Anti cancer plants

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Anti cancer DrugsBy : 

Anti cancer DrugsBy Dr. Mobasher Ahmad Ph.D (Wales)

Cancer chemotherapy: general principles : 

Cancer chemotherapy: general principles The term ‘cancer’ refers to a malignant neoplasm (new growth). Cancer cells can manifest : Un controlled proliferation (no differentiation) invasiveness the ability to metastasise . Most anticancer drugs are antiproliferative and will also affect rapidly dividing normal cells, and are thus likely to depress bone marrow, to impair healing, to depress growth, to cause sterility and hair loss, and to be teratogenic. Most cause nausea and vomiting.

Drugs used in cancer chemotherapy : 

Drugs used in cancer chemotherapy Cytotoxic drugs: Alkylating agents: These act by forming covalent bonds with DNA and thus impeding DNA replication. Antimetabolites: These block or subvert one or more of the metabolic pathways involved in DNA synthesis. Cytotoxic antibiotics: These are substances of microbial origin which prevent eukaryotic cell division. Vinca alkaloids: These are substances of plant origin that specifically affect microtubule function and hence the formation of the mitotic spindle.

Contd : 

Contd Hormones: Most important are steroids, namely glucocorticoids, oestrogens and androgens.

Sites of action of cytotoxic agents that act on dividing cells : 

Sites of action of cytotoxic agents that act on dividing cells Purine and Pyrimidine synthesis 6- Mercaptopurine, Thioguanine Inhibit purine sysnthesis, inhibit nucleotide interconversion. Methotrexate: inhibition of dihydrofolate Reductase leads to an inhibition of purine ring and dTMP biosysthesis Ribonucleotides

Contd : 

Contd Ribonucleotides Methotrexate 5-Fluorouracil (inhibit dTMP(2’deoxythymidylate)synthesis) . Cytarabine Terminates DNA chain elongation. Incorporated into DNA and RNA resulting in altered function of nucleic acids. Deoxy-ribonucleotides

Contd : 

Contd Deoxy-ribonucleotides . Cytarabine DNA Bleomycin, Doxorubicin, Daunorubicin Scission of DNA by an oxidative process.

Contd : 

Contd DNA Dactinomycin,Doxorubicin, Daunorubicin Intercalate with DNA, disrupting DNA function. Alkylating agents Nitrosoureas Cisplatin Alter structure and function of DNA by cross-linking and or fragmenting of DNA strands. RNA

Contd : 

Contd RNA Proteins

Anticancer drugs: alkylating agents and related compounds : 

Anticancer drugs: alkylating agents and related compounds Alkylating agents have alkyl groups which can form covalent bonds with cell substituents;a carbonium ion is the reactive intermediate. Most have two alkylating groups and can cross link two nucleophilic sites such as the N7 of guanine in DNA; cross-linking can cause : .defective replication .pairing of alkylguanine with thymine, and then substitution of At for GC .Excision of guanine and chain breakage. The principal effect occurs during DNA synthesis.

Contd : 

Contd Unwanted effects include myelosuppression, sterility and risk of non-lymphocytic leukaemia. The main alkylating agents are: Nitrogen mustards: e.g cyclophosphamide, which is activated to give aldophosphamide, which is then converted to phosphoramide mustard and acrolein. Cyclophosphamide myelosuppression affects particularly the lymphocytes. Given orally. Nitrosoureas: e.g lomustine may act on non-dividing cells;can cross the blood-brain barrier; causes delayed, cumulative myelotoxicity.Given orally. Cisplatin; It interacts with DNA;it has low myelotoxicity but causes severe nausea and vomiting and can be nephrotoxic. Given intravenously.

Anticancer drugs: antimetabolites : 

Anticancer drugs: antimetabolites These drugs block or subvert pathways in DNA synthesis. Folate antagonists: Methotrexate inhibits dihydrofolate reductase, preventing generation of tetrahydrofolate; the main result is interference with thymidylate synthesis. Methotrexate is taken up into cells by the folate carrier, and like folate, converted to the polyglutamate form. Given orally. Normal cells affected by high doses can be rescued by folinic acid.(Folate—FH2---FH4----MethyleneFH4—Deoxythymidylic acid Methionine) Unwanted effects: myelosuppression,possible nephrotoxicity.

Contd : 

Contd Pyrimidine analogues: Fluorouracil, given orally or intravenously, is converted to a fraudulent nucleotide and inhibits thymidylate synthesis. Cytarabine, given intravenously or subcutaneously; its triphosphate form inhibits DNA polymerase; potent myelosuppressive. Purine analogues: Mercaptopurine, given orally, is converted into a fraudulent nucleotide.

Anticancer drugs: cytotoxic antibiotics : 

Anticancer drugs: cytotoxic antibiotics Doxorubicin : It inhibits DNA and RNA synthesis; the DNA effect is due to interference with topoisomerase ll action. Given by intravenous infusion; it is excreted mainly in bile. Unwanted effects: nausea and vomiting, myelosuppression, hair loss; it is cardiotoxic in high doses. Biomycin: It causes fragmentation of DNA chains. It can act on non-dividing cells. Given by injection. Unwanted effects: fever,allergies, pulmonary fibrosis. Virtually no myelosuppression. Dactinomycin: It intercalates in DNA, interferes with RNA polymerase and inhibits transcription. Given by injection. Unwanted effects: nausea and vomiting, myelosuppression. Mitomycin : It is activated to give an alkylating metabolite. Given intravenously.

Anticancer drugs: miscellaneous agents : 

Anticancer drugs: miscellaneous agents Plant alkaloids: Vincristine It inhibits mitosis at metaphase by binding to tubulin. Given by injection. Relatively non-toxic, but can cause unwanted neuromuscular effects. Hormones: These are used in hormone-sensitive tumours: Glucocorticoids for leukaemias and lymphomas.Oestrogens for tumours in men. Androgens or tamoxifen for breast tumours. Radioactive isotopes: It can be targeted at specific tissuese. E.g I 131 for thyroid tumours.

Leukemia : 

Leukemia Malignant disorders of blood leukocytes. Support the patient with red cell and platelet transfusion. Remission induction chemotherapy and maintenance chemotherapy. Remission induction chemotherapy: The objective is to clear the body of all detectable leukemic leukocytes. The current practise is to employ a combination of vincristine and prednisone for initial induction of remission.

Contd : 

Contd Maintenance Chemotherapy: The objective of maintenance therapy is to keep the population of residual leukemic cells in check so that they do not repopulate the blood and bone marrow and lead to the return of symptoms. This usually consists of a combination of oral methortrexate, mercaptopurine and cyclophosphamide, administered either in pulses, simultaneously, or in various sequences.

Treatment for HBV : 

Treatment for HBV HBV infected persons should be evaluated by their doctor for liver disease. Adefovir dipivoxil, interferon alfa-2b, pegylated interferon alfa-2a, lamivudine, and entecavir are five drugs used for the treatment of persons with chronic hepatitis B. These drugs should not be used by pregnant women. Drinking alcohol can make your liver disease worse.