IRINOTECAN - Anticancer Topoisomerase 1 inhibitor

DESCRIPTION

PHARMACOLOGY-

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).

MECHANISM OF ACTION-

Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA. As a result, DNA damage is not efficiently repaired and apoptosis (programmed cell death) occurs.

severe or ongoing vomiting or diarrhea;

SIDE EFFECTS-

1.nausea or vomiting that keeps you from drinking enough fluids;

2.sudden chest pain or discomfort, wheezing, dry cough, feeling short of breath;

3.pain, redness, numbness, and peeling skin on your hands or feet;

4.dehydration symptoms--feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin.

5.low blood cell counts--fever, chills, flu-like symptoms, swollen gums, mouth sores, skin sores, rapid heart rate, pale skin, easy bruising, unusual bleeding, feeling light-headed.

DRUG-DRUG INTERACTIONS-

1.The serum concentration of Irinotecan can be increased when it is combined with Acetaminophen.

2 .Acetyldigitoxin may decrease the cardiotoxic activities of Irinotecan.

3.The serum concentration of the active metabolites of Irinotecan can be increased when Irinotecan is used in combination with Adenine.

4.The serum concentration of Irinotecan can be increased when it is combined with Afatinib.

5.The serum concentration of Irinotecan can be increased when it is combined with Albendazole.

6.The serum concentration of Irinotecan can be decreased when it is combined with Aldosterone.

7.The serum concentration of Irinotecan can be increased when it is combined with Alectinib.

USES-

Irinotecan is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Irinotecan is used to treat cancers of the colon and rectum. It is usually given with other cancer medicines in a combination chemotherapy

REFERENCE- Tripathi K.D. "Essentials of Medical Pharmacology", 7th Edition, page no- 867