This document discusses cancer chemotherapy and summarizes key points about various alkylating agents used for chemotherapy. It explains that cancer chemotherapy aims for total cell kill to cure cancer by destroying all malignant cells. Common alkylating agents discussed include nitrogen mustards like cyclophosphamide and chlorambucil, as well as busulfan and thiotepa. These alkylating agents work by forming reactive molecules that cause DNA damage through alkylation, crosslinking and strand breaks, inhibiting cell proliferation. The document reviews the mechanisms of action, uses, and adverse effects of different alkylating agents.
The document discusses various classes of chemotherapy drugs, including their mechanisms of action, therapeutic uses, and toxicities. It covers alkylating agents, antimetabolites, plant alkaloids, and other classes. For each drug class or individual drug, it provides details on the biochemical pathway affected, examples of diseases treated, and common side effects.
This document summarizes several classes of antimetabolite drugs, including their mechanisms of action and clinical uses. It discusses antifolate drugs like methotrexate and pemetrexed, which inhibit dihydrofolate reductase and other folate-dependent enzymes. It also covers fluoropyrimidines like 5-fluorouracil and capecitabine, which interfere with thymidylate synthase during DNA synthesis. Deoxycytidine analogs such as cytarabine and gemcitabine are described as inhibiting DNA polymerase. The document concludes by discussing purine antagonists including mercaptopurine, fludarabine, and cladribine, which
Cancer chemotherapy originated from observations of mustard gas exposure during World Wars I and II. Luis Goodman and Alfred Gillmen first demonstrated anti-cancer effects of chemotherapy drugs in 1943. Currently, nearly all successful cancer chemotherapy regimens use combination chemotherapy with multiple drugs given simultaneously to achieve synergistic tumor cell kill. Chemotherapy drugs can be classified based on their mechanism of action and cell cycle specificity. Alkylating agents are commonly used chemotherapy drugs that produce reactive carbonium ions to alkylate cellular macromolecules like DNA, causing cytotoxic and radiomimetic effects on both dividing and resting cells. Individual alkylating agent drugs have different dosing schedules and are used to treat various cancer types.
This document discusses anti-cancer or neoplastic drugs and is presented by Dr. Homan. It covers topics such as the definition of cancer, epidemiology, risk factors, characteristics, types, cell cycle, carcinogenesis, diagnosis, classification of anti-cancer drugs, mechanisms of action, and toxic effects. The document provides information on various classes of anti-cancer drugs including alkylating agents, antimetabolites, cytotoxic antibiotics, hormones, and their mechanisms of treating cancer by affecting DNA, RNA, or microtubules.
A 50-year-old man undergoing chemotherapy for a malignant tumor develops megaloblastic anemia. This is likely caused by methotrexate inhibiting folate metabolism. Folic acid supplementation could have prevented the toxicity. Anthracyclines like doxorubicin can cause cardiac toxicity through free radical generation, sometimes requiring dexrazoxane treatment. Bleomycin can cause pulmonary fibrosis.
The document discusses the mechanism of action, resistance mechanisms, and adverse effects of alkylating agents and anti-metabolites. Alkylating agents work by transferring alkyl groups to biologically important molecules like DNA, RNA, and proteins. This impairs cell function and can cause cross-linking of DNA. Anti-metabolites inhibit key enzymes in folate and purine synthesis pathways, interfering with DNA, RNA, and protein production. Both classes of drugs can cause myelosuppression and gastrointestinal toxicity as main adverse effects. Resistance can develop through increased DNA repair, reduced drug uptake, or alterations in target enzymes.
This document summarizes various anticancer drugs and their mechanisms of action. It discusses several classes of cytotoxic drugs that inhibit DNA synthesis in cancer cells, including alkylating agents like cyclophosphamide and chlorambucil, antimetabolites like 5-fluorouracil and methotrexate, and plant-derived drugs and their analogs such as the vinca alkaloids vinblastine and vincristine. It also covers the cell cycle specificity of different anticancer agents and factors influencing cancer sensitivity to treatment.
The document discusses various classes of chemotherapy drugs, including their mechanisms of action, therapeutic uses, and toxicities. It covers alkylating agents, antimetabolites, plant alkaloids, and other classes. For each drug class or individual drug, it provides details on the biochemical pathway affected, examples of diseases treated, and common side effects.
This document summarizes several classes of antimetabolite drugs, including their mechanisms of action and clinical uses. It discusses antifolate drugs like methotrexate and pemetrexed, which inhibit dihydrofolate reductase and other folate-dependent enzymes. It also covers fluoropyrimidines like 5-fluorouracil and capecitabine, which interfere with thymidylate synthase during DNA synthesis. Deoxycytidine analogs such as cytarabine and gemcitabine are described as inhibiting DNA polymerase. The document concludes by discussing purine antagonists including mercaptopurine, fludarabine, and cladribine, which
Cancer chemotherapy originated from observations of mustard gas exposure during World Wars I and II. Luis Goodman and Alfred Gillmen first demonstrated anti-cancer effects of chemotherapy drugs in 1943. Currently, nearly all successful cancer chemotherapy regimens use combination chemotherapy with multiple drugs given simultaneously to achieve synergistic tumor cell kill. Chemotherapy drugs can be classified based on their mechanism of action and cell cycle specificity. Alkylating agents are commonly used chemotherapy drugs that produce reactive carbonium ions to alkylate cellular macromolecules like DNA, causing cytotoxic and radiomimetic effects on both dividing and resting cells. Individual alkylating agent drugs have different dosing schedules and are used to treat various cancer types.
This document discusses anti-cancer or neoplastic drugs and is presented by Dr. Homan. It covers topics such as the definition of cancer, epidemiology, risk factors, characteristics, types, cell cycle, carcinogenesis, diagnosis, classification of anti-cancer drugs, mechanisms of action, and toxic effects. The document provides information on various classes of anti-cancer drugs including alkylating agents, antimetabolites, cytotoxic antibiotics, hormones, and their mechanisms of treating cancer by affecting DNA, RNA, or microtubules.
A 50-year-old man undergoing chemotherapy for a malignant tumor develops megaloblastic anemia. This is likely caused by methotrexate inhibiting folate metabolism. Folic acid supplementation could have prevented the toxicity. Anthracyclines like doxorubicin can cause cardiac toxicity through free radical generation, sometimes requiring dexrazoxane treatment. Bleomycin can cause pulmonary fibrosis.
The document discusses the mechanism of action, resistance mechanisms, and adverse effects of alkylating agents and anti-metabolites. Alkylating agents work by transferring alkyl groups to biologically important molecules like DNA, RNA, and proteins. This impairs cell function and can cause cross-linking of DNA. Anti-metabolites inhibit key enzymes in folate and purine synthesis pathways, interfering with DNA, RNA, and protein production. Both classes of drugs can cause myelosuppression and gastrointestinal toxicity as main adverse effects. Resistance can develop through increased DNA repair, reduced drug uptake, or alterations in target enzymes.
This document summarizes various anticancer drugs and their mechanisms of action. It discusses several classes of cytotoxic drugs that inhibit DNA synthesis in cancer cells, including alkylating agents like cyclophosphamide and chlorambucil, antimetabolites like 5-fluorouracil and methotrexate, and plant-derived drugs and their analogs such as the vinca alkaloids vinblastine and vincristine. It also covers the cell cycle specificity of different anticancer agents and factors influencing cancer sensitivity to treatment.
This document classifies and describes various anticancer drugs, including cytotoxic drugs like alkylating agents, platinum coordination drugs like cisplatin, antimetabolites, microtubule damaging agents like vincristine and vinblastine, topoisomerase inhibitors, antibiotics, targeted drugs, hormonal drugs, and miscellaneous drugs. It provides details on the mechanisms of action, uses, doses, and common side effects of representative drugs from each class, such as how cisplatin causes DNA cross-linking, how vinca alkaloids inhibit microtubule assembly, and how paclitaxel and docetaxel inhibit beta-tubulin.
This document discusses various central nervous system stimulants and cognitive enhancers. It describes how CNS stimulants generally increase muscular and mental activity from mild alertness to convulsions. It classifies stimulants into convulsants, analeptics, and psycho stimulants. Specific drugs are discussed in each category along with their mechanisms of action, uses, and side effects. Cognitive enhancers aimed at improving cognition in conditions like Alzheimer's are also reviewed, focusing on cholinergic activators like donepezil as well as memantine which acts by blocking glutamate receptors.
Opioids act on μ, κ, and δ opioid receptors in the central nervous system and peripheral tissues to produce analgesia, euphoria, and other effects. They are commonly used to treat both acute and chronic pain conditions. However, long-term opioid use can lead to tolerance, physical dependence, and risk of addiction. Treatment for opioid addiction involves medically-supervised detoxification followed by relapse prevention programs and sometimes long-term maintenance therapy.
This document discusses the use of hormones in cancer treatment. It describes several classes of drugs that work by blocking hormone receptors, including glucocorticoid receptor agonists, selective estrogen receptor modulators (SERMs) like tamoxifen, selective estrogen receptor downregulators (SERDs) like fulvestrant, aromatase inhibitors (AIs), and progesterone receptor agonists. These drugs are used to treat breast, prostate, and other hormone-dependent cancers based on their mechanisms of competing with or degrading hormone receptors. Common side effects include symptoms of hormone deprivation.
The document summarizes various toxicities caused by anticancer drugs and their management. It discusses acute and delayed toxicities affecting organs like bone marrow, gastrointestinal tract, liver, kidney, lung and heart. It provides examples of drugs causing specific toxicities like neutropenia, anemia, thrombocytopenia and strategies to ameliorate them, including hematopoietic growth factors, cytoprotective agents, dose adjustments and supportive care. The summary highlights management of common toxicities like nausea, diarrhea, stomatitis and alopecia through symptomatic measures and agents.
This document summarizes different types of central nervous system stimulants and cognition enhancers. It discusses convulsants, analeptics, psychostimulants like amphetamines and caffeine. It also covers what cognition is, types of dementia like Alzheimer's disease, and cognition enhancers like cholinergic activators like donepezil and rivastigmine, as well as memantine and Ginkgo biloba. The document provides information on their mechanisms of action and therapeutic uses.
The document discusses various aspects of cancer chemotherapy including:
1. Guiding principles of cancer chemotherapy aim for total cell kill through early diagnosis, combination chemotherapy, and intermittent regimens.
2. Chemotherapeutic agents are classified based on their mechanism of action and cell cycle specificity, and include alkylating agents, antimetabolites, natural products, and hormones/antagonists.
3. Common chemotherapeutic drugs are discussed including their mechanisms of action, uses, and adverse effects. Chemotherapy aims to destroy cancer cells while limiting toxicity to normal cells.
Methotrexate is a folate antagonist antimetabolite drug that works by inhibiting the enzyme dihydrofolate reductase, depleting tetrahydrofolate cofactors needed for DNA synthesis. It is used to treat cancers like acute lymphocytic leukemia, breast cancer, and rheumatoid arthritis. 5-Fluorouracil and capecitabine are pyrimidine antagonist antimetabolites that inhibit the enzyme thymidylate synthase, blocking DNA synthesis. They are used for cancers like colon cancer. Cytarabine is also a pyrimidine antagonist that incorporates into DNA, inhibiting its synthesis, and is used for acute leukemias. 6-Mercap
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.Dr. Ravi Sankar
The document discusses antineoplastic agents (anticancer drugs) and provides information on cancer and its diagnosis and treatment. It defines cancer as uncontrolled cell growth and discusses how cancer is classified. It also summarizes some common cancer types in children and adults. The document outlines several methods used to treat cancer, including surgery, radiation therapy, immunotherapy, hormonal therapy, chemotherapy and antibiotics. It provides classifications of antineoplastic drugs and examples.
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.
Chapter 18 pharmacokinetics and dynamics of anticancer drugsNilesh Kucha
This document summarizes pharmacokinetics and pharmacodynamics of anticancer drugs. It discusses the absorption, distribution, metabolism and excretion of drugs and how these processes influence drug action over time. Key pharmacokinetic parameters like bioavailability, volume of distribution, clearance and half-life are explained. The document also covers pharmacodynamic concepts such as dose-response relationships, drug potency, efficacy and therapeutic indices. Factors affecting variability in individual responses and the role of therapeutic drug monitoring are summarized. Finally, the document categorizes and provides examples of major classes of anticancer agents.
Antiamoebic drugs are used to treat infections caused by the protozoan Entamoeba histolytica. Metronidazole is the prototype nitroimidazole drug used as it is effective against both intestinal and extra-intestinal E. histolytica infections. It works by disrupting the DNA replication, transcription and repair processes of anaerobic protozoa and bacteria through reduction of its nitro group. Common side effects include nausea, vomiting and neurological effects. Other nitroimidazole derivatives and luminal amoebicides like diloxanide furoate are also used in combination to treat invasive amoebiasis.
This document describes alkylating agents, a class of chemotherapy drugs that work by alkylating DNA and proteins. It discusses their mechanism of action, including how they crosslink DNA and cause DNA damage, leading to cell death. It also covers resistance mechanisms, adverse effects like bone marrow toxicity and nausea/vomiting, and important alkylating agents like cisplatin, carboplatin, oxaliplatin, cyclophosphamide, and carmustine. For each drug, it provides absorption, indications, dosage ranges, and special considerations.
medicinal chemistry of Anticancer agentsGanesh Mote
1) Cancer is caused by abnormal cells dividing uncontrollably and spreading to other tissues. Chemotherapy uses drugs to kill cancer cells or slow their growth.
2) There are several types of chemotherapy drugs that work through different mechanisms such as alkylating agents, antimetabolites, plant-derived products, and monoclonal antibodies.
3) Alkylating agents work by adding alkyl groups to DNA, damaging its structure and preventing cell division. Common alkylating agents include cyclophosphamide, cisplatin, and carmustine.
This document summarizes key information about alkylating agents, a class of anticancer drugs. It describes their mechanisms of action involving alkylation of DNA, which interferes with its integrity and functions. Specific agents discussed include nitrogen mustards, nitrosoureas, triazines, and others. Toxicities involving bone marrow suppression and effects on other rapidly dividing tissues are also summarized. Pharmacological properties, indications, and dosing schedules are provided for several common alkylating agents including cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, dacarbazine, temozolamide, and procarbazine.
This document discusses immunopharmacology and the immune system. It describes how immunopharmacology studies how drugs modify immune mechanisms in the body, including autoimmune disorders, allergies, and cancer. The immune system involves cells like lymphocytes, neutrophils, and monocytes. Antigens stimulate antibody production while antibodies help fight antigens. Immunopharmacology therapies aim to suppress, modulate, or enhance the immune system through immunosuppressants, immunomodulators, or immunoenhancers respectively.
Antimetabolites are a class of chemotherapy drugs that work by interfering with DNA and RNA synthesis in cancer cells. They include folic acid analogs like methotrexate, purine analogs like mercaptopurine, and pyrimidine analogs like 5-fluorouracil. These drugs are used to treat many types of cancer including leukemias, lymphomas, and solid tumors in organs like breast, lung, and colon. While they can be effective, their use is often limited by bone marrow suppression and other toxicities due to their effects on rapidly dividing normal cells.
This document discusses various types of anticancer drugs, including their classification, mechanisms of action, and examples. It describes five main classes of anticancer agents: cytotoxic drugs like alkylating agents and antimetabolites that directly kill cancer cells; natural anticancer agents such as vinca alkaloids and taxanes that interfere with cell division; antibiotics that intercalate DNA; miscellaneous agents discovered through random synthesis; and drugs that act on hormones to manipulate the endocrine system and inhibit cancer growth. Recent FDA-approved drugs for various cancer types are also mentioned.
This document discusses principles of chemotherapy and classification of anticancer drugs. It begins by defining cancer and its differences from normal cells. The main principles of chemotherapy discussed are the cell kill hypothesis of Skipper and the Norton Simon hypothesis. It then covers classification of anticancer drugs based on cell cycle specificity and mechanism of action. Specific drug classes discussed in detail include alkylating agents, antimetabolites, antibiotics, and cisplatin.
Chemotherapy uses anti-cancer drugs to destroy cancer cells. It can be curative for some cancers like leukemias, Wilms tumor, and Hodgkin's lymphoma. The drugs work by interfering with cell division through different mechanisms and can be cell cycle specific or non-specific. Alkylating agents are a common class of chemotherapy drugs that work by transferring alkyl groups to DNA, causing cross-linkages and strand breaks to damage DNA and inhibit cell proliferation. Combination chemotherapy and intermittent dosing regimens are often used to improve outcomes.
This document classifies and describes various anticancer drugs, including cytotoxic drugs like alkylating agents, platinum coordination drugs like cisplatin, antimetabolites, microtubule damaging agents like vincristine and vinblastine, topoisomerase inhibitors, antibiotics, targeted drugs, hormonal drugs, and miscellaneous drugs. It provides details on the mechanisms of action, uses, doses, and common side effects of representative drugs from each class, such as how cisplatin causes DNA cross-linking, how vinca alkaloids inhibit microtubule assembly, and how paclitaxel and docetaxel inhibit beta-tubulin.
This document discusses various central nervous system stimulants and cognitive enhancers. It describes how CNS stimulants generally increase muscular and mental activity from mild alertness to convulsions. It classifies stimulants into convulsants, analeptics, and psycho stimulants. Specific drugs are discussed in each category along with their mechanisms of action, uses, and side effects. Cognitive enhancers aimed at improving cognition in conditions like Alzheimer's are also reviewed, focusing on cholinergic activators like donepezil as well as memantine which acts by blocking glutamate receptors.
Opioids act on μ, κ, and δ opioid receptors in the central nervous system and peripheral tissues to produce analgesia, euphoria, and other effects. They are commonly used to treat both acute and chronic pain conditions. However, long-term opioid use can lead to tolerance, physical dependence, and risk of addiction. Treatment for opioid addiction involves medically-supervised detoxification followed by relapse prevention programs and sometimes long-term maintenance therapy.
This document discusses the use of hormones in cancer treatment. It describes several classes of drugs that work by blocking hormone receptors, including glucocorticoid receptor agonists, selective estrogen receptor modulators (SERMs) like tamoxifen, selective estrogen receptor downregulators (SERDs) like fulvestrant, aromatase inhibitors (AIs), and progesterone receptor agonists. These drugs are used to treat breast, prostate, and other hormone-dependent cancers based on their mechanisms of competing with or degrading hormone receptors. Common side effects include symptoms of hormone deprivation.
The document summarizes various toxicities caused by anticancer drugs and their management. It discusses acute and delayed toxicities affecting organs like bone marrow, gastrointestinal tract, liver, kidney, lung and heart. It provides examples of drugs causing specific toxicities like neutropenia, anemia, thrombocytopenia and strategies to ameliorate them, including hematopoietic growth factors, cytoprotective agents, dose adjustments and supportive care. The summary highlights management of common toxicities like nausea, diarrhea, stomatitis and alopecia through symptomatic measures and agents.
This document summarizes different types of central nervous system stimulants and cognition enhancers. It discusses convulsants, analeptics, psychostimulants like amphetamines and caffeine. It also covers what cognition is, types of dementia like Alzheimer's disease, and cognition enhancers like cholinergic activators like donepezil and rivastigmine, as well as memantine and Ginkgo biloba. The document provides information on their mechanisms of action and therapeutic uses.
The document discusses various aspects of cancer chemotherapy including:
1. Guiding principles of cancer chemotherapy aim for total cell kill through early diagnosis, combination chemotherapy, and intermittent regimens.
2. Chemotherapeutic agents are classified based on their mechanism of action and cell cycle specificity, and include alkylating agents, antimetabolites, natural products, and hormones/antagonists.
3. Common chemotherapeutic drugs are discussed including their mechanisms of action, uses, and adverse effects. Chemotherapy aims to destroy cancer cells while limiting toxicity to normal cells.
Methotrexate is a folate antagonist antimetabolite drug that works by inhibiting the enzyme dihydrofolate reductase, depleting tetrahydrofolate cofactors needed for DNA synthesis. It is used to treat cancers like acute lymphocytic leukemia, breast cancer, and rheumatoid arthritis. 5-Fluorouracil and capecitabine are pyrimidine antagonist antimetabolites that inhibit the enzyme thymidylate synthase, blocking DNA synthesis. They are used for cancers like colon cancer. Cytarabine is also a pyrimidine antagonist that incorporates into DNA, inhibiting its synthesis, and is used for acute leukemias. 6-Mercap
ANTI CANCER DRUGS[ANTI-NEOPLASTIC DRUGS] MEDICINAL CHEMISTRY BY P. RAVISANKAR.Dr. Ravi Sankar
The document discusses antineoplastic agents (anticancer drugs) and provides information on cancer and its diagnosis and treatment. It defines cancer as uncontrolled cell growth and discusses how cancer is classified. It also summarizes some common cancer types in children and adults. The document outlines several methods used to treat cancer, including surgery, radiation therapy, immunotherapy, hormonal therapy, chemotherapy and antibiotics. It provides classifications of antineoplastic drugs and examples.
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.
Chapter 18 pharmacokinetics and dynamics of anticancer drugsNilesh Kucha
This document summarizes pharmacokinetics and pharmacodynamics of anticancer drugs. It discusses the absorption, distribution, metabolism and excretion of drugs and how these processes influence drug action over time. Key pharmacokinetic parameters like bioavailability, volume of distribution, clearance and half-life are explained. The document also covers pharmacodynamic concepts such as dose-response relationships, drug potency, efficacy and therapeutic indices. Factors affecting variability in individual responses and the role of therapeutic drug monitoring are summarized. Finally, the document categorizes and provides examples of major classes of anticancer agents.
Antiamoebic drugs are used to treat infections caused by the protozoan Entamoeba histolytica. Metronidazole is the prototype nitroimidazole drug used as it is effective against both intestinal and extra-intestinal E. histolytica infections. It works by disrupting the DNA replication, transcription and repair processes of anaerobic protozoa and bacteria through reduction of its nitro group. Common side effects include nausea, vomiting and neurological effects. Other nitroimidazole derivatives and luminal amoebicides like diloxanide furoate are also used in combination to treat invasive amoebiasis.
This document describes alkylating agents, a class of chemotherapy drugs that work by alkylating DNA and proteins. It discusses their mechanism of action, including how they crosslink DNA and cause DNA damage, leading to cell death. It also covers resistance mechanisms, adverse effects like bone marrow toxicity and nausea/vomiting, and important alkylating agents like cisplatin, carboplatin, oxaliplatin, cyclophosphamide, and carmustine. For each drug, it provides absorption, indications, dosage ranges, and special considerations.
medicinal chemistry of Anticancer agentsGanesh Mote
1) Cancer is caused by abnormal cells dividing uncontrollably and spreading to other tissues. Chemotherapy uses drugs to kill cancer cells or slow their growth.
2) There are several types of chemotherapy drugs that work through different mechanisms such as alkylating agents, antimetabolites, plant-derived products, and monoclonal antibodies.
3) Alkylating agents work by adding alkyl groups to DNA, damaging its structure and preventing cell division. Common alkylating agents include cyclophosphamide, cisplatin, and carmustine.
This document summarizes key information about alkylating agents, a class of anticancer drugs. It describes their mechanisms of action involving alkylation of DNA, which interferes with its integrity and functions. Specific agents discussed include nitrogen mustards, nitrosoureas, triazines, and others. Toxicities involving bone marrow suppression and effects on other rapidly dividing tissues are also summarized. Pharmacological properties, indications, and dosing schedules are provided for several common alkylating agents including cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, dacarbazine, temozolamide, and procarbazine.
This document discusses immunopharmacology and the immune system. It describes how immunopharmacology studies how drugs modify immune mechanisms in the body, including autoimmune disorders, allergies, and cancer. The immune system involves cells like lymphocytes, neutrophils, and monocytes. Antigens stimulate antibody production while antibodies help fight antigens. Immunopharmacology therapies aim to suppress, modulate, or enhance the immune system through immunosuppressants, immunomodulators, or immunoenhancers respectively.
Antimetabolites are a class of chemotherapy drugs that work by interfering with DNA and RNA synthesis in cancer cells. They include folic acid analogs like methotrexate, purine analogs like mercaptopurine, and pyrimidine analogs like 5-fluorouracil. These drugs are used to treat many types of cancer including leukemias, lymphomas, and solid tumors in organs like breast, lung, and colon. While they can be effective, their use is often limited by bone marrow suppression and other toxicities due to their effects on rapidly dividing normal cells.
This document discusses various types of anticancer drugs, including their classification, mechanisms of action, and examples. It describes five main classes of anticancer agents: cytotoxic drugs like alkylating agents and antimetabolites that directly kill cancer cells; natural anticancer agents such as vinca alkaloids and taxanes that interfere with cell division; antibiotics that intercalate DNA; miscellaneous agents discovered through random synthesis; and drugs that act on hormones to manipulate the endocrine system and inhibit cancer growth. Recent FDA-approved drugs for various cancer types are also mentioned.
This document discusses principles of chemotherapy and classification of anticancer drugs. It begins by defining cancer and its differences from normal cells. The main principles of chemotherapy discussed are the cell kill hypothesis of Skipper and the Norton Simon hypothesis. It then covers classification of anticancer drugs based on cell cycle specificity and mechanism of action. Specific drug classes discussed in detail include alkylating agents, antimetabolites, antibiotics, and cisplatin.
Chemotherapy uses anti-cancer drugs to destroy cancer cells. It can be curative for some cancers like leukemias, Wilms tumor, and Hodgkin's lymphoma. The drugs work by interfering with cell division through different mechanisms and can be cell cycle specific or non-specific. Alkylating agents are a common class of chemotherapy drugs that work by transferring alkyl groups to DNA, causing cross-linkages and strand breaks to damage DNA and inhibit cell proliferation. Combination chemotherapy and intermittent dosing regimens are often used to improve outcomes.
Chemotherapy is an aggressive form of chemical drug therapy meant to destroy rapidly growing cells in the body.It is usually used to treat cancer, as cancer cells grow and divide faster than other cells.
German chemist Paul Ehrlich coined the term "chemotherapy" to refer to treatment of disease with drugs or chemicals. By the 1950s, the term was primarily used to refer to drugs used to treat cancer. Chemotherapy involves the use of drugs to treat cancers caused by uncontrolled cell proliferation, invasion, and metastasis due to chromosomal abnormalities and oncogene expression. Common chemotherapy drugs act by interfering with cell division, DNA/RNA synthesis, and microtubule formation. Combination chemotherapy using multiple agents with different mechanisms of action has improved treatment outcomes but can also lead to drug resistance developing over time. Factors such as tumor type, stage, location, and patient health determine optimal chemotherapy approaches.
This document provides an overview of chemotherapy principles and common agents for internal medicine house staff. It begins with frameworks for understanding antineoplastic agents and reviews basic chemotherapy principles. It then discusses the different modalities of cancer treatment including surgery, radiation, chemotherapy, targeted therapies, immunotherapy and hormonal therapy. Specific sections cover common chemotherapy agents, their mechanisms of action, uses and side effects.
- German chemist Paul Ehrlich coined the term "chemotherapy" to refer to treatment of disease with chemical drugs. By the 1950s, the term was primarily used to refer to drugs used to treat cancer.
- Chemotherapy involves using drugs to treat cancer and typically involves drugs that interfere with cell division, such as methotrexate or fluorouracil.
- The choice of chemotherapy depends on factors like the location and stage of the tumor and the patient's health. While it can cure some cancers, it is most effective against cancer before metastasis.
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.
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,
Cancer is characterized by uncontrolled cell growth and spread. Some key points:
- Lung cancer is the most common cancer in men and breast cancer is most common in women.
- Risk factors include tobacco use, obesity, viruses, chemicals, radiation, and genetic mutations.
- Prevention focuses on healthy behaviors like not smoking, diet, exercise and limiting sun exposure.
- Treatment involves surgery, radiation, chemotherapy and other approaches depending on cancer type and stage. Combined therapies are often used but all treatments can cause side effects.
This document discusses different types of antineoplastic agents (anticancer drugs) used to treat cancer. It describes the goals of cancer treatment and types of agents that work during specific or non-specific phases of the cell cycle. It covers principles of chemotherapy including timing, combination therapy, and drug classifications. Major side effects of chemotherapy like bone marrow depression and nausea/vomiting are outlined. Specific drug classes are then described in more detail, including alkylating agents, antimetabolites, hormonal agents, antibiotics, and radioactive drugs.
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.
Management of adverse effects of cancer chemotherapy 1Dr. Pooja
This document discusses the management of adverse effects from cancer chemotherapy. It covers nausea and vomiting, myelosuppression, alopecia, mucositis, and teratogenicity. For nausea and vomiting, it describes the physiology and classifications, as well as antiemetic agents used for low, moderate, and high emetogenic chemotherapy. It also discusses the use of growth factors to manage chemotherapy-induced myelosuppression and thrombocytopenia. Methods for preventing and treating alopecia and mucositis are summarized.
The document discusses chemotherapy, describing its objectives of curing or palliating cancer, how dosages are determined, factors that affect response, classifications of chemotherapeutic agents, administration methods, responses to treatment, and common side effects like bone marrow suppression, digestive issues, nausea and vomiting. It also covers strategies to manage side effects like growth factors and antiemetics.
This document provides a classification and overview of various anticancer drugs. It divides the drugs into categories such as alkylating agents, antimetabolites, plant alkaloids, antitumor antibiotics, hormonal drugs, and miscellaneous drugs. For each drug category and individual drugs, it describes the mechanism of action, common uses, side effects, and other relevant information. The document aims to comprehensively summarize the different types of chemotherapy agents used to treat cancer.
Chemotherapy uses cytotoxic drugs to destroy cancer cells throughout the body. It aims to do maximum damage to cancer cells while causing minimum damage to healthy tissue. Common goals of chemotherapy include cure, increased survival, palliation of symptoms, and adjuvant or neoadjuvant treatment. Several classes of chemotherapy drugs exist including alkylating agents, antimetabolites, mitotic inhibitors, antibiotics, and others. While chemotherapy can be effective, some tumors develop resistance over time requiring alternative treatment approaches.
Chemotherapy uses cytotoxic drugs to treat cancer by interfering with cancer cell replication and metabolism. There are several classes of chemotherapy drugs including alkylating agents, antimetabolites, antitumor antibiotics, mitotic inhibitors, hormones and antagonists, and miscellaneous agents. Chemotherapy can be used adjuvantly after surgery or neoadjuvantly before surgery or radiation to destroy micrometastases or reduce tumor size. Common side effects include nausea, vomiting, bone marrow depression, alopecia, and organ toxicity.
This document discusses cancer and chemotherapy. It provides an overview of cancer physiology, causes, stages of development and treatments. It describes different classes of chemotherapeutic agents including alkylating agents, antimetabolites, anthracyclines and bleomycin. For each drug class and individual drugs, it discusses mechanisms of action, clinical applications, pharmacokinetics, resistance mechanisms and common adverse effects.
Chemotherapy drugs are managed by the trained healthcare professional with many standard precautions. Most of the cancer patients must gone through the chemotherapy treatment
This document discusses chemotherapy for cancer treatment. It describes the main types of anticancer drugs as cytotoxic, targeted, and hormonal drugs. Cytotoxic drugs are further broken down into categories like alkylating agents, platinum coordination compounds, antimetabolites, and microtubule damaging agents. The document also covers general principles of chemotherapy like using combination therapy to achieve total tumour cell kill and targeting actively dividing cancer cells. Adverse effects of cytotoxic drugs are explained, like bone marrow depression and immunosuppression. The goal of cancer therapy is outlined as cure, prolonging remission, or palliation depending on the cancer type and stage.
The story of Dr. Ranjit Jagtap's daughters is more than a tale of inherited responsibility; it's a narrative of passion, innovation, and unwavering commitment to a cause greater than oneself. In Poulami and Aditi Jagtap, we see the beautiful continuum of a father's dream and the limitless potential of compassion-driven healthcare.
Test bank clinical nursing skills a concept based approach 4e pearson educati...rightmanforbloodline
Test bank clinical nursing skills a concept based approach 4e pearson education
Test bank clinical nursing skills a concept based approach 4e pearson education
Test bank clinical nursing skills a concept based approach 4e pearson education
Digital Health in India_Health Informatics Trained Manpower _DrDevTaneja_15.0...DrDevTaneja1
Digital India will need a big trained army of Health Informatics educated & trained manpower in India.
Presently, generalist IT manpower does most of the work in the healthcare industry in India. Academic Health Informatics education is not readily available at school & health university level or IT education institutions in India.
We look into the evolution of health informatics and its applications in the healthcare industry.
HIMMS TIGER resources are available to assist Health Informatics education.
Indian Health universities, IT Education institutions, and the healthcare industry must proactively collaborate to start health informatics courses on a big scale. An advocacy push from various stakeholders is also needed for this goal.
Health informatics has huge employment potential and provides a big business opportunity for the healthcare industry. A big pool of trained health informatics manpower can lead to product & service innovations on a global scale in India.
The facial nerve, also known as cranial nerve VII, is one of the 12 cranial nerves originating from the brain. It's a mixed nerve, meaning it contains both sensory and motor fibres, and it plays a crucial role in controlling various facial muscles, as well as conveying sensory information from the taste buds on the anterior two-thirds of the tongue.
nursing management of patient with Empyema pptblessyjannu21
prepared by Prof. BLESSY THOMAS, SPN
Empyema is a disease of respiratory system It is defines as the accumulation of thick, purulent fluid within the pleural space, often with fibrin development.
Empyema is also called pyothorax or purulent pleuritis.
It’s a condition in which pus gathers in the area between the lungs and the inner surface of the chest wall. This area is known as the pleural space.
Pus is a fluid that’s filled with immune cells, dead cells, and bacteria.
Pus in the pleural space can’t be coughed out. Instead, it needs to be drained by a needle or surgery.
Empyema usually develops after pneumonia, which is an infection of the lung tissue. it is mainly caused due in infectious micro-organisms. It can be treated with medications and other measures.
English Drug and Alcohol Commissioners June 2024.pptxMatSouthwell1
Presentation made by Mat Southwell to the Harm Reduction Working Group of the English Drug and Alcohol Commissioners. Discuss stimulants, OAMT, NSP coverage and community-led approach to DCRs. Focussing on active drug user perspectives and interests
VEDANTA AIR AMBULANCE SERVICES IN REWA AT A COST-EFFECTIVE PRICE.pdfVedanta A
Air Ambulance Services In Rewa works in close coordination with ground-based emergency services, including local Emergency Medical Services, fire departments, and law enforcement agencies.
More@: https://tinyurl.com/2shrryhx
More@: https://tinyurl.com/5n8h3wp8
2024 Media Preferences of Older Adults: Consumer Survey and Marketing Implica...Media Logic
When it comes to creating marketing strategies that target older adults, it is crucial to have insight into their media habits and preferences. Understanding how older adults consume and use media is key to creating acquisition and retention strategies. We recently conducted our seventh annual survey to gain insight into the media preferences of older adults in 2024. Here are the survey responses and marketing implications that stood out to us.
Hypertension and it's role of physiotherapy in it.Vishal kr Thakur
This particular slides consist of- what is hypertension,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is summary of hypertension -
Hypertension, also known as high blood pressure, is a serious medical condition that occurs when blood pressure in the body's arteries is consistently too high. Blood pressure is the force of blood pushing against the walls of blood vessels as the heart pumps it. Hypertension can increase the risk of heart disease, brain disease, kidney disease, and premature death.
Enhancing Hip and Knee Arthroplasty Precision with Preoperative CT and MRI Im...Pristyn Care Reviews
Precision becomes a byword, most especially in such procedures as hip and knee arthroplasty. The success of these surgeries is not just dependent on the skill and experience of the surgeons but is extremely dependent on preoperative planning. Recognizing this important need, Pristyn Care commits itself to the integration of advanced imaging technologies like CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) into the surgical planning process.
This particular slides consist of- what is Pneumothorax,what are it's causes and it's effect on body, risk factors, symptoms,complications, diagnosis and role of physiotherapy in it.
This slide is very helpful for physiotherapy students and also for other medical and healthcare students.
Here is a summary of Pneumothorax:
Pneumothorax, also known as a collapsed lung, is a condition that occurs when air leaks into the space between the lung and chest wall. This air buildup puts pressure on the lung, preventing it from expanding fully when you breathe. A pneumothorax can cause a complete or partial collapse of the lung.
Health Tech Market Intelligence Prelim Questions -Gokul Rangarajan
The Ultimate Guide to Setting up Market Research in Health Tech part -1
How to effectively start market research in the health tech industry by defining objectives, crafting problem statements, selecting methods, identifying data collection sources, and setting clear timelines. This guide covers all the preliminary steps needed to lay a strong foundation for your research.
This lays foundation of scoping research project what are the
Before embarking on a research project, especially one aimed at scoping and defining parameters like the one described for health tech IT, several crucial considerations should be addressed. Here’s a comprehensive guide covering key aspects to ensure a well-structured and successful research initiative:
1. Define Research Objectives and Scope
Clear Objectives: Define specific goals such as understanding market needs, identifying new opportunities, assessing risks, or refining pricing strategies.
Scope Definition: Clearly outline the boundaries of the research in terms of geographical focus, target demographics (e.g., age, socio-economic status), and industry sectors (e.g., healthcare IT).
3. Review Existing Literature and Resources
Literature Review: Conduct a thorough review of existing research, market reports, and relevant literature to build foundational knowledge.
Gap Analysis: Identify gaps in existing knowledge or areas where further exploration is needed.
4. Select Research Methodology and Tools
Methodological Approach: Choose appropriate research methods such as surveys, interviews, focus groups, or data analytics.
Tools and Resources: Select tools like Google Forms for surveys, analytics platforms (e.g., SimilarWeb, Statista), and expert consultations.
5. Ethical Considerations and Compliance
Ethical Approval: Ensure compliance with ethical guidelines for research involving human subjects.
Data Privacy: Implement measures to protect participant confidentiality and adhere to data protection regulations (e.g., GDPR, HIPAA).
6. Budget and Resource Allocation
Resource Planning: Allocate resources including time, budget, and personnel required for each phase of the research.
Contingency Planning: Anticipate and plan for unforeseen challenges or adjustments to the research plan.
7. Develop Research Instruments
Survey Design: Create well-structured surveys using tools like Google Forms to gather quantitative data.
Interview and Focus Group Guides: Prepare detailed scripts and discussion points for qualitative data collection.
8. Sampling Strategy
Sampling Design: Define the sampling frame, size, and method (e.g., random sampling, stratified sampling) to ensure representation of target demographics.
Participant Recruitment: Plan recruitment strategies to reach and engage the intended participant groups effectively.
9. Data Collection and Analysis Plan
Data Collection: Implement methods for data gathering, ensuring consistency and validity.
Analysis Techniques: Decide on analytical approaches (e.g., statistical
Sectional dentures for microstomia patients.pptxSatvikaPrasad
Microstomia, characterized by an abnormally small oral aperture, presents significant challenges in prosthodontic treatment, including limited access for examination, difficulties in impression making, and challenges with prosthesis insertion and removal. To manage these issues, customized impression techniques using sectional trays and elastomeric materials are employed. Prostheses may be designed in segments or with flexible materials to facilitate handling. Minimally invasive procedures and the use of digital technologies can enhance patient comfort. Education and training for patients on prosthesis care and maintenance are crucial for compliance. Regular follow-up and a multidisciplinary approach, involving collaboration with other specialists, ensure comprehensive care and improved quality of life for microstomia patients.
2. • Cancer
– Uncontrolled multiplication and spread within the
body of abnormal forms of body's own cells
• Neoplasm
– A mass of tissue formed as a result of
• Abnormal
• Excessive
• Uncoordinated
• Autonomous and
• purposeless
Proliferation of cells
3. Cancer chemotherapy not as successful as
antimicrobial chemotherapy
• Metabolism in parasite differs qualitatively
from host cells, while metabolism in cancer
cells differ only quantitatively from normal host
cells
– Hence target selectivity is more difficult in cancer
– cancer there is no substantial immune response
– Diagnostic complexity: delay in institution of
treatment
4. Modalities of treatment in cancer
• Surgery
• Radiotherapy
• Chemotherapy: 50 % of the patients can be
treated with chemotherapy contributing to
cure in 15 -20 % of patients
1/3 of patients can be cured, effective
when tumor has not metastasized
5. Cancer chemotherapy can be curative in
• Acute Leukemias
• Wilm’s Tumour
• Ewing’s Sarcoma
• Choriocarcinoma
• Hodgkin’s Disease
• Lymphosarcoma
• Burkitts lymphoma
• Testicular Teratomas
• Seminomas
In children
6. Chemotherapy can have only Palliative effect in
• Breast Cancer
• Ovarian Cancer
• Endometrial Cancer
• Prostatic Cancer
• Chronic Lymphatic Leukemia
• Chronic Myeloid Leukemia
• Head & Neck Cancer
• Lung (small cell) Cancer
7. Chemotherapy is less sensitive in
• Colorectal Cancer
• Carcinoma Stomach
• Carcinoma of esophagus
• Renal carcinoma
• Hepatoma
• Bronchogenic (non small cell) carcinoma
• Malignant Melanoma
• Sarcoma
8. Pathogenesis of cancer
Chemicals, viruses, irradiation, etc
Acquired Mutations
Protooncogenes oncogenes ↓ expression of tumor
supressor genes (P53, Rb etc)
Promoters,
co-carcinogen,
hormones
Uncontrolled cell
proliferation,
dedifferentiation
↓ apoptosis, alterations
in telomerase
Inherited Mutations
Development of primary tumor
9. Pathogenesis of cancer
Development of primary tumor
Production of metalloproteinases
Invasion of nearby tissue by tumor cells
Angiogenesis
Metastasis
Development of secondary tumors
10. Cancer cells differ from normal cells by
• Uncontrolled proliferation
• De-differentiation & loss of function
• Invasiveness
• Metastasis
11. Guiding principles in cancer
chemotherapy
• To achieve cure a TOTAL CELL KILL must be
tried
• Early diagnosis and early institution of
treatment
• Combination chemotherapy
• Intermittent regimens
• Adjuvant and neoadjuvant chemotherapy
occasionally
12. Total cell kill
• Aimed at destroying all the malignant cells,
leaving none
• This approach ensures
– Early recovery
– Prevents relapse
– Prolongs survival
• Pharmacological sancturies
14. • Survival time inversely related to initial
number of cells
• Aging cancer cells are less susceptible to
chemotherapy, because there is
– ↑ cell cycle (division) time
– ↓No of actively dividing cells with more resting
cells
– ↑ cell death within tumor
– Overcrowding of cells
15. Combination chemotherapy?
• Heterogenicity of cells remaining in different
phase of growth cycle , showing different level
of sensitivity
– Nature of drug (with different biochemical site of
action)
– Avoid emergence of drug resistance
• Monotherapy adequate in Burkitts lymphoma
& choriocarcinoma
16. Why intermittent regimen?
• Favours risk –benefit ratio
• Allows time for damaged normal host cells to
recover
• Pulse therapy
– Type of intermittent chemotherapeutic regime
employing highest tolerated dose within a short
administration period
– Based on principle of drug conc. (C) x duration of
exposure (T) = constant
17. Adjuvant & Neoadjuvant chemotherapy
• Adjuvant chemotherapy:
– Chemotherapy given after surgery or irradiation to
destroy micrometastasis & prevent development of
secondary neoplasm.
• Neo-adjuvant chemotherapy:
– Chemotherapy given before surgery or
radiotherapy in order to diminish the volume of
large primary neoplasm
18. • Nausea & Vomiting
• Bone marrow depression
• Alopecia
• Gonads: Oligospermia, impotence, ↓ ovulation
• Foetus: Abortion, foetal death, teratogenicity
• Carcinogenicity
• Hyperuricemia
• Immunosupression: Fludarabine
• Hazards to staff
General toxicity of cytotoxic drugs
27. MOA of some anticancer drugs
Purine & Pyrimidine synthesis
Ribonucleotides
Deoxy ribonucleotides
DNA
RNA
Proteins
Purine/
Pyrimidine
antagonists Methotrexate
Inhibition of
purine ring &
dTMP
biosynthesis
5 FU inhibits
dTMP synthesis
Dactinomycin ,
Intercalate with DNA
disrupt DNA function
Alkylating agents
Alter structure &
function of DNA
by cross linking
and/or
fragmenting DNA
Cytarabine inhibits
DNA chain elongation
29. Mechanism of action
Alkylating Agents
Form highly reactive carbonium ion
Transfer alkyl groups to nucleophilic sites on DNA bases
Results in
Cross linkage Abnormal base pairing DNA strand breakage
↓ cell proliferation
Alkylation also damages RNA
and proteins
30.
31. • Cytotoxic action
– Hemopoetic system highly susceptible
• Chlorambucil – more against lymphoid series
• Busulfan – more against myeloid series
– Epithelial tissues, hair follicles
– Spermatogenesis , fetopathic effect
• Immunosupressant action
• Miscellaneous
– Severe nausea & vomiting
• Known as radiomimetic drugs
Pharmacological actions
33. • Very irritant drug
• Dose = 0.4 mg/kg single or divided
• Uses
– Hematological cancers , lymphomas , solid tumors
• Adverse effects
– Anorexia, nausea, vomiting
– Bone marrow depression, aplasia
– Menstrual irregularities
• Estramustine
Mechlorethamine (Mustine)
34. Melphalan
• Very effective in MULTIPLE MYELOMA
• Less irritant locally , less alopecia
• Dose:
0.25 mg/kg daily for 4 days every 4-6 weeks
• Adverse Effects :
– Bone marrow Depression
– Infections , diarrhoea and pancreatitis
35. • Most commonly used alkylating agent a prodrug
Cyclophosphamide
37. Uses of cyclophosphamide
• Neoplastic conditions
– Hodgkins and non hodgkins lymphoma
– ALL (Acute Lymphoblastic leukemia), CLL (Chronic
Lymphocytic leukemia), Multiple myeloma
– Burkits lymphoma
– Neuroblastoma , retinoblastoma
– Adenocarcinoma of ovaries
• Non neoplastic conditions
– Control of graft versus host reaction
– Rheumatoid arthritis
– Nephrotic syndrome
38. • Adverse effects:
– Hemorrhagic cystitis,
– alopecia,
– nausea & vomiting,
– SIADH
– hepatic damage
• Dose: 2-3 mg/kg/day oral
10-15 mg/kg IV every 7-10 days
• It can be administered IV, IM, IP, intrapleurally,
Intraarterialy, directly into tumor
Cyclophosphamide
39. Ifosfamide
• Congener of cyclophosphamide
• Longer half life than cyclophosphamide
• Less alopecia and less emetogenic than
cyclophosphamide
• Can cause hemorrhagic cystitis and severe
neurological toxicity
• Used for germ cell testicular tumors and adult
sarcomas
40. Chlorambucil (Leukeran)
• Slowest acting and least toxic alkylating agent
• Main action on lymphoid series produces
marked lympholytic action
• Drug of choice 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
41. ThioTEPA
• Triethylene phosphoramide
• Does not require to form active intermediate
• Active intravesicular agent can also be used
topicaly in superficial bladder cancer
• Not well absorbed orally given IV
• High toxicity
42. Busulfan (Myleran)
• Depresses bone marrow with selective action
on myeloid series
• Primarily used in Chronic myelogenous
leukemia 2-6 mg/day
• Adverse effect:
– Interstitial pulmonary fibrosis
– Venoocclusive disease of liver
– Hyperuricaemia
– Sterility
44. Triazenes
• Dacarbazine
– Primary inhibitory action on RNA
& protein synthesis
– Used in malignant melanoma
• Temozolamide
– New alkylating agent
– Approved for malignant glioma
– Rapidly absorbed after oral
absorption & crosses BBB
45. Mechanisms of resistance of alkylating
agents
• ↓ Influx of drug
• ↑ Production of nucleophilic substances like
glutathione that compete with target DNA for
alkylation
• ↑ Activity of DNA repair enzymes
• ↑ metabolic inactivation of drugs
46. Cisplatin
• Non cell cycle specific
killing
• Administered IV
• Highly bound to plasma
proteins
• Gets conc in kidney,
intestine, testes
• Poorly penetrates BBB
• Slowly excreted in urine
Pt
NH3Cl
Cl NH3
Dose:
20 mg/m2 for 5 days a
week
75 – 100 mg/m2 once in
4 weeks to treat ovarian
cancer
47. Mechanism of action of cisplatin
Cisplatin enters cells
Forms highly reactive platinum complexes
DNA damage
Intra strand & interstrand cross links
Inhibits cell proliferation
48. Cisplatin uses and adverse effects
• Uses
– Testicular cancer (85% - 95 % curative )
– Ovarian cancer
– Other solid tumors: lung, esophagus, gastric
• Adverse effects
– Emesis
– Nephrotoxicity
– Peripheral neuropathy
– Ototoxicity
49. Carboplatin
• Better tolerated
• Nephrotoxicity , ototoxicity , neurotoxicity low
• Less emetogenic
• But thrombocytopenia and leukopenia may
occur
• Less plasma protein binding
• Use:
– primarily in ovarian cancer of epithelial origin
– Squamous cell carcinoma of head and neck
51. Methotrexate
Adenine, guanine,
thymidine ,
methionine, serine
Folic acid not
useful in toxicity
Folinic acid N5
formyl FH4 should be
given which is
converted to N5,N10-
Methylene –FH4 and
bypasses the
inhibited reductase
52. Pharmacological actions
• Cytotoxic actions
– Predominant on bone marrow
– Ulceration of intestinal mucosa
– Crosses placenta interferes with embroyogenesis
foetal malformations and death
• Immunosupressive action
– Prevents clonal expansion of B & T lymphocytes
• Anti-Inflammatory action
– Interferes with release of inflammatory cytokines
IL-2, IL-6,IL-8 & TNF- , ↓ Rheumatoid Factor
production
53. Pharmacokinetics
• Absorbed orally, 50 %
protein bound
• Disappears rapidly
from blood , remains
in tissue longer than
folate thus causes
prolonged inhibitory
effect
• C/I in renal
impairment
54. Adverse effects
• Megaloblastic anemia
• Thrombocytopenia, leukopenia, aplasia
• Oral, intestinal ulcer , diarrhoea
• Alopecia , liver damage, nephrpathy
Folinic acid (citrovorum factor, N5 Formyl THF)
IM/IV 8 to 24 hrs after initiation of methotrexate
120 mg in divided doses in first 24 hrs, then 25
mg oral/IM 6 hrly for next 48 hrs
Treatment of methotrexate toxicity
55. Uses of methotrexate
• Antineoplastic
– Choriocarcinoma and tropoblast tumor
15 -30 mg/day orally for 5 days
– Remission of ALL in children 2.5 to 15 mg/day
– Ca breast, head & neck, bladder, ovarian cancer
• Immuno-supressive agent
– Rheumatoid arthritis, resistant asthma
– Crohns disease, wegeners granulomatosis
– Prevention of graft versus host reaction
• Psoriasis
• Medical termination of pregnancy
59. • Phosphorylates intracellularly to form
triphosphate
• Inhibits DNA polymerase and gets incorporated
to form dysfunctional DNA
• Effective in slow growing tumors: (apoptosis)
• Use:
– CLL and non hodgkins recurring after treatment
• Adverse events:
– chills, fever, opportunistic infection,
myelosupression
Fludarabine
60. • Like fludarabine converted to triphosphate
• Incorporated into DNA
• Inhibits DNA polymerase and thus inhibits
DNA synthesis and repair
• Used in treatment of Hairy cell leukemia, CLL
and low grade lymphomas
Cladirabine
61. Pentostatin
Inhibits adenosine deaminase
Accumulation of adenosine & deoxyadenosine
Inhibits ribonucleotide reductase
Blocks DNA synthesis
S adenosyl homocysteine accumulation
Toxic to lymphocytes Used in
Hairy cell leukemia
63. 5 fluorouracil
5 FU FdUMP
dUMP
Thymidine
Monophosphate
Thymidilate
synthetase
DNA Synthesis
(Selective failure)
Uses : stomach , colon,
breast ovaries , liver, skin
cancers
FdUMP = fluorodeoxyuridine
monophosphate
64. • Pyrimidine analog considered drug of choice
in inducing remission in AML
• Phosphorylated in body to triphosphate
• Triphosphate of cytarabine inhibits DNA
polymerase &
• Thus inhibit DNA synthesis and repair
Cytosine arabinoside
Gemcitabine
• Drug of choice in adenocarcinoma of pancreas
70. • Paclitaxel
– Administered IV
– Use: advanced breast & ovarian cancer also lungs,
esophagus, prostrate cancer
– Adverse effects:
• Anaphylactoid reaction because of solvent cremaphor
• Myalgia, myelosupression, peripheral neuropathy
• Docetaxel
– Oral
– Used in refractory breast & ovarian cancer
– Major toxicity neutropenia may cause
aarrhythmias , hypotension
72. Etoposide
• Act in S & G2 phase
• Inhibit topoisomerase II which results in
breakage of DNA strands & cell death
• Uses:
– Testicular tumors , squamous cell cancer of lungs
73. • Derived from camptotheca accuminata
• Inhibit Topoisomerase I: No resealing of DNA
after strand has untwisted
• Topotecan:
– Used in metastatic ovarian cancer
– Major toxicity is bone marrow depression
• Irinotecan
– Used in metastatic cancer of colon/rectum
– Toxicity: diarrhoea, neutropenia, thrombocytopenia,
cholinergic side effects
Camptothecin analogs
74. • Cell cycle non specific drugs
• Derived from streptomyces species
• MOA:
– Intercalation in the DNA between adjoining
nucleotide pairs – blocks DNA & RNA synthesis
– Generation of oxygen radicals which mediate
single strand scission of DNA
– Action on Topoisomerase II
Anticancer antibiotics
75. • Uses:
– Wilms tumor,
– gestational choriocarcinoma
• Adverse effects
– bone marrow supression
– Irritant like meclorethamine
– sensitizes to radiation, and
inflammation at sites of prior
radiation therapy may occur
– Gastrointestinal adverse effects
Dactinomycin
77. • Doxorubicin:
– Used in acute leukemias, malignant lymphoma
and many solid tumors, direct instillation in
bladder cancer
• Daunorubicin:
– Use limited to ALL and granulocytic leukemias
• Toxicity:
– Both cause cardiotoxicity (cardiomyopathy)
– Marrow Depression, Alopecia
78. • Mitoxantrone
– Analog of doxorubicin
– Lower cardiotoxicity
– Uses: Acute leukemia, CML, Non hodgkins
• Mitomycin C
– Highly toxic used only in resistant cancers of
stomach, colon, rectum
– Transformed to form which acts like alkylating agent
• Mithramycin
– Reduces blood calcium levels by inhibiting
osteoclasts
– Used in T/t of hypercalcemia with bone metastasis
79. Bleomycin
Reacts with iron,
copper & O2 in
presence of CYP -450
reductase
Also can intercalate
between DNA strands
DNA – bleomycin – Fe2+
DNA – bleomycin – Fe3+
87. Glucocorticoids
• Marked lympholytic effect so used in acute
leukaemias & lymphomas,
• They also
– Have Anti-inflammatory effect
– Increase appetite, prevent anemia
– Produce sense of well being
– Increase body weight
– Supress hypersensitivity reaction
– Control hypercalcemia & bleeding
– Non specific antipyretic effect
– Increase antiemetic effect of ondansetron
88. Estrogens
• Physiological antagonists of androgens
• Thus used to antagonize the effects of
androgens in androgen dependent prostatic
cancer
• Fofesterol
– Prodrug , phosphate derivative of stilbesterol
– 600-1200mg IV initially later 120-240 mg orally
89. • Tamoxifen : Non steroidal antiestrogen
Selective Estrogen Receptor Modulators
(SERMs)
Agonistic:
Uterus,
bone, liver,
pitutary
Antagonistic:
Breast and
blood vessels
90. Tamoxifen
• DOSE:10-20mg bd
• Standard hormonal
treatment in breast cancer
• Adverse effects:
– Hot flushes , vomiting, vaginal
bleeding, menstrual
irregularities, venous
thromboembolism,
dermatitis, rarely endometrial
cancer
91. • Pure estrogen antagonist
• USES: Metastatic ER+ Breast Ca in
postmenopausal women
• MOA:
• Inhibits ER dimerization & prevents interaction of
ER with DNA
• ER is down regulated resulting in more complete
supression of ER responsive gene function
Selective Estrogen Receptor Down regulator
(fulvestrant)
92. • Letrozole
• Orally active non steroidal compound
• MOA : Inhibits aromatisation of testosterone &
androstenedione to form estrogen.
• Uses : Breast Ca- & adj. to mastectomy
• Dose :2.5mg bd orally
• Anastrozole : more potent
• 1mg OD in ER+ Breast Ca
• A/E : hot flushes
Aromatase Inhibitors
93. • FLUTAMIDE & BICALUTAMIDE :
• Androgen Receptor antagonists
• Dose : 250 mg tds, 50mg od resp.
• Palliative effect in metastatic Prostatic Ca
after orchidectomy
Anti androgens
94. 5- reductase inhibitors
Finasteride
• Orally active
• DHT levels ↓
• Benign prostatic
hyperplasia
Dose: 5mg/day
Prostate volume
Symptom score
Peak urine flow
rate
DHT level in
prostate
Side effects: Loss of libido & impotence in 5 % pts.
Also used for prevention of hair loss
95. • NAFERELIN : nasal spray / SC inj
• ↓FSH & LH release from pituitary- ↓ the
release of estrogen & testosterone
• USE : Breast Ca, Prostatic Ca
• PROGESTINS:
• Hydroxyprogesterone – used in metastatic
endometrial Ca.
• A/E: bleeding
GnRH agonists
96.
97.
98. Newer anticancer drugs
• Inhibitors of growth factors receptors
– Imatinib: CML (BCR-ABL gene)
– Gefitinib: Non small cell cancer of lungs (EGFR)
– Nilotinib : CML (Tyrosine kinase inhibitor)
– Dasatinib : CML (Tyrosine kinase inhibitor)
– Lapatinib : metastatic breast cancer (HER2/neu)
– Sunitinib : renal cell carcinoma (VEGF)
– Sorafinib : renal cell carcinoma (VEGF)
99. • Monoclonal antibodies
– Trastuzumab : breast cancer (HER2/neu)
– Bevacizumab: metastatic colon cancer (VEGF)
– Rituximab : non hodgkins lymphoma (CD-20)
– Panitumumab : metastatic colon cancer (EGFR)
– Alemtuzumab : CLL (CD 52 antigen)
– Iodine tositumonab : Non hodgkins (CD-20)
Newer anticancer drugs
100.
101. Important drug combinations
REGIMEN CANCER DRUGS
MOPP Hodgkins Mechlorethamine, oncovin,
prednisolone, procarbazine
ABVD Hodgkins Doxorubicin, bleomycin, vinblastine,
dacarbazine
CMF Breast Cyclophosphamide, methotrexate, 5-FU
CAF Breast Cyclophosphamide, doxorubicin, 5FU
ALL Vincristine, prednisolone, aspargine,
daunorubicin
AML Cytarabine, methotrexate
CML Hydroxyurea, interferon
Wilms Actinomycin, vincristine, doxorubicin
Cancer is a disease in which there is uncontrolled multiplication and spread within the body of abnormal forms of bodys own cells. It is one of the major causes of death in developed nations atleast 1 in 5 of the population of europe and north america can expect to die of cancer. Cancers are more common in aged people as life expectancy is increasing the incidence of cancers is also increasing, with the present methods of treatment one third of the patients are cured with local modalities of treatment (surgery or irradiation therapy) which are quite effective when the tumor has not metastatized. In metastasis systemic chemotherpy is required along with surgery or irradiation at present 50 % of the patients of cancer can be treated with chemotherapy contributing to cure in 10 -15% of the patients.
The terms cancer,malignant neoplasm and malignant tumor are synonymous
Hence target selectivity is more difficult in cancer*(exception in lymphoma , there is substantial selectivity)
Chemotherapy is essentially required with surgery or irradiation when metastasis has occurred
Shrinkage of tumor , alleviation of symptoms
Other factors – promoters cocarcinogen, hormones, -- likely hood of mutation
Aimed at destroying all the malignant cells, leaving none (lack of participation of host defence/immune response)order kinetics i.e given dose of a drug destroys constant fraction of cells. Term log kill is used to describe this phenomenon e.g leukemia diagnosis made when load of cells is >109 consequently if t/t leads leads to kill 99.99% of the cells then 0.001% i.e 104 cells remain this is equivalent to 5 log kill i.e 100000 fold. At this point patient appears asymptomatic i.e patient is in remission. For most bacterial infections a 5 log fold reduction in no of micro-organisms leads to cure . Since immune system can eradicate remaining bacterial cells. However cancer cells are not so easily destroyed
Pharmacological sancturies: leukemia or other tumor cells find sanctury in tissues like CNS in which some chemotherapeutic agents can not enter, because of its transport constraints so pt may require irradiation of cerebrospinal axis or intrathecal administration of drugs at that site
Cells of solid tumors can be considered as belonging to 3 compartments
Compartment A: Consists of dividing cells, possibly being continously in cell cycle
Compartment B: consists of resting cell in Go phase , the cells though not dividing are potentially able to do so
Compartment C: cells no longer able to divide but contribute to tumor volume
Essentially only cells in compartment A which may form as little as 5 % of some solid tumors are currently susceptible to main available cytotoxic drugs.
Log kill: destruction of cancer cells by chemotherapeutic agents follows first
Overcrowding of cells: poor blood supply and nutrition and defective access of drugs
Heterogenecity of cells –
Majority of cytotoxic drugs have more profound effects on rapidly multiplying cells
Sulfur mustard in 1917 was first used alkylating agent in WW-1, it was used as chemical warfare and caused severe skin vesication, vesication in mucous membrane , GI ulcerations and myelosupression. The pharmacological actions became evident only after world war 2.
All alkylating agents have alkyl groups and they can transfer this alkyl group to suitable receptor site. Alkylating agents in neutral or alkaline solution form highly reactive carbonium ion which is quaternary ammonium derivative(The carbon atom has only six electrons in its outer space so highly reactive). This carbonium ion is highly reactive and can react with groups like NH2, SH, OH or PO4 in physiologically important molecules in cell and render them unavailable for normal metabolic reactions. One more property of this carbonium ion is its nucleophilicity it can react with nucleic acid bases and inhibit DNA synthesis . The nitogen at guanine position 7 is especially more susceptible. So this results in
cross linking inhibits DNA replication .
Abnormal base pairing (alkylated guanine pairs with thymine instead of cytosine) results in production of defective protein
DNA strands breakage – decreased cell proliferation
Alkylation also damages RNA and proteins
Non cycle specific
Alkylation of guanine bases in DNA MOA OF MECHLORETHAMINE
Common to the alkylating agents
Cytotoxic action in general damage nuclei of growing multiplying cells, hemopoetic system highly susceptible to this action leads to anemia, thrombocytopenia, leukopenia and in toxic doses bonemarrow supression.,
Net result similar mode of action may differ chlorambucil more effective against lymphoid series and busulfan more effective against myeloid series.
These drugs also effect epithelial tissues like cornea, intestinal mucosa leading to desquamation and ulcers
Hair follicles- alopecia’sprematogenesis, foetopathy sand ammenorrhoea
Immunosupressant action : supress antibody production
Miscellaneous: nausea, vomiting
Radiomimetic drugs: actions resemble that of biological or ionizing radiations, all alkylating agents different radiomimetic action.
First nitrogen mustard to be used in cancer chemotherapy
Very irritant drug: vesicant for skin, eyes, resp tract , should be given only IV , Special care sloughing can occur with extravasation
Available as 10 mg HCL with 90 mg NACL should be reconstituted in 10 ml NS or distilled water and given immediately because it becomes active in few minutes
Hodkins stage III and stage IV as a part of MOPP mechlor, oncovin (Vincristine), procarbazine, prednisolone
Chronic myelogenous leukemia, chronic lymphoblastic leulemia
Because of serious toxicity use replaced by less toxic drugs carmustine
Estramustine: stable combination of estrogen & mustine designed to deliver mustine to estrogen receptor site of tumor like prostrate cancer
Advantage: both cytostatic and hormonal effect
Also used in advanced ovarian tumor, otherwise toxic effects and properties similar to mechlorethamine
Pharmacological actions similar to mechlorethamine
Prodrug converted in body to active
Hemorrhagic cystitis is specific toxicity of cyclophosphamide it is associated with dysuria, hematuria due to irritation of bladder mucosa by acrolein it is dose limiting toxicity.
Mesna is also excreted in urine where it binds to and inactivates acrolein
Should be given simultaneously and also 4-8 hrs after
Acetyl cysteine can also be given Adequate hydration
IV mesna (2 mercapto ethane sulfonate )
Wegeners granulomatosis
Less damaging to the platelets can also cause transverse ridging of nails, increased pigmentation
Leucocyte count serves as guide to dosage adjustment in prolonged therapy neutrophil count = 500 to 1000cells /mm3 desired target
1g vial+3 mesna ampoules 200mg for IV
Bronchogenic, Breast, Testicular, Bladder , Head & Neck Carcinomas, Osteogenic Sarcoma& some lymphomas
Also used in hodkins and other solid tumors
Unique in that in conventional doses of busulfan exert few pharmacological actions other than myelosupression
Other use- polycythemia vera
Pigmentation of skin
Streptozocin indicated for T/t of islet cell carcinoma of pancreas 500mg/m2 for 5 days or 1000 mg/m2 weekly
Acquired resistance to one alkylating agent often but not always imparts cross resistance to others
Guanine –o-alkyl transferase
Heavy metal complex has water soluble planar coordination complex containing central platinium atom surrounded by 2 cl and 2 nh3
Nephrotoxicity can be reduced by hydration of patients and diuresis by litres of normal saline and mannitol,
Hyperuricaemia can occur
Neuropathy : large sensory fibres – numbness, tinglingfollowed by loss of joint position and disabling sensory ataxia
Ototoxicity : tinnitus and hearing loss in high frequency range , more pronounce in children
Rarely shock mutagenic, teratogenic , carcinogenic adverse events reversible on stoppage
Excreted by kidneys t1/2 4to 6 hrs
Oxaliplatin : less myelosupression but more paresthesia
Chemical substance which takes part in cellular metabolic reactions is called metabolite
Antimetabolite is a chemical substance which by virtue of its close structural resemblence to metabolite blocks its action it can achieve this by 2 methods
By preventing the combination of metabolite with its specific enzyme
By itself combining with specific enzyme and getting converted to either metabolically inactive or harmful to cell ( lethal synthesis)
One of most commonly used anticancer agents
Cell cycle specific drug acts in S phase
Methotrexate has antineoplastic, immunosuoressant and anti-inflammatory action
It produced the first striking although temporary remission of leukemia and first cure for choriocarcinoma
Mechanism of action of methotrexate:
methotrexate structurally resembles folic acid , it competitively inhibits dihydrofolate reductase enzyme and blocks conversion of DHFA to THFA
THFA is an essential coenzyme required for one carbon transfer reactions in denovo purine synthesis and synthesis of thymidilate , amino acid conversions which are required for DNA SYNTHESIS it also inhibits RNA and protein synthesis. More toxic to rapidly dividing cells likw bone marrow
Calcium folinate or calcium levofolinate
Thymidine also counteracts methotrexate toxicity
Choriocarcinoma and tropoblast tumor in women xure
RHEUMATOID ARTHRITIS :5-7.5MG PER WEEK ORALLY FOR 8 WEEKS
PSORIASIS
2.5-5MG AT 12HRLY INTERVALS WEEKLY
Also used in mycosis fungoides , Some role in AML and non hodgkins lymphoma
MTP: 25 TO 50 MG ORAL THEN 3-7 DAYS LATER misoprostol 800 microgram vaginally in early part of forst trimester < 8 weeks of gestation
Well absorbed orally, metabolized rapidly by xanthine oxidase, use of xanthine oxidase inhibitor allopurinol decreases the inactivation of 6 MP, xanthine oxidase also required in uric acid synthesis, so allopurinol may be used in cancer chemotherapy to reduce dose of 6 MP and also decrease the hyperuricaemia
6 MP ALSO METABOLISED BY METHYLATION IN PRESENCE OF ENZYME THIOPURINE METHYL TRANSFERASE, GENTIC DEFICIENCY OF THIS ENZYME MAKES INDIVIDUAL MORE SUSCEPTIBLE TO 6 MP toxicity , while over expression is important method of resistance. Azathiprine is also substrate for xanthine oxidase but 6 thiguanine is not.
Hyperuricaemia occurs due to massive destruction of cells of lymphoid series , urine should be maintained alkaline and its volume adequate.
Other purine analogs like 6 thioguanine and azathiprine also posses cytotoxic actions how ever they do not have any advantage over 6 mercaptopurine as antileukemic agents
Mercaptopurine with azathiprine decrease the dose by ¼ to ½
Azathiprine: Imuran
Used as immunosupressive agent in organ transplantation and autoimmune conditons like hemolytic anemia, glomerulonephritis, and rhe umatoid arthritis
Promotes tumor apoptosis
Extremely effective in complete remission of hairy cell leukemia iv 4 g/m2 alternate week , sufficient hydration 500 ml to 1 l of dextrose in 0.45 % saline
5 fluoro uracil is converted in body to corresponding nucleotide fluorodeoxyuridine monophosphate, Fluorinated analog of pyrimidine acts by inhibiting thymidilate synthesis
Also gets incorporated into DNA in place of uracil
Uses: topically intreatment of premalignant keratosis
Even resting cells are more affected though rapidly multipling cells are more susceptible
Toxic to bone marrow , alimentary epitheliumand CNS
Administered by slow IV infusion to prevent first pass metabolism.
ESPECIALLY IN ADULTS Uses : AML, Hodgkins & Non hodgkins
Gemcitabine
Forms triphosphate that inhibits DNA synthesis
Blocks DNA strand elongation
Drug of choice in adenocarcinoma of pancreas
1000 mg/m2 over 30 min
VX and VBL are both cell-cycle specific and phase specific, because they block mitosis in metaphase (M phase). Their binding to the microtubular protein, tubulin, is GTP dependent and blocks the ability of tubulin to polymerize to form microtubules. Instead, paracrystalline aggregates consisting of tubulin dimers and the alkaloid drug are formed. The resulting dysfunctional spindle apparatus, frozen in metaphase, prevents chromosomal segregation and cell proliferation
Resistance: Resistant cells have been shown to have an enhanced efflux of VX, VBL, and VRB via P-glycoprotein in the cell membrane. Alterations in tubulin structure may also affect binding of the vinca alkaloids.
AFE: Unpredictable oral absorption, extensively conc in platelets, vinca alkaloids are not well absorbed by oral route
Highly irritant drugs so given continously by iv infusion, vinca alkaloids are conc and metabolized by CYP450 in liuver excreted in bile in liver dysfunction decrease the dose
Phenytoin, phenobarbitone, carbamezepine may induce the metabolism and griseofulvin inhibits metabolism
Vinorelbine: semisynthetic derivative for ca breast, testicular cancer, epithelial ovarian cancers.
Taxanes bind to beta tubulin subunits of microtubules at a site different from binding site of vinca alkaloids, colchicine, podophyllotoxin, unlike vinca alkaloids they promote polymerization of microtubules & inhibit depolymerization, leading to stabilization of polymerized microtubules and arrests cells in mitosis and eventually leads to activation of apoptosis
The stabilization of microtubules is damaging to cells because of disturbances in in the dynamics of various microtubule dependent structures that are required for functions like mitosis, maintainence of cellular morphology, locomotion and secretion.
Dexamethasone, h1 antagonists supress the reaction
Abraxane: Albumin bound form of paclitaxel no anaphylactoid reaction
Type I topoisomerase cuts one strand of a DNA double helix, relaxation occurs, and then the cut strand is reannealed.
Type II topoisomerase cuts both strands of one DNA double helix, passes another unbroken DNA helix through it, and then reanneals the cut strand.
Testicular tumors in combination with bleomycin or cisplatin
Tenoposide used in ALL
Topoisomerase I modulates supercoiling of DNA by complexing with it and nicking one of its strands
Intercalation in the DNA: The drugs insert nonspecifically between adjacent base pairs and bind to the sugar-phosphate backbone of DNA. This causes local uncoiling and, thus, blocks DNA and RNA synthesis. Intercalation can interfere with the topoisomerase II–catalyzed breakage/reunion reaction of supercoiled DNA strands, causing irreparable breaks.
Generation of oxygen radicals: Cytochrome P450 reductase (present in cell nuclear membranes) catalyzes reduction of the anthracyclines to semiquinone free radicals. These in turn reduce molecular O2, producing superoxide ions and hydrogen peroxide, which mediate single-strand scission of DNA (Figure 39.18). Tissues with ample superoxide dismutase or glutathione peroxidase activity are protected.10 Tumors and heart tissue are generally low in SOD. In addition, cardiac tissue lacks catalase and, thus, cannot effectively scavenge hydrogen peroxide. Lipid peroxidation therefore may explain the cardiotoxicity of anthracyclines.
Mechanism of action: The drug intercalates into the minor groove of the double helix between guanine-cytosine base pairs of DNA,8 forming a stable dactinomycin-DNA complex. The complex interferes primarily with DNA-dependent RNA polymerase, although at high doses, dactinomycin also hinders DNA synthesis. The drug also causes single-strand breaks, possibly due to action on topoisomerase II or by generation of free radicals.
Adverse effects: The major dose-limiting toxicity is bone marrow depression. The drug is immunosuppressive. Other adverse reactions include nausea, vomiting, diarrhea, stomatitis, and alopecia. Extravasation during injection produces serious problems. Dactinomycin sensitizes to radiation, and inflammation at sites of prior radiation therapy may occur.
Acute: ecg changes, arrhythmia, hypotension, delayed CCF
Tissues with ample superoxide dismutase or glutathione peroxidase activity are protected.10 Tumors and heart tissue are generally low in SOD. In addition, cardiac tissue lacks catalase and, thus, cannot effectively scavenge hydrogen peroxide. Lipid peroxidation therefore may explain the cardiotoxicity of anthracyclines.
Mixture of closely related glycopeptide antibiotics
CLINICAL RESPONSE TO L-ASPARGINASE IS DISAPPOINTING, THOUGH REMISSIONINDUCED IN ACUTE LEUKEMIA IS SHORT LASTING , IT IS NOW USED WHWN OTHER DRUGS HAVE FAILED , INEFFECTIVE IN SOLID TUMORS
Blocks enzyme Less GI toxicity
Methyl hydrazine derivative, inactive as such but undergoes metabolic activation to highly reactive alkylating species which cause methylation of DNA
Emit b and gamma radiations disrupt cellular metabolism and cause cellular destruction.
Prevent anemia: prevent acceletated erythrocytic destruction,
They effectively counter hemolytic and hemorrhagic complications accompanying chronic lymphocytic and malignant lymphomas,
Prednisolone is generally started in doses of 60 – 100 mg daily in divided doses and then depending on response reduced to maintenance dose of 20 -40 mg /day
The use of this compound in the treatment of lymphomas arose when it was observed that patients with Cushing's syndrome, which is associated with hypersecretion of cortisol, have lymphocytopenia and decreased lymphoid mass. [Note: At high doses, cortisol is also lymphocytolytic and leads to hyperuricemia due to the breakdown of lymphocytes.] Prednisone is primarily employed to induce remission in patients with acute lymphocytic leukemia and in the treatment of both Hodgkin's and non-Hodgkin's lymphomas.
Glucocorticoids have some secondary role in hormone responsive breast cancers, they are also valuable for treatment of complications like treatment of hypercalcemia, hemolytic anemias, thrombocytopenia, incresed intracranial tension, mediastinal edema occuring after radiotherapy, they afford symptomatic relief by mood elevating and antipyretic effects and also adjuvants of antiemetics.
Useful in treating cerebral edemas due to intracranial cerebral metastasis
Fosfesterol is activated to slibesterol in prostatic tissue and acheives high conc in prostatic tissue thus it is used in prostrate cancer
Adverse effects – impotence and gynaecomastia
SERMS are non steroidal synthetic agents whose agonist or antagonist action on estrogen receptors are tissue selective, produces beneficial estrogenic actions in some tissues (bone, brain, liver), and prevent certain deleterious effect in breast and endometrium by exhibiting antagonistic or no action on ER
Tamoxifen: Non steroidal antiestrogen related structuraly to slilbesterol, given orally it competes with the circulating estrogen for cytoplasmic estrogen receptor binding site, the metabolites of tamoxifen have much stronger affinity for receptors and are not easily displaced by circulating estradiol. At low concentration they have cytostatic effect on ER positive cells, higher conc cause cytotoxic effect .
Because of antagonistic action in breast DOC in treatment of ca breast in ER+ AS WELL as some ER- breast cancer also male breast
Well absorbed orally, biphasic half life 10 hrs and also 7 days, and long duration ofaction some metabolites of tamoxifen are more potent antiestrogens, the drug is excreted primarily in bile.
Other SERMS- raloxifene – no risk of endometrial carcinoma, used as first line drug in treatment of postmenopausal osteoporosis, toremifene – new congener of tamoxifen with similar actions uses and adverse effects
ORMELOXIFENE – dub, acts as antagonist in breast and uterus
USES: Metastatic ER+ Breast Ca in postmenopausal women which has stopped responding to tamoxifen
Higher affinity for ER probably accounts for efficacy in tamoxifen resistant cases
Aromatization of A ring of testesterone and androstenedione is final and key step in production of estrogens estradiol and estrone in body, in addition to circulating hormone the locally produced hormone may play an important role in breast cancer development, exemestane also aromatase inhibitor