This document discusses cytotoxic drugs and the origins of chemotherapy. It provides information on various classes of cytotoxic drugs including alkylating agents, antimetabolites, plant alkaloids, and mitotic inhibitors. Key events in the development of chemotherapy are noted, such as the observation that nitrogen mustards caused bone marrow destruction in WWII, which led to their application against Hodgkin's disease. The mechanisms of cytotoxic drugs and their effects on the cell cycle are also summarized.
This document summarizes various alkylating agents and antimetabolites used in cancer chemotherapy. It discusses the history and mechanisms of alkylating agents such as nitrogen mustards, nitrosoureas, triazines, and platinum compounds. It provides details on specific alkylating agents including their mechanisms of action, uses, dosages, and adverse effects. The summary highlights the development of nitrogen mustard as the first alkylating agent to treat cancer and the discovery of platinum-based drugs like cisplatin through serendipity.
1. Chemotherapeutic agents can be classified according to their chemical structure, mechanism of action, or cell cycle specificity. Common classes include alkylating agents, antimetabolites, antitumor antibiotics, and mitotic spindle agents.
2. The mechanisms of action of these drug classes vary but include alkylating DNA, inhibiting nucleic acid synthesis, interfering with transcription and RNA synthesis, and influencing protein synthesis and function. Many agents act during specific phases of the cell cycle.
3. Examples of specific chemotherapeutic drugs discussed include cyclophosphamide, cisplatin, methotrexate, 5-fluorouracil, vincristine, paclitaxel, doxorubicin,
This document discusses chemotherapeutic drugs used to treat cancer. It begins by providing context on cancer treatment and then discusses several classes of anti-cancer drugs including: alkylating agents like cyclophosphamide; antimetabolites like methotrexate and 5-fluorouracil; antibiotics like doxorubicin; plant alkaloids like vinca alkaloids; hormones; and platinum compounds like cisplatin. For each drug class or example drug, the document discusses mechanisms of action, indications for use, and common adverse effects. It concludes by noting drug resistance can occur when cancer cells contain molecular changes making them insensitive to treatment.
This document summarizes cancer chemotherapy and the various classes of chemotherapeutic drugs. It describes the mechanisms of action, indications, and side effects of alkylating agents, antimetabolites, plant alkaloids, antibiotics, and other classes of drugs. The principles of cancer chemotherapy are to arrest tumor progression by causing cytotoxicity or apoptosis in cancer cells, often targeting DNA or metabolic pathways essential for cell replication. Drugs are generally used in combination to achieve maximal cell killing while remaining within a tolerable toxicity range.
This document discusses various modalities for treating cancer including chemotherapy. It provides details on the mechanisms of action, goals and classifications of different chemotherapeutic agents. It describes how certain drugs like methotrexate, cyclophosphamide and cisplatin directly damage DNA to inhibit cell proliferation. It also discusses concepts like drug resistance, cell cycle specificity and overcoming resistance through combination therapy. The document concludes by summarizing adverse effects of major drug classes and approaches to manage toxicities.
This document provides an overview of anticancer drugs, including their classification, mechanisms of action, and examples. It discusses 10 main classes of anticancer drugs: alkylating agents, platinum coordination complexes, antimetabolites, microtubule damaging agents, topoisomerase inhibitors, antibiotics, miscellaneous cytotoxic drugs, targeted drugs, and hormonal drugs. For each drug class and some examples, it describes indications, dosages, and mechanisms of inhibiting cancer cell growth and proliferation. The document concludes with nursing responsibilities in administering these drugs and educating patients.
This document discusses the pharmacology of glucocorticoids, purine analogs, and methotrexate for treatment of inflammatory bowel disease. It describes the mechanisms of action, pharmacokinetics, clinical uses, and adverse effects of these drugs. Glucocorticoids such as prednisone are commonly used orally or rectally to treat moderate to severe IBD. Purine analogs azathioprine and 6-mercaptopurine are used to induce and maintain remission. Methotrexate given weekly can also induce and maintain remission of Crohn's disease. Adverse effects include bone marrow suppression, liver toxicity, and opportunistic infections which require monitoring.
This document discusses anti-protozoal agents used to treat various protozoal infections. It begins by listing important protozoal infections and their causative organisms. It then describes the drugs used to treat each infection, including nitroimidazoles, amphotericin B, eflornithine, iodoquinol, melarsoprol, miltefosine, nifurtimox, benznidazole, and nitazoxanide. It provides details on the mechanisms of action, pharmacokinetics, therapeutic uses and dosages, toxicities, and side effects of these individual agents.
This document summarizes various alkylating agents and antimetabolites used in cancer chemotherapy. It discusses the history and mechanisms of alkylating agents such as nitrogen mustards, nitrosoureas, triazines, and platinum compounds. It provides details on specific alkylating agents including their mechanisms of action, uses, dosages, and adverse effects. The summary highlights the development of nitrogen mustard as the first alkylating agent to treat cancer and the discovery of platinum-based drugs like cisplatin through serendipity.
1. Chemotherapeutic agents can be classified according to their chemical structure, mechanism of action, or cell cycle specificity. Common classes include alkylating agents, antimetabolites, antitumor antibiotics, and mitotic spindle agents.
2. The mechanisms of action of these drug classes vary but include alkylating DNA, inhibiting nucleic acid synthesis, interfering with transcription and RNA synthesis, and influencing protein synthesis and function. Many agents act during specific phases of the cell cycle.
3. Examples of specific chemotherapeutic drugs discussed include cyclophosphamide, cisplatin, methotrexate, 5-fluorouracil, vincristine, paclitaxel, doxorubicin,
This document discusses chemotherapeutic drugs used to treat cancer. It begins by providing context on cancer treatment and then discusses several classes of anti-cancer drugs including: alkylating agents like cyclophosphamide; antimetabolites like methotrexate and 5-fluorouracil; antibiotics like doxorubicin; plant alkaloids like vinca alkaloids; hormones; and platinum compounds like cisplatin. For each drug class or example drug, the document discusses mechanisms of action, indications for use, and common adverse effects. It concludes by noting drug resistance can occur when cancer cells contain molecular changes making them insensitive to treatment.
This document summarizes cancer chemotherapy and the various classes of chemotherapeutic drugs. It describes the mechanisms of action, indications, and side effects of alkylating agents, antimetabolites, plant alkaloids, antibiotics, and other classes of drugs. The principles of cancer chemotherapy are to arrest tumor progression by causing cytotoxicity or apoptosis in cancer cells, often targeting DNA or metabolic pathways essential for cell replication. Drugs are generally used in combination to achieve maximal cell killing while remaining within a tolerable toxicity range.
This document discusses various modalities for treating cancer including chemotherapy. It provides details on the mechanisms of action, goals and classifications of different chemotherapeutic agents. It describes how certain drugs like methotrexate, cyclophosphamide and cisplatin directly damage DNA to inhibit cell proliferation. It also discusses concepts like drug resistance, cell cycle specificity and overcoming resistance through combination therapy. The document concludes by summarizing adverse effects of major drug classes and approaches to manage toxicities.
This document provides an overview of anticancer drugs, including their classification, mechanisms of action, and examples. It discusses 10 main classes of anticancer drugs: alkylating agents, platinum coordination complexes, antimetabolites, microtubule damaging agents, topoisomerase inhibitors, antibiotics, miscellaneous cytotoxic drugs, targeted drugs, and hormonal drugs. For each drug class and some examples, it describes indications, dosages, and mechanisms of inhibiting cancer cell growth and proliferation. The document concludes with nursing responsibilities in administering these drugs and educating patients.
This document discusses the pharmacology of glucocorticoids, purine analogs, and methotrexate for treatment of inflammatory bowel disease. It describes the mechanisms of action, pharmacokinetics, clinical uses, and adverse effects of these drugs. Glucocorticoids such as prednisone are commonly used orally or rectally to treat moderate to severe IBD. Purine analogs azathioprine and 6-mercaptopurine are used to induce and maintain remission. Methotrexate given weekly can also induce and maintain remission of Crohn's disease. Adverse effects include bone marrow suppression, liver toxicity, and opportunistic infections which require monitoring.
This document discusses anti-protozoal agents used to treat various protozoal infections. It begins by listing important protozoal infections and their causative organisms. It then describes the drugs used to treat each infection, including nitroimidazoles, amphotericin B, eflornithine, iodoquinol, melarsoprol, miltefosine, nifurtimox, benznidazole, and nitazoxanide. It provides details on the mechanisms of action, pharmacokinetics, therapeutic uses and dosages, toxicities, and side effects of these individual agents.
This document discusses inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease. It covers the etiology, pathogenesis, clinical features, and pharmacotherapy of IBD. Regarding treatment, it describes the use of 5-aminosalicylic acids, corticosteroids, immunomodulators, antibiotics/probiotics, biological therapies targeting TNF-α, and newer non-TNF-α inhibitors to induce and maintain remission of IBD. Adverse effects of the different drug classes are also outlined.
This document discusses chemotherapy for ovarian cancers. It begins by introducing chemotherapy and its history. It then covers the cell cycle and phases. It classifies chemotherapeutic agents and discusses their mechanisms of action. It describes principles of chemotherapy administration and contraindications. The rest of the document focuses specifically on chemotherapy protocols and considerations for ovarian cancer, including for early, advanced, recurrent, and germ cell ovarian cancers.
Treatment of tuberculosis aims to interrupt transmission and cure patients while preventing drug resistance. First-line drugs include isoniazid, rifampin, pyrazinamide, and ethambutol. Standard treatment involves 6 months of these drugs in two phases. Second-line drugs are used when resistance develops. Treatment is monitored for efficacy and toxicity. Directly observed therapy and prevention measures like the BCG vaccine and contact tracing help control tuberculosis.
This document discusses anticancer drugs and their classification and mechanisms of action. It provides details on several common cytotoxic drugs including alkylating agents like cyclophosphamide and ifosfamide; antimetabolites like methotrexate; cytotoxic antibiotics like doxorubicin; and plant derivatives like vincristine. It describes the mechanisms of these drug classes and highlights specific drugs, their indications, dosages, and common toxicities. The document provides an overview of the general approach to cancer management and use of chemotherapy.
This document discusses the pharmacotherapy of inflammatory bowel disease (IBD). IBD includes two major subtypes, ulcerative colitis and Crohn's disease, which are characterized by chronic inflammation of the intestinal tract. Treatment aims to induce and maintain remission of symptoms. First-line therapies include 5-aminosalicylic acid drugs and glucocorticoids. For cases that are steroid-dependent or resistant, immunosuppressants like azathioprine and anti-TNFα antibodies such as infliximab are used. Supportive care involves nutritional supplementation, antidiarrheals, and in severe cases of Crohn's, total parenteral nutrition may be given.
This document discusses various chemotherapeutic agents used in ENT. It describes the different phases of chemotherapeutic trials and principles of chemotherapy. It discusses single agent versus multidrug combination therapy and covers cell cycle concepts. It then details specific chemotherapeutic drugs like alkylating agents, antimetabolites, cytotoxic antibiotics, antimitotic plant products, and targeted therapies. It addresses limitations of cytotoxic agents in not being cancer-cell specific.
This document discusses various non-steroidal immunosuppressant drugs used to treat non-infectious uveitis. It describes corticosteroid-sparing immunomodulatory therapy as necessary for patients who require high corticosteroid doses or have intolerances. The document categorizes immunomodulatory options and provides details on mechanisms of action, dosing regimens, and side effects of common agents including antimetabolites, calcineurin inhibitors, cytotoxic drugs, and biologic response modifiers.
Pulse therapy involves administering high doses of drugs intermittently to enhance therapeutic effects and reduce side effects. It is commonly used in dermatology to treat conditions like pemphigus vulgaris. The most common agents used are methylprednisolone and dexamethasone, administered intravenously in high doses over 2-3 hours. Pulse therapy works through both genomic and non-genomic mechanisms at the cellular level to produce powerful anti-inflammatory effects. It provides indications, contraindications, administration protocols, mechanisms of action, and modifications for pulse therapy.
This document discusses opioids including their classification, mechanism of action, receptors, metabolism, pharmacokinetics, and management of opioid-dependent patients. It covers specific opioids like morphine, diamorphine, fentanyl, alfentanyl, remifentanyl, oxycodone, and codeine. Transdermal delivery systems and concerns using remifentanyl PCA in labor are also mentioned. The final section discusses anesthetic management and concerns for an addict pregnant female undergoing cesarean section.
Antigout pharmacology. Medicine use in goutPawan Maharjan
This document discusses drug use in the treatment of gout. It begins by describing gout as a disorder of purine metabolism that causes high uric acid levels and the precipitation of urate crystals in joints. It then covers the types and pathogenesis of gout. The main drug classes used for treatment are nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids for acute attacks. For chronic management, uricosuric agents like probenecid increase uric acid excretion, while allopurinol and febuxostat inhibit uric acid synthesis by blocking xanthine oxidase. The document provides details on the mechanisms of action, pharmacokinetics
inflammatory bowel disease and drug used for itIslam Home
This document discusses the practical management of patients with inflammatory bowel disease (IBD) taking immunomodulators. It covers two major types of IBD: Ulcerative Colitis and Crohn's Disease. It then discusses several common immunomodulators used to treat IBD, including azathioprine, mercaptopurine, ciclosporin, methotrexate, and tacrolimus. For each drug, it provides information on mechanisms of action, dosing protocols, monitoring, side effects, drug interactions and cautions. The document emphasizes the importance of safe and effective use of immunomodulators for long-term IBD management.
This document discusses principles of chemotherapy used in ENT (ear, nose, and throat) cancers. It describes how chemotherapies target rapidly dividing cancer cells by interfering with cell cycle processes. The cell cycle and phases like G1, S, G2, and M are explained. Different classes of chemotherapeutic agents are outlined, including how they work (e.g. alkylating agents cause DNA damage) and examples (e.g. cisplatin, doxorubicin). Combination chemotherapy and neoadjuvant chemotherapy strategies are also mentioned. The document provides an overview of basic concepts in chemotherapy for ENT cancer treatment.
This document discusses principles of chemotherapy used in ENT (ear, nose, and throat) cancers. It covers cell cycle phases, tumor biology principles like cell signaling and oncogenes. It describes different classes of chemotherapy drugs like alkylating agents, antimetabolites, cytotoxic antibiotics, spindle poisons, and monoclonal antibodies. It discusses strategies like combination chemotherapy and neoadjuvant chemotherapy. The key points are that chemotherapy targets rapidly dividing cancer cells, different drug classes have varying mechanisms of action and toxicities, and combining drugs may be more effective than single agents to reduce resistance.
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)pavithra vinayak
Therapeutic drug monitoring (TDM) is used to measure drug concentrations in body fluids to aid in managing drug therapy for diseases. TDM is integral for immunosuppressive drugs used after organ transplants as they have a narrow therapeutic index and concentrations vary between individuals. Common immunosuppressive drugs monitored include cyclosporine, tacrolimus, sirolimus, and mycophenolic acid. Monitoring is important as supratherapeutic and subtherapeutic concentrations of these drugs can have serious negative health outcomes for transplant recipients. Factors like metabolism, drug interactions, and individual pharmacokinetics require close monitoring to optimize efficacy and safety.
1. Solid cancer tumors generally have a low growth fraction and thus respond poorly to chemotherapy, often requiring surgery for removal. Disseminated cancers generally have a high growth fraction and often respond well to chemotherapy.
2. There are several classes of chemotherapeutic agents that work through different mechanisms such as alkylating DNA, inhibiting synthesis of DNA/RNA precursors, or inhibiting microtubule polymerization. Combination chemotherapy is often used to increase effectiveness.
3. Dosage must be modified based on toxicity monitoring like myelosuppression as measured by absolute neutrophil count and platelet count to minimize risks of side effects. Preventative measures and dose modifications can manage toxicities from chemotherapy.
Cytotoxic drugs, also known as antineoplastics, are a group of medicines used to treat cancer by preventing the replication or growth of cells. They work by damaging the cell's DNA. Combination chemotherapy using two or more agents leads to improved outcomes. Chemotherapy may be used alone or with other modalities like radiation and surgery. Alkylating agents are a major class of cytotoxic drugs that work by cross-linking DNA strands or causing DNA breaks. They are used to treat many cancer types and come in classes like nitrogen mustards, alkyl sulfonates, triazines, and ethylenimines. Adverse effects include bone marrow suppression and gastrointestinal issues.
This document discusses chemotherapy and its use in treating cancer. It begins by defining chemotherapy as using chemical agents that are selectively toxic to cancer cells. The objectives of chemotherapy are to maximize cancer cell death, cure the patient if possible, control tumor growth if a cure is not possible, and extend lifespan and quality of life. It then describes how chemotherapy works by targeting cells that are actively dividing, explains the cell cycle and how different drugs work at specific phases, and classifies common chemotherapy drugs like alkylating agents and antimetabolites. Side effects of chemotherapy like bone marrow suppression and nausea are also summarized.
Chemotherapy and rdiotherapy by heena mehtamehtaheena
This document discusses chemotherapy and its use in treating cancer. It begins by defining chemotherapy as using chemical agents that are selectively toxic to cancer cells. The objectives of chemotherapy are to maximize cancer cell death, cure the patient if possible, control tumor growth if a cure is not possible, and extend lifespan and quality of life. It then explains how chemotherapy works by targeting cells that are actively dividing, specifically during the S and M phases of the cell cycle. The document classifies chemotherapy drugs and discusses their mechanisms of action and side effects, focusing on alkylating agents and anti-metabolites.
This document discusses antiparasitic agents used to treat various protozoal and helminthic infections. It begins by classifying parasites and listing common protozoal infections and their causative organisms. It then describes various anti-protozoal drugs including their mechanisms of action, pharmacokinetics, therapeutic uses, and adverse effects. Drugs covered include amphotericin B, eflornithine, melarsoprol, nitroimidazoles, miltefosine, nifurtimox/benznidazole, nitazoxanide, paramomycin, pentamidine, sodium stibogluconate, and suramin. The document concludes with a brief section on hel
This document provides information on various types of anti-cancer drugs, including their mechanisms of action, uses, and side effects. It discusses alkylating agents, antimetabolites, natural products/taxanes, antibiotics, platinum compounds, and drugs that alter the hormonal milieu. It also classifies anti-cancer drugs according to how they directly act on cells and their mechanism of action. Key drugs discussed include chlorambucil, cyclophosphamide, busulfan, methotrexate, fluorouracil, doxorubicin, paclitaxel, etoposide, and hydroxyurea.
1) The document discusses the cell cycle, which includes interphase and the M phase. Interphase consists of G1, S, and G2 phases where the cell grows and replicates its DNA in preparation for division.
2) The M phase is when the cell divides, known as mitosis, which has four stages - prophase, metaphase, anaphase, and telophase. During these stages the chromosomes condense and align, separate, and decondense respectively.
3) Cell division, along with DNA replication and growth, must be coordinated through the cell cycle to ensure daughter cells receive intact genomes. The cycle allows a single cell to multiply into millions through repeated growth and division.
The document discusses principles and methods of immobilization in radiotherapy. It describes the role of immobilization in reducing geometric uncertainties and lists the ideal properties of an immobilization device. The history of immobilization devices is explored, from early uses of plastic cups and masking tapes to today's body conformal devices and stereotactic equipment. Various head and neck immobilization tools are presented, including thermoplastic molds, base plates, and accessories like mouth bites. Body conformal devices like alpha cradles and vacuum-lock bags are explained. Immobilization methods for specific treatment sites like breast, prostate, and intracranial regions are outlined.
This document discusses inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease. It covers the etiology, pathogenesis, clinical features, and pharmacotherapy of IBD. Regarding treatment, it describes the use of 5-aminosalicylic acids, corticosteroids, immunomodulators, antibiotics/probiotics, biological therapies targeting TNF-α, and newer non-TNF-α inhibitors to induce and maintain remission of IBD. Adverse effects of the different drug classes are also outlined.
This document discusses chemotherapy for ovarian cancers. It begins by introducing chemotherapy and its history. It then covers the cell cycle and phases. It classifies chemotherapeutic agents and discusses their mechanisms of action. It describes principles of chemotherapy administration and contraindications. The rest of the document focuses specifically on chemotherapy protocols and considerations for ovarian cancer, including for early, advanced, recurrent, and germ cell ovarian cancers.
Treatment of tuberculosis aims to interrupt transmission and cure patients while preventing drug resistance. First-line drugs include isoniazid, rifampin, pyrazinamide, and ethambutol. Standard treatment involves 6 months of these drugs in two phases. Second-line drugs are used when resistance develops. Treatment is monitored for efficacy and toxicity. Directly observed therapy and prevention measures like the BCG vaccine and contact tracing help control tuberculosis.
This document discusses anticancer drugs and their classification and mechanisms of action. It provides details on several common cytotoxic drugs including alkylating agents like cyclophosphamide and ifosfamide; antimetabolites like methotrexate; cytotoxic antibiotics like doxorubicin; and plant derivatives like vincristine. It describes the mechanisms of these drug classes and highlights specific drugs, their indications, dosages, and common toxicities. The document provides an overview of the general approach to cancer management and use of chemotherapy.
This document discusses the pharmacotherapy of inflammatory bowel disease (IBD). IBD includes two major subtypes, ulcerative colitis and Crohn's disease, which are characterized by chronic inflammation of the intestinal tract. Treatment aims to induce and maintain remission of symptoms. First-line therapies include 5-aminosalicylic acid drugs and glucocorticoids. For cases that are steroid-dependent or resistant, immunosuppressants like azathioprine and anti-TNFα antibodies such as infliximab are used. Supportive care involves nutritional supplementation, antidiarrheals, and in severe cases of Crohn's, total parenteral nutrition may be given.
This document discusses various chemotherapeutic agents used in ENT. It describes the different phases of chemotherapeutic trials and principles of chemotherapy. It discusses single agent versus multidrug combination therapy and covers cell cycle concepts. It then details specific chemotherapeutic drugs like alkylating agents, antimetabolites, cytotoxic antibiotics, antimitotic plant products, and targeted therapies. It addresses limitations of cytotoxic agents in not being cancer-cell specific.
This document discusses various non-steroidal immunosuppressant drugs used to treat non-infectious uveitis. It describes corticosteroid-sparing immunomodulatory therapy as necessary for patients who require high corticosteroid doses or have intolerances. The document categorizes immunomodulatory options and provides details on mechanisms of action, dosing regimens, and side effects of common agents including antimetabolites, calcineurin inhibitors, cytotoxic drugs, and biologic response modifiers.
Pulse therapy involves administering high doses of drugs intermittently to enhance therapeutic effects and reduce side effects. It is commonly used in dermatology to treat conditions like pemphigus vulgaris. The most common agents used are methylprednisolone and dexamethasone, administered intravenously in high doses over 2-3 hours. Pulse therapy works through both genomic and non-genomic mechanisms at the cellular level to produce powerful anti-inflammatory effects. It provides indications, contraindications, administration protocols, mechanisms of action, and modifications for pulse therapy.
This document discusses opioids including their classification, mechanism of action, receptors, metabolism, pharmacokinetics, and management of opioid-dependent patients. It covers specific opioids like morphine, diamorphine, fentanyl, alfentanyl, remifentanyl, oxycodone, and codeine. Transdermal delivery systems and concerns using remifentanyl PCA in labor are also mentioned. The final section discusses anesthetic management and concerns for an addict pregnant female undergoing cesarean section.
Antigout pharmacology. Medicine use in goutPawan Maharjan
This document discusses drug use in the treatment of gout. It begins by describing gout as a disorder of purine metabolism that causes high uric acid levels and the precipitation of urate crystals in joints. It then covers the types and pathogenesis of gout. The main drug classes used for treatment are nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids for acute attacks. For chronic management, uricosuric agents like probenecid increase uric acid excretion, while allopurinol and febuxostat inhibit uric acid synthesis by blocking xanthine oxidase. The document provides details on the mechanisms of action, pharmacokinetics
inflammatory bowel disease and drug used for itIslam Home
This document discusses the practical management of patients with inflammatory bowel disease (IBD) taking immunomodulators. It covers two major types of IBD: Ulcerative Colitis and Crohn's Disease. It then discusses several common immunomodulators used to treat IBD, including azathioprine, mercaptopurine, ciclosporin, methotrexate, and tacrolimus. For each drug, it provides information on mechanisms of action, dosing protocols, monitoring, side effects, drug interactions and cautions. The document emphasizes the importance of safe and effective use of immunomodulators for long-term IBD management.
This document discusses principles of chemotherapy used in ENT (ear, nose, and throat) cancers. It describes how chemotherapies target rapidly dividing cancer cells by interfering with cell cycle processes. The cell cycle and phases like G1, S, G2, and M are explained. Different classes of chemotherapeutic agents are outlined, including how they work (e.g. alkylating agents cause DNA damage) and examples (e.g. cisplatin, doxorubicin). Combination chemotherapy and neoadjuvant chemotherapy strategies are also mentioned. The document provides an overview of basic concepts in chemotherapy for ENT cancer treatment.
This document discusses principles of chemotherapy used in ENT (ear, nose, and throat) cancers. It covers cell cycle phases, tumor biology principles like cell signaling and oncogenes. It describes different classes of chemotherapy drugs like alkylating agents, antimetabolites, cytotoxic antibiotics, spindle poisons, and monoclonal antibodies. It discusses strategies like combination chemotherapy and neoadjuvant chemotherapy. The key points are that chemotherapy targets rapidly dividing cancer cells, different drug classes have varying mechanisms of action and toxicities, and combining drugs may be more effective than single agents to reduce resistance.
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)pavithra vinayak
Therapeutic drug monitoring (TDM) is used to measure drug concentrations in body fluids to aid in managing drug therapy for diseases. TDM is integral for immunosuppressive drugs used after organ transplants as they have a narrow therapeutic index and concentrations vary between individuals. Common immunosuppressive drugs monitored include cyclosporine, tacrolimus, sirolimus, and mycophenolic acid. Monitoring is important as supratherapeutic and subtherapeutic concentrations of these drugs can have serious negative health outcomes for transplant recipients. Factors like metabolism, drug interactions, and individual pharmacokinetics require close monitoring to optimize efficacy and safety.
1. Solid cancer tumors generally have a low growth fraction and thus respond poorly to chemotherapy, often requiring surgery for removal. Disseminated cancers generally have a high growth fraction and often respond well to chemotherapy.
2. There are several classes of chemotherapeutic agents that work through different mechanisms such as alkylating DNA, inhibiting synthesis of DNA/RNA precursors, or inhibiting microtubule polymerization. Combination chemotherapy is often used to increase effectiveness.
3. Dosage must be modified based on toxicity monitoring like myelosuppression as measured by absolute neutrophil count and platelet count to minimize risks of side effects. Preventative measures and dose modifications can manage toxicities from chemotherapy.
Cytotoxic drugs, also known as antineoplastics, are a group of medicines used to treat cancer by preventing the replication or growth of cells. They work by damaging the cell's DNA. Combination chemotherapy using two or more agents leads to improved outcomes. Chemotherapy may be used alone or with other modalities like radiation and surgery. Alkylating agents are a major class of cytotoxic drugs that work by cross-linking DNA strands or causing DNA breaks. They are used to treat many cancer types and come in classes like nitrogen mustards, alkyl sulfonates, triazines, and ethylenimines. Adverse effects include bone marrow suppression and gastrointestinal issues.
This document discusses chemotherapy and its use in treating cancer. It begins by defining chemotherapy as using chemical agents that are selectively toxic to cancer cells. The objectives of chemotherapy are to maximize cancer cell death, cure the patient if possible, control tumor growth if a cure is not possible, and extend lifespan and quality of life. It then describes how chemotherapy works by targeting cells that are actively dividing, explains the cell cycle and how different drugs work at specific phases, and classifies common chemotherapy drugs like alkylating agents and antimetabolites. Side effects of chemotherapy like bone marrow suppression and nausea are also summarized.
Chemotherapy and rdiotherapy by heena mehtamehtaheena
This document discusses chemotherapy and its use in treating cancer. It begins by defining chemotherapy as using chemical agents that are selectively toxic to cancer cells. The objectives of chemotherapy are to maximize cancer cell death, cure the patient if possible, control tumor growth if a cure is not possible, and extend lifespan and quality of life. It then explains how chemotherapy works by targeting cells that are actively dividing, specifically during the S and M phases of the cell cycle. The document classifies chemotherapy drugs and discusses their mechanisms of action and side effects, focusing on alkylating agents and anti-metabolites.
This document discusses antiparasitic agents used to treat various protozoal and helminthic infections. It begins by classifying parasites and listing common protozoal infections and their causative organisms. It then describes various anti-protozoal drugs including their mechanisms of action, pharmacokinetics, therapeutic uses, and adverse effects. Drugs covered include amphotericin B, eflornithine, melarsoprol, nitroimidazoles, miltefosine, nifurtimox/benznidazole, nitazoxanide, paramomycin, pentamidine, sodium stibogluconate, and suramin. The document concludes with a brief section on hel
This document provides information on various types of anti-cancer drugs, including their mechanisms of action, uses, and side effects. It discusses alkylating agents, antimetabolites, natural products/taxanes, antibiotics, platinum compounds, and drugs that alter the hormonal milieu. It also classifies anti-cancer drugs according to how they directly act on cells and their mechanism of action. Key drugs discussed include chlorambucil, cyclophosphamide, busulfan, methotrexate, fluorouracil, doxorubicin, paclitaxel, etoposide, and hydroxyurea.
1) The document discusses the cell cycle, which includes interphase and the M phase. Interphase consists of G1, S, and G2 phases where the cell grows and replicates its DNA in preparation for division.
2) The M phase is when the cell divides, known as mitosis, which has four stages - prophase, metaphase, anaphase, and telophase. During these stages the chromosomes condense and align, separate, and decondense respectively.
3) Cell division, along with DNA replication and growth, must be coordinated through the cell cycle to ensure daughter cells receive intact genomes. The cycle allows a single cell to multiply into millions through repeated growth and division.
The document discusses principles and methods of immobilization in radiotherapy. It describes the role of immobilization in reducing geometric uncertainties and lists the ideal properties of an immobilization device. The history of immobilization devices is explored, from early uses of plastic cups and masking tapes to today's body conformal devices and stereotactic equipment. Various head and neck immobilization tools are presented, including thermoplastic molds, base plates, and accessories like mouth bites. Body conformal devices like alpha cradles and vacuum-lock bags are explained. Immobilization methods for specific treatment sites like breast, prostate, and intracranial regions are outlined.
This document discusses brachytherapy techniques for treating carcinoma of the cervix. It describes the advantages of brachytherapy including its ability to deliver high radiation doses to tumors while sparing surrounding normal tissues. Several historical brachytherapy systems are summarized, including the Stockholm, Paris, and Manchester systems. The Manchester system defines dosimetry points A and B and provides rules for standardized applicator placement and radioactive source loading to achieve consistent dose distributions.
Radioisotopes such as cesium-137, iridium-192, and gold-198 have replaced radium in brachytherapy sources. Brachytherapy involves placing sealed radioactive sources close to or inside a tumor and can be delivered at low, medium, or high dose rates. Key factors in choosing radioisotopes include half-life, radiation output, specific activity, and photon energy. Proper selection of radioisotopes and dose rates optimizes treatment effectiveness while minimizing radiation exposure.
Epidemiology, Etiopathogenesis, Pathology, Staging of Plasma Cell Dyscrasias....adityasingla007
Plasma cell dyscrasias are a spectrum of monoclonal gammopathies involving overproduction of myeloma proteins by plasma cells. Key points include:
- Plasma cells normally secrete antibodies but in plasma cell dyscrasias a clone overproduces a single antibody type.
- Risk factors include radiation exposure and genetic predispositions. Cytogenetic abnormalities involving immunoglobulin loci and cell cycle genes contribute to pathogenesis.
- Presentations include bone pain, fatigue, infections due to anemia or renal impairment. Investigations show monoclonal protein and clonal bone marrow plasma cells.
- Multiple myeloma, monoclonal gammopathy of unknown significance (MGUS), and smoldering
This document discusses the late effects of radiotherapy. It notes that while radiotherapy effectively treats cancer by damaging DNA in cancer cells, it can also affect normal cells, leading to both acute and late effects. Late effects occur more than 3 months after treatment and involve tissues with slow turnover rates. Common late effects include fibrosis, atrophy, necrosis, vascular damage, and secondary malignancies. The document outlines late effects for various organs and tissues. It emphasizes the importance of prevention strategies like treatment planning and education to minimize complications and improve patient outcomes and quality of life.
Colorectal cancer begins in the inner lining of the colon or rectum and can spread deeper into the wall of the colon/rectum and to other parts of the body. Risk factors include increasing age, family history, lifestyle factors like smoking, obesity, and lack of physical activity. Symptoms often include changes in bowel habits and bleeding. Screening is recommended regularly beginning at age 50. Treatment depends on the stage and may include surgery, radiation, chemotherapy, and targeted therapies. Prognosis depends on tumor stage and extent at diagnosis.
This document provides information on principles of chemotherapy. It discusses how chemotherapy works by damaging rapidly dividing cells like cancer cells, outlines the cell cycle and phases cells go through when dividing, and explains how chemotherapy targets specific phases to kill cancer cells. It also describes common side effects of chemotherapy like nausea, vomiting, fatigue, bone marrow depression leading to neutropenia, thrombocytopenia and anemia. The document discusses approaches to managing these side effects.
Brachytherapy involves placing small radioactive sources inside or near a tumor. It allows a high radiation dose to be delivered to the tumor while sparing surrounding normal tissues. There are several types of brachytherapy classified by source placement (interstitial, intracavitary), loading pattern (pre-loading, after-loading), dose rate (LDR, HDR), and duration of implant (temporary, permanent). Common radioactive sources used include cesium-137, iridium-192, and iodine-125 seeds. Brachytherapy provides advantages of high tumor control with minimal side effects due to rapid dose fall-off and short treatment times.
This document discusses gastrointestinal stromal tumors (GISTs). It defines GISTs as mesenchymal neoplasms that originate in the interstitial cells of Cajal in the gut wall. The majority of GISTs have a mutation in either the KIT or PDGFRA gene. KIT mutations are present in around 95% of cases and result in uncontrolled KIT signaling. Treatment involves surgical resection with adjuvant imatinib therapy for higher risk cases. For advanced or imatinib-resistant GISTs, other tyrosine kinase inhibitors like sunitinib may be used.
Vulvar cancer is a rare malignancy that represents less than 1% of cancers in women. It occurs most commonly in two age groups - younger women who smoke and are HPV-positive, and older women who may have epithelial dystrophies as risk factors. Lymphatic drainage is primarily to the superficial inguinal lymph nodes, with potential spread to deep femoral and pelvic nodes. Positive lymph nodes, particularly those over 5mm or with extracapsular spread, are the strongest prognostic factors and reduce 5-year survival by 50%. Surgical margins of at least 8mm are also important to reduce the risk of local recurrence after resection. Radiation may help reduce recurrence risk when margins are close. Distant metastases generally occur
1. Carcinoma of the oral cavity is most commonly found on the tongue, floor of mouth, and lips. It spreads locally and via lymphatics, most often to cervical lymph nodes. Distant metastases occur in 15-20% of cases, most commonly to lungs.
2. Diagnosis involves history, physical exam, biopsy of the lesion and lymph nodes, imaging like OPG, CT/MRI to assess bone and lymph node involvement. Staging helps determine prognosis and management.
3. Treatment involves surgery, radiation, chemotherapy depending on stage. Close surveillance is needed due to high risk of recurrence and second primary cancers.
The document discusses radiation and its effects on the human body. It provides information on deterministic effects, which have a threshold dose below which no effect is observable, and severity increases with dose. Examples of deterministic effects like cataracts and sterility are given along with their dose thresholds. International standards from organizations like ICRP, IAEA, and UNSCEAR are mentioned. Occupational and public dose limits are provided. Methods of measuring radiation exposure through film, TLD and electronic dosimeters are listed. Information is also given on calculating effective dose and the tissues and organs considered. Background radiation exposures from cosmic, terrestrial and internal sources are detailed. Finally, fatal accident rates per million workers are shown for different occupations along with the radiation
- The document provides information on Acute Myeloid Leukemia (AML), including its etiology, pathogenesis, signs and symptoms, diagnosis, classification, and treatment.
- AML arises from the abnormal clonal expansion of immature myeloid precursors in the bone marrow that have impaired differentiation. It is diagnosed based on finding at least 20% myeloid blasts in the bone marrow.
- Classification involves cytogenetic and molecular testing to identify recurrent genetic abnormalities that inform prognosis and treatment approach.
Radiation therapy has evolved significantly in its use and techniques for managing Hodgkin lymphoma over the past century. Early approaches used low dose X-rays to treat only involved lymph node regions, but this led to high recurrence rates. Later approaches in the 1950s used extended field radiation therapy to treat both involved and adjacent uninvolved lymph node regions, improving outcomes. However, this also increased long-term toxicity risks. More recent decades have seen a shift to involved node radiation therapy and combined modality treatment with chemotherapy to improve cure rates while reducing radiation doses and volumes to minimize side effects like secondary cancers. Ongoing clinical trials continue refining therapies to maximize benefit and safety.
This randomized controlled trial compared preoperative chemoradiotherapy to immediate surgery for resectable or borderline resectable pancreatic cancer. It found no significant difference in overall survival between the two groups based on intention-to-treat analysis. However, the preoperative chemoradiotherapy group had higher R0 resection rates and more favorable pathological outcomes. Compliance with preoperative treatment was also better. For borderline resectable disease specifically, preoperative chemoradiotherapy showed a prolonged overall survival compared to immediate surgery.
Concomitant chemotherapy provides the greatest benefit for patients with locally advanced head and neck cancer according to the MACHNC 2021 meta-analysis. It improves 5-year overall survival by 6.5% and event-free survival by 5.8%, with the greatest decrease in locoregional failure rates. Induction chemotherapy provides smaller benefits of 2.2% for overall survival and 1.45% for event-free survival, as well as a significant decrease in distant failure rates. Adjuvant chemotherapy does not improve survival and increases 120-day mortality. Cisplatin-based regimens are preferred for concomitant and induction chemotherapy. This may be the final MACHNC analysis as no new patients have been
This study retrospectively analyzed exclusive radiotherapy (ERT), surgery, and both as local regional therapies (LRT) for denovo metastatic breast cancer patients. It found that both ERT and surgery plus radiotherapy (BMT) were associated with improved overall survival compared to no LRT or surgery alone. ERT showed similar overall survival as BMT and could be an acceptable alternative to avoid invasive surgeries. However, the study had limitations as a retrospective analysis and larger prospective studies are still needed to provide stronger evidence and guidelines on the role of LRT like ERT for metastatic breast cancer.
Hypofractionation delivers a full course of radiation treatment over a shorter period by using larger daily doses compared to conventional fractionation. Several trials have shown hypofractionation to be as effective as conventional fractionation for early stage breast cancer patients, with acceptable toxicity and cosmetic outcomes. Hypofractionation schedules of 42.9Gy/13#/5wk and 39Gy/13#/5wk were found to have 10-year local relapse rates of 9.6% and 14.8% respectively in one trial, comparable to the conventional dose of 50Gy/25#/5wk which had a rate of 12.1%. Other trials have also found hypofractionation to have similar rates of locoregional
1) BRCA1 and BRCA2 are tumor suppressor genes whose mutations significantly increase the risk of breast and ovarian cancers. Testing for BRCA mutations can help determine appropriate cancer screening and prevention strategies.
2) The HER2 receptor promotes cancer cell growth in around 20-30% of breast cancers. Drugs like trastuzumab, pertuzumab, lapatinib, and T-DM1 target HER2 and have improved outcomes for HER2-positive breast cancer.
3) Newer agents for breast cancer treatment include CDK4/6 inhibitors, PI3K inhibitors, everolimus, neratinib and immunotherapies which are being used alone or in combination with other drugs for
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
Current Ms word generated power point presentation covers major details about the micronuclei test. It's significance and assays to conduct it. It is used to detect the micronuclei formation inside the cells of nearly every multicellular organism. It's formation takes place during chromosomal sepration at metaphase.
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
The use of Nauplii and metanauplii artemia in aquaculture (brine shrimp).pptxMAGOTI ERNEST
Although Artemia has been known to man for centuries, its use as a food for the culture of larval organisms apparently began only in the 1930s, when several investigators found that it made an excellent food for newly hatched fish larvae (Litvinenko et al., 2023). As aquaculture developed in the 1960s and ‘70s, the use of Artemia also became more widespread, due both to its convenience and to its nutritional value for larval organisms (Arenas-Pardo et al., 2024). The fact that Artemia dormant cysts can be stored for long periods in cans, and then used as an off-the-shelf food requiring only 24 h of incubation makes them the most convenient, least labor-intensive, live food available for aquaculture (Sorgeloos & Roubach, 2021). The nutritional value of Artemia, especially for marine organisms, is not constant, but varies both geographically and temporally. During the last decade, however, both the causes of Artemia nutritional variability and methods to improve poorquality Artemia have been identified (Loufi et al., 2024).
Brine shrimp (Artemia spp.) are used in marine aquaculture worldwide. Annually, more than 2,000 metric tons of dry cysts are used for cultivation of fish, crustacean, and shellfish larva. Brine shrimp are important to aquaculture because newly hatched brine shrimp nauplii (larvae) provide a food source for many fish fry (Mozanzadeh et al., 2021). Culture and harvesting of brine shrimp eggs represents another aspect of the aquaculture industry. Nauplii and metanauplii of Artemia, commonly known as brine shrimp, play a crucial role in aquaculture due to their nutritional value and suitability as live feed for many aquatic species, particularly in larval stages (Sorgeloos & Roubach, 2021).
ESPP presentation to EU Waste Water Network, 4th June 2024 “EU policies driving nutrient removal and recycling
and the revised UWWTD (Urban Waste Water Treatment Directive)”
PPT on Direct Seeded Rice presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
2. ● WWI Exposure led to the observation that
alkylating agents caused destruction of bone
marrow and lymphatic tissues, which was further
studied in WW II.
● This led to observation to the direct application of
such agents to the patients with Hodgkin’s disease
and lymphocytic lymphomas at Yale Cancer
Centre in 1943.
● Louis Goodman and Alfred Gillman studied it for
the first time.
ORIGIN OF CHEMOTHERAPY
3. 1948, Sydney Farber successfully used Antifolates to induce remission in
children with Leukemias
1955, National Chemotherapy Program begins for drug screening
1958, Roy Hertz and Min Chiu Li demonstrate Methotrexate as a single
best agent for Choriocarcinoma
1959, FDA approve Alkylating agent Cyclophosphamide
1965, began the era of Combination Chemotherapy
4.
5. ● To achieve cure a TOTAL CELL KILL must be tried
● Complete remission is the goal thus, early and intensive
treatment
● Early diagnosis and early initiation of treatment
● Combination chemotherapy
● Intermittent regimens
● Adjuvant and neoadjuvant chemotherapy occasionally
Guiding principles in cancer
chemotherapy
6. • Cytotoxic chemotherapy refers to agents
which kills the rapidly dividing cells.
• Cytotoxic chemotherapy mechanisms of
action may be by either inhibiting mitosis or
DNA damage
• To fully understand chemotherapy it is
important to have an understanding of the
cell cycle.
7. CELL CYCLE
● The cell cycle comprises of four stages. The cell
must progress through these in order to duplicate
its chromosomes and divide.
● G0(Resting Phase) – Normal functions
● G1 phase (Gap 1) During this phase, the cell is
growing and preparing to double its DNA.
● S phase (DNA synthesis) This is the phase in which
the amount of DNA is doubled.
● G2 phase (Gap 2) The cell prepares for mitosis
● M phase (mitosis) Division of the nucleus.
8. ● All cells, normal or neoplastic, must traverse
through cell division
● Malignant cells spend time in each phase - longest
time at G1, but the time may vary
● Many of the effective anticancer drugs exert their
action on cells traversing the cell cycle - Cell Cycle
Specific (CCS) Drugs
● Cell cycle-nonspecific (CCNS) drugs sterilize
tumor cells whether they are cycling or resting in
the G0 compartment
● CCNS drugs can kill both G0 and cycling cells
● CCS are more effective on cycling cells
Cell Cycle and Clinical Importance
17. ● Very irritant drug (potent vesicant)
● MOA:
○ Analog of mustard gas.
○ Classic alkylating agent that forms interstrand and intrastrand cross-links
with DNA resulting in inhibition of DNA synthesis and function.
○ Cell cycle-nonspecific, with activity in all phases of the cell cycle.
● Uses:
● Haematological cancers, lymphomas- Hodgkin’s (as part of MOPP), CML, CLL
● Dose :
○ Hodgkin's lymphoma: 6 mg/m2 IV on days 1 and 8 every 28 days, as part of
the MOPP regimen.
MECHLORETHAMINE (MUSTINE)
18. ● Adverse effects
● Anorexia, nausea, vomiting
● Bone marrow depression, aplasia
● Menstrual irregularities
● Latent viral infection (herpes zoster) - supressed immunity
● Extravasation- (infiltrate with isotonic sodium Thiosulfite to inactivate)
● Estramustine is a combination of estradiol with nitrogen mustard.
MECHLORETHAMINE (MUSTINE)
20. ● Phenylalanine derivative of nitrogen
mustard
● It is an orally active drug; plasma
concentration varies with individual due to
variation in intestinal absorption and
metabolism
● Very effective in MULTIPLE MYELOMA
MELPHALAN
21. ● Dose:
● 9 mg/m2 daily for 4 days every 4-6 weeks
along with prednisone
● Dose should be adjusted by monitoring
platelets and WBCs count
● Adverse Effects :
● Less irritant locally, causes less alopecia
● Bone marrow Depression: Infections (low
WBC), low platelets count bleeding
● pancreatitis
● N/V, oral ulceration
MELPHALAN
22. ● Most commonly used alkylating agent as a prodrug
● Cytotoxic effect generate after formation of their
alkylating species
● Broad spectrum: used single/ as part of a regimen
● Both cyclophosphamide and ifosfamide orally active
● Can be given parenterally also
CYCLOPHOSPHAMIDE
23. ● Good bioavailability of 90% after per oral administration
● After administration, parent drug activated after
phosphorylation with cytochrome p450.
● T ½ : 4-6 hours
● Excreted into feces by biliary transporter
● Parent drug excreted via kidneys exclusively
CYCLOPHOSPHAMIDE
24.
25. Neoplastic conditions
● Hodgkin's and non-Hodgkin's lymphoma
● ALL, CLL, Multiple myeloma
● Burkitt's lymphoma
● Neuroblastoma , retinoblastoma
● Ca breast , adenocarcinoma of ovaries
Non neoplastic conditions
● Control of graft versus host reaction
● Rheumatoid arthritis
● Nephrotic syndrome
USES OF CYCLOPHOSPHAMIDE
26. ● Haemorrhagic cystitis,
● SIADH
● Effects on the germ cells:
● amenorrhea, testicular atrophy, aspermia, sterility
● hepatic damage: Veno-occlusive diseases
● Dose:
● Breast cancer-
● When given orally, the usual dose is 100 mg/m2 PO on days 1-14 given every
28 days.
● When administered IV, the usual dose is 600 mg/m2 given every 21 days as
part of the AC or CMF regimens.
ADVERSE EFFECTS
27. ● Congener of cyclophosphamide
● Longer half life than cyclophosphamide
● T ½ : 3-10 hours
● Only IV form available as Orally it is highly neurotoxic
● Less alopecia and less emetogenic than cyclophosphamide
● Used for germ cell testicular tumors and adult sarcomas; Ewing’s Sarcoma;
bladder cancers
● Dose:
● Testicular cancer: 1,200 mg/m2 IV on days 1-5 every 21 days, as part of the VelP
salvage regimen.
● Soft tissue sarcoma: 2,000 mg/m2 IV continuous infusion on days 1-3 every 21
days, as part of the MAID regimen.
IFOSFAMIDE
28. ● Aromatic analogue of Nitrogen Mustard
● Bifunctional alkylating agent
● Slowest acting and least toxic alkylating agent
● Oral bioavailability is 75% when taken along with food.
● Main action on lymphoid series produces marked
lympholytic action
● DOC for long term maintenance therapy of CLL
● Dose: 0.1-0.2 mg/kg daily for 3-6 weeks then 2 mg daily for
maintenance
● Adverse Effects: moderate GI upset and haematologic
toxicity
CHLORAMBUCIL (LEUKERAN)
29.
30. ● Triethylene phosphoramide
(TEPA)
● Both thiotepa and its
desulfurated primary metabolite,
TEPA rapidly converted by
hepatic cytochrome P450 to
form DNA cross-links
aziridine rings open after
pronation of the ring-nitrogen
reactive species which gives
cytotoxic effects
THIOTEPA
31. ● Uses
● Active intra-vesicular agent
● Used in superficial bladder cancer
● Not well absorbed orally so given IV
● Dose :
● for bladder instillation 60mg in 60ml sterile water for upto 4
weeks
● Adverse Reactions :
● Myelosuppression; Nausea and Vomiting are dose limiting.
Highly neurotoxic can lead to seizure and coma
THIOTEPA
32. ● Bifunctional alkylating agent
● Cell cycle non specific
● Depresses bone marrow with selective action on myeloid series
● Primarily used in Chronic Myelogenous Leukemia(CML)
● Good oral Bioavailability, T1/2 : 2-3 hours
● Dose: Dose for remission is 4-6 mg/ per day/ PO, and dose for maintenance
is 1-3 mg/ per day/ PO
● Adverse effect:
● Interstitial pulmonary fibrosis
● Impotence and Sterility
● CNS toxicities: seizures - anti convulsant drug - always useful in high dose
regimen of busulfan (0.8mg/kg, every 6hours for 4 days)
BUSULFAN (MYLERAN)
37. ● Oral drugs
● MOA: uncertain, still these are mechanism works:
○ inhibits the synthesis of DNA, RNA, and protein; prolongs interphase; and
produces chromosome breaks.
○ Oxidative metabolism by microsomal enzymes azo-procarbazine and
H202 DNA strand scissoring.
● Used in Combination regimens to treat Hodgkin's & non Hodgkin's lymphoma, brain
tumor
● Leukemogenic , Teratogenic, Mutagenic
● Variety of this drug's metabolites have cytotoxic activity one metabolite, is act as MAO
inhibitor
● Higher risk to cause secondary cancer as a form of acute Leukemia
Procarbazine (methylhydrazine)
38. ● Initially developed as a purine metabolite
● Metabolic activation by liver microsomal enzymes
oxidative N-demethylation to the monomethyl
derivative Spontaneous decomposes to 5-
aminoimidazole-4-carboxamide (Excreted) and
diazomethan
● Later metabolite forms methyl carbonium ion which
is believed to be cytotoxic.
● Para-enterally active, there is slow and variable oral
absorption
● Non-schedule dependent
● CCNS drug
Dacarbazine
39. ● Uses :
● malignant melanoma; Hodgkin’s diseases; soft tissue sarcoma
● Metabolized by P450 and excreted unchanged via urine
● T ½ : 5-6 hours
● ADR:
● Nausea and vomiting(highly emetogenic)
● flu-like symptoms,
● neuropathy (paraesthesia; ataxia; increased photosensitivity)
● myelosuppression
Dacarbazine
40. ● New alkylating agent
● Imidazole ring analogue structurally and functionally similar to
Dacarbazine
● Approved for use against treatment-resistant gliomas and
anaplastic astrocytomas
● Rapidly absorbed after oral absorption & crosses BBB
● Unlike dacarbazine, temozolamide:
does not not require cytochrome P450 system for metabolic
transformation
● Undergoes chemical transformation under normal physiological
pH
● It has the property of inhibiting the repair enzyme, O6-guanine-
DNA-alkyltransferase
Temozolamide
41. ● Taken orally and has excellent oral bioavailability
● Food reduces the rate and extent of drug absorption
● Able to cross BBB due to lipophilicity
● T 1/2: 2 hours
● Dose :
● Anaplastic astrocytoma: 150 mg/m2 PO daily for 5 days every 28
days.
● Newly diagnosed GBM: 75 mg/m2 PO daily for 42 days along
with radiotherapy (60 Gy in 30 fractions).
Temozolamide
43. ● Inorganic metal complex
● Serendipitous drugs
● Broad activities
● Synergistic action with other anticancer agents
● Used to treat ovarian, head neck, bladder, esophagus, lung and colon cancers
PLATINUM COORDINATION
COMPLEXES
44. ● CDDP : cis-diamine di-chloro platinum
● Non cell cycle specific killing
● Administered IV
● Highly bound to plasma proteins
● Less than 10% remains in plasma after infusion
● T ½ : 20-30 minutes
● Gets concentrated in kidney, intestine, testes
● Poorly penetrates BBB
● Slowly excreted in urine
Cisplatin
45.
46. ● Uses :
● Testicular cancer (85% - 95 % curative rates)
● Head and Neck Cancers
● Nonseminomatous testicular cancer (combination regimens)
● Ovarian cancer, bladder cancer
● Other solid tumors: lung (small & non small), esophagus, gastric
● Adverse effects:
● Highly Emetogenic
● Nephrotoxicity (reduced by hydration with iv saline infusion /saline &
mannitol/ other diuretics)
● Peripheral neuropathy
● Ototoxicity
CISPLATIN
47. ● Second generation platinum analogues with Better tolerability
● Crosses the BBB and enters the CSF
● Less plasma protein binding
● Vigorous I/v hydration not required
● Excreted exclusively via kidneys with 60-70% drug excreted within
24 hours
● T ½: 2-6 hours
● Nephrotoxicity , ototoxicity , neurotoxicity however low
● Less emetogenic, but thrombocytopenia and leukopenia may occur
(dose liming toxicities)
CARBOPLATIN
48. ● Can be Used in place of Cisplatin
● Uses :
● Solid tumours
● Primarily in ovarian cancer of epithelial origin
● Germ cell tumours; Bladder Cancer; Relapsed
Acute Leukemia
● CALVERT formula is used to calculate the dose
● Total dose = Target AUC x (GFR + 25)
● Target AUC is usually between 5-7 mg/ml/min in
previously untreated cases; and 4-6 mg/ml/min
CARBOPLATIN
49. ● 3rd generation diaminocyclohexane platinum analogues
● No cross-resistance to cancer cells that are resistant to cisplatin or
carboplatin on the basis of mismatch repair defects
● 50 times higher volume of distribution than Cisplatin
● About 40% of the drug gets sequestered in RBCs within 2-5 hours of
administration
● Approved for second-line therapy in metastatic colorectal cancer following
treatment with 5-fluorouracil-leucovorin and irinotecan
● First line drug for this disease
● Also used in metastatic pancreatic and Gastro-esophageal cancers
OXALIPLATIN
50. ● Adverse Effects:
● Neurotoxicity : dose-limiting, is seen in acute and chronic forms;
peripheral sensory neuropathy(worsened upon cold exposure)
● Dysesthesias in the upper extremities and laryngopharyngeal region with
episodes of difficulty breathing or swallowing can be observed and usually
within hours or 1-3 days after therapy.
● Myelosuppression is relatively mild with anemia and thrombocytopenia
more common that neutropenia
OXALIPLATIN
54. ● Analogues related to the normal components of DNA or of
coenzymes involved in nucleic acid synthesis
● Competitively inhibit utilization of the normal substrate or get
themselves incorporated forming dysfunctional
macromolecules
● Folic acid analogue - Methotrexate, Pemetrexed
● Purine analogue - 6-MP, 6-TG, Fludarabine, Cytarabine,
Pentostatin
● Pyrimidine analogue - 5-Fluorouracil, Cytarabine (cytosine
arabinoside), Capecitabine, Gemcitabine
Anti-Metabolites
55. ● Folate antagonist
● Most commonly used and oldest anticancer
drug
● Cell Cycle Specific drug
● Acts during S phase of the cell cycle
● Has Antineoplastic, immunosuppressant
and anti-inflammatory effects
Methotrexate
56. ● Methotrexate structurally resembles folic acid - competitively inhibits dihydrofolate
reductase enzyme and prevents the conversion of DHFA to THFA - depletes
intracellular THFA
● THFA is necessary for synthesis of purines and thymidylate which is necessary for
DNA and RNA synthesis
● Utilizing the folate carrier - enters the cells - transforms into more active
polyglutamate form by enzyme foly-polyglutamate synthase (FPGS)
Methotrexate
57.
58. ● Methotrexate well absorbed after oral
administration, can be given i.m, i.v or
intrathecally
● 50% bound to plasma proteins
● Poorly crosses BBB and most of the drug
excreted unchanged in urine
● DOC - choriocarcinoma; 15-30 mg/m2/day for 5
days orally or 20-40 mg/m2 i.m or i.v twice weekly
● Also used in Acute Leukemia, Burkitt's Lymphoma
and Breast Ca.
● Low dose Methotrexate ( 7.5-30 mg once weekly)
– Rheumatoid Arthritis (DMARDS)
● Other Uses - Psoriasis, IBD and in Organ
transplantation
Methotrexate
59. ● Toxic effects of Methotrexate on normal cells can
be minimized by giving folinic acid
● Availability of folinic acid has helped the use of
very high doses of Methotrexate for better
antineoplastic effect
● A nearly 100 times higher dose (250-1000
mg/m2) of Methotrexate infused i.v over 6 hrs,
followed by 3-15 mg i.v calcium leucovorin within
3 hrs, repeated as required
● Can be repeated weekly
● Folinic acid (Active CoA) - bypasses the block
produced by Methotrexate and rapidly reverses
the toxicity
Folinic acid rescue/ Leucovorin rescue
60. ● Newer congener of Methotrexate
● Primarily targets the enzyme Thymidylate
synthase
● Though not a DHFRase inhibitor, the pool of
THFA is not markedly reduced
● Like Methotrexate, it utilizes the folate carrier to
enter cells and requires transformation into
polyglutamate form by FPGS for activity
enhancement
● Adverse effects - Mucositis, Diarrhoea,
Myelosuppression (same as Methotrexate)
● Painful, itching erythematous rash, mostly
involving the hands and feet 'hands foot
syndrome’ is common
Pemetrexed
61. ● Only administered IV, peak plasma levels reach at about 30 mins
● Dose - 500 mg/m2 i.v every 3 weeks
● All patients should receive vitamin supplementation with 350 mcg/day
of folic acid PO and 1,000 mcg of vitamin B12 IM every 3 cycles to
reduce the risk and incidence of toxicity while on drug therapy.
● Folic acid supplementation should begin 7 days prior to initiation of
pemetrexed treatment, and the first vitamin B12 injection should be
administered at least 1 week prior to the start of pemetrexed.
● Prophylactic use of steroids may ameliorate and/or completely
eliminate the development of skin rash.
● Dexamethasone can be given at a dose of 4 mg PO bid for 3 days
beginning the day before therapy.
Pemetrexed
64. ● Highly effective anti-neoplastic drugs synthesised in the body
● Mono-ribonucleotides : inhibit the conversion of Inosine
monophosphate to adenine and guanine nucleotides which are the
building blocks for DNA and RNA
● Also cause Feedback inhibition of de novo purine synthesis, get
incorporated into RNA and DNA rendering them dysfunctional
● Indicated in ALL only
● Especially useful in childhood acute leukemias, choriocarcinoma
and few solid tumors
6-MERCAPTOPURINE and 6-
THIOGUANINE
65. ● CCS with activity in S phase
● Absorbed orally , poor penetration BBB
● Plasma half life after oral administration is 1.5 hours only
● Does not cross BBB
● Metabolized in Liver exclusively vis oxidation by xanthine oxidase.
● Allopurinol inhibits xanthine oxidase and the catabolic breakdown of
6-MP, resulting in enhanced toxicity.
● Dose of mercaptopurine must be reduced by 50%-75% when given
concurrently with allopurinol.
6-MERCAPTOPURINE and 6-
THIOGUANINE
66. ● Newer purine anti-metabolite
● Phosphorylated intracellularly active triphosphate form which inhibits
DNA polymerase and ribonucleotide polymerase interferes with DNA
repair as well as gets incorporated to form dysfunctional DNA
● Indicated in Chronic Lymphatic Leukemia and Non-Hodgkin's lymphoma
that have recured after treatment
● Adverse effects - chills, fever, myalgia, arthralgia and vomiting after
injection, myelosuppression and oppurtunistic infections
● Dose - 25 mg/m2 daily for 5 days every 28 days by i.v infusion
Fludarabine
69. ● Mechanism of the cytotoxic action of 5-FU
● 5-FU is converted to 5-FdUMP, which competes with
deoxyuridine monophosphate (dUMP) for the enzyme
thymidylate synthetase.
● Causes Thymidine-less death of the cells
● Resistance is due to decreased activation of 5-FU and
decreased thymidylate synthase activity
5-FU
70. ● Uses :
● Mainly used in treatment of slowly growing tumours
● Colorectal, Upper GIT, Breast and Ovarian carcinomas
● Oral absorption of 5-FU is unreliable, primarily used by i.v
infusion
● 5-FU rapidly metabolized by dihydro-pyrimidine dehydrogenase
(DPD) which is already present in plasma
● Thus; T1/2 : 15-20 mins after i.v infusion
● Genetic deficiency of DPD - severe 5-FU toxicity
5-FU
71. ● Adverse Reactions –
● Myelosuppression
● Peripheral Neuropathy (Hand-foot Syndrome)
● Nausea, Vomiting, Diarrhea
● Alopecia,
● Severe Ulceration Of The Oral And GI Mucosa,
● Bone Marrow Depression (With Bolus Injection),
● Allopurinol Mouthwash: Used To Reduce Oral Toxicity
5-FU
72. ● palmar-plantar erythrodysesthesia
● It is a side effect of
some chemotherapy drugs that can cause
redness, swelling and blistering on the
palms of the hands and soles of the feet.
Hand-foot syndrome
73. ● Newer, Oral Fluoro-pyrimidine Carbamate
● Unlike 5-FU, orally well absorded
● After being absorbed it undergoes a series of
enzymatic reactions, the last of which is hydrolysis to
5-FU
● Thus, Oral Prodrug of 5-FU
● Metabolised into fluoro-b-alanine and CO2
Excreted in urine
● Peak plasma levels are reached in 1.5 hours but rate
and amount of absorption decreases with food.
CAPECITABINE
74. ● FDA approved drug for metastatic breast cancer that
is resistant to first-line drugs
● Currently used in colorectal cancer Treatment
● DOSAGE RANGE
● Recommended dose is 1,250 mg/m2 PO BD (morning
and evening) for 2 weeks with 1 week rest.
● May decrease dose of capecitabine to 850-1,000
mg/m2 BD to reduce risk of toxicity without
compromising efficacy
CAPECITABINE
75. ● Adverse Reactions:
● Peripheral Neuropathy (Hand-foot Syndrome)
● Myelosuppression
● Nausea and Vomiting, Diarrhoea
● Caution with renal & kidney function impaired patients
CAPECITABINE
76. ● Cytidine analogue
● Originally isolated from the sponge
Cryptotethya crypta
● Single most effective agent for induction
of remission in AML
● Drug is activated and phosphorylated by
deoxy-cytidine kinases to Ara C - inhibitor
of DNA polymerases
● Of all antimetabolites - Cytarabine is the
most specific for the S phase of the cell
cycle
CYTARABINE
77. ● Crosses BBB
● T ½ : 2-6 hours but in CSF, T ½ is prolonged 2-11 hours
● Can be administered iv, as oral bioavailability <20%
● Highly schedule dependent and should be given by continuous
infusion or every 8-12 hours for 5-7 days
● Adverse Reactions
● Thrombocytopenia and leukopenia
● Mild to moderate emetogenic
● High dose - Neurotoxicity (Cerebellar Ataxia and peripheral
neuropathy)
CYTARABINE
78. ● Ara-C syndrome
● Seen in paediatric patients and represents an allergic reaction to
cytarabine.
● Characterized by fever, myalgia, malaise, bone pain, maculopapular
skin rash, conjunctivitis, and occasional chest pain.
● Usually occurs within 12 hours of drug infusion.
● Steroids appear to be effective in treating and/or preventing the onset
of this syndrome.
CYTARABINE
79. ● Deoxy-Cytidine analogue
● Converted to active diphosphate and triphopshate nucleotide form
● Gemcitabine diphosphate - inhibits ribonucleotide reductase -
diminish pool of deoxyribonucleoside triphosphates required for
DNA synthesis
● Can be incorporated into DNA and leads to chain termination
● Administered only via IV route as extensively deamination takes
place in GI tract
● Elimination mainly by metabolism
● Uses: initially Pancreatic Ca, nowadays widely Non-Small Cell
Lung Ca, Bladder Ca, and Non-Hodgkin's lymphoma
GEMCITABINE
81. ● Most important of these plant derived, CCS drugs are
● Vinca Alkaloids( Vinblastine, Vincristine, Vinorelbine),
● Podophyllotoxins( Etoposide, Teniposide),
● The Camptothecins (Topotecan, Irinotecan),
● The Taxanes(Paclitaxel, Docetaxel)
Mitotic Spindle Inhibitors
82. ● Vinblastine and Vincristine are derived from
the periwinkle plant
● CCS agent, act during M phase of the cycle
● Block the formation of Mitotic Spindle by
preventing the assembly of tubulin dimers into
microtubules
● These drugs block the formation of mitotic
spindle by preventing the assembly of tubulin
dimers into microtubules
VINKA ALKALOIDS
83.
84. ● DISTRIBUTION
● Widely and rapidly distributed into body tissues within 30 minutes of
administration.
● Poor penetration across the blood-brain barrier and into the CSF.
● Given parenterally
● METABOLISM
● Metabolized in the liver by the cytochrome P450 microsomal system.
● The majority of vinka alkaloids are excreted in bile and feces.
● Only 15%-20% of the drug is recovered in urine.
● T 1/2 is long, on the order of 85 hours (VINCRISTINE)
● T ½ for VinBlastine is 25 hours
Vinca alkaloids
85. ● Special caution to be taken during administration as they cause
EXTRAVASCATION
● Clinical use:
● Vincristine - Acute leukemias, lymphomas, Wilm's Tumor and
Neuroblastoma
● Vinblastine - Lymphomas, Neuroblastomas, Testicular cancers and
Kaposi's sarcoma
● Vinorelbine - non-small cell lung carcinoma and breast Ca
Vinca alkaloids
86. Vinca alkaloids
VinBlastine
VinCristine
(oncovin)
MOPP(Hodgkin's disease)
Childhood leukemias
Childhood tumors-Wilm's tumor,
Neuroblastoma
Toxicity:
Peripheral neuritis with
Paresthesia, Muscle weakness,
Foot Drop
*Vincristine has marrow sparing
effect
Hodgkin's disease(ABVD)
Lymphomas
Carcinoma Breast
Testicular tumors
Toxicity:
Bone marrow suppression,
nausea and vomiting,
Diarrhea, Alopecia
Use with Bleomycin increases risk
for Reynaud’s Syndrome
87. ● The inappropriate or accidental infiltration of chemotherapy into the
subcutaneous tissue or subdermal tissues surrounding the administration
site.
● VESICANTS : Drugs which have corrosive properties and have the
potential to cause tissue destruction if extravasated.
● Varying degrees of pain, oedema, erythema, blistering and necrosis may
occur.
EXTRAVASCATION
88. ● Vesicants (Paclitaxel; Vinblastine; Vincristine; Vinorelbine )
● First step is always to STOP the infusion and try to aspirate the leaked
solution through the catheter.
● Firmly apply a heat pack to the extravasated area for 20 minutes every 6
hours for the first 24 hours.
● For extravasations of <5ml, infiltrate the site with 1500 units of
hyaluronidase in 1ml water for injection.
● Inject subcutaneously at several areas around site.
● Gently massage area to facilitate dispersion.
● For Paclitaxel extravasations, follow this with application of 1%
hydrocortisone cream every 6 hours for 7 days.
EXTRAVASCATION
91. ● Plant derivative of Podophyllum
peltatum (Mayapples)
● Etoposide is a semisynthetic derivative
of podophyllotoxin
● Induces DNA breakage through its
inhibition of topoisomerase lI
● Teniposide is an analogue with similar
properties
● Most active in late S and early G phase
of the cell cycle
ETOPOSIDE and TENIPOSIDE
92. ● Oral bioavailability is 50% which means
it requires twice the oral dose as the of
IV dose
● Well absorbed and distributes to most
body tissues
● Elimination is mainly via kidneys
● T ½ : 3- 10 hours
● Clinical use :
● Germ cell tumours
● Testicular cancer
● Lung cancer
● Non-hodgkin's lymphoma and
● AIDS related Kaposi's Sarcoma
ETOPOSIDE
93. ● Adverse Drug Reactions:
● Myelosuppression
● Alopecia with podophyllotoxins is well
documented and seen in approximately
2/3rd of the patients.
● Increases risk of secondary malignancies
(associated with translocation 11:23 )
ETOPOSIDE
95. ● Obtained from Camptotheca acuminata tree
● Camptothecins, Topotecan and Irinotecan, produce
DNA damage by inhibiting Topoisomerase I
● Irinotecan is a prodrug - converted to active
metabolite (SN 38) in Liver
● Topotecan is a semisynthetic derivative of
Camptotheca acuminata tree.
● Only IV route of administration
TOPOTECAN and IRINOTECAN
96. ● Irinotecan and its metabolite are eliminated via bile
and feces
● Topotecan is eliminated renally
● Clinical use:
● Topotecan - 2nd line agent - Advanced Ovarian Ca
and Recurrent/ relapsed/ stage IV B Cervical
Cancer and for small cell lung Ca.
● Irinotecan - Metastatic Colorectal Ca and Lung
carcinoma
TOPOTECAN and IRINOTECAN
97. ● Toxicity :
● Myelosuppression
● Moderately emetogenic
● “Early Diarrhoea” which is a cholinergic response
and happens within 24 hours of drug administration
and is managed with Atropine
● Late diarrhoea typically 3-10 days after treatment.
TOPOTECAN and IRINOTECAN