Cancer is caused by genetic alterations that lead to uncontrolled cell growth. Anticancer therapies include chemotherapy, radiotherapy, immunotherapy, and surgery. Chemotherapies work by killing cancer cells or stopping their growth. Major classes of chemotherapies discussed were alkylating agents, antimetabolites, microtubule-targeting drugs, topoisomerase inhibitors, and antibiotics. Each class has specific mechanisms of action and side effects that were outlined. The presentation provided an overview of different anticancer drug classes and their mechanisms and uses for treating cancer.
Cisplatin is a chemotherapy drug used to treat several types of cancer. It works by binding to DNA in cancer cells, interfering with transcription and replication and killing the cells. Common side effects include nausea, low blood cell counts, kidney problems and hearing loss. It is administered intravenously and eliminated primarily through urine within days of administration, though tissue levels can remain elevated for months.
Capecitabine is an oral chemotherapy drug that is converted to 5-fluorouracil in the body. It is used to treat cancers like breast, colorectal, gastric and others. It works by inhibiting thymidylate synthase and blocking DNA synthesis in rapidly dividing cancer cells. Common side effects include nausea, vomiting, diarrhea and hand-foot syndrome. Carboplatin is another chemotherapy drug used to treat various cancers. As an alkylating agent, it works by cross-linking DNA and preventing cell division. Low blood cell counts are a common side effect.
This slide includes the basic physical, pharmacological, pharmacokinetics, warning, and side effects of the anticancer drug "Mitoxantrone Hydrochloride".
Alkylating agents are a class of chemotherapy drugs that work by alkylating DNA. Key points about alkylating agents from the document include:
1) Common alkylating agents discussed include cyclophosphamide, ifosfamide, melphalan, chlorambucil, thiotepa, busulfan, and nitrosoureas.
2) They work by adding alkyl groups to DNA, forming covalent bonds that lead to cross-linking of DNA strands and cell death.
3) Toxicities include myelosuppression, nausea/vomiting, alopecia, and secondary cancers, among others. Special precautions are often required due to toxicities.
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.
Mechanism of toxicity,signs and symptoms,diagnostic tests,antidote and its mode of action.safety profile for the antidote for Cisplatin,Doxorubicin,Tricyclic antidepressants
This document discusses opioid receptors and their effects when activated, including opening potassium channels, closing calcium channels, and reducing neurotransmitter release. It then describes various opioid analgesics that are μ receptor agonists like morphine, methadone, fentanyl, and heroin. The document also discusses the organ system effects of full opioid agonists such as analgesia, euphoria, sedation, respiratory depression, and others. Codeine and buprenorphine are also described.
Topoisomerases are enzymes that regulate DNA topology during replication and transcription by introducing temporary breaks in DNA strands. Topoisomerase inhibitors can be classified as topoisomerase I or II inhibitors. Camptothecins like irinotecan and topotecan are topoisomerase I inhibitors that stabilize the covalent complex between topoisomerase I and DNA, preventing rejoining of DNA strands. They are used to treat colorectal cancer and other cancers. Anthracyclines like doxorubicin are topoisomerase II inhibitors that stabilize cleavable complexes and cause DNA damage. They are commonly used to treat breast cancer, lymphomas, sarcomas and other cancers. Both classes
Cisplatin is a chemotherapy drug used to treat several types of cancer. It works by binding to DNA in cancer cells, interfering with transcription and replication and killing the cells. Common side effects include nausea, low blood cell counts, kidney problems and hearing loss. It is administered intravenously and eliminated primarily through urine within days of administration, though tissue levels can remain elevated for months.
Capecitabine is an oral chemotherapy drug that is converted to 5-fluorouracil in the body. It is used to treat cancers like breast, colorectal, gastric and others. It works by inhibiting thymidylate synthase and blocking DNA synthesis in rapidly dividing cancer cells. Common side effects include nausea, vomiting, diarrhea and hand-foot syndrome. Carboplatin is another chemotherapy drug used to treat various cancers. As an alkylating agent, it works by cross-linking DNA and preventing cell division. Low blood cell counts are a common side effect.
This slide includes the basic physical, pharmacological, pharmacokinetics, warning, and side effects of the anticancer drug "Mitoxantrone Hydrochloride".
Alkylating agents are a class of chemotherapy drugs that work by alkylating DNA. Key points about alkylating agents from the document include:
1) Common alkylating agents discussed include cyclophosphamide, ifosfamide, melphalan, chlorambucil, thiotepa, busulfan, and nitrosoureas.
2) They work by adding alkyl groups to DNA, forming covalent bonds that lead to cross-linking of DNA strands and cell death.
3) Toxicities include myelosuppression, nausea/vomiting, alopecia, and secondary cancers, among others. Special precautions are often required due to toxicities.
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.
Mechanism of toxicity,signs and symptoms,diagnostic tests,antidote and its mode of action.safety profile for the antidote for Cisplatin,Doxorubicin,Tricyclic antidepressants
This document discusses opioid receptors and their effects when activated, including opening potassium channels, closing calcium channels, and reducing neurotransmitter release. It then describes various opioid analgesics that are μ receptor agonists like morphine, methadone, fentanyl, and heroin. The document also discusses the organ system effects of full opioid agonists such as analgesia, euphoria, sedation, respiratory depression, and others. Codeine and buprenorphine are also described.
Topoisomerases are enzymes that regulate DNA topology during replication and transcription by introducing temporary breaks in DNA strands. Topoisomerase inhibitors can be classified as topoisomerase I or II inhibitors. Camptothecins like irinotecan and topotecan are topoisomerase I inhibitors that stabilize the covalent complex between topoisomerase I and DNA, preventing rejoining of DNA strands. They are used to treat colorectal cancer and other cancers. Anthracyclines like doxorubicin are topoisomerase II inhibitors that stabilize cleavable complexes and cause DNA damage. They are commonly used to treat breast cancer, lymphomas, sarcomas and other cancers. Both classes
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.
Recent advances in cancer treatment include new drug carrier systems and nanotechnology to more precisely target cancer cells. New drug carrier systems such as polymer drug conjugates, cyclodextrins, and self-emulsifying drug delivery formulations aim to enhance drug delivery to tumors while avoiding healthy tissues to reduce side effects. Nanotechnology uses carbon nanotubes and nanoparticles to transport drugs across biological barriers and directly into cancer cells. Additionally, newer cancer vaccines using antigens, dendritic cells, and DNA aim to stimulate the immune system to recognize and destroy cancerous cells.
This document summarizes several alkylating agents used in chemotherapy. Alkylating agents work by alkylating DNA and RNA, which can cause DNA breaks or abnormal sequences and damage cells' ability to replicate. Common side effects include myelosuppression, nausea/vomiting, and alopecia. Specific agents discussed include cyclophosphamide, ifosfamide, melphalan, busulfan, carmustine, lomustine, procarbazine, dacarbazine, streptozocin, bendamustine, altretamine, and chlorambucil. Each has unique indications and toxicity profiles involving bone marrow suppression, gastrointestinal upset, organ toxicity, secondary cancers, and more.
Cisplatin and its platinum analogs are important chemotherapy drugs. The document discusses the properties and mechanisms of several platinum analogs including carboplatin, oxaliplatin, and lobaplatin. It describes how their chemical structures differ from cisplatin in ways that impact properties like stability, reactivity, mechanisms of DNA damage, and toxicity profiles. The document also summarizes key mechanisms of resistance to platinum drugs, like reduced accumulation, inactivation by thiols, increased DNA repair, and enhanced damage tolerance.
This document discusses antineoplastic agents, which are used to treat cancer. It begins by explaining how normal cell growth becomes dysregulated, leading to neoplasms or tumors. Tumors can be benign or malignant. The goals of cancer treatment are curative, palliative, or adjuvant therapy. The main treatment modalities are surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy, and biological therapy. The document then focuses on the mechanisms and classes of chemotherapeutic agents, including alkylating agents, antimetabolites, antibiotics, alkaloids, hormones, and other drugs. It provides details on specific examples like cyclophosphamide, methotrexate, and 6-mercaptopurine.
Anti-VEGF drugs and HDAC inhibitors are used in cancer treatment. Anti-VEGF drugs inhibit VEGF signaling by blocking the VEGF ligand or receptor and include monoclonal antibodies like bevacizumab and small molecule inhibitors like sunitinib. They are used to treat cancers like colorectal, lung, and kidney cancer. HDAC inhibitors increase histone acetylation, activate tumor suppressor genes, and induce cell cycle arrest. Panobinostat, romidepsin, and vorinostat are examples used for blood cancers and lymphomas. Both classes of drugs can cause side effects like hypertension, bleeding, and fatigue.
1) Recent advances in cancer chemotherapy include the development of newer alkylating agents, platinum compounds, antimetabolites, mitotic spindle inhibitors, and topoisomerase inhibitors with improved efficacy and reduced toxicity profiles.
2) Many newer agents aim to overcome resistance to existing drugs by bypassing drug efflux pumps or having activity in cisplatin/taxane resistant settings.
3) Several new drugs have received FDA approval in the last decade for cancers like breast cancer, lung cancer, and leukemia, offering additional treatment options.
This document discusses the use of enzymes in therapy. It provides examples of enzymes that are used to treat various disorders, such as DNase 1 to treat cystic fibrosis by reducing mucus viscosity, lipase to treat Gaucher's disease by breaking down lipid accumulations, and streptokinase to treat heart attacks by breaking down blood clots. The document also discusses the criteria for enzymes used in therapy, such as having low Km and high Vmax, and being purified and specific. Enzyme replacement therapy is described as a treatment for lysosomal storage diseases where the deficient enzyme is replaced.
The document discusses several inborn errors of amino acid metabolism, including phenylketonuria (PKU), maple syrup urine disease, tyrosinaemia type 1, homocystinuria, defects in dibasic amino acid transport, and nonketotic hyperglycinaemia. It describes the genetic defects involved, characteristic clinical features and biochemical abnormalities, methods of diagnosis, and approaches to treatment for each condition.
This document discusses platinum-containing anticancer compounds, focusing on cisplatin. It provides an overview of cancer and mechanisms of action of platinum compounds, which involve forming DNA adducts to disrupt DNA function. Cisplatin pharmacokinetics, uses for various cancer types, dosing guidelines, adverse effects and interactions are summarized. The document is a report on platinum compounds submitted to a pharmacy professor and faculty.
This document contains questions and answers about various chemotherapeutic agents. It discusses drugs used to treat different types of cancers like breast cancer, leukemia, lung cancer and their mechanisms of action, side effects, and conditions of use. For example, it mentions that imatinib is used to treat gastrointestinal stromal tumors by inhibiting tyrosine kinase, and that bleomycin toxicity affects type II pneumocytes in the lungs. The document quizzes on properties of many chemotherapy drugs.
This document discusses mood disorders like mania, depression and bipolar disorder. It provides details about lithium carbonate, which is a primary drug used to treat mania and bipolar disorder but has a low therapeutic index. The document summarizes lithium's mechanism of action, efficacy, adverse effects, drug interactions and monitoring considerations. It also mentions alternatives to lithium like various anti-convulsants and atypical antipsychotics that are now commonly used to control mania.
Unit 2: Proteins, abnormalities and methods of proteins investigation DrElhamSharif
This document outlines the objectives and content of a lecture series on proteins, abnormalities, and methods of protein investigation. The objectives include identifying various proteins, distinguishing acute phase reactants, identifying causes of abnormal protein levels, and differentiating types of proteinuria. The document then covers topics such as protein structure and function, classification of proteins, plasma proteins including albumin and globulins, medical relevance of amino acids and total protein, and details on specific proteins like prealbumin and albumin. Laboratory methods for analyzing proteins are also discussed.
This document discusses various aspects of anticancer drugs and chemotherapy, including:
1. Types of chemotherapy drugs like alkylating agents, antimetabolites, antibiotics, and their mechanisms of action and cell cycle effects.
2. Goals and principles of cancer therapy like cure, remission, combination chemotherapy, and developing resistance.
3. Toxicities of chemotherapy drugs and methods to counter them, like growth factors and protective agents.
4. Targeted therapies like monoclonal antibodies and tyrosine kinase inhibitors used to treat specific cancers.
Alkylating agents and antimetabolites are two classes of chemotherapy drugs. Alkylating agents work by binding to DNA and RNA, causing crosslinking or breaks that prevent replication. The main types are nitrogen mustards, alkyl sulphonates, nitrosoureas, and thiazines. Antimetabolites mimic normal metabolites and inhibit DNA or RNA synthesis by becoming incorporated. Major types are folate antagonists like methotrexate, pyrimidine analogs like 5-fluorouracil, and purine analogs like mercaptopurine. Both classes cause bone marrow suppression and gastrointestinal toxicity, and resistance can develop through drug inactivation or changes to drug targets.
- Omega-3 fatty acids exert various beneficial cardiometabolic effects through diverse mechanisms of action. They can reduce inflammation, lower triglycerides, inhibit platelet aggregation, improve endothelial function, stabilize plaques, and reduce arrhythmias.
- Supplementation of up to 1 gram per day of omega-3 fatty acids from fish oil is generally well tolerated, except for occasional dysgeusia. It does not increase the risk of bleeding.
- While some recent large trials did not show effects of omega-3 fatty acids on cardiovascular outcomes, current guidelines still encourage omega-3 fatty acid supplementation for risk reduction in conditions like coronary artery disease and heart failure.
Evaluation of Hepatoprotective and Antioxidant activity of Euphorbia cyanthop...pharmaindexing
This document describes a study that evaluated the hepatoprotective and antioxidant effects of the methanolic extract of Euphorbia cyathophora (MEEC) in rats. Rats were induced with hepatotoxicity using acetaminophen. MEEC at 400 mg/kg was found to decrease elevated liver enzyme levels, restore antioxidant levels in the liver tissue, and reduce lipid peroxidation caused by acetaminophen toxicity. Histopathological analysis also supported the hepatoprotective effects of MEEC. The study demonstrates the significant hepatoprotective and antioxidant properties of MEEC.
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.
Alkylating agents are a class of cytotoxic chemotherapy drugs that work by adding alkyl groups to electron-rich nucleophilic atoms in DNA, RNA, and proteins, forming covalent bonds. This disrupts the DNA structure and prevents cell division. The two main types are monofunctional agents that bind one DNA strand, and bifunctional agents that form cross-links between both strands. Common alkylating agents include nitrogen mustards, nitrosoureas, alkyl sulfonates, and aziridines. They are used to treat many cancers but can cause toxic effects like myelosuppression, cystitis, and secondary cancers due to their DNA damaging properties. Resistance mechanisms include increased glutathione and DNA repair pathways
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 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.
Recent advances in cancer treatment include new drug carrier systems and nanotechnology to more precisely target cancer cells. New drug carrier systems such as polymer drug conjugates, cyclodextrins, and self-emulsifying drug delivery formulations aim to enhance drug delivery to tumors while avoiding healthy tissues to reduce side effects. Nanotechnology uses carbon nanotubes and nanoparticles to transport drugs across biological barriers and directly into cancer cells. Additionally, newer cancer vaccines using antigens, dendritic cells, and DNA aim to stimulate the immune system to recognize and destroy cancerous cells.
This document summarizes several alkylating agents used in chemotherapy. Alkylating agents work by alkylating DNA and RNA, which can cause DNA breaks or abnormal sequences and damage cells' ability to replicate. Common side effects include myelosuppression, nausea/vomiting, and alopecia. Specific agents discussed include cyclophosphamide, ifosfamide, melphalan, busulfan, carmustine, lomustine, procarbazine, dacarbazine, streptozocin, bendamustine, altretamine, and chlorambucil. Each has unique indications and toxicity profiles involving bone marrow suppression, gastrointestinal upset, organ toxicity, secondary cancers, and more.
Cisplatin and its platinum analogs are important chemotherapy drugs. The document discusses the properties and mechanisms of several platinum analogs including carboplatin, oxaliplatin, and lobaplatin. It describes how their chemical structures differ from cisplatin in ways that impact properties like stability, reactivity, mechanisms of DNA damage, and toxicity profiles. The document also summarizes key mechanisms of resistance to platinum drugs, like reduced accumulation, inactivation by thiols, increased DNA repair, and enhanced damage tolerance.
This document discusses antineoplastic agents, which are used to treat cancer. It begins by explaining how normal cell growth becomes dysregulated, leading to neoplasms or tumors. Tumors can be benign or malignant. The goals of cancer treatment are curative, palliative, or adjuvant therapy. The main treatment modalities are surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy, and biological therapy. The document then focuses on the mechanisms and classes of chemotherapeutic agents, including alkylating agents, antimetabolites, antibiotics, alkaloids, hormones, and other drugs. It provides details on specific examples like cyclophosphamide, methotrexate, and 6-mercaptopurine.
Anti-VEGF drugs and HDAC inhibitors are used in cancer treatment. Anti-VEGF drugs inhibit VEGF signaling by blocking the VEGF ligand or receptor and include monoclonal antibodies like bevacizumab and small molecule inhibitors like sunitinib. They are used to treat cancers like colorectal, lung, and kidney cancer. HDAC inhibitors increase histone acetylation, activate tumor suppressor genes, and induce cell cycle arrest. Panobinostat, romidepsin, and vorinostat are examples used for blood cancers and lymphomas. Both classes of drugs can cause side effects like hypertension, bleeding, and fatigue.
1) Recent advances in cancer chemotherapy include the development of newer alkylating agents, platinum compounds, antimetabolites, mitotic spindle inhibitors, and topoisomerase inhibitors with improved efficacy and reduced toxicity profiles.
2) Many newer agents aim to overcome resistance to existing drugs by bypassing drug efflux pumps or having activity in cisplatin/taxane resistant settings.
3) Several new drugs have received FDA approval in the last decade for cancers like breast cancer, lung cancer, and leukemia, offering additional treatment options.
This document discusses the use of enzymes in therapy. It provides examples of enzymes that are used to treat various disorders, such as DNase 1 to treat cystic fibrosis by reducing mucus viscosity, lipase to treat Gaucher's disease by breaking down lipid accumulations, and streptokinase to treat heart attacks by breaking down blood clots. The document also discusses the criteria for enzymes used in therapy, such as having low Km and high Vmax, and being purified and specific. Enzyme replacement therapy is described as a treatment for lysosomal storage diseases where the deficient enzyme is replaced.
The document discusses several inborn errors of amino acid metabolism, including phenylketonuria (PKU), maple syrup urine disease, tyrosinaemia type 1, homocystinuria, defects in dibasic amino acid transport, and nonketotic hyperglycinaemia. It describes the genetic defects involved, characteristic clinical features and biochemical abnormalities, methods of diagnosis, and approaches to treatment for each condition.
This document discusses platinum-containing anticancer compounds, focusing on cisplatin. It provides an overview of cancer and mechanisms of action of platinum compounds, which involve forming DNA adducts to disrupt DNA function. Cisplatin pharmacokinetics, uses for various cancer types, dosing guidelines, adverse effects and interactions are summarized. The document is a report on platinum compounds submitted to a pharmacy professor and faculty.
This document contains questions and answers about various chemotherapeutic agents. It discusses drugs used to treat different types of cancers like breast cancer, leukemia, lung cancer and their mechanisms of action, side effects, and conditions of use. For example, it mentions that imatinib is used to treat gastrointestinal stromal tumors by inhibiting tyrosine kinase, and that bleomycin toxicity affects type II pneumocytes in the lungs. The document quizzes on properties of many chemotherapy drugs.
This document discusses mood disorders like mania, depression and bipolar disorder. It provides details about lithium carbonate, which is a primary drug used to treat mania and bipolar disorder but has a low therapeutic index. The document summarizes lithium's mechanism of action, efficacy, adverse effects, drug interactions and monitoring considerations. It also mentions alternatives to lithium like various anti-convulsants and atypical antipsychotics that are now commonly used to control mania.
Unit 2: Proteins, abnormalities and methods of proteins investigation DrElhamSharif
This document outlines the objectives and content of a lecture series on proteins, abnormalities, and methods of protein investigation. The objectives include identifying various proteins, distinguishing acute phase reactants, identifying causes of abnormal protein levels, and differentiating types of proteinuria. The document then covers topics such as protein structure and function, classification of proteins, plasma proteins including albumin and globulins, medical relevance of amino acids and total protein, and details on specific proteins like prealbumin and albumin. Laboratory methods for analyzing proteins are also discussed.
This document discusses various aspects of anticancer drugs and chemotherapy, including:
1. Types of chemotherapy drugs like alkylating agents, antimetabolites, antibiotics, and their mechanisms of action and cell cycle effects.
2. Goals and principles of cancer therapy like cure, remission, combination chemotherapy, and developing resistance.
3. Toxicities of chemotherapy drugs and methods to counter them, like growth factors and protective agents.
4. Targeted therapies like monoclonal antibodies and tyrosine kinase inhibitors used to treat specific cancers.
Alkylating agents and antimetabolites are two classes of chemotherapy drugs. Alkylating agents work by binding to DNA and RNA, causing crosslinking or breaks that prevent replication. The main types are nitrogen mustards, alkyl sulphonates, nitrosoureas, and thiazines. Antimetabolites mimic normal metabolites and inhibit DNA or RNA synthesis by becoming incorporated. Major types are folate antagonists like methotrexate, pyrimidine analogs like 5-fluorouracil, and purine analogs like mercaptopurine. Both classes cause bone marrow suppression and gastrointestinal toxicity, and resistance can develop through drug inactivation or changes to drug targets.
- Omega-3 fatty acids exert various beneficial cardiometabolic effects through diverse mechanisms of action. They can reduce inflammation, lower triglycerides, inhibit platelet aggregation, improve endothelial function, stabilize plaques, and reduce arrhythmias.
- Supplementation of up to 1 gram per day of omega-3 fatty acids from fish oil is generally well tolerated, except for occasional dysgeusia. It does not increase the risk of bleeding.
- While some recent large trials did not show effects of omega-3 fatty acids on cardiovascular outcomes, current guidelines still encourage omega-3 fatty acid supplementation for risk reduction in conditions like coronary artery disease and heart failure.
Evaluation of Hepatoprotective and Antioxidant activity of Euphorbia cyanthop...pharmaindexing
This document describes a study that evaluated the hepatoprotective and antioxidant effects of the methanolic extract of Euphorbia cyathophora (MEEC) in rats. Rats were induced with hepatotoxicity using acetaminophen. MEEC at 400 mg/kg was found to decrease elevated liver enzyme levels, restore antioxidant levels in the liver tissue, and reduce lipid peroxidation caused by acetaminophen toxicity. Histopathological analysis also supported the hepatoprotective effects of MEEC. The study demonstrates the significant hepatoprotective and antioxidant properties of MEEC.
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.
Alkylating agents are a class of cytotoxic chemotherapy drugs that work by adding alkyl groups to electron-rich nucleophilic atoms in DNA, RNA, and proteins, forming covalent bonds. This disrupts the DNA structure and prevents cell division. The two main types are monofunctional agents that bind one DNA strand, and bifunctional agents that form cross-links between both strands. Common alkylating agents include nitrogen mustards, nitrosoureas, alkyl sulfonates, and aziridines. They are used to treat many cancers but can cause toxic effects like myelosuppression, cystitis, and secondary cancers due to their DNA damaging properties. Resistance mechanisms include increased glutathione and DNA repair pathways
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 caused by uncontrolled cell growth and can spread through the body. Risk factors include tobacco, sunlight, viruses, and family history. Diagnosis involves biopsy and imaging tests while treatment aims to cure, palliate, or induce remission through surgery, radiation, chemotherapy, and targeted therapy. Chemotherapy drugs work by various mechanisms including alkylating DNA, blocking DNA synthesis, and affecting microtubule function. Major classes include alkylating agents, antimetabolites, antitumor antibiotics, plant alkaloids, and miscellaneous cytotoxic drugs. Combination regimens and consideration of each drug's cell cycle specificity can improve outcomes.
This document discusses several antineoplastic agents - carmustine, aminopretin, and 6-mercaptopurine. It describes their general modes of action as alkylating agents or antimetabolites that inhibit DNA synthesis and replication, preventing cell division. Specific details are provided about each drug's chemical structure, methods of synthesis, mechanisms of inhibiting DNA and RNA production, and approved medical uses for treating various cancers.
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.
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.
Capecitabine and 5-fluorouracil are oral and intravenous chemotherapy drugs, respectively, that are converted in the body to fluorouracil, which inhibits thymidylate synthase and blocks DNA synthesis in cancer cells. Carboplatin is a platinum-based chemotherapy drug used to treat several types of cancer by forming crosslinks in DNA to prevent cell division. The document discusses the mechanisms, uses, and side effects of these chemotherapy drugs for treating cancer.
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.
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.
Chemotherapy is the main treatment for disseminated cancers. It involves using multiple drugs in cycles to target rapidly dividing cancer cells. Common drugs include alkylating agents, antimetabolites, microtubule inhibitors, and monoclonal antibodies. Combination chemotherapy aims to maximize responses while avoiding overlapping toxicities. Doses are based on body surface area and adjusted for individual factors. Treatment intervals allow time for normal tissues to recover between cycles. Toxicities include myelosuppression, nausea/vomiting, and alopecia. Response is evaluated based on tumor shrinkage or progression.
This document summarizes recent advances in cancer treatment. It discusses newer drugs that have been developed within several classes of chemotherapy drugs, including alkylating agents, platinum compounds, antimetabolites, mitotic spindle inhibitors, and topoisomerase inhibitors. For each class, currently used drugs and their mechanisms of action and side effects are described. Newer drugs within each class are then outlined, noting their improved properties such as lesser toxicity, oral availability, or ability to overcome resistance to existing drugs. The document provides details on several dozen newer chemotherapy drugs in development or recently approved for cancers.
This document discusses anti-cancer drugs and their mechanisms and uses for treating cancer. It begins by defining cancer and describing how it spreads. It then discusses the various classes of anti-cancer drugs, including alkylating agents, platinum complexes, antimetabolites, microtubule damaging agents, antibiotics, and other miscellaneous cytotoxic drugs. For each class or drug, it summarizes the mechanism of action, common uses for treating different cancer types, and common toxicities. The goal of anti-cancer drugs is to either kill cancer cells or modify their growth, though selectivity is limited and they are highly toxic medications.
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.
Cancer cells have altered metabolism compared to normal cells. They rely more on glycolysis even in the presence of oxygen (Warburg effect). This produces less ATP but helps cancer cells proliferate rapidly. Glutamine can also be used as an energy source. Targeting cancer cell metabolism through drugs like dichloroacetate is a potential treatment strategy. Cancers are heterogeneous so their metabolic profiles vary between cancer types and individual cells.
Chemotherapy drugs are managed by the trained healthcare professional with many standard precautions. Most of the cancer patients must gone through the chemotherapy treatment
Transcription and Translation Inhibitors in Cancer Treatment
Cancer arises from abnormalities in cell growth control mechanisms. Several drug targets aim to inhibit uncontrolled cell proliferation by targeting transcription and translation processes. RNA polymerase inhibitors like CX-5461 target RNA polymerase I to induce nucleolar stress and cell cycle arrest. CDK inhibitors including palbociclib, ribociclib, and abemaciclib target cyclin-dependent kinases to prevent cell cycle progression. Mutations in the RAS pathway activate oncogenes, and inhibitors like sotorasib and adagrasib target the KRAS G12C mutation. The mTOR pathway integrates signals from growth factors and nutrients to regulate cell growth, and
Overview and classification of chemotherapeutic agents and theorySaurabh Gupta
This document provides an overview of chemotherapy. It discusses key figures in the development of chemotherapy like Paul Ehrlich and Sidney Farber. It describes different classes of chemotherapeutic agents including alkylating agents, antimetabolites, antitubulins, topoisomerase inhibitors, antibiotics, and their mechanisms and uses for treating various cancers. Side effects of different drug classes are also outlined.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kol...rightmanforbloodline
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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Histololgy of Female Reproductive System.pptxAyeshaZaid1
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2. • Cancer is a disease in which normal cells are
transformed into neoplastic cells through
alteration of their genetic material,leading to
expression of oncogenes, inhibition of tumor
suppressor genes, and uncontrolled growth.
• Oncogenes typically encode growth factors,
many of which are kinases that activate
cellular regulatory proteins that promote cell
division.
• For example, the cyclins are proteins that
activate cyclindependent
4/12/2019 2kmch college of pharmacy
3. • 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 cells4/12/2019 3kmch college of pharmacy
4. • The anticancer drug either kill cancer cells or
modify their growth.
• Cancer treatment:
Chemotherapy
Radiotherapy
Immunotherapy
surgery
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11. DNA alkylating drugs
• These compounds produce highly reactive
carbonium ion intermediates which transfer
alkyl groups to cellular macromolecules by
forming covalent bonds.
• Alkylating agents have cytotoxic and
radiomimetic (like ionizing radiation) actions
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12. Mechanism
Alkaylating agents produces reactive carbonium ion
Transfer the alkyl group to N7 guanine of DNA
Alkylation results in cross linking/abnormal base
pairing/ scission of DNA strand
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13. ADR
• Bone marrow toxicity
Suppersion of cellular and humoral immunity
Myelosuppression
• Lukemogenesis
• Female and male reproductive toxicity
• Alpoceia
• Nausea and vomitting 30-60 min after
administration of mechlorethamine,
cyclophosphamide, or carmustine.
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14. Cyclophosphamide
• Cyclophosphamide is a prodrug that must be
converted to active metabolites by hepatic
mixed-function oxidase (cytochrome P450)
enzymes.
• The active alkylating metabolite of
cyclophosphamide is thought to be
phosphoramide mustard.
• Cyclophosphamide is partly converted to acrolein,
which is probably responsible for hemorrhagic
cystitis,an adverse effect that sometimes occurs
with use of drugs.
4/12/2019 14kmch college of pharmacy
16. Pharmacological actions
• 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
4/12/2019 16kmch college of pharmacy
17. Platinum coordination complexes
• It is a platinum coordination complex that is
hydrolysed intracellularly to produce a highly
reactive moiety which causes cross linking of
DNA.
• The favoured site is N7 of guanine residue.
• It can also react with –SH groups in proteins
and has radiomimetic property.
• Cisplatin is very effective in metastatic
testicular and ovarian carcinoma.
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18. Cisplatin enters cells
Forms highly reactive platinum complexes
Intra strand & interstrand cross link
DNA damage
Inhibits cell proliferation
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19. ADR
• Emesis
• Nephrotoxicity
(The use of mannitol and sodium thiosulfate will decrease
the severity of nephrotoxicity, an adverse effect
associated with loss of potassium and magnesium,
reducedglomerular filtration, and renal failure.)
• Peripheral neuropathy
• Ototoxicity (Tinnitus, deafness, neuropathy
• and hyperuricaemia are other problems)
• thrombocytopenia
• Leukopenia
• mild myelosuppression
4/12/2019 19kmch college of pharmacy
20. Indications
• It is given intravenously as a first-line drug
fortreating testicular, ovarian, cervical, and
bladder cancers,
• it is also useful in the treatment of melanoma
and a number of other solid tumors
• Carboplatin has a similar spectrum of activity,
but it is approved only for ovarian cancer.
• Oxaliplatin is used in treating advanced colon
cancer.
4/12/2019 20kmch college of pharmacy
21. Antimetabolites
• Antimetabolites generally interfere with the
availabilty of normal purine or pyrimidine
nucleotide precurssor,either by inhibiting their
synthesis or by competing with them in DNA
or RNA synthesis.
• Their maximal cytotoxic effect are in s- phase.
4/12/2019 21kmch college of pharmacy
22. Folate antagonist
• MTX is actively transported into mammalian
cells and inhibits dihydrofolate reductase,
the enzyme that normally converts dietary
folate to the tetrahydrofolate form required for
thymidine and purine synthesis
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23. Mechanism
• The structures of MTX and folic acid are similar.
MTX, however, has an amino group substituted
for a hydroxyl group on the pteridine ring, and it
also has an additional methyl group.
• MTX is actively transported into mammalian cells
and inhibits dihydrofolate reductase, the
enzyme that normally converts dietary folate to
the tetrahydrofolate form required for thymidine
and purine synthesis
4/12/2019 23kmch college of pharmacy
25. Indications
• The use of MTX in the treatment of
choriocarcinoma, a trophoblastic tumor, was
the first demonstration of curative
chemotherapy.
• Used for the treatment of trophoblastic tumors,
breast cancer, and osteosarcoma. It is routinely
given by intrathecal administration to prevent
meningeal metastases during chemotherapy
of acute lymphocytic leukemia
4/12/2019 25kmch college of pharmacy
26. ADR
• It exerts major toxicity on bone marrow
• —low doses given repeatedly cause megaloblastic
anaemia, but high doses produce pancytopenia.
• Mucositis anddiarrhoea are common side effects.
• Desquamation and bleeding may occur in g.i.t.
Megaloblastic anemia
• Thrombocytopenia, leukopenia, aplasia
• Alopecia , liver damage, nephrpathy
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27. Purine antagonists
• The first purine analogue to be used in cancer chemotherapy
was mercaptopurine,a drug introduced almost 60 years ago for
the treatment of acute lymphocytic leukemia.
• Mercaptopurine and thioguanine are the this analogues of
the urine bases hypoxanthine and guanine, respectively.
• The active metabolites of mercaptopurine and thioguanine
inhibit several steps in the biosynthesis of purine bases
(adenine and guanine) and in purine recycling pathways that
supply purine precursors, thereby impairing DNA synthesis.
• Mercaptopurine is metabolized by xanthine oxidase, whereas
thioguanine is degraded by other enzymes.
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29. ADR
• The main toxic effect of antipurines is bone
marrow depression, which develops slowly.
• Mercaptopurine causes more nausea and
vomiting than 6-TG. It also produces a high
incidence of reversible jaundice.
• Cancer chemotherapy places patients at risk
for these problems because the destruction of
cancer cells increases purine catabolism and
uric acid formation, called tumor lysis
syndrome.
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30. • Doses of mercaptopurine must be reduced by
at least 50% in patients who are taking
allopurinol, which inhibits xanthine oxidase
and thereby elevates plasma levels of
mercaptopurine.
• Allopurinol is often given to patients
undergoing cancer chemotherapy because it
inhibits the synthesis of uric acid and thereby
prevents hyperuricemia and gout.
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31. Pyrimidine Analogues
• 5-fluro uracil is converted into 5-fluro 2 deoxy
uridine monophosphate,it inhibits thymidylate
synthase and blocks the conversion of deoxy
uridilic acid to deoxy thymidiylic acid
• 5-FU produces anticancer effect in the s phase
of the cell cycle.
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33. ADR
• Nausea,vomiting diarrhea and alopecia
• Severe ulceration of the oral and GI mucosa
,bone marrow depression and anorexia
• Hand foot syndrome
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34. Indications
• Cancers of Colon, Breast, Ovary, Liver,
Pancreas, Rectum, Stomach
• Glioblastoma Multiforme (Orphan)
• Advanced Colorectal Carcinoma (Orphan)
• Esophageal Carcinoma (Orphan)
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35. Microtuble damaging agents
Obtained from periwinkle plant ( Vinca Rosea)
• Vincristine, vinblastine, vindesine, vinorelbine
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36. • Paclitaxel & docetaxel
• Plant product obtained from bark of Pacific
Yew ( Taxus Brevifolia) & European Yew
(Taxus Buccata)
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38. A, In normal mitosis, the mitotic spindle is formed
by microtubules that continuously undergo
assembly and disassembly as a result of tubulin
polymerization and depolymerization,
respectively.
B, Vincristine and other vinca alkaloids bind to
tubulin and prevent the polymerization of tubulin
dimers.
C, Paclitaxel and other taxanes bind to tubulin,
stabilize the tubulin polymer, and thereby prevent
depolymerization. As with vinca alkaloids,
taxanes cause metaphase arrest.
4/12/2019 38kmch college of pharmacy
39. Indications
• Vincristine is often used to treat hematologic
cancers, including acute lymphocytic leukemia,
Hodgkin and non-Hodgkin lymphomas, and
multiple myeloma.
• It also is used in the treatment of some solid
tumors (e.g., small cell lung cancer,
neuroblastoma, and sarcoma).
• Vinblastine is used for lymphomas and for
bladder, breast, ovarian, and testicular cancers.
4/12/2019 39kmch college of pharmacy
40. Topoisomers 2 inhibitor
• It is a semisynthetic derivative of
podophyllotoxin, a plant glycoside.
• It is not a mitotic inhibitor, but arrests cells in the
G2 phase and causes DNA breaks by affecting
DNA topoisomerase-2 function.
• While the cleaving of double stranded DNA is not
interfered, the subsequent resealing of the strand
is prevented.
• Alopecia, leucopenia
• and g.i.t. disturbances are the main toxicity
4/12/2019 40kmch college of pharmacy
42. INDICATIONS
• Etoposide is used in testicular tumours, lung
cancer, Hodgkin’s and other lymphomas,
carcinoma bladder and stomach
ADR
• Alopecia
• Mild nausea and vomiting
• Dose-limiting myelosuppression.
• They have also been associated with a low
incidence of secondary nonlymphocytic
leukemias.
4/12/2019 42kmch college of pharmacy
43. Topoisomerase 1 inhibitor
Camptothecin analogues
• Irinotecan is approved for the treatment of colorectal
cancer that has recurred or progressed after fluorouracil
therapy.
• It is also active against lymphomas and breast, cervical,
gastric, lung, and other tumors.
• Topotecan is active against glioma, sarcoma, and lung and
ovarian tumors.
• The dose-limiting toxicity of both camptothecin analogues
is myelosuppression.
• Irinotecan produces diarrhea in a significant percentage
of patients, and both drugs can cause alopecia and mild
nausea and vomiting.
4/12/2019 43kmch college of pharmacy
45. ADR
• The major toxicity is bone marrow depression,
especially neutropenia.
• Other adverse effects are pain abdomen,
vomiting ,anorexia and diarrhoea.
• thrombocytpenia
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46. ANTIBIOTICS
• These are products obtained from
microorganisms and have prominent
antitumour activity.
• Practically all of them intercalate between
DNA strands and interfere with its template
function.
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47. Anthracyclines
• Daunorubicin and doxorubicin are antibiotics
obtained from a Streptomyces species, and
idarubicin is a semisynthetic derivative.
• These drugs have a four-member anthracene ring
with attached sugars.
• Two of the four rings are quinone and
hydroquinone moieties that enable the compounds
to accept and donate electrons and thereby
promote the formation of free radicals.
• The anthracene ring accounts for the intense red
color of the drug compounds.
4/12/2019 47kmch college of pharmacy
49. • Doxorubicin and other anthracycline drugs
intercalate between DNA base pairs.
• Anthracyclines are reduced to intermediates
that donate electrons to oxygen to form
superoxide.
• Superoxide then reacts with itself to make
hydrogen peroxide, which is cleaved in the
presence of iron to form the destructive
hydroxyl radical that cleaves DNA.
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50. ADR
• myelosuppression
• nausea and vomiting
• alopecia; and mucosal ulcerations.
• The anthracyclines cause both acute and chronic
cardiotoxicity.
• Manifestations of acute toxicity include sinus tachycardia and
ventricular premature beats.
• These cardiac rhythm disturbances often occur during the first
24 hours and are self-limited.
• Chronic toxicity leads to congestive cardiomyopathy and
limits the cumulative dose of anthracycline that can be given
to any patient.
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51. INDICATION
• Daunorubicin and idarubicin are agents used in
induction and consolidation therapy for acute
myeloid leukemia.
• Doxorubicin has a broader spectrum of
activity.
• It is one of the most active drugs against breast
cancer, and it is also useful in the treatment of
Hodgkin disease, bladder cancer, ovarian
cancer, and other hematologic cancers and
solid tumors
4/12/2019 51kmch college of pharmacy
52. Bleomycin
• Bleomycin is a mixture of two peptides obtained
from Streptomyces verticillus.
• The drug has its greatest effect on neoplastic cells
in the G2 phase of the cell replication cycle.
• Although bleomycin intercalates DNA, the major
cytotoxicity is believed to result from
ironcatalyzed free radical formation and DNA
strand breakage.
• The iron-bleomycin complex binds to DNA,
which reduces molecular oxygen to oxygen free
radicals that cause single strands of DNA to break
4/12/2019 52kmch college of pharmacy
54. MISCELLANEOUS CYTOTOXIC
DRUGS
Hydroxyurea
• It blocks the conversion of ribonucleotides to
deoxyribonucleotides by inhibiting the enzyme
ribonucleoside diphosphate reductase—thus
interferes with DNA synthesis;exerts S-phase
specific action.
4/12/2019 54kmch college of pharmacy
56. • Hydroxyurea is well absorbed orally and is
eliminated in urine with a plasma t½ of ~ 4
hours.
• Myelosuppression is the major toxicity.
• Gastrointestinal disturbances and cutaneous
reactions including pigmentation also occur
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57. INDICATIONS
• Its primary therapeutic value is in chronic
myeloid leukaemia,psoriasis, polycythaemia
vera and occasionally in some solid tumours.
• It is also employed as a radiosensitizer before
radiotherapy, and is a first-line drug for sickle
cell disease in adults.
4/12/2019 57kmch college of pharmacy
58. • L-Asparaginase (L-ASPase)
• The enzyme L-ASPase (from E. coli.) degrades L-
asparagine to L-aspartic acid, depriving the
leukaemic cells of an essential metabolite, and
causes cell death.
• L-asparaginase is a component of regimen for
inducing remission in acute lymphoblastic
leukaemia along with Mtx., prednisolone,
vincristine,etc.
• Moreover, L-ASPase is antigenic, produces
neutralizing antibodies which inactivate and clear
the enzyme rapidly.
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60. ADR
• Many of the typical adverse effects of
anticancerdrugs are not seen with L-ASPase
(no leukopenia, alopecia, or mucosal damage), but
it produces effects due to defective protein
synthesis—hyperglycaemia, raised
triglyceridelevels, pancreatitis, liver damage,
clotting defects and CNS symptoms.
• develop allergic reactions (urticaria, chills, fever,
rash), including anaphylaxis; deaths are reported.
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61. TARGETED DRUGS
Tyrosine-protein kinase inhibitors
• protein kinase inhibitors have been among the
most successful of the targeted anticancer drugs.
• These agents inhibit various kinases that
phosphorylate tyrosine or serine and threonine
residues of growth factor receptors and other
regulatory proteins, and thereby impede pathways
promotingmalignant cell transformation and
proliferation.
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62. • Imatinib, dasatinib, and nilotinib inhibit the BCR-ABL
tyrosine kinase expressed by the Philadelphia chromosome in
CML cells .
• BCR-ABL tyrosine kinase invokes malignant transformation
and proliferation by activating small cytoplasmic GTPases
(Ras and Raf ) and various serine/threonine kinases, including
the Jun kinase and sarcoma family kinases.
• The activated kinases stimulate transcription factors, including
c-Jun, NF-κB (nuclear factor–kappa B), and STAT5 (signal
transducer and activator of transcription 5).
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BCR-ABL signal transduction
63. • Some of these factors increase expression of cyclins
and other positive regulators of the cell cycle
• The activated kinases and transcription factors also
modulate mitochondrial apoptotic regulators, including
a proapoptotic caspase (BAD) and the antiapoptotic
BCL-XL.
• Together, these effects lead to inhibition of apoptosis
(programmed cell death) and promotion of cell
replication.
• BCR-ABL also activates cytoskeletal regulators,
leading to altered cell adhesion and motility .
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66. EGF receptor inhibitors
• Epidermal growth factor (EGF) receptor is a
transmembrane receptor-tyrosinekinase which
regulates growth and differentiation of epitheilal
cells.
• Binding of ligand (EGF) to the extracellular
domain of the receptor induces dimerization
leading to activation of tyrosine kinase activity of
the intracellular domain → autophosphorylation
of the kinase and phosphorylation of several
cytoplasmic regulatory proteins which modify
gene transcription to regulate growth
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68. Indication
• For the continued treatment of patients with
locally advanced or metastatic non-small cell
lung cancer after failure of either platinum-
based or docetaxel chemotherapies.
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69. Angiogenesis inhibitors
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•Angiogenesis
(proliferation of new
blood vessels)
is essential for growth
and metastasis of cancers.
70. • The vascular endothelial growth factor(VEGF) is
the most important stimulus for
neovascularization and increase in microvessel
density within solid tumours.
• VEGF interacts with cell surface VEGF receptor,
that is another receptor tyrosine kinase, which
promotes angiogenesis by phosphorylating
intracellular regulatory proteins.
• Several cancers over express VEGF receptor and
inhibitors of this receptor have been developed as
antitumour drugs.
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72. Adverse effects
• rise in BP,
• arterial thromboembolism leading to
hearattack and stroke
• vessel injury and haemorrhages
• proteinurea
• gastrointestinal perforations
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73. Proteasome inhibitors
• Proteasomes are packaged complexes of
proteolytic enzymes which degrade several
intracellular signalling proteins that control cell
cycle,apoptosis and survival response.
• drugs that target apoptosis inhibiting proteins,
such as the X-linked inhibitor of apoptosis
protein and the B-cell lymphoma gene–2 (Bcl-2)
protein.
• The proteasome inhibitor bortezomib has
recently been approved for treating multiple
myeloma.
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74. Bortezomib
• It is a unique boron containing compound that covalently
binds to proteasome and inhibits its proteolytic activity
disrupting many intracellular signalling pathways.
• The most important of these is nuclear factor-κB (NF-
κB)mediated signalling.
• NF-κB is a transcription factor that normally resides in the
cytoplasm bound to an inhibitory protein IκB.
• Hypoxia, cytotoxic drugs, DNA breaks and other stressful
stimuli activate proteasome which cleaves and degrades IκB
to release NF-κB which then translocates to the nucleus and
transcripts certain genes to produce molecules that oppose
apoptosis and promote cell proliferation.
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75. • Some neoplasms overexpress NFκΒ which
plays an important role in their survival.
• By inhibiting proteasome,bortezomib prevents
the breakup and degradation of IκB, so that
NFκB is not released to transcript survival
molecules.
• It also causes build up of‘Bax’, an apoptosis
promoting protein, and affects other regulators
of cell cycle.
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76. Unarmed monoclonal antibodies
• Monoclonal antibodies are a fast-growing class of
targeted anticancer agents.
• The fragment antigen binding (Fab) portion of an
antibody binds to a specific antigen on a particular type
of cancer cell, leading to disruption of an essential
cancer cell process.
• Some antibodies target growth factors or their
receptors, whereas others release a cytotoxic isotope or
enhance host immunity.
• Because of their protein structure, these agents must be
given intravenously, and they are prone to cause
immune system toxicities.
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77. • The names of monoclonal antibodies end in
mab or monab.
• The letters before mab indicate the source of
the antibody: o for mouse, u for human, and xi
for chimeric.
• An internal letter or syllable identifies the
therapeutic use of the antibody, for example, tu
for tumor, vi for virus, and c or ci for
circulation.
• For example, rituximab is a chimeric human
murine antibody used in treating tumors.
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78. • Malignant cells express certain unique antigens on
their surface to which MAbs could be directed.
• These unmodified (also called unarmed or naked)
MAbs kill the target cells by several mechanisms
including direct signalling of apoptosis, or
antibody-dependent cellular cytotoxicity (ADCC),
or complement-dependent cytotoxicity (CDC).
• They could also be used as missiles to carry
biological bombs (toxins) and are called
immunotoxins, or a radioactive isotope as
radiopharmaceuticals. These are called
‘armed’MAbs.
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81. • They have marked lympholytic action—are
primarily used in acute childhood leukaemia
and lymphomas.
• They induce remission rapidly but relapses
inevitably occur after variable intervals and
gradually the responsiveness is lost.
• Glucocorticoids have a secondary role in some
hormone responsive breast cancers.
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84. Selective estrogen receptor down
regulators
Mechanism
• Inhibits ER dimerization & prevents
interaction of ER with DNA
• ER is down regulated resulting in more
complete supression of ER responsive gene
function
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86. Aromatase inhibitors
Mechanism
• Aromatase ,hormane that produces estrogen,is
found in high level in endometrial tissues.
• Inhibit aromatase which catalyses conversion
of androstenedione (androgenic precursor) to
estrone ( estrogenic hormone
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