Lecture 10 pharmacology of cytotoxins II Flashcards
Describe Anti-Metabolites in pharmacology.
Anti-Metabolites have structures similar to DNA synthesis substrates, interfering with purine or pyrimidine nucleotide precursors. They act as false bases during DNA replication and transcription, with maximal effect in the S phase.
What is the mechanism of action of Raltitrexed in pharmacology?
Raltitrexed inhibits thymidylate synthase, blocking the conversion of dUMP to dTMP. This leads to increased levels of dUTP, causing DNA damage.
How does Capecitabine function in pharmacology?
Capecitabine is a prodrug activated in tumor cells by a 3-enzyme cascade process. It is designed for specific activation within the tumor cells.
Define Gemcitabine in pharmacology.
Gemcitabine is a prodrug that requires cellular uptake and intracellular phosphorylation to exert its action. It replaces cytidine during DNA replication, leading to tumor growth arrest through apoptosis.
Describe the mechanism of action of 5-fluorouracil (5-FU) in pharmacology.
5-FU converts to active metabolites FdUMP, FdUTP, and FUTP, acting as a false base to inhibit RNA and DNA damage. It inhibits transcription to further damage DNA.
What are Cytotoxic antibiotics in pharmacology?
Cytotoxic antibiotics are cell-cycle non-specific drugs derived from microbes like Streptomyces. They are used for slow-growing tumors and work better in the S phase but can act in all phases.
Describe the mechanism of action of anthracyclines as cytotoxic antibiotics in cancer treatment.
Anthracyclines inhibit topoisomerase II, bind to DNA through intercalation, generate free radicals, and bind to cellular membranes.
What is the primary target of vinca alkaloids like vinblastine in cancer treatment?
Vinca alkaloids target tubulins and interfere with the dynamics of the mitotic spindle during M-phase.
How do taxanes, as natural product agents, affect microtubules in cancer cells?
Taxanes bind tightly to tubulin residues, stabilize microtubules, and increase polymerization, leading to inhibition of mitosis.
Define the role of topoisomerase II during DNA replication.
Topoisomerase II cuts both strands of DNA, allowing unwinding of two twists, which is crucial for DNA replication.
Describe the sensitivity of cells in S-phase to epirubicin, a cytotoxic antibiotic.
Epirubicin blocks RNA and DNA synthesis equally, intercalates, and is most effective on cells in S-phase due to its mechanism of action.
What are the major mechanisms of action of cytotoxic antibiotics like anthracyclines in cancer treatment?
The major mechanisms include inhibition of topoisomerase II, high affinity binding to DNA through intercalation, generation of free radicals, and binding to cellular membranes.
How does vinblastine induce mitotic arrest in cancer cells during M-phase?
Vinblastine inhibits tubulin polymerization, disrupts microtubule formation, and leads to mitotic arrest, halting cell division.
Define the function of topoisomerase I during DNA replication.
Topoisomerase I cuts single-strand DNA, passes it through the other strand before rejoining, facilitating the unwinding of one twist of DNA during replication.
Describe the mechanism of action of taxanes like paclitaxel and docetaxel.
They are mitotic spindle poisons that block spindle breakdown.
What is the main difference between paclitaxel and docetaxel?
Docetaxel is a semisynthetic taxane with a similar mechanism of action as paclitaxel but differs in structure.
How does irinotecan work to treat colon cancer?
Irinotecan inhibits TOPO II.
Define the role of UGT1A1 in the activation of SN-38 for its anti-tumor effect.
UGT1A1 transfers glucuronic acid from UDP-G to SN-38, forming SN-38-G, which inactivates SN-38.
What is the competition for substrate that affects the activity of irinotecan?
There is competition between CYP3A enzymes, which inactivate irinotecan, and CE, which activates irinotecan.
