Cyclophosphamide and Nitrosoureas Overview
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Questions and Answers

Which cancer drug is most widely employed among alkylating agents?

  • Melphalan
  • Cyclophosphamide (correct)
  • Chlorambucil
  • Carmustine
  • What is the primary mechanism by which nitrosoureas achieve their effect?

  • Inhibition of protein synthesis
  • Cross-linking of DNA (correct)
  • Blocking RNA transcription
  • Inhibition of DNA synthesis
  • Among the following, which adverse effect is a major concern with alkylating agents?

  • Delayed bone marrow suppression (correct)
  • Peripheral neuropathy
  • Acute renal failure
  • Cardiotoxicity
  • Which route of administration is used for Chlorambucil?

    <p>Orally only</p> Signup and view all the answers

    For which specific cancers is Cisplatin primarily approved?

    <p>Metastatic testicular and ovarian cancers, and advanced bladder cancer</p> Signup and view all the answers

    What is the primary reason for the critical role of thymidylate biosynthesis inhibition by methotrexate?

    <p>It inhibits DNA synthesis by depriving cells of thymidylate.</p> Signup and view all the answers

    How does leucovorin rescue function in the context of methotrexate treatment?

    <p>It helps normal cells to bypass the metabolic block and synthesize necessary compounds.</p> Signup and view all the answers

    Why are some neoplastic cells unresponsive to methotrexate?

    <p>They lack the transport system needed for methotrexate uptake.</p> Signup and view all the answers

    Which of the following statements about methotrexate is true?

    <p>It induces apoptosis by lowering thymidine levels.</p> Signup and view all the answers

    What effect does methotrexate have on normal cells at high concentrations?

    <p>It puts them at risk while trying to target malignant cells.</p> Signup and view all the answers

    Why is anemia less common than neutropenia or thrombocytopenia in patients undergoing chemotherapy?

    <p>Erythrocytes typically recover production quickly.</p> Signup and view all the answers

    Which side effect of chemotherapy is most likely to be life-threatening due to severe injury?

    <p>Digestive tract injury</p> Signup and view all the answers

    What common adverse effect can result in a patient refusing further chemotherapy treatment?

    <p>Severe nausea and vomiting</p> Signup and view all the answers

    What is a potential consequence of alkylating agents on reproductive health?

    <p>High risk of fetal malformation during first trimester</p> Signup and view all the answers

    How soon after starting chemotherapy does hair loss typically begin?

    <p>7 to 10 days after the onset of treatment</p> Signup and view all the answers

    Which statement regarding the body's recovery from chemotherapy-induced neutropenia is accurate?

    <p>Neutrophils have a much shorter life span than erythrocytes.</p> Signup and view all the answers

    What effect do cytotoxic drugs have on hair follicles?

    <p>Reversible injury causing temporary hair loss</p> Signup and view all the answers

    During which stage of pregnancy is the risk most significant for fetal malformation due to chemotherapy?

    <p>First trimester</p> Signup and view all the answers

    What is a significant risk associated with hyperuricemia in cancer patients?

    <p>Kidney damage due to uric acid crystals</p> Signup and view all the answers

    What is the recommended method to prevent kidney damage due to hyperuricemia in patients receiving chemotherapy?

    <p>Increasing fluid intake</p> Signup and view all the answers

    Why are vesicants typically administered through a central line?

    <p>To reduce the risk of local tissue injury</p> Signup and view all the answers

    Which complication is most associated with extravasation of vesicants?

    <p>Severe local tissue damage and necrosis</p> Signup and view all the answers

    What should be done immediately if extravasation of a vesicant occurs?

    <p>Stop the infusion right away</p> Signup and view all the answers

    What potential outcome might severe tissue damage from a vesicant lead to?

    <p>Need for surgical débridement and skin grafting</p> Signup and view all the answers

    What characterizes vesicants that makes them particularly hazardous when extravasated?

    <p>Severe chemical reactivity with surrounding tissues</p> Signup and view all the answers

    What is a common condition that can lead to hyperuricemia, especially following aggressive treatment?

    <p>Acute myeloid leukemia and lymphomas</p> Signup and view all the answers

    What is the primary risk associated with neutropenia in patients undergoing chemotherapy?

    <p>Higher incidence of infection</p> Signup and view all the answers

    What should be the immediate action if a patient's absolute neutrophil count falls below 500/mm3?

    <p>Withhold chemotherapy until counts normalize</p> Signup and view all the answers

    Which sign would most likely indicate an infection in a neutropenic patient?

    <p>Fever</p> Signup and view all the answers

    What is a common bleeding site in patients with thrombocytopenia?

    <p>Nasal passages</p> Signup and view all the answers

    Which analgesic is preferred for a patient with thrombocytopenia to avoid promoting bleeding?

    <p>Acetaminophen</p> Signup and view all the answers

    Why is seminal care necessary when performing procedures on patients with thrombocytopenia?

    <p>Possible bruising or bleeding</p> Signup and view all the answers

    What defines anemia in the context of circulating blood components?

    <p>Reduction in erythrocytes</p> Signup and view all the answers

    What impact does the absence of neutrophils have on diagnosing infections?

    <p>Masks the usual signs of infection</p> Signup and view all the answers

    Study Notes

    Cyclophosphamide and Nitrosoureas

    • Cyclophosphamide, known as Cytoxan and Neosar, is a broadly active bifunctional alkylating agent for various neoplastic diseases including Hodgkin’s disease, non-Hodgkin’s lymphomas, and multiple myeloma.
    • Nitrosoureas, such as Carmustine, also function as bifunctional alkylators, effectively targeting a wide range of cancers, particularly those in the central nervous system due to their ability to cross the blood-brain barrier.
    • Major dose-limiting toxicity for nitrosoureas includes delayed bone marrow suppression.

    Routes of Administration

    • Melphalan and cyclophosphamide can be administered orally or intravenously; chlorambucil is given orally.
    • Specific clinical uses: Melphalan for myeloma and solid tumors; cyclophosphamide for leukemias, lymphomas, and solid tumors; chlorambucil for leukemias, lymphomas, and ovarian tumors.

    Adverse Effects of Alkylating Agents

    • High growth fraction tissues (bone marrow, hair follicles, GI mucosa) are particularly vulnerable to alkylating agents, leading to concerns of blood dyscrasias such as neutropenia and thrombocytopenia.
    • Common side effects include nausea and vomiting; many alkylating agents are vesicants, requiring careful administration.

    Platinum Compounds

    • Cisplatin, carboplatin, and oxaliplatin form cross-links in DNA, mirroring the action of alkylating agents and are considered cell-cycle phase nonspecific.
    • Cisplatin is indicated for metastatic testicular and ovarian cancers, as well as advanced bladder cancer.

    Methotrexate

    • Methotrexate inhibits dihydrofolate reductase, crucial for synthesizing tetrahydrofolate, thus affecting DNA, RNA, and protein synthesis; thymidylate synthesis inhibition is particularly harmful, leading to cell death.
    • S-phase specific, it induces apoptosis via thymidine depletion; leucovorin rescue is utilized to protect normal cells during high-dose treatments.

    Pharmacokinetics of Methotrexate

    • Administered through multiple routes (oral, intramuscular, intravenous, intrathecal); it is highly polar, requiring a transport system for cellular entry and primarily eliminated via the kidneys.
    • Poor blood-brain barrier penetration, necessitating intrathecal administration for CNS cancers.

    Toxicity and Resistance

    • Dose-limiting toxicities for methotrexate include bone marrow suppression and gastrointestinal ulceration; renal damage risk increases at high doses.
    • Cancer cells can develop resistance to methotrexate through decreased uptake, target enzyme overproduction, modified targets, and increased drug efflux.

    Clinical Uses and Adverse Effects

    • Methotrexate is curative for choriocarcinoma and active against non-Hodgkin’s lymphoma and acute lymphocytic leukemia; fluorouracil similarly requires metabolic conversion for action.
    • Cytarabine is effective for acute myelogenous leukemia, available in conventional and liposomal forms.

    Cytotoxic Antibiotics

    • Dactinomycin inhibits RNA polymerase, while doxorubicin blocks topoisomerase II, leading to disrupted transcription and DNA replication; bleomycin creates DNA chain fragments.
    • Doxorubicin induces significant cardiotoxicity due to free radical damage.

    Combination Therapy and Treatment Schedules

    • Combination therapies enhance cytotoxicity while reducing overall toxicity and resistance potential.
    • Administering large doses intermittently allows bone marrow recovery and maximizes total drug effectiveness.

    Drug Resistance Mechanisms

    • Resistance can be primary (existing at treatment onset) or acquired (developing during treatment), often through tumor adaptation and mutation.
    • Mechanisms include increased drug efflux, decreased uptake, insufficient drug activation, and enhanced repair of drug-induced damage.

    Anemia and Anticancer Drugs

    • Erythrocyte production suppression can occur due to anticancer drugs, yet anemia is less common than neutropenia or thrombocytopenia.
    • Circulating erythrocytes have a lifespan of 120 days, allowing time for recovery before levels drop significantly.
    • Anemia treatment options include blood transfusions and erythropoietin (epoetin alfa or darbepoetin alfa), which stimulates red blood cell production.

    Digestive Tract Injury

    • The GI tract's epithelial lining is sensitive due to its high growth fraction, leading to common issues like stomatitis and diarrhea.
    • Severe gastrointestinal injury poses life-threatening risks.

    Nausea and Vomiting

    • Common side effects of cancer chemotherapy involve nausea and vomiting resulting from chemoreceptor trigger zone stimulation.
    • Reactions can occur immediately and may last for hours or days, sometimes causing patients to refuse further treatment.

    Alopecia

    • Reversible hair loss occurs as a result of anticancer drugs damaging hair follicles.
    • Hair loss typically begins 7 to 10 days after treatment initiation and peaks around 1 to 2 months, with regeneration starting after 1 to 2 months post-treatment.

    Reproductive Toxicity

    • Cytotoxic drugs, especially alkylating agents, pose risks to the developing fetus and testes due to their high growth fractions.
    • Potential impacts include embryonic death and fetal malformation, with the highest risk in the first trimester; chemotherapy is generally avoided during this period.

    Hyperuricemia

    • Hyperuricemia is characterized by elevated uric acid levels in the blood due to DNA breakdown following cell death.
    • Particularly common after leukemia and lymphoma treatment, the concern lies in potential kidney injury from uric acid crystal deposition.
    • Increasing fluid intake helps mitigate the risk of crystal formation, and allopurinol is routinely used for prophylaxis in susceptible patients.

    Local Injury from Extravasation of Vesicants

    • Vesicant drugs can cause severe local injury upon contact with tissues, necessitating their administration through IV routes, preferably central lines.
    • Extravasation may result in prolonged pain, infection, and potential necrosis; immediate cessation of infusion is required if leakage occurs.
    • Administration should be conducted by trained clinicians to minimize risks.

    Cytotoxic Agents

    • The largest class of anticancer drugs directly targets cancer cells to induce cell death and is comprised of eight major groups, including alkylating agents.

    Neutropenia

    • Neutropenia (low neutrophil count) increases the risk of infections, with typical onset occurring days after chemotherapy, reaching nadir at days 10-14.
    • Normal neutrophil counts range from 2,500 to 7,000 cells/mm³, and significant drops below 500/mm³ necessitate withholding chemotherapy.
    • Fever becomes the main early sign of infection in neutropenic patients due to lack of typical signs associated with neutrophils.

    Thrombocytopenia

    • Bone marrow suppression can lead to thrombocytopenia (low platelet count), raising the risk of serious bleeding, especially from the nose and gums.
    • Recommendations to minimize bleeding include avoiding vigorous tooth brushing and using acetaminophen instead of aspirin for pain relief.
    • Care is essential during procedures that might induce bleeding, and caution is advised when using blood pressure cuffs to prevent bruising.

    General Anemia Information

    • Anemia is defined as a reduction in circulating erythrocyte levels.

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    Description

    This quiz covers the uses and mechanisms of cyclophosphamide and nitrosoureas in treating neoplastic diseases. It includes indications for various cancers and compares the effectiveness of bifunctional alkylating agents. Test your knowledge on these essential chemotherapy agents.

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