Podcast Beta
Questions and Answers
What is the unique toxicity of cyclophosphamide and nitrogen mustard?
What is the primary binding site of cisplatin in DNA?
What is the major limiting toxicity of cisplatin?
What is the mechanism of action of cisplatin?
Signup and view all the answers
Which of the following platinum compounds has less nephro-, neuro-, and ototoxicity?
Signup and view all the answers
What is the purpose of premedication with antiemetic agents before administering cisplatin?
Signup and view all the answers
What is the primary site where cyclophosphamide is biotransformed to hydroxylated intermediates?
Signup and view all the answers
What is the primary strategy to minimize the development of drug resistance in cancer treatment?
Signup and view all the answers
What is the mechanism of cytotoxicity of alkylating agents?
Signup and view all the answers
What is a potential long-term adverse effect of alkylating agents?
Signup and view all the answers
Which of the following mechanisms of resistance involves the production of enzymes that repair damaged DNA?
Signup and view all the answers
What is a characteristic of alkylating agents?
Signup and view all the answers
What is the primary reason for the toxic manifestations of chemotherapy?
Signup and view all the answers
What is the term for the increased efflux of the drug outside the cells, leading to resistance?
Signup and view all the answers
What is the consequence of starting leucovorin too early when used with methotrexate?
Signup and view all the answers
What is the name of the metabolite of cyclophosphamide that reacts with DNA, leading to cytotoxicity?
Signup and view all the answers
Which of the following is NOT a mechanism of resistance to chemotherapeutic agents?
Signup and view all the answers
What is the result of the production of chemically altered enzymes that are no longer recognized by drugs that inhibit unaltered enzymes?
Signup and view all the answers
Study Notes
Tumor Resistance to Chemotherapy
- Tumors can develop resistance to chemotherapy through mutations, especially after prolonged administration of suboptimal drug doses
- Short-term, intensive, intermittent therapy with combinations of drugs minimizes the development of drug resistance
- Drug combinations are effective against a broader range of resistant cells in the tumor population
Resistance Mechanisms
- Enhanced production of enzymes that repair damaged DNA (gene amplification)
- Production of chemically altered enzymes that are no longer recognized by drugs (mutations)
- Decreased intracellular drug activation
- Increased intracellular drug catabolism into inactive metabolites
- Reduced uptake of drug into cell
- Increased efflux of the drug outside the cells (multidrug resistance)
Chemotherapeutic Agents (Toxicity)
- Chemotherapy affects normal cells undergoing rapid proliferation, contributing to toxic manifestations
- Cells affected include those of the buccal mucosa, bone marrow, gastrointestinal mucosa, and hair follicles
Alkylating Agents
- Nitrogen Mustard: cyclophosphamide
- Adverse effects: hemorrhagic cystitis, which can lead to fibrosis of the bladder
- Bladder toxicity is attributed to acrolein in the urine
- Adequate hydration and IV injection of mesna can minimize bladder toxicity
Platinum Compounds
- Cisplatin enters the cell and loses its chlorides, binding to guanine in DNA, forming inter- and intrastrand crosslinks
- The resulting cytotoxic lesion inhibits DNA replication and RNA synthesis
- Cytotoxicity can occur at any stage of the cell cycle, but cells are most vulnerable in the G1 and S-phases
- The primary binding site is the N7 of guanine, but covalent interaction with adenine and cytosine also occurs
Adverse Effects of Platinum Compounds
- Severe, persistent vomiting occurs for at least 1 hour after administration of cisplatin and may continue for as long as 5 days
- Dose-related nephrotoxicity is a major limiting toxicity, prevented by aggressive hydration
- Other toxicities include ototoxicity
- Carboplatin has less nephro-, neuro-, and ototoxicity compared to cisplatin
Mechanism of Action of Alkylating Agents
- Exert cytotoxic effects by covalently binding to nucleophilic groups on various cell constituents
- Alkylation of DNA is probably the crucial cytotoxic reaction that is lethal to tumor cells
- Do not discriminate between cycling and resting cells, but are most toxic for rapidly dividing cells
- Are mutagenic and carcinogenic, leading to secondary malignancies such as acute leukemia
- Are cell cycle non-specific
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Test your knowledge of alkylating agents, including nitrogen mustard and cyclophosphamide, and platinum compounds like cisplatin. Learn about their mechanisms of action and adverse effects, such as hemorrhagic cystitis.
