YW - Cytotoxic Drugs (chemotherapy) Flashcards
What are Anti-PD-1 drugs? (6)
- Nivolumab (BMS)
- Pembrolizumab (Merck)
- Pidilizumab (Curetech)
- MEDI-0680 (MedImmune-AZ)
- PDR001 (Novartis)
- REGN2810 (Regeneron)
What are Anti-PD-L1 drugs? (4)
- Atezolizumab (MPDL3280, GNE)
- Durvalumab (MEDI-4736, MedImmune-AZ)
- Avelumab (MSB0010718C, EMD Serono)
- MDX-1105 (BMS)
What is Bevacizumab (Avastin)? (2)
- Monoclonal antibody targeting VEGF (vascular endothelial growth factor).
- Blocks VEGF, inhibiting tumor angiogenesis and starving tumors of oxygen/nutrients.
What are the phases of the cell cycle? (5)
- G1 phase: Cell grows and prepares for DNA synthesis.
- S phase: DNA replication occurs.
- G2 phase: Cell prepares for mitosis.
- M phase: Mitosis and cell division into two daughter cells.
- G0 phase: Resting state, regulated by complex protein networks.
What are the major classes of chemotherapy agents and examples of each? (8)
- Alkylating Agents: Nitrogen mustards (Thiotepa, busulfan), nitrosoureas (mitomycin), procarbazine, dacarbazine.
- Taxanes: Paclitaxel, docetaxel, nab-paclitaxel.
- Topoisomerase II Inhibitors: Etoposide.
- Platinum Complexes: Cisplatin, carboplatin, oxaliplatin.
- Anthracyclines: Doxorubicin, daunorubicin, idarubicin, mitoxantrone.
- Antimetabolites: Methotrexate, purine antagonists, pyrimidine antagonists.
- Tubulin-Interactive Agents: Vincristine, vinblastine.
- Miscellaneous Agents: Bleomycin, asparaginase, hydroxyurea.
What are the two main classes of chemotherapy drugs based on cell cycle specificity?
Cell Cycle Phase-Specific Drugs: Target specific phases; effective during active cell division.
Cell Cycle Phase-Nonspecific Drugs: Effective regardless of the cell cycle phase; act on both dividing and resting cancer cells.
What are common side effects (4) of chemotherapy and why do they occur?
Chemotherapy targets rapidly dividing cells, including cancer and some healthy cells.
Affected Tissues and Side Effects:
- Bone Marrow: Anemia, infection risk, easy bruising.
- Hair Follicles: Hair loss (alopecia).
- Digestive Tract: Nausea, vomiting, mouth sores, loss of appetite, diarrhea, constipation.
- Skin: Dryness, rash, increased sensitivity to sunlight.
What are alkylating agents, and how do they work? (3)
Mechanism: Generate unstable alkyl groups (R-CH₂⁺) that react with nucleophilic centers in proteins and nucleic acids. Often bifunctional, enabling DNA cross-linking.
Cell Cycle Specificity: Generally cell cycle nonspecific, though mitosis and G1 phases are most sensitive.
Properties: Many decompose rapidly in water and are effective against rapidly dividing cells
What are the key features of mechlorethamine (Nitrogen Mustard)? (5)
- Chemical Nature: Cl-CH₂-CH₂-N(CH₃)-CH₂-CH₂-Cl; unstable, decomposes in water.
- Mechanism: Bifunctional alkylating agent.
- Resistance: Enhanced DNA repair mechanisms.
- Specificity: Nonphase specific, but most effective in mitosis and G1 phases.
- Toxicity: Nausea, vomiting, myelosuppression, and local vesicant action.
What are the mechanisms of resistance to alkylating agents? (6)
- Decreased Transport: Reduced uptake of the drug into the cell.
- Gene Amplification: Increased gene copy number, leading to overexpression of resistance-related proteins.
- Increased DNA Repair: Enhanced ability to repair DNA damage caused by alkylating agents.
- Increased Deactivating Enzymes: Increased enzyme activity that inactivates the drug.
- Modified Enzymes: Altered target enzymes with reduced affinity for the drug.
- Multiple Drug Resistance (MDR): Overexpression of P-glycoprotein (p170), an ATP-dependent pump that exports a variety of drugs, including daunomycin, vinblastine, etoposide, and taxol.
What are the benefits of combination therapy in cancer treatment? (4)
- Increased Log Kill: More effective at killing tumor cells.
- Sub-additive Host Toxicity: Reduced overall toxicity to the host compared to single-agent therapy.
- Less Severe Side Effects: A broader range of side effects, but less intense than with single drugs.
Example: Hodgkin’s lymphoma is often treated with a combination of cisplatin, bleomycin, vincristine, and daunorubicin.
What are the key details about Cisplatin and its use? (4)
- Mechanism of Action: Forms DNA cross-links, inhibiting DNA replication and transcription.
- Clinical Use: Effective against testicular and ovarian cancer.
- Side Effects: Nephrotoxicity and neurotoxicity.
- Carboplatin: A platinum-based drug with reduced nephrotoxicity compared to cisplatin.
What are antimetabolites and how do they work? (4)
- Mechanism of Action: Interfere with DNA and RNA synthesis by mimicking essential metabolites and inhibiting their incorporation into nucleic acids.
Examples of Antimetabolites:
- Methotrexate: An analog of folic acid, it inhibits the synthesis of thymidylate, a building block of DNA.
- 5-Fluorouracil (5-FU): An analog of thymine, it inhibits the synthesis of thymidylate and uracil, disrupting DNA and RNA synthesis.
- Cytarabine: An analog of cytidine, it inhibits DNA synthesis by interfering with the incorporation of cytosine into DNA.
What are the types of plant alkaloids used in chemotherapy and their mechanisms? (4)
Vinca Alkaloids:
- Examples: Vincristine, vinblastine, vinorelbine.
- Mechanism: Inhibit cell division by disrupting microtubule formation.
Taxanes:
- Examples: Paclitaxel, docetaxel.
- Mechanism: Inhibit cell division by stabilizing microtubules.
Podophyllotoxins:
- Examples: Etoposide, teniposide.
- Mechanism: Inhibit topoisomerase II, an enzyme involved in DNA replication.
Camptothecan Analogs:
- Examples: Irinotecan, topotecan.
- Mechanism: Inhibit topoisomerase I, another enzyme involved in DNA replication.
What is Vinblastine (Velban)? (5)
Chemical Nature:
- Dimeric alkaloid derived from Vinca rosea.
Mechanism of Action:
- Binds to tubulin, disrupting spindle assembly during mitosis.
Resistance:
- Decreased cellular uptake or increased efflux.
Cell Cycle Specificity:
- Primarily targets mitosis; at high concentrations, also inhibits S and G1 phases.
Toxicity:
- Leukopenia, nausea, and vomiting.
