抗肿瘤药(英文版).ppt
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1、Anticancer Drugs,Dr.Qamar Barakzai Department of Pharmacology Ziauddin Medical University Karachi.Pakistan,“CANCER” Refers to a Malignant neoplasm (New growth) Cancer cells can manifest: Uncontrolled Proliferation. Loss of function due to lack of ability to differentiate. Invasiveness. The ability t
2、o metastasize. Cancer arises as a result of a series of genetic changes in the cell, the main genetic lesions being: Inactivation of tumor suppressor genes. The activation of oncogenes.,Antineoplastic agents Are cytotoxic not tumoricidal Only kill cells during mitosis, and Not all cancer cells are d
3、ividing at the same time. SUCCESS DEPENDS ON: Stage of cancer at time of diagnosis Type of cancer Development of drug resistance Overall health of patient.,R,Tumor Suppressor Genes -ve (p53) Growth Factors Oncogenes +ve,S DNA Synthesis,G2 Premitotic Interval,M,PROPHASE METAPHASE ANAPHASE TELOPHASE,M
4、ITOSIS,G0,G1,S PHASE SPECIFIC Cytosine Arbinoside Hydroxyurea S PHASE SPECIFIC SELF LIMITING 6-Mercaptpurine Methotrexate.,M PHASE SPECIFIC vincristine vinblastine paclitaxel,PHASE NONSPECIFIC alkylating agents, cis-platinum nitrosoureas, dacarbazine antibiotics procarbazine,G0,Differentiation,CELL
5、GROWTH CYCLE 5 DISTINCT PHASES OF MITOSIS 1. G0 - Resting - no mitosis 2. G1 - Postmitotic - first growth 3. S - DNA synthesis phase 4. G2 - Premitotic - second growth 5. M - Mitosis phase GENERATION TIME - one complete cycle different in all tumors, from hours to days,PENTOSTATIN,Inhibits adenosine
6、 Deaminase,PALA,Inhibits Pyrimidine Biosynthesis,Purine synthesis,Pyrimidine synthesis,Ribonucleotides,Deoxyribonucleotides,DNA,HYDROXYUREA,Inhibit Ribonucleotide Reductase,6-MERCAPTOPURINE 6-THIOGAUNINE,Inhibit Puring ring biosynthesis,Inhibit Neocleotide interconversions,5-FLOUROURACIL,Inhibit TMP
7、 Synthesis,METHOTREXATE,Inhibit dihydrofolate reduction, blocks TMP and Purine synthesis,DNA,RNA,(Transfer, messenger, ribosomal),CYTARABINE FLUDARABINE 2-CHLORODEOXY ADENOSINE,Inhibit DNA Synthesis,ALKYLATING AGENTS MITOMYCETIN CISPLATIN PROCARBAZINE DACARBAZINE,Form adducts w/ DNA,BLEOMYCIN ETOPOS
8、IDE TENIPOSIDE,Damage DNA and Prevent repair,DACTINOMYCINE DAUNORUBICIN DOXORUBICIN MITOXANTRONE,Intercalate with DNA Inhibit RNA synthesis,PROTEINS,Enzymes,Microtubules,A-ASPARAGINASE,Deaminate asparagine,Inhibits protein synthesis,PACLITAXEL VINCA ALKALOIDS COLCHICINE,Inhibit function of Microtubu
9、les,ANTINEOPLASTIC AGENTS DEFINITIONS: ALKYLATION - chemical reaction that cleaves DNA and interferes with mitosis BIFUNCTIONAL ALKYLATING AGENTS - have 2 alkyl groups and alkalate 2 DNA strands DOSE-LIMITED SIDE EFFECTS - adverse effects that prevent an agent from being given in higher doses EMETIC
10、 POTENTIAL - potential of an agent to cause N & V,ANTINEOPLASTIC AGENTS ADVERSE EFFECTS: Kills all fast growing cells Hair follicles GI tract mucosa Bone marrow suppression (BMS) causing anemiaand leukopenia All are pregnancy category D ! Most are nephro- hepato- and ototoxic Extravasation of IV can
11、 result in loss of limb,Antineoplastic Agents ADVERSE EFFECTS: (Contd) All have a BMS and emetic index All have wide interaction with other drugs. Special training required for nursing Most agents can be harmful to nurse administering them,DEFINITIONS: GROWTH FRACTION % of cells in mitosis at any gi
12、ven time LEUCOVORIN RESCUE - use of leucovorin to reverse methotrexate-induced toxicity MITOTIC INDEX number of cells per unit undergoing mitosis during a given time NADIR lowest point (as in blood count) after being depressed by chemotherapy PARANEOPLASTIC SYNDROME (PNS) S/S of cancer located dista
13、nt from tumor or its metastatic sites,ANTINEOPLASTIC AGENTS 2 MAIN GROUPS OF AGENTS: CELL CYCLE - NONSPECIFIC (CCNS) ALKYLATING AGENTS cytotoxic in any phase of cell cycle effective against slowly growing tumors CELL CYCLE - SPECIFIC (CCS) 3 TYPES ANTIMETABOLITES - cytotoxic is S phase MITOTIC INHIB
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