Carbamezapine
  • Nicotine
  • Phenothiazines
  • Cyclophosphamide
  • Tricyclic antidepressants
  • M40 inhibitors
  • Serotonin reuptake inhibitors

Q. 8

Mechanism of action of paclitaxel is ‑

 A

Topoisomerase inhibition

 B

Increase the polymerization of tubulin

 C

Inhibition of protein synthesis

 D

Alkylation of DNA

Q. 8

Mechanism of action of paclitaxel is ‑

 A

Topoisomerase inhibition

 B

Increase the polymerization of tubulin

 C

Inhibition of protein synthesis

 D

Alkylation of DNA

Ans. B

Explanation:

Ans. is ‘b’ i.e., Increase the polymerization of tubulin

Taxanes

  • Paclitaxel and docetaxel function as a mitotic spindle poison through high affinity binding to microtubules with enhancement of tubulin polymerization.
  • The microtubules are stabilized and their depolymerization is prevented → inhibition of mitosis and cell division.
  • Paclitaxel is metabolized in liver and undergoes enterohepatic circulation → dose should be reduced in liver dysfunction.
  • Paclitaxel can cause hypersensivity reaction which does not occur with a novel albumin-bound paclitaxel preparation.
  • Paclitaxel and docetaxel both can cause bone marrow depression & peripheral neuropathy.

Q. 9

Peripheral neuropathy as a side effect is caused by which of the following anti cancer drugs ‑

 A

Vincristine

 B

Cyclophosphamide

 C

Etoposide

 D

Irinotecan

Q. 9

Peripheral neuropathy as a side effect is caused by which of the following anti cancer drugs ‑

 A

Vincristine

 B

Cyclophosphamide

 C

Etoposide

 D

Irinotecan

Ans. A

Explanation:

Ans. is ‘a’ i.e., Vincristine

Vincristine (Oncovin)

  • Alkaloid derived from Vinca rosae.
  • Vincristine belongs to the plant alkaloid group of anticancer.
  • Rapidly acting anticancer
  • This class of drugs are also known as spindle poison.
  • These drugs bind to microtubular protein (tubulin)
  • The drug-tubulin complex then attaches itself to microtubules and causes depolymerization of microtubules.
  • Depolymerization of microtubule causes
  1. Mitotic arrest at metaphase
  2. Dissolution of mitotic spindle
  3. Interference with chromosome segregation
  • Useful for inducing remission in childhood ALL (not useful in maintenance therapy)
  • It can also be used for pediatric solid tumors (Wilm’s tumor, neuroblastoma, rhabdomyosarcoma) and lymphomas. 
  • Prominent adverse effects‑

Peripheral neuropathy  Alopecia   SIADH

  • Vincristine is a marrow sparing drug but some times it may cause myelosuppression which is very less than vinblastin. 
  • Indications of vincristine‑

Hodgkins disease           Wilms’s tumour       Carcinoma lung

Non hodgkin:s. disease  Ewing’s sarcoma      Myeloma

  • Vinblastine and vinorelbine are other vinca alkaloids.
  • o Vinblastine’s most important clinical use is the curative therapy of metastatic testicular tumor.
  • o Vinblastine can cause bone marrow suppression (in contrast with vincristin), alopecia, and nausea & vomiting. o As they arrest mitosis, all vinca alkaloids act in M phase.

Quiz In Between



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