06d Intercalating Agents Camarero Flashcards
What are Intercalating Agents?
Chemicals that do not bind chemically to DNA, but intercalate between the base pairs of DNA, thereby preventing both replication and/or transcription. Intercalated drug molecules affect the structure of the DNA, preventing polymerase and other DNA binding proteins from functioning properly. The result is prevention of DNA synthesis, inhibition of transcription
What are the three types of Intercalating agents used for treating cancer patients?
Bleomycins (A2, B2), Actynomycins (D). Plicamycin
What is Bleomycin (Blenoxane)?
A glycopeptide antibiotic. When used as an anti-cancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2
What is Bleomycin used for?
Treatment of Hodgkin lymphoma, squamous cell carcinomas, and testicular cancer
What is the MOA of Bleomycin?
Binds DNA, which results in single and double strand breaks following free radical formation and inhibition of DNA synthesis. The DNA fragmentation is due to oxidation of a DNA-Bleomycin-Fe (II) complex and leads to chromosomal aberrations
How is Bleomycin administered?
By Intramuscular (IM), Subcutaneous (SC), or Intravenous (IV) routes. Metabolized by aminopeptidase B-like enzyme in deamido bleomycin (inactive)
What are the toxicity and side-effects associated with Bleomycin?
Lethal anaphylactoid reactions. Blistering. Pulmonary fibrosis
What is Actinomycin D (Dactinomycin, Cosmegen)?
A polypeptide antibiotic. Binds DNA at the transcription inhibition complex and prevent elongation by RNA polymerase. Bind also to double stranded DNA through intercalation between adjacent guanine-cytosine base pairs. Inhibit all forms of DNA-dependent RNA and DNA synthesis
What is Actinomycin D used for?
Most commonly used in treatment of a variety of cancers including gestational trophoblastic neoplasia, Wilms’ tumor, and Rhabdomyosarcoma
How is Actinomycin D administered?
Intravenously
What are the toxicity and side-effects associated with Actinomycin D?
Veno-occlusive disease (VOD, primarily hepatic) may result in fatality. Carcinogen. Bone marrow depression
What is Plicamycin (Mithracin)?
An antieoplastic agent. DNA intercalating agent. Binds to DNA through an antibiotic-Mg complex. This interaction interrupts DNA-directed RNA synthesis
What is Plicamycin (Mithracin) used for?
Useful in the treatment of carefully selected hospitalized patients with malignant tumors in whom successful treatment by surgery and/or radiation is impossible. Mostly used in the treatment of testicular cancer, Paget’s disease of bone, and, rarely, the management of Hypercalcemia
How is Plicamaycin administered?
Only through IV route
What are the toxicity and side-effects of Plicamycin?
Hypocalcemia. Bleeding disorders. Liver and kidney toxicity
