Topoisomerase Inhibitors

TOPOISOMERASE INHIBITORS


TOPOISOMERASE INHIBITORS

  • Drug groups included: Camptothecins & Epipodophyllotoxins.

1. Camptothecins:

  • Obtained from Camptotheca acuminata tree.
  • Drug included: 
    • Irinotecan & topotecan.

MOA:

  • Act by inhibiting topoisomerase I enzyme.
  • Topoisomerase I enzyme nicks introduces negative supercoils & reseals DNA strand.

Individual drug details:

  • Topotecan:
    • Excreted by renal route.
    • Used for advanced ovarian carcinoma.
    • Dose-limiting toxicity – Neutropenia.
  • Irinotecan:
    • Prodrug.
    • Converted in liver to active metabolite, SN-38.
    • Eliminated in bile & feces.
      • Hence, dose reduction required in hepatic failure.
    • DOC for advanced colorectal carcinoma in combination with 5-FU.
  • Specific adverse effects:
    • Dose-limiting toxicity – Diarrhea.
    • Myelosuppression.
    • Cause cholinergic syndrome:
      • Manifested as diarrhea, sweating, hypersalivation, lacrimation, rhinorrhea, abdominal cramps & bradycardia.
      • Due to inhibition of acetylcholine esterase.
      • Occurs within 24 hours.

2. Epipodophyllotoxins:

  • Drug included:
    • Podophyllotoxin (Semisynthetic derivatives – Etoposide & teniposide).
    • Used for its emetic, cathartic & antihelminthic effects.
  • MOA:
    • Acts by binding to tubulin.
    • Acts at junction of late S & early G2 phase of cell cycle.
  • General adverse effects:
    • Gastrointestinal distress & myelosuppression.

Individual drug details:

Etoposide:

  • Indicated for testicular, prostatic & oat cell carcinoma of lung.

Specific adverse effects:

  • Cause acute non-lymphocytic (acute monocytic or mono-myelocytic) leukemia.
    • Develops at a short time interval (1 to 3 years) after end of therapy.
    • Compared to alkylating agents induced leukemia (require 4-5 years).
  • Distinguishing feature – Absence of myelodysplastic period preceding leukemia.
  • Hepatotoxic – At high doses.

Exam Important

  • Topoisomerase inhibitors act by inhibiting topoisomerase I enzyme.
  • Topotecan is used for advanced ovarian carcinoma.
  • Dose-limiting toxicity of Topotecan is Neutropenia.
  • Irinotecan is a prodrug converted in liver to active metabolite, SN-38.
  • Irinotecan is DOC for advanced colorectal carcinoma in combination with 5-FU.
  • Irinotecan causes cholinergic syndrome, due to inhibition of acetylcholine esterase.
  • Dose-limiting toxicity of Irinotecan is diarrhea.
  • Semisynthetic derivatives of Podophyllotoxin includes Etoposide & teniposide.
  • Etoposide is indicated for testicular, prostatic & oat cell carcinoma of lung.
  • Etoposide causes acute non-lymphocytic (acute monocytic or mono-myelocytic) leukemia within short time interval (1 to 3 years) after end of therapy with a distinguishing feature of absence of myelodysplastic period preceding leukemia.
  • Etoposide is hepatotoxic at higher doses.
Don’t Forget to Solve all the previous Year Question asked on TOPOISOMERASE INHIBITORS

Module Below Start Quiz

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this:
Malcare WordPress Security